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Molecules, Volume 18, Issue 11 (November 2013), Pages 13124-14454

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Open AccessArticle Polyethylene Glycol (PEG-400): An Efficient and Recyclable Reaction Medium for the Synthesis of Pyrazolo[3,4-b]pyridin-6(7H)-one Derivatives
Molecules 2013, 18(11), 13139-13147; doi:10.3390/molecules181113139
Received: 27 September 2013 / Revised: 16 October 2013 / Accepted: 16 October 2013 / Published: 24 October 2013
Cited by 4 | PDF Full-text (239 KB) | HTML Full-text | XML Full-text
Abstract
A mild and efficient synthesis of pyrazolo[3,4-b]pyridine-6(7H)-one derivatives via a three-component reaction of an aldehyde, Meldrum’s acid and 3-methyl-1H-pyrazol-5-amine using recyclable polyethylene glycol (PEG)-400 as a reaction medium is described. This method has the advantages of [...] Read more.
A mild and efficient synthesis of pyrazolo[3,4-b]pyridine-6(7H)-one derivatives via a three-component reaction of an aldehyde, Meldrum’s acid and 3-methyl-1H-pyrazol-5-amine using recyclable polyethylene glycol (PEG)-400 as a reaction medium is described. This method has the advantages of accessible starting materials, good yields, mild reaction conditions and begin environmentally friendly. Full article
Open AccessArticle Physiological Effects of l-Theanine on Drosophila melanogaster
Molecules 2013, 18(11), 13175-13187; doi:10.3390/molecules181113175
Received: 8 August 2013 / Revised: 15 October 2013 / Accepted: 15 October 2013 / Published: 24 October 2013
Cited by 2 | PDF Full-text (1291 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Green tea has been consumed as the most popular drink in East Asia for centuries, and is believed to have a wide range of health benefits. l-Theanine, the major component of the free amino acids in green tea, has been reported to [...] Read more.
Green tea has been consumed as the most popular drink in East Asia for centuries, and is believed to have a wide range of health benefits. l-Theanine, the major component of the free amino acids in green tea, has been reported to display neuronal protection and tumor inhibition in vitro, but its physiological effects on animal development and behavior remain elusive. In this report, we used Drosophila melanogaster, the fruit fly, as a model organism to investigate the physiological effects of L-theanine. Flies were fed with three different concentrations of theanine as a dietary supplement after eclosion, and were examined for a variety of physiological parameters at different time points. We found theanine treatment results in significantly increased locomotion and courtship ability, and decreased resistance against wet and dry starvation in males, but not in females. Furthermore, theanine application diminished UV tolerance in females, but not in males. However, we did not perceive distinguishable effect of theanine on animal development, life span, weight, and tolerance of heat and anoxia. This work represents the first comprehensive physiological investigation of L-theanine at the whole animal level, and shall shed light on the mechanistic study of theanine in the future. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Following the Mechanisms of Bacteriostatic versus Bactericidal Action Using Raman Spectroscopy
Molecules 2013, 18(11), 13188-13199; doi:10.3390/molecules181113188
Received: 13 August 2013 / Revised: 10 October 2013 / Accepted: 17 October 2013 / Published: 24 October 2013
Cited by 14 | PDF Full-text (762 KB) | HTML Full-text | XML Full-text
Abstract
Antibiotics cure infections by influencing bacterial growth or viability. Antibiotics can be divided to two groups on the basis of their effect on microbial cells through two main mechanisms, which are either bactericidal or bacteriostatic. Bactericidal antibiotics kill the bacteria and bacteriostatic [...] Read more.
Antibiotics cure infections by influencing bacterial growth or viability. Antibiotics can be divided to two groups on the basis of their effect on microbial cells through two main mechanisms, which are either bactericidal or bacteriostatic. Bactericidal antibiotics kill the bacteria and bacteriostatic antibiotics suppress the growth of bacteria (keep them in the stationary phase of growth). One of many factors to predict a favorable clinical outcome of the potential action of antimicrobial chemicals may be provided using in vitro bactericidal/bacteriostatic data (e.g., minimum inhibitory concentrations—MICs). Consequently, MICs are used in clinical situations mainly to confirm resistance, and to determine the in vitro activities of new antimicrobials. We report on the combination of data obtained from MICs with information on microorganisms’ “fingerprint” (e.g., DNA/RNA, and proteins) provided by Raman spectroscopy. Thus, we could follow mechanisms of the bacteriostatic versus bactericidal action simply by detecting the Raman bands corresponding to DNA. The Raman spectra of Staphylococcus epidermidis treated with clindamycin (a bacteriostatic agent) indeed show little effect on DNA which is in contrast with the action of ciprofloxacin (a bactericidal agent), where the Raman spectra show a decrease in strength of the signal assigned to DNA, suggesting DNA fragmentation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G2/M Cell Cycle Arrest and Apoptosis
Molecules 2013, 18(11), 13200-13217; doi:10.3390/molecules181113200
Received: 18 September 2013 / Revised: 14 October 2013 / Accepted: 18 October 2013 / Published: 24 October 2013
Cited by 11 | PDF Full-text (2063 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to investigate the radiosensitizing effect of genistein, and the corresponding mechanisms of action on breast cancer cells with different estrogen receptor (ER) status. Human breast cancer cell lines such as MCF-7 (ER-positive, harboring wild-type p53) [...] Read more.
The aim of the present study was to investigate the radiosensitizing effect of genistein, and the corresponding mechanisms of action on breast cancer cells with different estrogen receptor (ER) status. Human breast cancer cell lines such as MCF-7 (ER-positive, harboring wild-type p53) and MDA-MB-231 (ER-negative, harboring mutant p53) were irradiated with X-rays in the presence or absence of genistein. Cell survival, DNA damage and repair, cell cycle distribution, cell apoptosis, expression of proteins related to G2/M cell cycle checkpoint and apoptosis were measured with colony formation assays, immunohistochemistry, flow cytometry and western blot analysis, respectively. Genistein showed relatively weak toxicity to both cell lines at concentrations in the range of 5–20 μM. Using the dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at a 10% cell survival (IC10) were 1.43 for MCF-7 and 1.36 for MDA-MB-231 cells, respectively. Significantly increased DNA damages, arrested cells at G2/M phase, decreased homologous recombination repair protein Rad51 foci formation and enhanced apoptotic rates were observed in both cell lines treated by genistein combined with X-rays compared with the irradiation alone. The combined treatment obviously up-regulated the phosphorylation of ATM, Chk2, Cdc25c and Cdc2, leading to permanent G2/M phase arrest, and up-regulated Bax and p73, down-regulated Bcl-2, finally induced mitochondria-mediated apoptosis in both cell lines. These results suggest that genistein induces G2/M arrest by the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway and ultimately enhances the radiosensitivity of both ER+ and ER- breast cancer cells through a mitochondria-mediated apoptosis pathway. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle One Lignanoid Compound and Four Triterpenoid Compounds with Anti-Inflammatory Activity from the Leaves of Elaeagnus oldhamii Maxim.
Molecules 2013, 18(11), 13218-13227; doi:10.3390/molecules181113218
Received: 4 September 2013 / Revised: 10 October 2013 / Accepted: 22 October 2013 / Published: 25 October 2013
Cited by 2 | PDF Full-text (303 KB) | HTML Full-text | XML Full-text
Abstract
One lignanoid compound, isoamericanol B (1), along with four triterpenoid compounds—cis-3-O-p-hydroxycinnamoyloleanolic acid (2), trans-3-O-p-hydroxy cinnamoyloleanolic acid (3), cis-3-O-p-hydroxycinnamoylursolic acid ( [...] Read more.
One lignanoid compound, isoamericanol B (1), along with four triterpenoid compounds—cis-3-O-p-hydroxycinnamoyloleanolic acid (2), trans-3-O-p-hydroxy cinnamoyloleanolic acid (3), cis-3-O-p-hydroxycinnamoylursolic acid (4), trans-3-O-p-hydroxycinnamoylursolic acid (5) have been isolated for the first time from the leaves of Elaeagnus oldhamii Maxim. Compounds 14 significantly inhibited the expression of NO (nitric oxide) produced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The IC50 value for inhibition of nitrite production of compound 1 was about 10.3 ± 0.4 μg/mL. In the cell viability test, however, among compounds 14 compound 1 did not significantly change cell viability. Therefore, in this study compound 1 possessed anti-inflammatory effects. The result suggests compound 1 as a potential lead compound for the treatment of inflammatory diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Inflammatory Effect of Neoechinulin A from the Marine Fungus Eurotium sp. SF-5989 through the Suppression of NF-кB and p38 MAPK Pathways in Lipopolysaccharide-Stimulated RAW264.7 Macrophages
Molecules 2013, 18(11), 13245-13259; doi:10.3390/molecules181113245
Received: 13 September 2013 / Revised: 5 October 2013 / Accepted: 18 October 2013 / Published: 25 October 2013
Cited by 11 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the course of a bioassay-guided study of metabolites from the marine fungus Eurotium sp. SF-5989, two diketopiperazine type indole alkaloids, neoechinulins A and B, were isolated. In this study, we investigated the anti-inflammatory effects of neoechinulins A (1) and [...] Read more.
In the course of a bioassay-guided study of metabolites from the marine fungus Eurotium sp. SF-5989, two diketopiperazine type indole alkaloids, neoechinulins A and B, were isolated. In this study, we investigated the anti-inflammatory effects of neoechinulins A (1) and B (2) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Neoechinulin A (1) markedly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner ranging from 12.5 µM to 100 µM without affecting the cell viability. On the other hand, neoechinulin B (2) affected the cell viability at 25 µM although the compound displayed similar inhibitory effect of NO production to neoechinulin A (1) at lower doses. Furthermore, neoechinulin A (1) decreased the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). We also confirmed that neoechinulin A (1) blocked the activation of nuclear factor-kappaB (NF-κB) in LPS-stimulated RAW264.7 macrophages by inhibiting the phosphorylation and degradation of inhibitor kappa B (IκB)-α. Moreover, neoechinulin A (1) decreased p38 mitogen-activated protein kinase (MAPK) phosphorylation. Therefore, these data showed that the anti-inflammatory effects of neoechinulin A (1) in LPS-stimulated RAW264.7 macrophages were due to the inhibition of the NF-κB and p38 MAPK pathways, suggesting that neoechinulin A (1) might be a potential therapeutic agent for the treatment of various inflammatory diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Isosakuranetin-5-O-rutinoside: A New Flavanone with Antidepressant Activity Isolated from Salvia elegans Vahl.
Molecules 2013, 18(11), 13260-13270; doi:10.3390/molecules181113260
Received: 21 August 2013 / Revised: 12 October 2013 / Accepted: 22 October 2013 / Published: 25 October 2013
Cited by 4 | PDF Full-text (284 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ursolic acid (1) and a new flavanone, 5-O-(6-rhamnosylglucoside)-7-hydroxy-4'-methoxyflavanone (2), were isolated from the leaves of Salvia elegans Vahl. These natural products displayed antidepressant activity in mice as determined by means of a forced swimming test (FST) [...] Read more.
Ursolic acid (1) and a new flavanone, 5-O-(6-rhamnosylglucoside)-7-hydroxy-4'-methoxyflavanone (2), were isolated from the leaves of Salvia elegans Vahl. These natural products displayed antidepressant activity in mice as determined by means of a forced swimming test (FST) evaluation. Structural elucidation was carried out by chemical derivatization (acetylation) and spectroscopic analyses, such as 1H- and 13C-NMR and two-dimensional (2-D) COSY, heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple-bond correlation (HMBC) spectroscopy experiments. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Effect of HT042, Herbal Formula, on Longitudinal Bone Growth in Spontaneous Dwarf Rats
Molecules 2013, 18(11), 13271-13282; doi:10.3390/molecules181113271
Received: 23 September 2013 / Revised: 15 October 2013 / Accepted: 16 October 2013 / Published: 28 October 2013
PDF Full-text (499 KB) | HTML Full-text | XML Full-text
Abstract
HT042 is a new herbal prescription consisting of Astragalus membranaceus, Phlomis umbrosa and Eleutherococcus senticosus, which are used in Korean medicine to stimulate growth in children. We investigated the effects of HT042 on the body weight, longitudinal bone growth, and [...] Read more.
HT042 is a new herbal prescription consisting of Astragalus membranaceus, Phlomis umbrosa and Eleutherococcus senticosus, which are used in Korean medicine to stimulate growth in children. We investigated the effects of HT042 on the body weight, longitudinal bone growth, and bone length in spontaneous dwarf rats (SDR). Male and female SDRs were divided into three groups: the control group (DW, 10 mL/kg/day), the recombinant human GH group (rhGH; 500 µg/kg/day), and the HT042 (100 mg/kg/day) group. Each group received the respective treatments for 10 days. Body weight was measured on day 10 of treatment. On day 8, tetracycline (20 mg/kg) was injected intraperitoneally into all individuals to form a fluorescent band on the newly synthesized bone. On day 10, femur and tibia lengths were measured using PIXImus. Body weight, longitudinal bone growth, and bone length were not affected in the HT042 group. In contrast, the rhGH group showed significantly increased body weight, longitudinal bone growth, and bone length. In conclusion, HT042 does not act through a GH-like effect to promote longitudinal bone growth. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Conformational Analysis of Geometric Isomers of Pitavastatin Together with Their Lactonized Analogues
Molecules 2013, 18(11), 13283-13296; doi:10.3390/molecules181113283
Received: 24 September 2013 / Revised: 17 October 2013 / Accepted: 19 October 2013 / Published: 28 October 2013
Cited by 4 | PDF Full-text (899 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Super-statins are synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is the rate-limiting enzyme responsible for the biosynthesis of cholesterol. All of the super-statins with a C=C double bond spacer between the heterocyclic and the dihydroxycarboxylic moiety that are currently on the market [...] Read more.
Super-statins are synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is the rate-limiting enzyme responsible for the biosynthesis of cholesterol. All of the super-statins with a C=C double bond spacer between the heterocyclic and the dihydroxycarboxylic moiety that are currently on the market exist as E-isomers. To extend the understanding of conformational and thermodynamic preferences of Z-isomeric super-statin analogues, this study focused on analyzing pitavastatin and its lactonized derivatives via NMR spectroscopy and ab initio calculations. Z-isomeric pitavastatin analogues exist in solution as a pair of interconverting rotamers, where the Gibbs free energies between the major and minor rotamers are within 0.12 and 0.25 kcal mol−1 and the rotational energy barriers are between 15.0 and 15.9 kcal mol−1. The analysis of long-range coupling constants and ab initio calculations revealed that rotation across the C5'–C7 single bond is essential for generating a pair of atropisomers. The overall comparison of the results between Z-isomeric pitavastatin and rosuvastatin analogues demonstrated that the former are to some extent more flexible to attain numerous conformations. Demonstrating how structural differences between super-statin analogues induce distinctive conformational preferences provides important insight into the super-statins’ conformational variability and may well improve future drug design. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
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Open AccessArticle Dillenia Suffruticosa Extract Inhibits Proliferation of Human Breast Cancer Cell Lines (MCF-7 and MDA-MB-231) via Induction of G2/M Arrest and Apoptosis
Molecules 2013, 18(11), 13320-13339; doi:10.3390/molecules181113320
Received: 5 August 2013 / Revised: 20 October 2013 / Accepted: 20 October 2013 / Published: 29 October 2013
Cited by 11 | PDF Full-text (3383 KB) | HTML Full-text | XML Full-text
Abstract
The present research was designed to evaluate the anticancer properties of Dillenia suffruticosa extract. Our focus was on the mode of cell death and cell cycle arrest induced in breast cancer cells by the active fractions (designated as D/F4, D/F5 and EA/P2) [...] Read more.
The present research was designed to evaluate the anticancer properties of Dillenia suffruticosa extract. Our focus was on the mode of cell death and cell cycle arrest induced in breast cancer cells by the active fractions (designated as D/F4, D/F5 and EA/P2) derived from chromatographic fractionation of D. suffruticosa extracts. The results showed that the active fractions are more cytotoxic towards MCF-7 (estrogen positive breast cancer cells) and MDA-MB-231 (estrogen negative breast cancer cells) as compared to other selected cancer cell lines that included HeLa, A459 and CaOV3. The induction of cell death through apoptosis by the active fractions on the breast cancer cells was confirmed by Annexin V-FITC and PI staining. Cell cycle analysis revealed that D/F4 and EA/P2 induced G2/M phase cell cycle arrest in MCF-7 cells. On the other hand, MDA-MB-231 cells treated with D/F4 and D/F5 accumulated in the sub-G1 phase without cell cycle arrest, suggesting the induction of cell death through apoptosis. The data suggest that the active fractions of D. suffruticosa extract eliminated breast cancer cells through induction of apoptosis and cell cycle arrest. The reason why MCF-7 was more sensitive towards the treatment than MDA-MB-231 remains unclear. This warrants further work, especially on the role of hormones in response towards cytotoxic agents. In addition, more studies on the mechanisms underlying the induction of apoptosis and cell cycle arrest by the plant extract also need to be carried out. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Preparation and Optimization of Triptolide-Loaded Solid Lipid Nanoparticles for Oral Delivery with Reduced Gastric Irritation
Molecules 2013, 18(11), 13340-13356; doi:10.3390/molecules181113340
Received: 26 August 2013 / Revised: 18 October 2013 / Accepted: 21 October 2013 / Published: 29 October 2013
Cited by 10 | PDF Full-text (1599 KB) | HTML Full-text | XML Full-text
Abstract
Triptolide (TP) often causes adverse reactions in the gastrointestinal tract when it is administered orally. This study aimed to prepare and optimize triptolide-loaded solid lipid nanoparticles (TP-SLN) with reduced gastric irritation. The microemulsion technique was used to formulate TP-SLN employing a five-level [...] Read more.
Triptolide (TP) often causes adverse reactions in the gastrointestinal tract when it is administered orally. This study aimed to prepare and optimize triptolide-loaded solid lipid nanoparticles (TP-SLN) with reduced gastric irritation. The microemulsion technique was used to formulate TP-SLN employing a five-level central composite design (CCD) that was developed for exploring the optimum levels of three independent variables on particle size, encapsulation efficiency (EE) and drug loading (DL). Quadratic polynomial models were generated to predict and evaluate the three independent variables with respect to the three responses. The optimized TP-SLN was predicted to comprise fraction of lipid of 49.73%, surfactant to co-surfactant ratio of 3.25, and lipid to drug ratio of 55.27, which showed particle size of 179.8 ± 5.7 nm, EE of 56.5 ± 0.18% and DL of 1.02 ± 0.003% that were in good agreement with predicted values. In addition, the optimized nanoparticles manifested a sustained-release pattern in vitro and were stable during 3 h of incubation in simulated gastric fluids without significant size change and the majority (91%) of the drug was protected. Furthermore, the nanoparticles did not show obvious gastric irritation caused by oral administration of TP in rats. Full article
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Open AccessArticle Anti-Tumor Effects of Atractylenolide I Isolated from Atractylodes macrocephala in Human Lung Carcinoma Cell Lines
Molecules 2013, 18(11), 13357-13368; doi:10.3390/molecules181113357
Received: 2 September 2013 / Revised: 1 October 2013 / Accepted: 16 October 2013 / Published: 29 October 2013
Cited by 17 | PDF Full-text (337 KB) | XML Full-text
Abstract
Atractylenolide I (ATL-1) is the major sesquiterpenoid of Atractylodes macrocephala. This study was designed to investigate whether ATL-1 induced apoptosis in A549 and HCC827 cells in vitro and in vivo. In our results, ATL-1 significantly decreased the percentage of in [...] Read more.
Atractylenolide I (ATL-1) is the major sesquiterpenoid of Atractylodes macrocephala. This study was designed to investigate whether ATL-1 induced apoptosis in A549 and HCC827 cells in vitro and in vivo. In our results, ATL-1 significantly decreased the percentage of in vitro viability, in a dose-dependent manner. In addition, DAPI staining and flow cytometry tests demonstrated the induction of apoptosis by ATL-I. Western blot analysis indicated that the protein levels of caspase-3, caspase-9 and Bax were increased in A549 and HCC827 cells after ATL-I exposure; to the contrary, the expressions of Bcl-2, Bcl-XL were decreased after treatment with ATL-1. In the in vivo study, ATL-I effectively suppressed tumor growth (A549) in transplanted tumor nude mice with up-regulation of caspase-3, caspase-9, and Bax and down-regulation of Bcl-2 and Bcl-XL. In conclusion, our results demonstrated that ATL-I has significant antitumor activity in lung carcinoma cells, and the possible mechanism of action may be related to apoptosis induced by ATL-I via a mitochondria-mediated apoptosis pathway. Full article
Open AccessArticle Synthesis, Characterization, X-ray Structure and Biological Activities of C-5-Bromo-2-hydroxyphenylcalix[4]-2-methyl resorcinarene
Molecules 2013, 18(11), 13369-13384; doi:10.3390/molecules181113369
Received: 23 September 2013 / Revised: 14 October 2013 / Accepted: 14 October 2013 / Published: 29 October 2013
Cited by 4 | PDF Full-text (2055 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
C-5-bromo-2-hydroxyphenylcalix[4]-2-methylresorcinarene (I) was synthesized by cyclocondensation of 5-bromo-2-hydroxybenzaldehyde and 2-methylresorcinol in the presence of concentrated HCl. Compound I was characterized by infrared and nuclear magnetic resonance spectroscopic data. X-ray analysis showed that this compound crystallized in a triclinic system with [...] Read more.
C-5-bromo-2-hydroxyphenylcalix[4]-2-methylresorcinarene (I) was synthesized by cyclocondensation of 5-bromo-2-hydroxybenzaldehyde and 2-methylresorcinol in the presence of concentrated HCl. Compound I was characterized by infrared and nuclear magnetic resonance spectroscopic data. X-ray analysis showed that this compound crystallized in a triclinic system with space group of Pī, a = 15.9592(16)Å, b = 16.9417(17)Å, c = 17.0974(17)Å, α = 68.656(3)°, β = 85.689(3)°, γ = 81.631(3)°, Z = 2 and V = 4258.6(7)Å3. The molecule adopts a chair (C2h) conformation. The thermal properties and antioxidant activity were also investigated. It was strongly antiviral against HSV-1 and weakly antibacterial against Gram-positive bacteria. Cytotoxicity testing on Vero cells showed that it is non-toxic, with a CC50 of more than 0.4 mg/mL. Full article
Open AccessArticle The Novel [4,5-e][1,3]Diazepine-4,8-dione and Acyclic Carbamoyl Imino-Ureido Derivatives of Imidazole: Synthesis, Anti-Viral and Anti-Tumor Activity Evaluations
Molecules 2013, 18(11), 13385-13397; doi:10.3390/molecules181113385
Received: 29 August 2013 / Revised: 5 October 2013 / Accepted: 17 October 2013 / Published: 30 October 2013
PDF Full-text (317 KB) | HTML Full-text | XML Full-text
Abstract
In the present paper, we report on the synthesis, and in vitro antiviral and cytostatic activities of a series of novel imidazole[4,5-e][1,3]diazepine-4,8-dione (compounds 911) and acyclic carbamoyl imino-ureido imidazole (compounds 12 and 13) derivatives. These new type of [...] Read more.
In the present paper, we report on the synthesis, and in vitro antiviral and cytostatic activities of a series of novel imidazole[4,5-e][1,3]diazepine-4,8-dione (compounds 911) and acyclic carbamoyl imino-ureido imidazole (compounds 12 and 13) derivatives. These new type of chemical entities showed no significant activity on the broad spectrum of DNA and RNA viruses. Results of antiproliferative assays performed on a panel of selected human tumor cell lines revealed that only compounds 1 and 5 showed moderate and selective cytostatic effect against HeLa cells (IC50 = 24 and 32 µM) with no concomitant cytotoxic effects on human normal fibroblasts (BJ). Importantly, an imidazole derivative containing a pyrrolidine moiety linked via an ethylenic spacer (3) showed a selective cytostatic effect toward cervical carcinoma (HeLa) cells (IC50 = 9.5 µM) with no apparent cytotoxicity on human normal fibroblasts (BJ). This compound can be therefore considered as a potential anti-tumor lead compound for further synthetic structure optimization. Full article
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Open AccessArticle A Piston-Rotaxane with Two Potential Stripes: Force Transitions and Yield Stresses
Molecules 2013, 18(11), 13398-13409; doi:10.3390/molecules181113398
Received: 18 September 2013 / Revised: 18 October 2013 / Accepted: 22 October 2013 / Published: 30 October 2013
Cited by 5 | PDF Full-text (645 KB) | HTML Full-text | XML Full-text
Abstract
We examine a rod piston-rotaxane system, where the positions of several mobile rings on the axle are controlled by an external force acting on one of the rings. This allows us to access the translational entropy of the rings. For a simple [...] Read more.
We examine a rod piston-rotaxane system, where the positions of several mobile rings on the axle are controlled by an external force acting on one of the rings. This allows us to access the translational entropy of the rings. For a simple rotaxane molecule with an axle that has uniform ring-axle interactions along its length, the molecule behaves like a miniature piston filled with a one-dimensional ideal gas. We then examine the effect of two stripes on the axle, having different ring-axle interactions with the mobile rings, so that one section is of high energy (repulsive) for the rings and another section is of lower energy (or attractive). This kind of rotaxane can exhibit rapid changes in displacement or force, and in particular, this molecule can exhibit a yield stress in which the piston suddenly compresses under a small increase in the applied force. Full article
(This article belongs to the Special Issue Rotaxanes)
Open AccessArticle One-Pot Chemoenzymatic Multicomponent Synthesis of Thiazole Derivatives
Molecules 2013, 18(11), 13425-13433; doi:10.3390/molecules181113425
Received: 19 August 2013 / Revised: 20 October 2013 / Accepted: 21 October 2013 / Published: 30 October 2013
Cited by 5 | PDF Full-text (270 KB) | HTML Full-text | XML Full-text
Abstract
A novel chemoenzymatic one-pot multicomponent synthesis of thiazole derivatives was developed. A series of thiazole derivatives were synthesized with high yields up to 94% under mild enzyme-catalyzed conditions. The blank and control experiments reveal that trypsin from porcine pancreas (PPT) displayed great [...] Read more.
A novel chemoenzymatic one-pot multicomponent synthesis of thiazole derivatives was developed. A series of thiazole derivatives were synthesized with high yields up to 94% under mild enzyme-catalyzed conditions. The blank and control experiments reveal that trypsin from porcine pancreas (PPT) displayed great catalytic activity to promote this reaction and showed a wide tolerance range towards different substrate amines. This trypsin-catalyzed multicomponent conversion method provides a novel strategy to synthesize thiazole derivatives and expands the application of enzymes in organic synthesis. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Polyphenolic Extracts of Edible Flowers Incorporated onto Atelocollagen Matrices and Their Effect on Cell Viability
Molecules 2013, 18(11), 13435-13445; doi:10.3390/molecules181113435
Received: 30 August 2013 / Revised: 3 October 2013 / Accepted: 23 October 2013 / Published: 30 October 2013
Cited by 2 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text
Abstract
The phenolic extract of chives flowers (Allium schoenoprasum, Liliaceae), introduced Sage (Salvia pratensis, Lamiaceae), European elderberry (Sambucus nigra, Caprifoliaceae) and common dandelion (Taraxacum officinale, Asteraceae) were characterised by High Performance Liquid [...] Read more.
The phenolic extract of chives flowers (Allium schoenoprasum, Liliaceae), introduced Sage (Salvia pratensis, Lamiaceae), European elderberry (Sambucus nigra, Caprifoliaceae) and common dandelion (Taraxacum officinale, Asteraceae) were characterised by High Performance Liquid Chromatography and incorporated in different concentrations onto atelocollagen thin films. In order to assess the biological impact of these phenolic compounds on cell viability, human immortalised non-tumorigenic keratinocyte cell line was seeded on the thin films and cell proliferation was determined by using an MTT assay. In addition, their antimicrobial activity was estimated by using an agar diffusion test. Data indicated the concomitance between cell viability and concentration of polyphenols. These findings suggest that these phenolic-endowed atelocollagen films might be suitable for tissue engineering applications, on account of the combined activity of polyphenols and collagen. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands
Molecules 2013, 18(11), 13446-13470; doi:10.3390/molecules181113446
Received: 27 September 2013 / Revised: 21 October 2013 / Accepted: 23 October 2013 / Published: 30 October 2013
Cited by 6 | PDF Full-text (798 KB) | HTML Full-text | XML Full-text
Abstract
Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and [...] Read more.
Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric “bridged” form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
Open AccessArticle Characterization of Different Capsicum Varieties by Evaluation of Their Capsaicinoids Content by High Performance Liquid Chromatography, Determination of Pungency and Effect of High Temperature
Molecules 2013, 18(11), 13471-13486; doi:10.3390/molecules181113471
Received: 25 September 2013 / Revised: 18 October 2013 / Accepted: 21 October 2013 / Published: 31 October 2013
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Abstract
The chili pepper is a very important plant used worldwide as a vegetable, as a spice, and as an external medicine. In this work, eight different varieties of Capsicum annuum L. have been characterized by their capsaicinoids content. The chili pepper fruits [...] Read more.
The chili pepper is a very important plant used worldwide as a vegetable, as a spice, and as an external medicine. In this work, eight different varieties of Capsicum annuum L. have been characterized by their capsaicinoids content. The chili pepper fruits were cultivated in the Comarca Lagunera region in North of Mexico. The qualitative and quantitative determination of the major and minor capsaicinoids; alkaloids responsible for the pungency level, has been performed by a validated chromatographic procedure (HPLC-DAD) after a preliminary drying step and an opportune extraction procedure. Concentrations of total capsaicinoids varied from a not detectable value for Bell pepper to 31.84 mg g−1 dried weight for Chiltepín. Samples were obtained from plants grown in experimental field and in greenhouse without temperature control, in order to evaluate temperature effect. Analysis of the two principal capsaicinoids in fruits showed that the amount of dihydrocapsaicin was always higher than capsaicin. In addition, our results showed that the content of total capsaicinoids for the varieties Serrano, Puya, Ancho, Guajillo and Bell pepper were increased with high temperature, while the content of total capsaicinoids and Scoville heat units (SHU) for the varieties De árbol and Jalapeño decreased. However, the pungency values found in this study were higher for all varieties analyzed than in other studies. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors
Molecules 2013, 18(11), 13487-13509; doi:10.3390/molecules181113487
Received: 29 July 2013 / Revised: 13 October 2013 / Accepted: 25 October 2013 / Published: 31 October 2013
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Abstract
There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available [...] Read more.
There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar®) and nilotinib (Tasigna®), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets. Full article
Open AccessArticle Additional Minor Diterpene Glycosides from Stevia rebaudiana Bertoni
Molecules 2013, 18(11), 13510-13519; doi:10.3390/molecules181113510
Received: 24 September 2013 / Revised: 26 October 2013 / Accepted: 28 October 2013 / Published: 31 October 2013
Cited by 6 | PDF Full-text (404 KB) | HTML Full-text | XML Full-text
Abstract
Two additional novel minor diterpene glycosides were isolated from the commercial extract of the leaves of Stevia rebaudiana Bertoni. The structures of the new compounds were identified as 13-{β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-xylopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucupyranosyl-ester} (1), [...] Read more.
Two additional novel minor diterpene glycosides were isolated from the commercial extract of the leaves of Stevia rebaudiana Bertoni. The structures of the new compounds were identified as 13-{β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-xylopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucupyranosyl-ester} (1), and 13-{β-D-6-deoxy-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)-β-D-gluco-pyranosyl-ester} (2), on the basis of extensive 1D (1H- and 13C-) 2D NMR (COSY, HSQC and HMBC) and MS spectroscopic data as well as chemical studies. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle 3-Ishwarone, a Rare Ishwarane Sesquiterpene from Peperomia scandens Ruiz & Pavon: Structural Elucidation through a Joint Experimental and Theoretical Study
Molecules 2013, 18(11), 13520-13529; doi:10.3390/molecules181113520
Received: 12 September 2013 / Revised: 24 October 2013 / Accepted: 29 October 2013 / Published: 31 October 2013
Cited by 2 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
3-Ishwarone, (1), a sesquiterpene with a rare ishwarane skeleton, was isolated from Peperomia scandens Ruiz & Pavon (Piperaceae). Its structure was unambiguously determined by 1D- and 2D-NMR and infrared analyses, as well as by comparative theoretical studies which involved calculations [...] Read more.
3-Ishwarone, (1), a sesquiterpene with a rare ishwarane skeleton, was isolated from Peperomia scandens Ruiz & Pavon (Piperaceae). Its structure was unambiguously determined by 1D- and 2D-NMR and infrared analyses, as well as by comparative theoretical studies which involved calculations of 13C-NMR chemical shifts, using the Density Functional Theory (DFT) with the mPW1PW91 hybrid functional and Pople’s 6-31G(d) basis set, and of vibrational frequencies, using the B3LYP hybrid functional and triple ζ Dunning’s correlation consistent basis set (cc-pVTZ), of (1) and three of its possible diastereomers, compounds 24. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Optimization of Ultrasonic Extraction of Phenolic Antioxidants from Green Tea Using Response Surface Methodology
Molecules 2013, 18(11), 13530-13545; doi:10.3390/molecules181113530
Received: 24 September 2013 / Revised: 21 October 2013 / Accepted: 26 October 2013 / Published: 31 October 2013
Cited by 12 | PDF Full-text (611 KB) | HTML Full-text | XML Full-text
Abstract
Response surface methodology (RSM) has been used to optimize the extraction conditions of antioxidants with relatively low caffeine content from green tea by using ultrasonic extraction. The predicted optimal conditions for the highest antioxidant activity and minimum caffeine level were found at [...] Read more.
Response surface methodology (RSM) has been used to optimize the extraction conditions of antioxidants with relatively low caffeine content from green tea by using ultrasonic extraction. The predicted optimal conditions for the highest antioxidant activity and minimum caffeine level were found at 19.7% ethanol, 26.4 min extraction time, and 24.0 °C extraction temperature. In the predicted optimal conditions, the experimental values were very close to the predicted values. Moreover, the ratio of (EGCg + ECg)/EGC was identified a major factor contributing to the antioxidant activity of green tea extracts. In this study, ultrasonic extraction showed that the ethanol concentration and extraction time used for antioxidant extraction could be remarkably reduced without a decrease in antioxidant activity compared to the conventional extraction conditions. Full article
Open AccessArticle Synthesis and Thermotropic Phase Behavior of Four Glycoglycerolipids
Molecules 2013, 18(11), 13546-13573; doi:10.3390/molecules181113546
Received: 16 September 2013 / Revised: 15 October 2013 / Accepted: 19 October 2013 / Published: 1 November 2013
Cited by 3 | PDF Full-text (799 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four glycoglycerolipids with different head groups have been synthesized and their physicochemical properties studied. The lengths of the head groups from a mono-saccharide to a trisaccharide, in addition to the anomeric stereochemistry for the smaller glycoglycerolipids, have been modified. The synthesis has [...] Read more.
Four glycoglycerolipids with different head groups have been synthesized and their physicochemical properties studied. The lengths of the head groups from a mono-saccharide to a trisaccharide, in addition to the anomeric stereochemistry for the smaller glycoglycerolipids, have been modified. The synthesis has been optimized to avoid glycerol epimerization and to allow up-scaling. The physicochemical properties of the glycoglycerolipids were studied and a strong de-mixing of the gel-phase, depending on the head-group, was observed. Full article
(This article belongs to the Special Issue Synthesis, Structure, Analysis and Properties of Glycolipids)
Open AccessArticle The Seasonal Variation of the Chemical Composition of Essential Oils from Porcelia macrocarpa R.E. Fries (Annonaceae) and Their Antimicrobial Activity
Molecules 2013, 18(11), 13574-13587; doi:10.3390/molecules181113574
Received: 22 August 2013 / Revised: 22 October 2013 / Accepted: 24 October 2013 / Published: 1 November 2013
Cited by 7 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
This study investigates the impact of seasonal variation on the chemical composition of essential oils from the leaves of Porcelia macrocarpa (Annonaceae) obtained over the course of one year (January–December 2011) and the chemical composition of the essential oils obtained from the [...] Read more.
This study investigates the impact of seasonal variation on the chemical composition of essential oils from the leaves of Porcelia macrocarpa (Annonaceae) obtained over the course of one year (January–December 2011) and the chemical composition of the essential oils obtained from the ripe fruits of the same plant. Furthermore, the essential oils of the leaves were investigated with respect to their antimicrobial activity. The essential oils of the leaves contain a mixture of monoterpenes, one diterpene and several sesquiterpenes. The main components were identified as the sesquiterpenes germacrene D (29%–50%) and bicyclogermacrene (24%–37%). No significant variation was observed for the composition of the essential oil of the leaves over the course ofthe year, except for the month of November, when the ripe fruit were collected. In this month, substantially decreased concentrations of germacrene D (28.8 ± 0.8%) and bicyclogermacrene (23.9 ± 0.6%) were measured and the emergence of spathulenol (10.4 ± 0.2%) was observed. The essential oils extracted from the ripe fruit revealed the presence of a variety of monoterpenes, sesquiterpenes and hydrocarbons. The main constituents of these oils were neryl (8.8 ± 0.2%) and geranyl (27.3 ± 0.7%) formates, γ-muurolene (10.3 ± 0.9%) and dendrolasin (8.23 ± 0.06%). The antimicrobial activity of the essential oil obtained from the leaves of P. macrocarpa towards a range of bacterial and yeast strains was examined. In order to determine the minimum inhibitory concentration (MIC) of essential oils obtained from the January collection of the leaves, broth microdilution assays were carried out, which showed a significant antimicrobial activity towards Cryptococcus neoformans serotypes A and D as well as C. gattii serotypes B and C. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines
Molecules 2013, 18(11), 13588-13607; doi:10.3390/molecules181113588
Received: 30 August 2013 / Revised: 26 October 2013 / Accepted: 29 October 2013 / Published: 4 November 2013
Cited by 9 | PDF Full-text (1736 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that [...] Read more.
A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary KD values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Open AccessArticle Pressure Dependent Product Formation in the Photochemically Initiated Allyl + Allyl Reaction
Molecules 2013, 18(11), 13608-13622; doi:10.3390/molecules181113608
Received: 27 August 2013 / Revised: 17 October 2013 / Accepted: 22 October 2013 / Published: 4 November 2013
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Abstract
Photochemically driven reactions involving unsaturated radicals produce a thick global layer of organic haze on Titan, Saturn’s largest moon. The allyl radical self-reaction is an example for this type of chemistry and was examined at room temperature from an experimental and kinetic [...] Read more.
Photochemically driven reactions involving unsaturated radicals produce a thick global layer of organic haze on Titan, Saturn’s largest moon. The allyl radical self-reaction is an example for this type of chemistry and was examined at room temperature from an experimental and kinetic modelling perspective. The experiments were performed in a static reactor with a volume of 5 L under wall free conditions. The allyl radicals were produced from laser flash photolysis of three different precursors allyl bromide (C3H5Br), allyl chloride (C3H5Cl), and 1,5-hexadiene (CH2CH(CH2)2CHCH2) at 193 nm. Stable products were identified by their characteristic vibrational modes and quantified using FTIR spectroscopy. In addition to the (re-) combination pathway C3H5+C3H5 → C6H10 we found at low pressures around 1 mbar the highest final product yields for allene and propene for the precursor C3H5Br. A kinetic analysis indicates that the end product formation is influenced by specific reaction kinetics of photochemically activated allyl radicals. Above 10 mbar the (re-) combination pathway becomes dominant. These findings exemplify the specificities of reaction kinetics involving chemically activated species, which for certain conditions cannot be simply deduced from combustion kinetics or atmospheric chemistry on Earth. Full article
(This article belongs to the Special Issue Gas Phase Reactions)
Open AccessArticle Synthesis and Anti-TMV Activity of Dialkyl/dibenzyl 2-((6-Substituted-benzo[d]thiazol-2-ylamino)(benzofuran-2-yl)methyl) Malonates
Molecules 2013, 18(11), 13623-13635; doi:10.3390/molecules181113623
Received: 13 September 2013 / Revised: 24 October 2013 / Accepted: 29 October 2013 / Published: 4 November 2013
Cited by 3 | PDF Full-text (263 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Starting from benzofuran-2-methanal, 6-substituted benzothiazole-2-amines and malonic esters, sixteen title compounds were designed and synthesized seeking to introduce anti-TMV activity. The structures of the newly synthesized compounds were confirmed by 1H-NMR, 13C-NMR, IR spectra, and MS (HREI) analysis. The bioassays [...] Read more.
Starting from benzofuran-2-methanal, 6-substituted benzothiazole-2-amines and malonic esters, sixteen title compounds were designed and synthesized seeking to introduce anti-TMV activity. The structures of the newly synthesized compounds were confirmed by 1H-NMR, 13C-NMR, IR spectra, and MS (HREI) analysis. The bioassays identified some of these new compounds as having moderate to good anti-TMV activity. The compounds 5i and 5m have good antiviral activity against TMV with a curative rate of 52.23% and 54.41%, respectively, at a concentration of 0.5 mg/mL. Full article
(This article belongs to the Special Issue Organobismuth Chemistry)
Open AccessArticle A New Tetrahydrofuran Lignan Diglycoside from Viola tianshanica Maxim
Molecules 2013, 18(11), 13636-13644; doi:10.3390/molecules181113636
Received: 11 September 2013 / Revised: 10 October 2013 / Accepted: 18 October 2013 / Published: 4 November 2013
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Abstract
A new lignan glycoside, tianshanoside A (1), together with a known phenylpropanoid glycoside, syringin (2) and two known lignan glycosides, picraquassioside C (3), and aketrilignoside B (4), were isolated from the whole plant of [...] Read more.
A new lignan glycoside, tianshanoside A (1), together with a known phenylpropanoid glycoside, syringin (2) and two known lignan glycosides, picraquassioside C (3), and aketrilignoside B (4), were isolated from the whole plant of Viola tianshanica Maxim. The structure of the new compound was elucidated by extensive NMR (1H, 13C, COSY, HSQC, HMBC and ROESY) and high resolution mass spectrometry analysis. The three lignans 1, 3, and 4 did not exhibit significant cytotoxicity against human gastric cancer Ags cells or HepG2 liver cancer cells. This is the first report of the isolation of a lignan skeleton from the genus Viola L. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Clean and Efficient Synthesis of Isoxazole Derivatives in Aqueous Media
Molecules 2013, 18(11), 13645-13653; doi:10.3390/molecules181113645
Received: 5 August 2013 / Revised: 22 October 2013 / Accepted: 31 October 2013 / Published: 5 November 2013
Cited by 5 | PDF Full-text (231 KB) | HTML Full-text | XML Full-text
Abstract A series of 5-arylisoxazole derivatives were synthesized via the reaction of 3-(dimethyl-amino)-1-arylprop-2-en-1-ones with hydroxylamine hydrochloride in aqueous media without using any catalyst. This method has the advantages of easier work-up, mild reaction conditions, high yields, and an environmentally benign procedure. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Pd0-Catalyzed Methyl Transfer on Nucleosides and Oligonucleotides, Envisaged as a PET Tracer
Molecules 2013, 18(11), 13654-13665; doi:10.3390/molecules181113654
Received: 26 August 2013 / Revised: 14 October 2013 / Accepted: 23 October 2013 / Published: 5 November 2013
Cited by 2 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under “ligandless” conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute [...] Read more.
The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under “ligandless” conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute conditions, thus affording a rapid and efficient new method for oligonucleotide labelling with carbon-11. Full article
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
Open AccessArticle Synthesis and Properties of Annulated 2-(Azaar-2-yl)- and 2,2'-Di(azaar-2-yl)-9,9'-spirobifluorenes
Molecules 2013, 18(11), 13680-13690; doi:10.3390/molecules181113680
Received: 5 August 2013 / Revised: 29 October 2013 / Accepted: 30 October 2013 / Published: 5 November 2013
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Abstract
A series of 9,9'-spirobifluorene-derived N-heterocycles were prepared by the reactions of 8,9-dihydrospiro(benzo[b]fluorene-11,9'-fluoren)-6(7H)-one and 8,8',9,9'-tetrahydro-11,11'-spirobi(benzo[b]fluorene)-6,6'(7H,7'H)-dione with a series of 2-amino-arenecarbaldehydes such as 2-aminobenzaldehyde, 2-aminonicotinealdehyde, 1-amino-2-naphthaldehyde, and 8-aminoquinoline-7-carbaldehyde. In addition to the absorption [...] Read more.
A series of 9,9'-spirobifluorene-derived N-heterocycles were prepared by the reactions of 8,9-dihydrospiro(benzo[b]fluorene-11,9'-fluoren)-6(7H)-one and 8,8',9,9'-tetrahydro-11,11'-spirobi(benzo[b]fluorene)-6,6'(7H,7'H)-dione with a series of 2-amino-arenecarbaldehydes such as 2-aminobenzaldehyde, 2-aminonicotinealdehyde, 1-amino-2-naphthaldehyde, and 8-aminoquinoline-7-carbaldehyde. In addition to the absorption maxima based on the parent 9,9'-spirobifluorene skeleton in the 225–234, 239–280, 296–298, and 308–328 nm regions, the absorptions due to the π-π* transitions of the heterocycles were observed in the 351–375 nm region in the UV absorption spectra. All the compounds showed strong photoluminescences in the 390–430 nm region. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Deep Oxidative Desulfurization of Dibenzothiophene in Simulated Oil and Real Diesel Using Heteropolyanion-Substituted Hydrotalcite-Like Compounds as Catalysts
Molecules 2013, 18(11), 13691-13704; doi:10.3390/molecules181113691
Received: 18 September 2013 / Revised: 29 October 2013 / Accepted: 31 October 2013 / Published: 5 November 2013
Cited by 7 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text
Abstract
Three heteropolyanion substituted hydrotalcite-like compounds (HPA-HTLcs) including Mg9Al3(OH)24[PW12O40](MgAl-PW12), Mg9Al3(OH)24[PMo12O40] (MgAl-PMo12) and Mg12Al4(OH)32[SiW [...] Read more.
Three heteropolyanion substituted hydrotalcite-like compounds (HPA-HTLcs) including Mg9Al3(OH)24[PW12O40](MgAl-PW12), Mg9Al3(OH)24[PMo12O40] (MgAl-PMo12) and Mg12Al4(OH)32[SiW12O40] (MgAl-SiW12), were synthesized, characterized and used as catalysts for the oxidative desulfurization of simulated oil (dibenzothiophene, DBT, in n-octane). MgAl-PMo12 was identified as an effective catalyst for the oxidative removal of DBT under very mild conditions of atmospheric pressure and 60 °C in a biphasic system using hydrogen peroxide as oxidant and acetonitrile as extractant. The conversion of DBT was nearly 100%. As a result, because of the influence of the electron density and the space steric hindrance, the oxidation reactivity of the different sulfur compounds in simulated oil followed the order DBT > 4,6-dimethyldibenzothiophene (4,6-DMDBT) > benzothiophene (BT) > thiophene (TH). When the reaction is finished, the catalysts can be recovered from the acetonitrile phase by filtration. The recovered MgAl-PMo12 retains nearly the same catalytic activity as the fresh material. Moreover, MgAl-PMo12 was found to exhibit an ideal catalytic activity in the oxidative desulfurization of real diesel resulting in a total remaining sulfur content of 9.12 ppm(w). Full article
Open AccessArticle A Structurally Diverse Heterocyclic Library by Decoration of Oxcarbazepine Scaffold
Molecules 2013, 18(11), 13705-13722; doi:10.3390/molecules181113705
Received: 8 October 2013 / Revised: 1 November 2013 / Accepted: 4 November 2013 / Published: 6 November 2013
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Abstract
A library of new heterocyclic systems was synthesized starting from oxcarbazepine (OXC, Trileptal®, 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide). The key for these transformations is the α-enolizable ketone present on the [d]-side of our starting material OXC, thus, an [...] Read more.
A library of new heterocyclic systems was synthesized starting from oxcarbazepine (OXC, Trileptal®, 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide). The key for these transformations is the α-enolizable ketone present on the [d]-side of our starting material OXC, thus, an in depth investigation of the literature to find heteroannulation reactions for substrates carrying an α-enolizable ketone gave us a boost to discover an excellent derivatization strategy and [3+2], [4+2] and [4+1] approaches were successfully developed. Almost always a pre-functionalization was needed, but also the direct one-pot heterocycle construction was also explored. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Headspace Solid-Phase Microextraction Analysis of Volatile Components in Narcissus tazetta var. chinensis Roem
Molecules 2013, 18(11), 13723-13734; doi:10.3390/molecules181113723
Received: 9 October 2013 / Revised: 28 October 2013 / Accepted: 1 November 2013 / Published: 6 November 2013
Cited by 4 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
The volatile components in single-flowered and double-flowered Chinese narcissus were identified by headspace-solid phase microextraction (HS-SPME) coupled with GC and GC/MS. Changes in aroma during the vase-life (days 0, 1, 2, 3, 4, 5 and 6) of two samples were also studied. [...] Read more.
The volatile components in single-flowered and double-flowered Chinese narcissus were identified by headspace-solid phase microextraction (HS-SPME) coupled with GC and GC/MS. Changes in aroma during the vase-life (days 0, 1, 2, 3, 4, 5 and 6) of two samples were also studied. A total of 35 compounds were identified, of which all were present in single-flowered and 26 in double-flowered samples. The main aroma components were (E)-β-ocimene, and benzyl acetate. Single-flowered narcissus have a higher percentage of benzyl acetate, while double-flowered narcissus have a higher percentage of 1,8-cineole. In vase-life, the total volatile component content peaked on day 2 for single-flowered and day 3 for the double-flowered narcissus. For both single-flowered and double-flowered narcissus flowers, the total content of volatile components had decreased significantly by day 4. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Physicochemical, Antimicrobial and Antioxidant Properties of Chitosan Films Incorporated with Carvacrol
Molecules 2013, 18(11), 13735-13753; doi:10.3390/molecules181113735
Received: 25 September 2013 / Revised: 23 October 2013 / Accepted: 25 October 2013 / Published: 7 November 2013
Cited by 11 | PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan films (CF) with carvacrol (CAR) [0.5%, 1.0% and 1.5% v/v] were prepared by the emulsion method. The retained CAR, water solubility, water vapor permeability (WVP), optical, mechanical properties, antibacterial and antioxidant capacity of films were analyzed. The results indicate that the [...] Read more.
Chitosan films (CF) with carvacrol (CAR) [0.5%, 1.0% and 1.5% v/v] were prepared by the emulsion method. The retained CAR, water solubility, water vapor permeability (WVP), optical, mechanical properties, antibacterial and antioxidant capacity of films were analyzed. The results indicate that the retention of CAR in the CF was ≈50%. The incorporation of CAR to CF decreased the water solubility, the WVP, the yellowing and transparency and the tensile strength, but increased the stiffness. Microcapsules with diameters of 2 to 7 µm were found on the surface CF-CAR. The CF-CAR with highest CAR concentrations showed antibacterial activity against S. typhimurium and E. coli O157:H7. The CF-CAR had higher antioxidant capacity and an increased protective effect against oxidation of erythrocytes in different grades. These results suggest potential applications of CF-CAR as active packaging to preserve food products. Full article
Open AccessArticle Selective Oxidation Reactions of Natural Compounds with Hydrogen Peroxide Mediated by Methyltrioxorhenium
Molecules 2013, 18(11), 13754-13768; doi:10.3390/molecules181113754
Received: 17 September 2013 / Revised: 24 October 2013 / Accepted: 25 October 2013 / Published: 7 November 2013
Cited by 1 | PDF Full-text (404 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have investigated the oxidative behaviour of natural compounds such as methyl abietate (1), farnesyl acetate (2), α-ionone (3), β-ionone (4), methyl linolelaidate (5), methyl linolenate (6) and bergamottin ( [...] Read more.
We have investigated the oxidative behaviour of natural compounds such as methyl abietate (1), farnesyl acetate (2), α-ionone (3), β-ionone (4), methyl linolelaidate (5), methyl linolenate (6) and bergamottin (7) with the oxidant system methyltrioxo-rhenium/ H2O2/pyridine. The reactions, performed in CH2Cl2/H2O at 25 °C, have shown good regio- and stereoselectivity. The oxidation products were isolated by HPLC or silica gel chromatography and characterized by MS(EI), 1H-, 13C-NMR, APT, gCOSY, HSQC, TOCSY and NOESY measurements. The selectivity seems to be controlled by the nucleophilicity of double bonds and by stereoelectronic and steric effects. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum
Molecules 2013, 18(11), 13812-13822; doi:10.3390/molecules181113812
Received: 8 September 2013 / Revised: 28 October 2013 / Accepted: 30 October 2013 / Published: 7 November 2013
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Abstract
The biotransformation of androsterone (1), epiandrosterone (2), androstanedione (3) and DHEA (dehydroepiandrosterone) (4) by Penicillium lanosocoeruleum—a fungal species not used in biotransformations so far—were described. All the substrates were converted in high yield [...] Read more.
The biotransformation of androsterone (1), epiandrosterone (2), androstanedione (3) and DHEA (dehydroepiandrosterone) (4) by Penicillium lanosocoeruleum—a fungal species not used in biotransformations so far—were described. All the substrates were converted in high yield (70%–99%) into D ring δ-lactones. The oxidation of 1 produced 3α-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (5). The oxidation of 2 led to 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (6). The biotransformation of 3 resulted in the formation of 3α-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (5) and 17a-oxa-D-homo-5α-androstan-3,17-dione (7). An analysis of the transformation progress of the studied substrates as a function of time indicates that the Baeyer-Villiger monooxygenase of this fungus does not accept the 3β-hydroxy-5-ene functionality of steroids. In this microorganism steroidal 3β-hydroxy-dehydrogenase (3β-HSD) was active, and as a result DHEA (4) was transformed exclusively to testololactone (8). Apart from the observed oxidative transformations, a reductive pathway was revealed with the C-3 ketone being reduced to a C-3α-alcohol. It is demonstrated for the first time that the reduction of the 3-keto group of the steroid nucleus can occur in the presence of a ring-D lactone functionality. Full article
(This article belongs to the Special Issue Biosynthesis and Biotransformation)
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Open AccessArticle Corncobs as a Potential Source of Functional Chemicals
Molecules 2013, 18(11), 13823-13830; doi:10.3390/molecules181113823
Received: 8 October 2013 / Revised: 6 November 2013 / Accepted: 7 November 2013 / Published: 8 November 2013
Cited by 5 | PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical examination of corncob extracts led to the isolation of a new lignan identified as 7,7'-dihydroxy-3'-O-demethyl-4-methoxymatairesinol, together with seven known compounds, identified as β-sitosterol, β-sitosteryl-β-D-glucoside, 6β-hydroxy-campest-4-en-3-one, 5α,8α-epidioxyergosta-6,22-dien-3β-ol, tricin, kaempferol and p-coumaric acid. The isolated compounds [...] Read more.
Phytochemical examination of corncob extracts led to the isolation of a new lignan identified as 7,7'-dihydroxy-3'-O-demethyl-4-methoxymatairesinol, together with seven known compounds, identified as β-sitosterol, β-sitosteryl-β-D-glucoside, 6β-hydroxy-campest-4-en-3-one, 5α,8α-epidioxyergosta-6,22-dien-3β-ol, tricin, kaempferol and p-coumaric acid. The isolated compounds were identified by one and two-dimensional NMR spectroscopies and mass spectrometry. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle One-Pot Tandem Synthesis of 2-Arylquinazolines by a Multicomponent Cyclization Reaction
Molecules 2013, 18(11), 13860-13869; doi:10.3390/molecules181113860
Received: 8 October 2013 / Revised: 21 October 2013 / Accepted: 21 October 2013 / Published: 8 November 2013
Cited by 1 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
A series of 2-arylquinazolines have been synthesized in moderate to excellent yields by one-pot tandem reaction of (2-aminophenyl)methanols, aldehydes and ceric ammonium nitrate (CAN). The utility of this transformation was demonstrated by its compatibility with a wide range of functional groups. Thus, [...] Read more.
A series of 2-arylquinazolines have been synthesized in moderate to excellent yields by one-pot tandem reaction of (2-aminophenyl)methanols, aldehydes and ceric ammonium nitrate (CAN). The utility of this transformation was demonstrated by its compatibility with a wide range of functional groups. Thus, the method represents a simple and practical procedure to access 2-arylquinazolines. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle 3D-QSAR and Cell Wall Permeability of Antitubercular Nitroimidazoles against Mycobacterium tuberculosis
Molecules 2013, 18(11), 13870-13885; doi:10.3390/molecules181113870
Received: 24 September 2013 / Revised: 4 November 2013 / Accepted: 6 November 2013 / Published: 8 November 2013
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Abstract
Inhibitory activities of monocyclic nitroimidazoles against Mycobacterium tuberculosis (Mtb) deazaflavin-dependent nitroreductase (DDN) were modeled by using docking, pharmacophore alignment and comparative molecular similarity indices analysis (CoMSIA) methods. A statistically significant model obtained from CoMSIA was established based on a training set using [...] Read more.
Inhibitory activities of monocyclic nitroimidazoles against Mycobacterium tuberculosis (Mtb) deazaflavin-dependent nitroreductase (DDN) were modeled by using docking, pharmacophore alignment and comparative molecular similarity indices analysis (CoMSIA) methods. A statistically significant model obtained from CoMSIA was established based on a training set using pharmacophore-based molecular alignment. The leave-one out cross-validation correlation coefficients q2 (CoMSIA) were 0.681. The CoMSIA model had a good correlation (/CoMSIA = 0.611) between the predicted and experimental activities against excluded test sets. The generated model suggests that electrostatic, hydrophobic and hydrogen bonding interactions all play important roles for interaction between ligands and receptors. The predicted cell wall permeability (logPapp) for substrates with high inhibitory activity against Mtb were investigated. The distribution coefficient (logD) range was 2.41 < logD < 2.89 for the Mtb cell wall membrane permeability. The larger the polar surface area is, the better the permeability is. A larger radius of gyration (rgry) and a small fraction of rotatable bonds (frtob) of these molecules leads to higher cell wall penetration ability. The information obtained from the in silico tools might be useful in the design of more potent compounds that are active against Mtb. Full article
Open AccessArticle A Comparative Study of Ferulic Acid on Different Monosaccharide-Mediated Protein Glycation and Oxidative Damage in Bovine Serum Albumin
Molecules 2013, 18(11), 13886-13903; doi:10.3390/molecules181113886
Received: 9 October 2013 / Revised: 4 November 2013 / Accepted: 6 November 2013 / Published: 11 November 2013
Cited by 9 | PDF Full-text (473 KB) | HTML Full-text | XML Full-text
Abstract
Three dietary monosaccharides, (glucose, fructose, and ribose), have different rates of protein glycation that accelerates the production of advanced glycation end-products (AGEs). The present work was conducted to investigate the effect of ferulic acid (FA) on the three monosaccharide-mediated protein glycations and [...] Read more.
Three dietary monosaccharides, (glucose, fructose, and ribose), have different rates of protein glycation that accelerates the production of advanced glycation end-products (AGEs). The present work was conducted to investigate the effect of ferulic acid (FA) on the three monosaccharide-mediated protein glycations and oxidation of BSA. Comparing the percentage reduction, FA (1–5 mM) reduced the level of fluorescence AGEs (F-AGEs) and Nε-(carboxymethyl) lysine (Nε-CML) in glucose-glycated BSA (F-AGEs = 12.61%–36.49%; Nε-CML = 33.61%–66.51%), fructose-glycated BSA (F-AGEs = 25.28%–56.42%; Nε-CML = 40.21%–62.91%), and ribose-glycated BSA (F-AGEs = 25.63%–51.18%; Nε-CML = 26.64%–64.08%). In addition, the percentages of FA reduction of fructosamine (Frc) and amyloid cross β-structure (Amy) were Frc = 20.45%–43.81%; Amy = 17.84%–34.54% in glucose-glycated BSA, Frc = 25.17%–36.92%; Amy = 27.25%–39.51% in fructose-glycated BSA, and Frc = 17.34%–29.71%; Amy = 8.26%–59.92% in ribose-glycated BSA. FA also induced a reduction in protein carbonyl content (PC) and loss of protein thiol groups (TO) in glucose-glycated BSA (PC = 37.78%–56.03%; TO = 6.75%–13.41%), fructose-glycated BSA (PC = 36.72%–52.74%; TO = 6.18%–20.08%), and ribose-glycated BSA (PC = 25.58%–33.46%; TO = 20.50%–39.07%). Interestingly, the decrease in fluorescence AGEs by FA correlated with the level of Nε-CML, fructosamine, amyloid cross β-structure, and protein carbonyl content. Therefore, FA could potentially be used to inhibit protein glycation and oxidative damage caused by monosaccharides, suggesting that it might prevent AGEs-mediated pathologies during diabetic complications. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication A Bicyclic Diterpenoid with a New 15,16-Dinorlabdane Carbon Skeleton from Leonurus japonicus and Its Coagulant Bioactivity
Molecules 2013, 18(11), 13904-13909; doi:10.3390/molecules181113904
Received: 10 October 2013 / Revised: 29 October 2013 / Accepted: 5 November 2013 / Published: 11 November 2013
Cited by 6 | PDF Full-text (230 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new 15,16-dinorlabdane diterpenoid 1 and a known labdane diterpenoid 2, together with three known ergosterols 35, were isolated from the EtOAc-soluble portion of the EtOH extract of Leonurus japonicus. Their structures were elucidated by physical and [...] Read more.
A new 15,16-dinorlabdane diterpenoid 1 and a known labdane diterpenoid 2, together with three known ergosterols 35, were isolated from the EtOAc-soluble portion of the EtOH extract of Leonurus japonicus. Their structures were elucidated by physical and spectroscopic analysis. Compound 1 showed in vitro coagulant activity in the APTT, PT, TT, and FIB assays. Full article
Open AccessArticle The Henry Reaction in [Bmim][PF6]-based Microemulsions Promoted by Acylase
Molecules 2013, 18(11), 13910-13919; doi:10.3390/molecules181113910
Received: 21 October 2013 / Revised: 4 November 2013 / Accepted: 5 November 2013 / Published: 11 November 2013
Cited by 3 | PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
An environmentally-friendly, enzyme-promoted procedure for the Henry reaction was first studied using water-in-[Bmim][PF6] microemulsions as reaction medium. The Amano acylase from Aspergillus oryzae showed better catalytic activity for the addition reactions of nitromethane with a series of aromatic aldehydes, and [...] Read more.
An environmentally-friendly, enzyme-promoted procedure for the Henry reaction was first studied using water-in-[Bmim][PF6] microemulsions as reaction medium. The Amano acylase from Aspergillus oryzae showed better catalytic activity for the addition reactions of nitromethane with a series of aromatic aldehydes, and a highest yield of 90% was obtained. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle A Combination of Alkaloids and Triterpenes of Alstonia scholaris (Linn.) R. Br. Leaves Enhances Immunomodulatory Activity in C57BL/6 Mice and Induces Apoptosis in the A549 Cell Line
Molecules 2013, 18(11), 13920-13939; doi:10.3390/molecules181113920
Received: 30 September 2013 / Revised: 6 November 2013 / Accepted: 6 November 2013 / Published: 12 November 2013
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Abstract
Experiments were conducted to evaluate the induction of apoptosis and the immunomodulatory activities of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves (ASL). Importantly, their possible synergistic properties were also explored in this study. Human lung adenocarcinoma cell line A549 [...] Read more.
Experiments were conducted to evaluate the induction of apoptosis and the immunomodulatory activities of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves (ASL). Importantly, their possible synergistic properties were also explored in this study. Human lung adenocarcinoma cell line A549 and Lewis tumor-bearing C57BL/6 mice were used for the evaluation of their activities. A MTT assay was used to determine the proliferation inhibition in A549 cells. Annexin-V/PI double staining as well as flow cytometry was performed to detect apoptosis and cell cycle status. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the levels of inflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum. Furthermore, western blot analysis was applied to evaluate the expressions of proteins associated with cell death. Alkaloids or triterpenes showed a high anti-proliferative activity in A549 cells, with IC50 values of 14.4 µg/mL and 9.3 µg/mL, respectively. The alkaloids and triterpenes combination could significantly inhibit tumor growth in tumor-bearing C57BL/6 mice, compared with alkaloids or triterpenes alone (7.5, 15, 30 g raw material/kg). The immune organs indexes including spleen index and thymus index were increased remarkably by the combination of alkaloids and triterpenes, whereas the levels of IL-6 and TNF-α were up-regulated significantly. Moreover, Annexin-V/PI double staining and flow cytometry showed that the combination of alkaloids and triterpenes (1, 2 and 3 mg raw material/kg) could induce apoptosis and cause S cell cycle arrest in A549 cells. Western blot analysis also showed that their combination (2 mg raw material/kg) significantly down-regulated Bcl-2 expression and pro-casp8 level, whereas it remarkably increased the level of cleaved caspase-8 leading to apoptosis in A549 cells. These observations provide preliminary evidence that both alkaloids and triterpenes possess immune regulation and induction apoptosis activities. Their combination has a stronger activity than that of either class alone. Our findings suggested that these components might be beneficial for the prevention and treatment of NSCLC through a significant synergy effect. Full article
Open AccessArticle Synthesis of a Versatile Building Block Combining Cyclen-derivative DO3A with a Polyamine via a Rigid Spacer
Molecules 2013, 18(11), 13940-13956; doi:10.3390/molecules181113940
Received: 8 October 2013 / Revised: 5 November 2013 / Accepted: 6 November 2013 / Published: 12 November 2013
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Abstract
The five-step synthesis of a polydentate building block combining a cyclen-based macrocycle (DO3A) with N-(2-aminoethyl)propane-1,3-diamine, which are linked through the xylylen moiety as a rigid C-spacer is described. These two molecular parts were coupled by subsequent bromine atom substitution in 1,4-bis(bromomethyl)benzene. [...] Read more.
The five-step synthesis of a polydentate building block combining a cyclen-based macrocycle (DO3A) with N-(2-aminoethyl)propane-1,3-diamine, which are linked through the xylylen moiety as a rigid C-spacer is described. These two molecular parts were coupled by subsequent bromine atom substitution in 1,4-bis(bromomethyl)benzene. First, N-(2-aminoethyl)propane-1,3-diamine was protected by phthaloyl moieties and then it was reacted with 1,4-bis(bromomethyl)benzene to form (2-phthalimidoethyl)(3-phthalimido-prop-1-yl)(4-bromomethylbenzyl)amine (2). This compound underwent a substitution reaction with DO3A in the form of its tert-butyl esters leading to the intermediate 1-{4-[(2-phthalimidoethyl)(3-phthalimidoprop-1-yl)aminomethyl]phenylmethyl}-4,7,10-tris(t-butoxy-carbonylmethyl)-1,4,7,10-tetraazacyclododecane (3). The phthaloyl as well as the t-butyl protecting groups were removed in the next two reaction steps to form the final product 1-{4-[(2-aminoethyl)(3-aminoprop-1-yl)aminomethyl]phenylmethyl}-4,7,10-tris(carboxy-methyl)-1,4,7,10-tetraazacyclododecane (5). The intermediates 14 as well as the final product 5 were characterized by elemental analysis, mass spectrometry, and multinuclear (1H and 13C) and two-dimensional NMR spectroscopy. The final product 5 could serve as a potential building block in subsequent syntheses of binuclear complexes of lanthanides and/or transition metals. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy
Molecules 2013, 18(11), 13957-13978; doi:10.3390/molecules181113957
Received: 27 September 2013 / Revised: 12 October 2013 / Accepted: 15 October 2013 / Published: 12 November 2013
Cited by 4 | PDF Full-text (863 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor—PD0325901—have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9ag showed anti-proliferation activity in melanoma A375 cells by the same mechanism as [...] Read more.
Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor—PD0325901—have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9ag showed anti-proliferation activity in melanoma A375 cells by the same mechanism as that of PD0325901. PEGylation increased the IC50 value of 9f three-fold in the A375 assay, and the multi-cRGD peptide cargo significantly improved the receptor specific anti-proliferation activity of 9g in integrin-overexpressing U87 cells. In the second series, RGD-PD0325901 13 exhibited significantly increased antitumor properties compared to the alkoxylamine analogs by both inhibition of the ERK pathway activity and DNA replication of the cancer cells. Furthermore, 13 displayed more potent anti-proliferation activity in the U87 assay than PD0325901 in a dose-dependent manner. All these data demonstrate that RGD-MEKI conjugates with an ester bond linkage enhanced anticancer efficacy with improved targeting capability toward integrin-overexpressing tumor cells. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle The Synthesis and Characterization of Hydroxyapatite-β-Alanine Modified by Grafting Polymerization of γ-Benzyl-L-glutamate-N-carboxyanhydride
Molecules 2013, 18(11), 13979-13991; doi:10.3390/molecules181113979
Received: 14 October 2013 / Revised: 8 November 2013 / Accepted: 8 November 2013 / Published: 13 November 2013
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Abstract
In this study, hydroxyapatite (HAP) was surface-modified by the addition of β-alanine (β-Ala), and the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxy-anhydride (BLG-NCA) was subsequently initiated. HAP containing surface poly-γ-benzyl-L-glutamates (PBLG) was successfully prepared in this way. With the [...] Read more.
In this study, hydroxyapatite (HAP) was surface-modified by the addition of β-alanine (β-Ala), and the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxy-anhydride (BLG-NCA) was subsequently initiated. HAP containing surface poly-γ-benzyl-L-glutamates (PBLG) was successfully prepared in this way. With the increase of PBLG content in HAP-PBLG, the solubility of HAP-PBLG increased gradually and it was ultimately soluble in chloroform. HAP-PLGA with surface carboxyl groups was obtained by the catalytic hydrogenation of HAP-PBLG. In the process of HAP modification, the morphology changes from rod to sheet and from flake to needle. The effect of BLG-NCA concentration on the character of hydroxyapatite-β-alanine-poly(γ-benzyl-L-glutamate) (HAP-PBLG) was investigated. The existence of amino acids on the HAP surfaces was confirmed in the resulting Fourier transform infrared (FTIR) spectra. The resulting powder X-ray diffraction patterns indicated that the crystallinity of HAP decreased when the ratio of BLG-NCA/HAP-NH2 increased to 20/1. Transmission electron microscopy (TEM) indicated that the particle size of HAP-PBLG decreased significantly and that the resulting particles appeared less agglomerated relative to that of the HAP-NH2 crystals. Furthermore, 1H-NMR spectra and FTIR spectra revealed that hydroxyapatite-β-alanine-poly (L-glutamic acid) (HAP-PLGA) was able to successfully bear carboxylic acid groups on its side chains. Full article
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Open AccessArticle Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings
Molecules 2013, 18(11), 13992-14012; doi:10.3390/molecules181113992
Received: 16 September 2013 / Revised: 4 November 2013 / Accepted: 5 November 2013 / Published: 13 November 2013
Cited by 6 | PDF Full-text (409 KB) | HTML Full-text | XML Full-text
Abstract
A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, [...] Read more.
A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC50 values ranging from 0.59 to 2.90 μM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Optimization of a Pre-MEKC Separation SPE Procedure for Steroid Molecules in Human Urine Samples
Molecules 2013, 18(11), 14013-14032; doi:10.3390/molecules181114013
Received: 30 August 2013 / Revised: 5 October 2013 / Accepted: 6 October 2013 / Published: 13 November 2013
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Abstract
Many steroid hormones can be considered as potential biomarkers and their determination in body fluids can create opportunities for the rapid diagnosis of many diseases and disorders of the human body. Most existing methods for the determination of steroids are usually time- [...] Read more.
Many steroid hormones can be considered as potential biomarkers and their determination in body fluids can create opportunities for the rapid diagnosis of many diseases and disorders of the human body. Most existing methods for the determination of steroids are usually time- and labor-consuming and quite costly. Therefore, the aim of analytical laboratories is to develop a new, relatively low-cost and rapid implementation methodology for their determination in biological samples. Due to the fact that there is little literature data on concentrations of steroid hormones in urine samples, we have made attempts at the electrophoretic determination of these compounds. For this purpose, an extraction procedure for the optimized separation and simultaneous determination of seven steroid hormones in urine samples has been investigated. The isolation of analytes from biological samples was performed by liquid-liquid extraction (LLE) with dichloromethane and compared to solid phase extraction (SPE) with C18 and hydrophilic-lipophilic balance (HLB) columns. To separate all the analytes a micellar electrokinetic capillary chromatography (MECK) technique was employed. For full separation of all the analytes a running buffer (pH 9.2), composed of 10 mM sodium tetraborate decahydrate (borax), 50 mM sodium dodecyl sulfate (SDS), and 10% methanol was selected. The methodology developed in this work for the determination of steroid hormones meets all the requirements of analytical methods. The applicability of the method has been confirmed for the analysis of urine samples collected from volunteers—both men and women (students, amateur bodybuilders, using and not applying steroid doping). The data obtained during this work can be successfully used for further research on the determination of steroid hormones in urine samples. Full article
(This article belongs to the Special Issue Steroids)
Open AccessCommunication Synthesis of Some Green Dopants for OLEDs Based on Arylamine 2,3-disubstituted Bithiophene Derivatives
Molecules 2013, 18(11), 14033-14041; doi:10.3390/molecules181114033
Received: 20 September 2013 / Revised: 4 November 2013 / Accepted: 7 November 2013 / Published: 13 November 2013
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Abstract
A series of green dopants based on 2,2-diphenylvinyl end-capped bithiophene and three different arylamine moieties (9-phenylcarbazole, triphenylamine, and N,N’-di-(p-tolyl)benzeneamine) were successfully synthesized by the Suzuki and Wittig coupling reactions. The photophysical properties of these compounds are reported. The strongest [...] Read more.
A series of green dopants based on 2,2-diphenylvinyl end-capped bithiophene and three different arylamine moieties (9-phenylcarbazole, triphenylamine, and N,N’-di-(p-tolyl)benzeneamine) were successfully synthesized by the Suzuki and Wittig coupling reactions. The photophysical properties of these compounds are reported. The strongest PL emitting compound with the 9-phenylcarbazole moiety has been used for fabricating an OLED device with good overall performance. Full article
Open AccessArticle Design, Synthesis and Cytotoxic Activities of Novel Aliphatic Amino-Substituted Flavonoids
Molecules 2013, 18(11), 14070-14084; doi:10.3390/molecules181114070
Received: 29 September 2013 / Revised: 31 October 2013 / Accepted: 4 November 2013 / Published: 13 November 2013
PDF Full-text (272 KB) | HTML Full-text | XML Full-text
Abstract
A series of flavonoids 9af, 13b, 13d, 13e and 14af bearing diverse aliphatic amino moieties were designed, synthesized and evaluated for their cytotoxic activities against the ECA-109, A-549, HL-60, and PC-3 cancer cell lines. Most [...] Read more.
A series of flavonoids 9af, 13b, 13d, 13e and 14af bearing diverse aliphatic amino moieties were designed, synthesized and evaluated for their cytotoxic activities against the ECA-109, A-549, HL-60, and PC-3 cancer cell lines. Most of the compounds exhibited moderate to good activities. The structure-activity relationships were studied, revealing that the chalcone skeleton is the most preferable for cytotoxic activities. Chalcone 9d was the most promising compound due to its high potency against the examined cancer cell lines (its IC50 values against ECA-109, A549, HL-60 and PC-3 cells were 1.0, 1.5, 0.96 and 3.9 μM, respectively). Full article
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Open AccessArticle The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells
Molecules 2013, 18(11), 14085-14095; doi:10.3390/molecules181114085
Received: 29 October 2013 / Revised: 6 November 2013 / Accepted: 6 November 2013 / Published: 14 November 2013
Cited by 7 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
MS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated [...] Read more.
MS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK) signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α  MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1), an endogenous suppressor of p38α  in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation) of p38α  was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2), monocyte chemotactic protein-2 (MCP-2) and macrophage migration inhibitory factor (MIF) in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors. Full article
Open AccessArticle Bioactive Quinic Acid Derivatives from Ageratina adenophora
Molecules 2013, 18(11), 14096-14104; doi:10.3390/molecules181114096
Received: 22 September 2013 / Revised: 23 October 2013 / Accepted: 28 October 2013 / Published: 14 November 2013
Cited by 7 | PDF Full-text (266 KB) | HTML Full-text | XML Full-text
Abstract
A novel quinic acid derivative, 5-O-trans-o-coumaroylquinic acid methyl ester (1), together with three known ones, chlorogenic acid methyl ester (2), macranthoin F (3) and macranthoin G (4), were [...] Read more.
A novel quinic acid derivative, 5-O-trans-o-coumaroylquinic acid methyl ester (1), together with three known ones, chlorogenic acid methyl ester (2), macranthoin F (3) and macranthoin G (4), were isolated from the aerial parts of the invasive plant Ageratina adenophora (Spreng.). The structure of new compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 24 were isolated from plant A. adenophora for the first time. All the compounds showed in vitro antibacterial activity toward five assayed bacterial strains, especially 3 and 4, which showed in vitro antibacterial activity against Salmonella enterica with MIC values of 7.4 and 14.7 μM, respectively. Compound 1 was further found to display in vitro anti-fungal activity against spore germination of Magnaporthe grisea with an IC50 value 542.3 µM. These four compounds were also tested for their antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Composition and Antioxidant Activity of Tánara Ótó (Dracocephalum palmatum Stephan), a Medicinal Plant Used by the North-Yakutian Nomads
Molecules 2013, 18(11), 14105-14121; doi:10.3390/molecules181114105
Received: 11 October 2013 / Revised: 6 November 2013 / Accepted: 8 November 2013 / Published: 14 November 2013
Cited by 7 | PDF Full-text (659 KB) | HTML Full-text | XML Full-text
Abstract
Dracocephalum palmatum Stephan (Lamiaceae) is a medicinal plant used by the North-Yakutian nomads. From the crude ethanolic extract of the aerial parts of this plant, 23 compounds (phenylpropanoids, coumarins, flavonoids, and triterpenes) were isolated. Among these, eight compounds (salvianolic acid B, caftaric [...] Read more.
Dracocephalum palmatum Stephan (Lamiaceae) is a medicinal plant used by the North-Yakutian nomads. From the crude ethanolic extract of the aerial parts of this plant, 23 compounds (phenylpropanoids, coumarins, flavonoids, and triterpenes) were isolated. Among these, eight compounds (salvianolic acid B, caftaric acid, cichoric acid, umbelliferone, aesculetin, apigenin-7-O-β-d-glucuronopyranoside, isorhoifolin, and luteolin-4'-O-β-d-glucopyranoside) were detected for the first time in the genus Dracocephalum. Their structures were elucidated based on chemical and spectral data. The levels of most of the compounds detected in the cultivated sample were close to that of the wild sample, indicating the reproducibility of the biologically active compounds of D. palmatum through cultivation. Investigation into the biological activity of D. palmatum under in vitro conditions demonstrated that its extracts have a strong antioxidant effect due to the presence of high concentrations of phenolic compounds. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Three New Germacrane-Type Sesquiterpenes with NGF-Potentiating Activity from Valeriana officinalis var. latiofolia
Molecules 2013, 18(11), 14138-14147; doi:10.3390/molecules181114138
Received: 12 October 2013 / Revised: 9 November 2013 / Accepted: 12 November 2013 / Published: 14 November 2013
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Abstract
Three new germacrane-type sesquiterpenoids, volvalerenal F (1), volvalerenal G (2) and volvalerenic acid D (3), along with five known compounds 48, were isolated from the CHCl3 soluble partition of the ethanol extract [...] Read more.
Three new germacrane-type sesquiterpenoids, volvalerenal F (1), volvalerenal G (2) and volvalerenic acid D (3), along with five known compounds 48, were isolated from the CHCl3 soluble partition of the ethanol extract of Valeriana officinalis var. latiofolia. The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, as well as mass spectrometry. The eight germacrane-type sesquiterpenoids showed nerve growth factor (NGF) potentiating activity, which mediates the neurite outgrowth in PC 12D cells. This study intends to reveal the chemical basis of the use of V. officinalis var. latiofolia as a dietary supplement. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Applications of Lactobacillus rhamnosus Spent Culture Supernatant in Cosmetic Antioxidation, Whitening and Moisture Retention Applications
Molecules 2013, 18(11), 14161-14171; doi:10.3390/molecules181114161
Received: 16 October 2013 / Revised: 12 November 2013 / Accepted: 13 November 2013 / Published: 15 November 2013
Cited by 6 | PDF Full-text (244 KB) | HTML Full-text | XML Full-text
Abstract
This study was aimed at investigating the antioxidant, whitening, and moisture-retention properties of Lactobacillus rhamnosus spent culture supernatant (Lr-SCS) in cosmetic applications. Results reveal that Lr-SCS effectively and gradually scavenges 1,1-diphenyl-2-picrylhydrazyl as well as 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cations, and increases reducing power [...] Read more.
This study was aimed at investigating the antioxidant, whitening, and moisture-retention properties of Lactobacillus rhamnosus spent culture supernatant (Lr-SCS) in cosmetic applications. Results reveal that Lr-SCS effectively and gradually scavenges 1,1-diphenyl-2-picrylhydrazyl as well as 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cations, and increases reducing power in a dose-dependent manner. Additionally, Lr-SCS can also suppress tyrosinase activity in vitro and effectively promote moisture retention. Heat treatment at 100 °C for 30 min does not influence the functions of Lr-SCS. We conclude that Lr-SCS can be used effectively in skin care cosmetics. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Secondary Metabolites in Durian Seeds: Oligomeric Proanthocyanidins
Molecules 2013, 18(11), 14172-14185; doi:10.3390/molecules181114172
Received: 29 September 2013 / Revised: 6 November 2013 / Accepted: 7 November 2013 / Published: 15 November 2013
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Abstract
Ethanolic extract of durian seeds was fractionated by reverse phase flash column chromatography and the fractions characterized by electrospray ionization mass spectroscopy. Among a few unknown compounds collected, oligomeric proanthocyanidins (OPCs) were found to be one of the main compounds. Based on [...] Read more.
Ethanolic extract of durian seeds was fractionated by reverse phase flash column chromatography and the fractions characterized by electrospray ionization mass spectroscopy. Among a few unknown compounds collected, oligomeric proanthocyanidins (OPCs) were found to be one of the main compounds. Based on this result, the OPCs were purified the first time from the durian seeds using standard procedures and gave a yield of 1.8 mg/g dry matter after fractionation by Sephadex LH-20 column. Structural analysis by 13C{1H} NMR and ESI-MS spectra showed the presence of primarily B-type procyanidins with mainly epicatechin as the extension units, which was further verified by matrix assisted laser desorption/ionization–time of flight mass spectra (MALDI-TOF MS), which shows a distribution of dimers to decamers. In addition, hydroxylated peaks with molecular weight 16 units more than the poly-epicatechins represented significant peaks. We suggest this might be due to hydroxylation occurring under the MALDI-TOF MS conditions. Consistently, depolymerization with α-toluenethiol resulted in epicatechin thioether as the major product, but undetectable amount of gallocatechin or its α-toluenethiol derivatives. The oligomershave a mean degree of polymerization of 7.30. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Dual Histamine H1 and H2 Receptor Antagonist Activity of Cyanoguanidine Derivatives
Molecules 2013, 18(11), 14186-14202; doi:10.3390/molecules181114186
Received: 8 October 2013 / Revised: 10 November 2013 / Accepted: 11 November 2013 / Published: 15 November 2013
Cited by 3 | PDF Full-text (380 KB) | HTML Full-text | XML Full-text
Abstract
Premedication with a combination of histamine H1 receptor (H1R) and H2 receptor (H2R) antagonists has been suggested as a prophylactic principle, for instance, in anaesthesia and surgery. Aiming at pharmacological hybrids combining H1R and [...] Read more.
Premedication with a combination of histamine H1 receptor (H1R) and H2 receptor (H2R) antagonists has been suggested as a prophylactic principle, for instance, in anaesthesia and surgery. Aiming at pharmacological hybrids combining H1R and H2R antagonistic activity, a series of cyanoguanidines 1435 was synthesized by linking mepyramine-type H1R antagonist substructures with roxatidine-, tiotidine-, or ranitidine-type H2R antagonist moieties. N-desmethylmepyramine was connected via a poly-methylene spacer to a cyanoguanidine group as the “urea equivalent” of the H2R antagonist moiety. The title compounds were screened for histamine antagonistic activity at the isolated ileum (H1R) and the isolated spontaneously beating right atrium (H2R) of the guinea pig. The results indicate that, depending on the nature of the H2R antagonist partial structure, the highest H1R antagonist potency resided in roxatidine-type compounds with spacers of six methylene groups in length (compound 21), and tiotidine-type compounds irrespective of the alkyl chain length (compounds 28, 32, 33), N-cyano-N'-[2-[[(2-guanidino-4-thiazolyl)methyl]thio]ethyl]-N″-[2-[N-[2-[N-(4-methoxybenzyl)-N-(pyridyl)-amino] ethyl]-N-methylamino]ethyl] guanidine (25, pKB values: 8.05 (H1R, ileum) and 7.73 (H2R, atrium) and the homologue with the mepyramine moiety connected by a six-membered chain to the tiotidine-like partial structure (compound 32, pKB values: 8.61 (H1R) and 6.61 (H2R) were among the most potent hybrid compounds. With respect to the development of a potential pharmacotherapeutic agent, structural optimization seems possible through selection of other H1R and H2R pharmacophoric moieties with mutually affinity-enhancing properties. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Targeting C-myc G-Quadruplex: Dual Recognition by Aminosugar-Bisbenzimidazoles with Varying Linker Lengths
Molecules 2013, 18(11), 14228-14240; doi:10.3390/molecules181114228
Received: 7 October 2013 / Revised: 4 November 2013 / Accepted: 8 November 2013 / Published: 18 November 2013
Cited by 9 | PDF Full-text (831 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
G-quadruplexes are therapeutically important biological targets. In this report, we present biophysical studies of neomycin-Hoechst 33258 conjugates binding to a G-quadruplex derived from the C-myc promoter sequence. Our studies indicate that conjugation of neomycin to a G-quadruplex binder, Hoechst 33258, enhances [...] Read more.
G-quadruplexes are therapeutically important biological targets. In this report, we present biophysical studies of neomycin-Hoechst 33258 conjugates binding to a G-quadruplex derived from the C-myc promoter sequence. Our studies indicate that conjugation of neomycin to a G-quadruplex binder, Hoechst 33258, enhances its binding. The enhancement in G-quadruplex binding of these conjugates varies with the length and composition of the linkers joining the neomycin and Hoechst 33258 units. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
Open AccessArticle Simultaneous Determination of 14 Phenolic Compounds in Grape Canes by HPLC-DAD-UV Using Wavelength Switching Detection
Molecules 2013, 18(11), 14241-14257; doi:10.3390/molecules181114241
Received: 18 September 2013 / Revised: 7 November 2013 / Accepted: 13 November 2013 / Published: 18 November 2013
Cited by 4 | PDF Full-text (594 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The paper described a novel chromatographic method for the simultaneous determination of phenolic compounds such as gallic, protocatechuic, vanillic, caffeic, syringic, p-coumaric and salicylic acid, (+)-catechin, (‒)-epicatechin, rutin, morin, quercetin, coumarin and trans-resveratrol at their maximum absorbance wavelengths (MAW) employing [...] Read more.
The paper described a novel chromatographic method for the simultaneous determination of phenolic compounds such as gallic, protocatechuic, vanillic, caffeic, syringic, p-coumaric and salicylic acid, (+)-catechin, (‒)-epicatechin, rutin, morin, quercetin, coumarin and trans-resveratrol at their maximum absorbance wavelengths (MAW) employing reverse-phase high performance liquid chromatography combined with DAD and UV detection via detection wavelength switching. The method was based on MAW acquisition by DAD and quantification by UV. The separation process was performed on a Shim-Pack VP-ODS C18 column (250 mm × 4.6 mm, 5 μm) held at 30 °C, utilizing 3.0% acetic acid and acetonitrile as mobile phase at a flow rate of 0.8 mL/min in the gradient elution mode. The method was fully validated in terms of linearity (r2 > 0.9990, 10‒350 mg/L), precision (both intra-day and inter-day RSD < 4.22%), accuracy (97.31%‒104.66%), specificity, robustness (0.59% < RSD < 2.86%), limit of detection and quantification. The switching method significantly improved the sensitivities of most phenolics studied in comparison with the standard constant wavelength detection (280 nm). The proposed method has been successfully applied to the determination of 14 phenolic compounds in 89 varieties of one-year-old Chinese grape one-year-canes. Grape canes contain many phenolics, especially trans-resveratrol, (‒)-epicatechin, and (+)-catechin. Full article
Open AccessArticle Gold Nanoparticles on Mesoporous SiO2-Coated Magnetic Fe3O4 Spheres: A Magnetically Separatable Catalyst with Good Thermal Stability
Molecules 2013, 18(11), 14258-14267; doi:10.3390/molecules181114258
Received: 22 October 2013 / Revised: 11 November 2013 / Accepted: 12 November 2013 / Published: 18 November 2013
Cited by 4 | PDF Full-text (1299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fe3O4 spheres with an average size of 273 nm were prepared in the presence of CTAB by a solvothermal method. The spheres were modified by a thin layer of SiO2, and then coated by mesoporous SiO2 [...] Read more.
Fe3O4 spheres with an average size of 273 nm were prepared in the presence of CTAB by a solvothermal method. The spheres were modified by a thin layer of SiO2, and then coated by mesoporous SiO2 (m-SiO2) films, by using TEOS as a precursor and CTAB as a soft template. The resulting m-SiO2/Fe3O4 spheres, with an average particle size of 320 nm, a high surface area (656 m2/g), and ordered nanopores (average pore size 2.5 nm), were loaded with gold nanoparticles (average size 3.3 nm). The presence of m-SiO2 coating could stabilize gold nanoparticles against sintering at 500 °C. The material showed better performance than a conventional Au/SiO2 catalyst in catalytic reduction of p-nitrophenol with NaBH4. It can be separated from the reaction mixture by a magnet and be recycled without obvious loss of catalytic activity. Relevant characterization by XRD, TEM, N2 adsorption-desorption, and magnetic measurements were conducted. Full article
Open AccessArticle Triterpenoids and Steroids from Ganoderma mastoporum and Their Inhibitory Effects on Superoxide Anion Generation and Elastase Release
Molecules 2013, 18(11), 14285-14292; doi:10.3390/molecules181114285
Received: 27 September 2013 / Revised: 6 November 2013 / Accepted: 15 November 2013 / Published: 19 November 2013
Cited by 2 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
The methanol extracts of the fruiting bodies of Ganoderma mastoporum collected in Vietnam was purified to afford eight compounds, including three triterpenoids and five steroids. The purified compounds were examined for their inhibitory effects against superoxide anion generation and elastase release. Among [...] Read more.
The methanol extracts of the fruiting bodies of Ganoderma mastoporum collected in Vietnam was purified to afford eight compounds, including three triterpenoids and five steroids. The purified compounds were examined for their inhibitory effects against superoxide anion generation and elastase release. Among the tested compounds, ergosta-4,6,8(14),22-tetraen-3-one (3) exhibited the most significant inhibition towards superoxide anion generation and elastase release with IC50 values of 2.30 ± 0.38 and 1.94 ± 0.50 µg/mL, respectively. Full article
Open AccessCommunication The Formation of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5-Benzodiazepine from 1,2-Diaminobenzene in the Presence of Acetone
Molecules 2013, 18(11), 14293-14305; doi:10.3390/molecules181114293
Received: 11 September 2013 / Revised: 11 November 2013 / Accepted: 11 November 2013 / Published: 19 November 2013
PDF Full-text (376 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation [...] Read more.
In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation of two moles of acetone with the amine groups resulted in the formation of the benzodiazepine which crystallized as an iminium cation forming a salt with the isophthalate anion. The formation of benzodiazepine was also confirmed by performing the reaction of o-phenylenediamine with excess acetone in ethanol under conventional heating conditions. The compounds were characterized by NMR, FTIR, HRMS and microanalysis as well as X-ray crystallography. The reaction mechanism leading to the formation of benzodiazepine is also discussed. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Synthesis of Quaternary Heterocyclic Salts
Molecules 2013, 18(11), 14306-14319; doi:10.3390/molecules181114306
Received: 7 October 2013 / Revised: 28 October 2013 / Accepted: 28 October 2013 / Published: 19 November 2013
Cited by 5 | PDF Full-text (301 KB) | HTML Full-text | XML Full-text
Abstract The microwave synthesis of twenty quaternary ammonium salts is described. The syntheses feature comparable yields to conventional synthetic methods reported in the current literature with reduced reaction times and the absence of solvent or minimal solvent. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Tuning a 96-Well Microtiter Plate Fluorescence-Based Assay to Identify AGE Inhibitors in Crude Plant Extracts
Molecules 2013, 18(11), 14320-14339; doi:10.3390/molecules181114320
Received: 12 October 2013 / Revised: 7 November 2013 / Accepted: 14 November 2013 / Published: 19 November 2013
Cited by 13 | PDF Full-text (619 KB) | HTML Full-text | XML Full-text
Abstract
Advanced glycation end-products (AGEs) are involved in the pathogenesis of numerous diseases. Among them, cellular accumulation of AGEs contributes to vascular complications in diabetes. Besides using drugs to lower blood sugar, a balanced diet and the intake of herbal products potentially limiting [...] Read more.
Advanced glycation end-products (AGEs) are involved in the pathogenesis of numerous diseases. Among them, cellular accumulation of AGEs contributes to vascular complications in diabetes. Besides using drugs to lower blood sugar, a balanced diet and the intake of herbal products potentially limiting AGE formation could be considered beneficial for patients’ health. The current paper presents a simple and cheap high-throughput screening (HTS) assay based on AGE fluorescence and suitable for plant extract screening. We have already implemented an HTS assay based on vesperlysines-like fluorescing AGEs quickly (24 h) formed from BSA and ribose under physiological conditions. However, interference was noted when fluorescent compounds and/or complex mixtures were tested. To overcome these problems and apply this HTS assay to plant extracts, we developed a technique for systematic quantification of both vesperlysines (λexc 370 nm; λem 440 nm) and pentosidine-like (λexc 335 nm; λem 385 nm) AGEs. In a batch of medicinal and food plant extracts, hits were selected as soon as fluorescence decreased under a fixed threshold for at least one wavelength. Hits revealed during this study appeared to contain well-known and powerful anti-AGE substances, thus demonstrating the suitability of this assay for screening crude extracts (0.1 mg/mL). Finally, quercetin was found to be a more powerful reference compound than aminoguanidine in such assay. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Antibacterial Activity of Glucomoringin Bioactivated with Myrosinase against Two Important Pathogens Affecting the Health of Long-Term Patients in Hospitals
Molecules 2013, 18(11), 14340-14348; doi:10.3390/molecules181114340
Received: 25 October 2013 / Revised: 8 November 2013 / Accepted: 11 November 2013 / Published: 20 November 2013
Cited by 11 | PDF Full-text (1071 KB) | HTML Full-text | XML Full-text
Abstract
Glucosinolates (GLs) are natural compounds present in species of the order Brassicales and precursors of bioactive isothiocyanates (ITCs). In the recent years, they have been studied mainly for their chemopreventive as well as novel chemotherapeutics properties. Among them 4-(α-L-rhamnosyloxy)benzyl glucosinolate (glucomoringin; GMG), [...] Read more.
Glucosinolates (GLs) are natural compounds present in species of the order Brassicales and precursors of bioactive isothiocyanates (ITCs). In the recent years, they have been studied mainly for their chemopreventive as well as novel chemotherapeutics properties. Among them 4-(α-L-rhamnosyloxy)benzyl glucosinolate (glucomoringin; GMG), purified from seeds of Moringa oleifera Lam., a plant belonging to the Moringaceae family, represents an uncommon member of the GL family with peculiar characteristics. This short communication reports new evidences about the properties of GMG and presents a new innovative utilization of the molecule. The bioactivation of GMG by myrosinase enzyme just before treatment, permits to maximize the power of the final product of the reaction, which is the 4-(α-L-rhamnosyloxy)benzyl isothiocyanate (GMG-ITC). We tested the antibiotic activity of this latter compound on two strains of pathogens affecting the health of patients in hospital, namely Staphylococcus aureus and Enterococcus casseliflavus, and on the yeast Candida albicans. Results show that the sensibility of S. aureus BAA-977 strain and E. casseliflavus to GMG-ITC treatment reveals an important possible application of this molecule in the clinical care of patients, more and more often resistant to traditional therapies. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Modulation of the Microenvironment Surrounding the Active Site of Penicillin G Acylase Immobilized on Acrylic Carriers Improves the Enzymatic Synthesis of Cephalosporins
Molecules 2013, 18(11), 14349-14365; doi:10.3390/molecules181114349
Received: 9 September 2013 / Revised: 20 October 2013 / Accepted: 28 October 2013 / Published: 20 November 2013
Cited by 8 | PDF Full-text (648 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled synthesis of β-lactam antibiotics are negatively affected upon immobilization on hydrophobic acrylic carriers. Two strategies have been here pursued to improve the synthetic performance of PGA immobilized on [...] Read more.
The catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled synthesis of β-lactam antibiotics are negatively affected upon immobilization on hydrophobic acrylic carriers. Two strategies have been here pursued to improve the synthetic performance of PGA immobilized on epoxy-activated acrylic carriers. First, an aldehyde-based spacer was inserted on the carrier surface by glutaraldehyde activation (immobilization yield = 50%). The resulting 3-fold higher synthesis/hydrolysis ratio (vs/vh1 = 9.7 ± 0.7 and 10.9 ± 0.7 for Eupergit® C and Sepabeads® EC-EP, respectively) with respect to the unmodified support (vs/vh1 = 3.3 ± 0.4) was ascribed to a facilitated diffusion of substrates and products as a result of the increased distance between the enzyme and the carrier surface. A second series of catalysts was prepared by direct immobilization of PGA on epoxy-activated acrylic carriers (Eupergit® C), followed by quenching of oxiranes not involved in the binding with the protein with different nucleophiles (amino acids, amines, amino alcohols, thiols and amino thiols). In most cases, this derivatization increased the synthesis/hydrolysis ratio with respect to the non derivatized carrier. Particularly, post-immobilization treatment with cysteine resulted in about 2.5-fold higher vs/vh1 compared to the untreated biocatalyst, although the immobilization yield decreased from 70% (untreated Eupergit® C) to 20%. Glutaraldehyde- and cysteine-treated Eupergit® C catalyzed the synthesis of cefazolin in 88% (±0.9) and 87% (±1.6) conversion, respectively, whereas untreated Eupergit® C afforded this antibiotic in 79% (±1.2) conversion. Full article
(This article belongs to the Special Issue Enzyme Chemistry)
Open AccessArticle Optimization of Extraction of Novel Pectinase Enzyme Discovered in Red Pitaya (Hylocereus polyrhizus) Peel
Molecules 2013, 18(11), 14366-14380; doi:10.3390/molecules181114366
Received: 20 August 2013 / Revised: 20 October 2013 / Accepted: 1 November 2013 / Published: 20 November 2013
Cited by 5 | PDF Full-text (371 KB) | HTML Full-text | XML Full-text
Abstract
Plant peels could be a potential source of novel pectinases for use in various industrial applications due to their broad substrate specificity with high stability under extreme conditions. Therefore, the extraction conditions of a novel pectinase enzyme from pitaya peel was optimized [...] Read more.
Plant peels could be a potential source of novel pectinases for use in various industrial applications due to their broad substrate specificity with high stability under extreme conditions. Therefore, the extraction conditions of a novel pectinase enzyme from pitaya peel was optimized in this study. The effect of extraction variables, namely buffer to sample ratio (2:1 to 8:1, X1), extraction temperature (−15 to +25 °C, X2) and buffer pH (4.0 to 12.0, X3) on specific activity, temperature stability, storage stability and surfactant agent stability of pectinase from pitaya peel was investigated. The study demonstrated that the optimum conditions for the extraction of pectinase from pitaya sources could improve the enzymatic characteristics of the enzyme and protect its activity and stability during the extraction procedure. The optimum extraction conditions cause the pectinase to achieve high specific activity (15.31 U/mg), temperature stability (78%), storage stability (88%) and surfactant agent stability (83%). The most desirable conditions to achieve the highest activity and stability of pectinase enzyme from pitaya peel were the use of 5:1 buffer to sample ratio at 5 °C and pH 8.0. Full article
Open AccessArticle An In Vitro Study of the Antimicrobial Effects of Indigo Naturalis Prepared from Strobilanthes formosanus Moore
Molecules 2013, 18(11), 14381-14396; doi:10.3390/molecules181114381
Received: 10 September 2013 / Revised: 24 October 2013 / Accepted: 25 October 2013 / Published: 21 November 2013
Cited by 3 | PDF Full-text (517 KB) | HTML Full-text | XML Full-text
Abstract
Indigo naturalis is effective in treating nail psoriasis coexisting with microorganism infections. This study examines the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore. Eight bacterial and seven fungal strains were assayed using the agar diffusion method to examine the [...] Read more.
Indigo naturalis is effective in treating nail psoriasis coexisting with microorganism infections. This study examines the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore. Eight bacterial and seven fungal strains were assayed using the agar diffusion method to examine the effects of indigo naturalis and its bioactive compounds. The bioactive compounds of indigo naturalis were purified sequentially using GFC, TLC, and HPLC. Their structures were identified using mass spectrometry and NMR spectroscopy. UPLC-MS/MS was applied to compare the metabolome profiles of indigo naturalis ethyl-acetate (EA) extract and its source plant, Strobilanthes formosanus Moore. The results of in vitro antimicrobial assays showed that indigo naturalis EA-extract significantly (≥1 mg/disc) inhibits Gram-positive bacteria (Staphylococcus aureus, S. epidermis and methicillin-resistant S. aureus (MRSA)) and mildly inhibits non-dermatophytic onychomycosis pathogens (Aspergillus fumigates and Candida albicans), but has little effect on dermatophyes. Isatin and tryptanthrin were identified as the bioactive compounds of indigo naturalis using S. aureus and S. epidermis as the bioassay model. Both bioactive ingredients had no effect on all tested fungi. In summary, indigo naturalis prepared from Strobilanthes formosanus Moore exhibits antimicrobial effects on Staphylococcus and non-dermatophytic onychomycosis pathogens. Tryptanthrin and isatin may be its major bioactive ingredients against Staphylococcus and the inhibitory effect on MRSA may be due to other unidentified ingredients. Full article
Open AccessArticle Biological Activity of Propolis-Honey Balm in the Treatment of Experimentally-Evoked Burn Wounds
Molecules 2013, 18(11), 14397-14413; doi:10.3390/molecules181114397
Received: 23 September 2013 / Revised: 11 November 2013 / Accepted: 12 November 2013 / Published: 21 November 2013
Cited by 6 | PDF Full-text (2782 KB) | HTML Full-text | XML Full-text
Abstract
Medicines of biogenic origin with micro-organic, regenerative and analgesic properties are becoming more and more significant in the treatment of burn wounds. These properties are found in apitherapeutics such as propolis and honey—products collected and processed by a honey bee. Their effect [...] Read more.
Medicines of biogenic origin with micro-organic, regenerative and analgesic properties are becoming more and more significant in the treatment of burn wounds. These properties are found in apitherapeutics such as propolis and honey—products collected and processed by a honey bee. Their effect on the course of the healing processes is multidirectional. The aim of the study was a histopathological and biochemical analysis of the processes of scar formation in experimentally evoked burn wounds in white pigs treated with the 1% and 3% Sepropol balms containing standardized extracts of propolis and honey. The results were compared with the therapeutic effects obtained with dermazin cream (1% silver sulfadiazine). The level of collagen was determined in the wounds treated with 1% and 3% Sepropol and compared with the collagen level in healthy skin and wounds treated with dermazin. Granulation and regenerated epithelium formation times were compared, with the 3% Sepropol being by far the most effective. The 3% Sepropol also increased the collagen level to 116% with the control sub-groups scoring between 80% and 98%. The results show the healing process of burn wounds in pigs treated with the Sepropol balm starts earlier and has a faster course than the standard dermazin therapy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Solution Structure of the Circular γ-Domain Analog from the Wheat Metallothionein Ec-1
Molecules 2013, 18(11), 14414-14429; doi:10.3390/molecules181114414
Received: 16 October 2013 / Revised: 6 November 2013 / Accepted: 19 November 2013 / Published: 21 November 2013
Cited by 5 | PDF Full-text (3029 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The first cyclic analog of a metallothionein (MT) was prepared and analyzed by UV and (magnetic) circular dichroism spectroscopy, ESI-MS as well as NMR spectroscopy. Results reveal that the evaluated cyclic g-Ec-1 domain of the wheat MT Ec-1 [...] Read more.
The first cyclic analog of a metallothionein (MT) was prepared and analyzed by UV and (magnetic) circular dichroism spectroscopy, ESI-MS as well as NMR spectroscopy. Results reveal that the evaluated cyclic g-Ec-1 domain of the wheat MT Ec-1 retains its ability to coordinate two Zn(II) or Cd(II) ions and adopts a three-dimensional structure that is highly similar to the one of the linear wild-type form. However, the reduced flexibility of the protein backbone facilitates structure solution significantly and results in a certain stabilization of metal binding to the protein. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessArticle Deracemization of Axially Chiral Nicotinamides by Dynamic Salt Formation with Enantiopure Dibenzoyltartaric Acid (DBTA)
Molecules 2013, 18(11), 14430-14447; doi:10.3390/molecules181114430
Received: 15 October 2013 / Revised: 13 November 2013 / Accepted: 19 November 2013 / Published: 21 November 2013
Cited by 3 | PDF Full-text (1560 KB) | HTML Full-text | XML Full-text
Abstract
Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection [...] Read more.
Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of enantiopure DBTA as a chiral auxiliary. The axial chirality generated by dynamic salt formation was retained for a long period after dissolving the chiral salt in solution even after removal of the chiral acid. The rate of racemization of nicotinamides could be controlled based on the temperature and solvent properties, and that of the salts was prolonged compared to free nicotinamides, as the molecular structure of the pyridinium ion in the salts was different from that of acid-free nicotinamides. Full article
(This article belongs to the Special Issue Dynamic Stereochemistry)
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Open AccessArticle Determination and Comparison of Seed Oil Triacylglycerol Composition of Various Soybeans (Glycine max (L.)) Using 1H-NMR Spectroscopy
Molecules 2013, 18(11), 14448-14454; doi:10.3390/molecules181114448
Received: 15 September 2013 / Revised: 2 November 2013 / Accepted: 12 November 2013 / Published: 21 November 2013
Cited by 3 | PDF Full-text (319 KB) | HTML Full-text | XML Full-text
Abstract
Seed oil triacylglycerol (TAG) composition of 32 soybean varieties were determined and compared using 1H-NMR. The contents of linolenic (Ln), linoleic (L), and oleic (O) ranged from 10.7% to 19.3%, 37.4%–50.1%, and 15.7%–34.1%, respectively. As is evident, linoleic acid was the [...] Read more.
Seed oil triacylglycerol (TAG) composition of 32 soybean varieties were determined and compared using 1H-NMR. The contents of linolenic (Ln), linoleic (L), and oleic (O) ranged from 10.7% to 19.3%, 37.4%–50.1%, and 15.7%–34.1%, respectively. As is evident, linoleic acid was the major fatty acid of soybean oil. Compositional differences among the varieties were observed. Natural oils containing unsaturated groups have been regarded as important nutrient and cosmetic ingredients because of their various biological activities. The TAG profiles of the soy bean oils could be useful for distinguishing the origin of seeds and controlling the quality of soybean oils. To the best of our knowledge, this is the first study in which the TAG composition of various soybean oils has been analyzed using the 1H-NMR method. Full article
(This article belongs to the Section Natural Products)

Review

Jump to: Research, Other

Open AccessReview Synthesis of 3,4-Dibenzyltetrahydrofuran Lignans (9,9′-Epoxylignanes)
Molecules 2013, 18(11), 13124-13138; doi:10.3390/molecules181113124
Received: 28 August 2013 / Revised: 23 September 2013 / Accepted: 25 September 2013 / Published: 24 October 2013
Cited by 3 | PDF Full-text (478 KB) | HTML Full-text | XML Full-text
Abstract
Different strategies for the racemic or enantiospecific total syntheses of plant and mammalian 3,4-dibenzyltetrahydrofuran lignans are reviewed and compared. The multi-step approaches have various key step strategies: Diels–Alder reactions, Stobbe condensations, Michael additions, alkylations, nitrile oxide cycloadditions, radical cyclisations, dianion and oxidative [...] Read more.
Different strategies for the racemic or enantiospecific total syntheses of plant and mammalian 3,4-dibenzyltetrahydrofuran lignans are reviewed and compared. The multi-step approaches have various key step strategies: Diels–Alder reactions, Stobbe condensations, Michael additions, alkylations, nitrile oxide cycloadditions, radical cyclisations, dianion and oxidative couplings. Full article
(This article belongs to the Special Issue Steroids)
Open AccessReview Peptide Conjugation via CuAAC ‘Click’ Chemistry
Molecules 2013, 18(11), 13148-13174; doi:10.3390/molecules181113148
Received: 6 September 2013 / Revised: 9 October 2013 / Accepted: 10 October 2013 / Published: 24 October 2013
Cited by 25 | PDF Full-text (1173 KB) | HTML Full-text | XML Full-text
Abstract
The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or ‘click’ reaction, is a highly versatile reaction that can be performed under a variety of reaction conditions including various solvents, a wide pH and temperature range, and using different copper sources, with or [...] Read more.
The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or ‘click’ reaction, is a highly versatile reaction that can be performed under a variety of reaction conditions including various solvents, a wide pH and temperature range, and using different copper sources, with or without additional ligands or reducing agents. This reaction is highly selective and can be performed in the presence of other functional moieties. The flexibility and selectivity has resulted in growing interest in the application of CuAAC in various fields. In this review, we briefly describe the importance of the structural folding of peptides and proteins and how the 1,4-disubstituted triazole product of the CuAAC reaction is a suitable isoster for an amide bond. However the major focus of the review is the application of this reaction to produce peptide conjugates for tagging and targeting purpose, linkers for multifunctional biomacromolecules, and reporter ions for peptide and protein analysis. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
Open AccessReview 11β-Hydroxyandrostenedione Returns to the Steroid Arena: Biosynthesis, Metabolism and Function
Molecules 2013, 18(11), 13228-13244; doi:10.3390/molecules181113228
Received: 11 September 2013 / Revised: 18 October 2013 / Accepted: 21 October 2013 / Published: 25 October 2013
Cited by 4 | PDF Full-text (469 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The biological significance of 11β-hydroxyandrostenedione (11OHA4) has eluded researchers for the past six decades. It is now known that 11OHA4 is biosynthesized in the androgen arm of the adrenal steroidogenesis pathway and subsequently metabolized by steroidogenic enzymes in vitro, serving as [...] Read more.
The biological significance of 11β-hydroxyandrostenedione (11OHA4) has eluded researchers for the past six decades. It is now known that 11OHA4 is biosynthesized in the androgen arm of the adrenal steroidogenesis pathway and subsequently metabolized by steroidogenic enzymes in vitro, serving as precursor to recognized and novel androgenic steroids. These in vitro findings extend beyond the adrenal, suggesting that 11OHA4 could be metabolized in steroid-responsive peripheral tissues, as is the case for androgen precursor metabolites of adrenal origin. The significance thereof becomes apparent when considering that the metabolism of 11OHA4 in LNCaP androgen dependent prostate cancer cells yields androgenic steroid metabolites. It is thus possible that 11OHA4 may be metabolized to yield ligands for steroid receptors in not only the prostate but also in other steroid-responsive tissues. Future investigations of 11OHA4 may therefore characterize it as a vital steroid with far-reaching physiological consequences. An overview of the research on 11OHA4 since its identification in 1953 will be presented, with specific focus on the most recent works that have advanced our understanding of its biological role, thereby underscoring its relevance in health and disease. Full article
(This article belongs to the Special Issue Steroids)
Open AccessReview Effect of Pressure on Thermal Stability of G-Quadruplex DNA and Double-Stranded DNA Structures
Molecules 2013, 18(11), 13297-13319; doi:10.3390/molecules181113297
Received: 30 August 2013 / Revised: 5 October 2013 / Accepted: 24 October 2013 / Published: 29 October 2013
Cited by 5 | PDF Full-text (1527 KB) | HTML Full-text | XML Full-text
Abstract
Pressure is a thermodynamic parameter that can induce structural changes in biomolecules due to a volumetric decrease. Although most proteins are denatured by pressure over 100 MPa because they have the large cavities inside their structures, the double-stranded structure of DNA is [...] Read more.
Pressure is a thermodynamic parameter that can induce structural changes in biomolecules due to a volumetric decrease. Although most proteins are denatured by pressure over 100 MPa because they have the large cavities inside their structures, the double-stranded structure of DNA is stabilized or destabilized only marginally depending on the sequence and salt conditions. The thermal stability of the G-quadruplex DNA structure, an important non-canonical structure that likely impacts gene expression in cells, remarkably decreases with increasing pressure. Volumetric analysis revealed that human telomeric DNA changed by more than 50 cm3 mol−1 during the transition from a random coil to a quadruplex form. This value is approximately ten times larger than that for duplex DNA under similar conditions. The volumetric analysis also suggested that the formation of G-quadruplex DNA involves significant hydration changes. The presence of a cosolute such as poly(ethylene glycol) largely repressed the pressure effect on the stability of G-quadruplex due to alteration in stabilities of the interactions with hydrating water. This review discusses the importance of local perturbations of pressure on DNA structures involved in regulation of gene expression and highlights the potential for application of high-pressure chemistry in nucleic acid-based nanotechnology. Full article
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
Open AccessReview NMR Study on Small Proteins from Helicobacter pylori for Antibiotic Target Discovery: A Review
Molecules 2013, 18(11), 13410-13424; doi:10.3390/molecules181113410
Received: 21 June 2013 / Revised: 24 October 2013 / Accepted: 27 October 2013 / Published: 30 October 2013
Cited by 2 | PDF Full-text (588 KB) | HTML Full-text | XML Full-text
Abstract
Due to the widespread and increasing appearance of antibiotic resistance, a new strategy is needed for developing novel antibiotics. Especially, there are no specific antibiotics for Helicobacter pylori (H. pylori). H. pylori are bacteria that live in the stomach [...] Read more.
Due to the widespread and increasing appearance of antibiotic resistance, a new strategy is needed for developing novel antibiotics. Especially, there are no specific antibiotics for Helicobacter pylori (H. pylori). H. pylori are bacteria that live in the stomach and are related to many serious gastric problems such as peptic ulcers, chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Because of its importance as a human pathogen, it’s worth studying the structure and function of the proteins from H. pylori. After the sequencing of the H. pylori strain 26695 in 1997, more than 1,600 genes were identified from H. pylori. Until now, the structures of 334 proteins from H. pylori have been determined. Among them, 309 structures were determined by X-ray crystallography and 25 structures by Nuclear Magnetic Resonance (NMR), respectively. Overall, the structures of large proteins were determined by X-ray crystallography and those of small proteins by NMR. In our lab, we have studied the structural and functional characteristics of small proteins from H. pylori. In this review, 25 NMR structures of H. pylori proteins will be introduced and their structure-function relationships will be discussed. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessReview OSBP-Related Proteins: Liganding by Glycerophospholipids Opens New Insight into Their Function
Molecules 2013, 18(11), 13666-13679; doi:10.3390/molecules181113666
Received: 11 September 2013 / Revised: 1 November 2013 / Accepted: 1 November 2013 / Published: 5 November 2013
Cited by 6 | PDF Full-text (666 KB) | HTML Full-text | XML Full-text
Abstract
Oxysterol-binding protein (OSBP) and its homologs designated OSBP-related (ORP) or OSBP-like (OSBPL) proteins constitute a conserved family of lipid binding/transfer proteins (LTP) in eukaryotes. The mechanisms of ORP function have remained incompletely understood, but they have been implicated as intracellular sterol sensors [...] Read more.
Oxysterol-binding protein (OSBP) and its homologs designated OSBP-related (ORP) or OSBP-like (OSBPL) proteins constitute a conserved family of lipid binding/transfer proteins (LTP) in eukaryotes. The mechanisms of ORP function have remained incompletely understood, but they have been implicated as intracellular sterol sensors or transporters. A number of studies have provided evidence for the roles of ORPs at membrane contact sites (MCS), where endoplasmic reticulum is closely apposed with other organelle limiting membranes. ORPs are postulated to either transport sterols over MCSs or control the activity of enzymatic effectors or assembly of protein complexes with functions in signaling and lipid metabolism. Studies of yeast Saccharomyces cerevisiae ORPs Osh4p, Osh3p, Osh6p and Osh7p have revealed that ORPs do not exclusively bind sterols within their OSBP-related ligand-binding domain (ORD): The Osh4p ORD accommodates either sterols or phosphatidylinositol-4-phosphate (PI4P), and the Osh3p ORD was shown to specifically bind PI4P, the binding cavity being too narrow for a sterol to fit in. Most recently, Osh6p and Osh7p were demonstrated to show specific affinity for phosphatidylserine (PS), and to play a role in the intracellular transport of this glycerophospholipid; Additionally, two mammalian ORPs were shown to bind PS. Thus, the term frequently used for ORPs/OSBPLs, oxysterol-binding proteins, is a misnomer. While a number of ORPs bind oxysterols or cholesterol, other family members appear to interact with phospholipid ligands to regulate lipid fluxes, organelle lipid compositions and cell signaling. As a conclusion, ORPs are LTPs with a wide ligand spectrum and marked functional heterogeneity. Full article
(This article belongs to the Special Issue Steroids)
Open AccessReview The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
Molecules 2013, 18(11), 13769-13811; doi:10.3390/molecules181113769
Received: 1 July 2013 / Revised: 30 October 2013 / Accepted: 31 October 2013 / Published: 7 November 2013
Cited by 7 | PDF Full-text (6376 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes [...] Read more.
Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amido)amine (PAMAM) dendrimers (G2, G3 and G4) have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessReview Photoaffinity Labeling of Plasma Proteins
Molecules 2013, 18(11), 13831-13859; doi:10.3390/molecules181113831
Received: 20 August 2013 / Revised: 22 October 2013 / Accepted: 4 November 2013 / Published: 8 November 2013
Cited by 3 | PDF Full-text (1974 KB) | HTML Full-text | XML Full-text
Abstract
Photoaffinity labeling is a powerful technique for identifying a target protein. A high degree of labeling specificity can be achieved with this method in comparison to chemical labeling. Human serum albumin (HSA) and α1-acid glycoprotein (AGP) are two plasma proteins [...] Read more.
Photoaffinity labeling is a powerful technique for identifying a target protein. A high degree of labeling specificity can be achieved with this method in comparison to chemical labeling. Human serum albumin (HSA) and α1-acid glycoprotein (AGP) are two plasma proteins that bind a variety of endogenous and exogenous substances. The ligand binding mechanism of these two proteins is complex. Fatty acids, which are known to be transported in plasma by HSA, cause conformational changes and participate in allosteric ligand binding to HSA. HSA undergoes an N-B transition, a conformational change at alkaline pH, that has been reported to result in increased ligand binding. Attempts have been made to investigate the impact of fatty acids and the N-B transition on ligand binding in HSA using ketoprofen and flunitrazepam as photolabeling agents. Meanwhile, plasma AGP is a mixture of genetic variants of the protein. The photolabeling of AGP with flunitrazepam has been utilized to shed light on the topology of the protein ligand binding site. Furthermore, a review of photoaffinity labeling performed on other major plasma proteins will also be discussed. Using a photoreactive natural ligand as a photolabeling agent to identify target protein in the plasma would reduce non-specific labeling. Full article
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
Open AccessReview Molecular MRI of Atherosclerosis
Molecules 2013, 18(11), 14042-14069; doi:10.3390/molecules181114042
Received: 9 September 2013 / Revised: 29 October 2013 / Accepted: 29 October 2013 / Published: 13 November 2013
Cited by 8 | PDF Full-text (5828 KB) | HTML Full-text | XML Full-text
Abstract
Despite advances in prevention, risk assessment and treatment, coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western countries. The lion’s share is due to acute coronary syndromes (ACS), which are predominantly triggered by plaque rupture or erosion [...] Read more.
Despite advances in prevention, risk assessment and treatment, coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western countries. The lion’s share is due to acute coronary syndromes (ACS), which are predominantly triggered by plaque rupture or erosion and subsequent coronary thrombosis. As the majority of vulnerable plaques does not cause a significant stenosis, due to expansive remodeling, and are rather defined by their composition and biological activity, detection of vulnerable plaques with x-ray angiography has shown little success. Non-invasive vulnerable plaque detection by identifying biological features that have been associated with plaque progression, destabilization and rupture may therefore be more appropriate and may allow earlier detection, more aggressive treatment and monitoring of treatment response. MR molecular imaging with target specific molecular probes has shown great promise for the noninvasive in vivo visualization of biological processes at the molecular and cellular level in animals and humans. Compared to other imaging modalities; MRI can provide excellent spatial resolution; high soft tissue contrast and has the ability to simultaneously image anatomy; function as well as biological tissue composition and activity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Polymeric Systems of Antimicrobial Peptides—Strategies and Potential Applications
Molecules 2013, 18(11), 14122-14137; doi:10.3390/molecules181114122
Received: 8 October 2013 / Revised: 31 October 2013 / Accepted: 5 November 2013 / Published: 14 November 2013
Cited by 13 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
The past decade has seen growing interest in the investigation of peptides with antimicrobial activity (AMPs). One approach utilized in infection control is incorporation of antimicrobial agents conjugated with the polymers. This review presents the recent developments on polymeric AMP carriers and [...] Read more.
The past decade has seen growing interest in the investigation of peptides with antimicrobial activity (AMPs). One approach utilized in infection control is incorporation of antimicrobial agents conjugated with the polymers. This review presents the recent developments on polymeric AMP carriers and their potential applications in the biomedical and pharmaceutical fields. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessReview Investigating the Role of Polyunsaturated Fatty Acids in Bone Development Using Animal Models
Molecules 2013, 18(11), 14203-14227; doi:10.3390/molecules181114203
Received: 13 September 2013 / Revised: 7 November 2013 / Accepted: 8 November 2013 / Published: 15 November 2013
Cited by 8 | PDF Full-text (446 KB) | HTML Full-text | XML Full-text
Abstract
Incorporating n-3 polyunsaturated fatty acids (PUFA) in the diet may promote the development of a healthy skeleton and thereby reduce the risk of developing osteoporosis in later life. Studies using developing animal models suggest lowering dietary n-6 PUFA and increasing n-3 PUFA [...] Read more.
Incorporating n-3 polyunsaturated fatty acids (PUFA) in the diet may promote the development of a healthy skeleton and thereby reduce the risk of developing osteoporosis in later life. Studies using developing animal models suggest lowering dietary n-6 PUFA and increasing n-3 PUFA intakes, especially long chain n-3 PUFA, may be beneficial for achieving higher bone mineral content, density and stronger bones. To date, the evidence regarding the effects of α-linolenic acid (ALA) remain equivocal, in contrast to evidence from the longer chain products, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This review reports the results of investigations into n-3 PUFA supplementation on bone fatty acid composition, strength and mineral content in developing animal models as well as the mechanistic relationships of PUFA and bone, and identifies critical areas for future research. Overall, this review supports a probable role for essential (ALA) and long chain (EPA and DHA) n-3 PUFA for bone health. Understanding the role of PUFA in optimizing bone health may lead to dietary strategies that promote bone development and maintenance of a healthy skeleton. Full article
(This article belongs to the Special Issue Fatty Acids)
Open AccessReview Synthesis of DNA/RNA and Their Analogs via Phosphoramidite and H-Phosphonate Chemistries
Molecules 2013, 18(11), 14268-14284; doi:10.3390/molecules181114268
Received: 8 October 2013 / Revised: 8 November 2013 / Accepted: 8 November 2013 / Published: 18 November 2013
Cited by 14 | PDF Full-text (680 KB) | HTML Full-text | XML Full-text
Abstract
The chemical synthesis of DNA and RNA is universally carried out using nucleoside phosphoramidites or H-phosphonates as synthons. This review focuses on the phosphorus chemistry behind these synthons and how it has been developed to generate procedures whereby yields per condensation approach [...] Read more.
The chemical synthesis of DNA and RNA is universally carried out using nucleoside phosphoramidites or H-phosphonates as synthons. This review focuses on the phosphorus chemistry behind these synthons and how it has been developed to generate procedures whereby yields per condensation approach 100% with very few side products. Additionally the synthesis and properties of certain DNA and RNA analogs that are modified at phosphorus will also be discussed. These analogs include boranephosphonates, metallophosphonates, and alkylboranephosphines. Full article
(This article belongs to the Special Issue Organophosphorus Chemistry)

Other

Jump to: Research, Review

Open AccessCorrection Correction: Jerković, I., et al. Composition of Sulla (Hedysarum coronarium L.) Honey Solvent Extractives Determined by GC/MS: Norisoprenoids and Other Volatile Organic Compounds. Molecules 2010, 15, 6375-6385
Molecules 2013, 18(11), 13434; doi:10.3390/molecules181113434
Received: 3 September 2013 / Revised: 21 October 2013 / Accepted: 30 October 2013 / Published: 30 October 2013
PDF Full-text (129 KB) | HTML Full-text | XML Full-text
Abstract The authors wish to make the following correction to paper [1], doi:10.3390/molecules15096375, website: http://www.mdpi.com/1420-3049/15/9/6375. The correct name of the second author is: Carlo I. G. Tuberoso. [...] Full article
Open AccessConcept Paper Topography of Photochemical Initiation in Molecular Materials
Molecules 2013, 18(11), 14148-14160; doi:10.3390/molecules181114148
Received: 14 October 2013 / Revised: 8 November 2013 / Accepted: 12 November 2013 / Published: 15 November 2013
Cited by 10 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
We propose a fluctuation model of the photochemical initiation of an explosive chain reaction in energetic materials. In accordance with the developed model, density fluctuations of photo-excited molecules serve as reaction nucleation sites due to the stochastic character of interactions between photons [...] Read more.
We propose a fluctuation model of the photochemical initiation of an explosive chain reaction in energetic materials. In accordance with the developed model, density fluctuations of photo-excited molecules serve as reaction nucleation sites due to the stochastic character of interactions between photons and energetic molecules. A further development of the reaction is determined by a competition of two processes. The first process is growth in size of the isolated reaction cell, leading to a micro-explosion and release of the material from the cell towards the sample surface. The second process is the overlap of reaction cells due to an increase in their size, leading to the formation of a continuous reaction zone and culminating in a macro-explosion, i.e., explosion of the entire area, covering a large part of the volume of the sample. Within the proposed analytical model, we derived expressions of the explosion probability and the duration of the induction period as a function of the initiation energy (exposure). An experimental verification of the model was performed by exploring the initiation of pentaerythritol tetranitrate (PETN) with the first harmonic of YAG: Nd laser excitation (1,064 nm, 10 ns), which has confirmed the adequacy of the model. This validation allowed us to make a few quantitative assessments and predictions. For example, there must be a few dozen optically excited molecules produced by the initial fluctuations for the explosive decomposition reaction to occur and the life-time of an isolated cell before the micro-explosion must be of the order of microseconds. Full article
(This article belongs to the Special Issue Surface Chemistry)
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