Search Results (105)

Houttuynia cordata is a culinary herb from Asia. Its edible rhizomes and leaves have a fishy aroma, the molecular background of which was unknown. A comparative aroma extract dilution analysis applied to fresh rhizomes and leaves resulted in 44 and 41 odorants, respectively, 38 of which were present with FD factors ≥1 in both samples. The odorant with the highest FD factors, whether in the rhizomes or leaves, was identified as metallic, soapy, fishy smelling 3-oxododecanal. Toward clarifying its tautomeric composition, quantum calculations suggested a predominance of the enol forms in the plant. However, the form perceived at the sniffing port during GC–O remained unclear. Full article

The anticancer activity of 3′-deoxyadenosine (Cordycepin, or dCor) is known to be linked to the inhibition of the MAPK/ERK signalling and Hedgehog pathways, as well as the termination of primer elongation by primase in DNA lagging-strand synthesis. In this study, the electronic properties of dCor, 7,8-dihydro-8-oxo-3′-deoxyadenosine (^OXOdCor), and 8-hydroxy-3′deoxyadenosie (^HOdCor), together with their spin densities, charge distributions, and global reactive descriptors, have been taken into consideration at the M06-2x/6-31++G** level of theory in the aqueous phase. It was found that dCor predominantly adopts a 3′-endo,anti conformation, while ^OXOdCor and ^HOdCor adopt a 2′-endo,syn conformation. Also, the keto form of oxidised dCor was found to be energetically preferred to its enolic form. The adiabatic ionisation potentials (AIPs) were noted as follows (in eV): 6.29 for dCor, 6.21 for ^OXOdCor, and 6.17 for ^HOdCor. The lowest adiabatic electron affinity among all the discussed adenine nucleosides analogues was assigned for ^OXOdCor at 1.12 eV. A thorough analysis of the spin density distribution of the adiabatic radical cation reveals that it has a higher accumulation at N6 > C5 > C8 > 3 of dCor, C5 > N6 > N7 > O8 of ^OXOdCor, and N6 > C5 > C8 > C2 of ^HOdCor. The results suggest that Cordycepin is more easily converted to ^OXOdCor and ^HOdCor than canonical adenine nucleosides. Much like typical drugs, after its administration and release, Cordycepin is exposed to various physiological factors and can be exposed to ionisation radiation during combined therapy. These factors can influence the therapeutic potential of Cordycepin. Therefore, further studies on its stability are of utmost importance. Full article

A novel Schiff base, (E)-4-acetyl-N-(4-hydroxy-3-methoxybenzylidene)aniline (abbreviated as ANHMA), was synthesized and characterized using infrared and ¹H- and ¹³C-NMR spectroscopies. Optical properties in different solvents were evaluated using UV-vis absorption spectroscopy. The compound is shown to exhibit both positive and negative solvatochromism with reversal occurring for solvents with E_T(30)~45 (e.g., DMSO). The solvatochromic behavior of the compound was found to be strongly dependent on the hydrogen bond abilities and polarizability of the solvent, the observed reversal in solvatochromism being explained by the change in the dominant solvent effects in non-polar and polar–aprotic solvents (H-bond acceptor ability of the solvent and polarizability) compared to polar–protic solvents (H-bond donor ability), according to the developed Catalán multiparametric solvatochromic model. In all freshly prepared solutions studied, the (E)-enol-imine tautomer of the compound was found to strongly predominate over the keto-amine tautomeric forms, the latter increasing their populations over time in the presence of H-bond donor/acceptor species. Irradiation of ANHMA with UV light (λ ≥ 311 nm) was also investigated in several solvents and shown to follow a general pattern, with the conversion of the (E)-enol-imine tautomer into the keto-amine forms in a solvent-mediated enol-imine/keto-amine tautomerism, and (Z)→(E) C=C isomerization between the keto-imine forms. The experimental results received support from an extensive series of calculations on the structure and UV-vis spectra of the relevant tautomeric/isomeric forms of the compound performed at the DFT(B3LYP)/6-311++G(d,p) level of approximation (including time-dependent DFT calculations and solvent consideration). Full article

In spite of the many chemical reports on polyacetylenes of the genus Artemisia, combined conclusions regarding their distribution and biological functions are widely missing. The aim of the present review was to arrange the diversity of polyacetylenes in the genus following biogenetic aspects and group them together into characteristic structural types. The co-occurrence of the dehydrofalcarinol type with the aromatic capillen-isocoumarin type represents a characteristic biogenetic trend, clearly segregating species of the subgenus Dracunculus from those of the subgenera Artemisia and Absinthium, distinguished by the spiroketal enol ether and/or linear triyne type. Various accumulation trends toward specific structures additionally contribute to a more natural species grouping within the subgenera. Biological activities were reported for all four structural types, ranging from antifungal, insecticidal, nematicidal, and cytotoxic properties to allelopathic effects. Of particular interest were their remarkable cytotoxic potencies, from which the very high values of dehydrofalcarin-3,8-diol may be associated with the pronounced affinity of this type to form extremely stable bonds to proteins acting in signaling pathways. The aromatic acetylene capillin inhibited the viability of various tumor cells in a dose- and time-dependent manner. Its potent apoptosis-inducing activity was induced via the mitochondrial pathway. A group of spiroketal enol ethers was identified as inhibitors of PMA-induced superoxide generation. Among them, the epoxide of the isovalerate ester exhibited the highest potency. The ecological impact of acetylene formation was made apparent by the allelopathic effects of DME of the linear triyne type, and the aromatic capillen by inhibiting seed germination and growth of widespread weeds. Full article

The current paradigm of low-T combustion and autoignition of hydrocarbons is based on the sequential two-step oxygenation of fuel radicals. The key chain-branching occurs when the second oxygenation adduct (OOQOOH) is isomerized releasing an OH radical and a key ketohydroperoxide (KHP) intermediate. The subsequent homolytic dissociation of relatively weak O–O bonds in KHP generates two more radicals in the oxidation chain leading to ignition. Based on the recently introduced intramolecular “catalytic hydrogen atom transfer” mechanism (J. Phys. Chem. 2024, 128, 2169), abbreviated here as I-CHAT, we have identified a novel unimolecular decomposition channel for KHPs to form their classical isomers—enol hydroperoxides (EHP). The uncertainty in the contribution of enols is typically due to the high computed barriers for conventional (“direct”) keto–enol tautomerization. Remarkably, the I-CHAT dramatically reduces such barriers. The novel mechanism can be regarded as an intramolecular version of the intermolecular relay transfer of H-atoms mediated by an external molecule following the general classification of such processes (Catal. Rev.-Sci. Eng. 2014, 56, 403). Here, we present a detailed mechanistic and kinetic analysis of the I-CHAT-facilitated pathways applied to n-hexane, n-heptane, and n-pentane models as prototype molecules for gasoline, diesel, and hybrid rocket fuels. We particularly examined the formation kinetics and subsequent dissociation of the γ-enol-hydroperoxide isomer of the most abundant pentane-derived isomer γ-C5-KHP observed experimentally. To gain molecular-level insight into the I-CHAT catalysis, we have also explored the role of the internal catalyst moieties using truncated models. All applied models demonstrated a significant reduction in the isomerization barriers, primarily due to the decreased ring strain in transition states. In addition, the longer-range and sequential H-migration processes were also identified and illustrated via a combined double keto–enol conversion of heptane-2,6-diketo-4-hydroperoxide as a potential chain-branching model. To assess the possible impact of the I-CHAT channels on global fuel combustion characteristics, we performed a detailed kinetic analysis of the isomerization and decomposition of γ-C5-KHP comparing I-CHAT with key alternative reactions—direct dissociation and Korcek channels. Calculated rate parameters were implemented into a modified version of the n-pentane kinetic model developed earlier using RMG automated model generation tools (ACS Omega, 2023, 8, 4908). Simulations of ignition delay times revealed the significant effect of the new pathways, suggesting an important role of the I-CHAT pathways in the low-T combustion of large alkanes. Full article

In the present study, we analyzed the bioactive curcuminoids content in eight capsules (DS-1-DS-7 and DS-9), one tablet (DS-8), three ground turmeric samples (DS-10-DS-12), and three ground turmeric rhizomes (TR-1, TR-2, and TR-3). Initial screening with infrared and ultraviolet–visible spectroscopy coupled with a principal component analysis (PCA) revealed distinct differences between the samples analyzed. Hence, targeted and untargeted analyses were performed using ultra-high-performance liquid chromatography and gas chromatography coupled with mass spectrometry detections. The results show that the total curcuminoids content ranged from 1.3 to 69.8 mg/100 mg and the volatile component ranged from 0.7 to 9.1 mg/100 mg. The percentage ratio of the three prominent curcuminoids, bisdesmethoxycurcumin (BMC), desmethoxycurcumin (DMC), and curcumin (CUR), also varied remarkably compared to the expected ratio (BMC:DMC:CUR ratio of 1:2:6) described in the literature. The three prominent volatile compounds identified in most samples were ar-turmerone, turmerone, and curlone. The results demonstrated significant differences in the volatile compound levels among the DS and dried rhizome samples. The non-targeted analysis resulted in the identification of over 40 compounds, including bioactives such as piperine, phenolic acids, and amino acids. A disintegration study was performed on limited DS according to the United States Pharmacopeia protocol. The results reveal that all the selected DS samples passed the disintegration test. An analysis of curcuminoids from DS samples in neutral and acidic solutions demonstrated that all curcuminoids (BMC, DMC, and CUR) existed in the keto and enol forms and their concentrations changed with pH. This study will be of significant interest to manufacturers, consumers, and pharmacologists to accurately understand the bioactivities of three curcuminoids in different isomeric forms. Full article

Human lactate dehydrogenase A (hLDHA) is a homotetrameric isozyme involved in the conversion of glyoxylate into oxalate in the cytosol of liver cells (hepatocytes) and partially responsible for the overproduction of oxalate in patients with the rare disease called primary hyperoxaluria (PH). Recently, hLDHA inhibition has been validated as a safe therapeutic method to try to control the PH disease. Stiripentol (STP) is an approved drug used in the treatment of seizures associated with Dravet’s syndrome (a severe form of epilepsy in infancy) which, in addition, has been drawing interest in recent years also for potentially treating PH, due to its hLDHA inhibitory activity. In this work, several new STP-related compounds have been synthesized and their hLDHA inhibitory activity has been compared to that of STP. The synthesis of these analogues to STP was accomplished using crossed-aldol condensation guided by lithium enolate chemistry and a successive regioselective reduction of the resulting α,β-unsaturated ketones. The target molecules were obtained as racemates, which were separated into their enantiomers by chiral HPLC. The absolute configurations of pure enantiomers were determined by the modified Mosher’s method and electronic circular dichroism (ECD) spectroscopy. For the inhibitory effect over the hLDHA catalytic activity, a kinetic spectrofluorometric assay was used. All the new synthesized compounds turned out to be more active at 500 μM (46–72% of inhibition percentage) than STP (10%), which opens a new line of study on the possible capacity of these analogues to reduce urinary oxalate levels in vivo more efficiently. Full article

In recent years, Lawesson’s reagent has been explored for the synthesis of both open-chain P,S-containing derivatives and P,S-heterocyclic systems, with potential biological activity. The character of the interaction between arylmethylene-2H-pyran-2-ones and Lawesson’s reagent depends on the structure and position of the substituent in the aromatic ring of the substrate and on the polarity of the reaction medium. Three main pathways were shown to be realized for this group of compounds. In the absence of a substituent in the ring, the reaction proceeds as a classical thionation followed by S-heterocyclization. In the presence of the electron-withdrawing group, the enol form of the substrate is stabilized, which promotes the formation of a new pyran ring or a phosphorus-sulfur-organic compound. Full article

α- or 4-Substituted curcumin analogues are scarce. We describe herein the syntheses and crystal structures of the first α-halogenated curcumin derivatives: (1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl)-4-bromo-5-hydroxy-1,3,6-heptatriene-3-one or (4-bromocurcumin) (1) and (1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl)-4-chloro-5-hydroxy-1,3,6-heptatriene-3-one or (4-chlorocurcumin) (2). We note that the key step in the successful synthesis of the bromo-analog is the use of slightly acidic media to favor the diketo form of curcumin prior to carrying out the reaction. Both newly prepared compounds assume the keto–enol form in the solid state and crystallize in the monoclinic space group P2₁/c with four molecules in the unit cell each with slightly different dimensions. Inter- and intra- molecular hydrogen bonds were observed in the two structures. Most significant observed features were the inter-molecular O…O distances of 2.842 and 2.840 Å and intra-molecular O…O distances of 2.460 and 2.451 Å for bromo-or (1) and chloro- or (2) derivatives, respectively. No close halogen…halogen contacts were observed in either of the two structures. Both molecules are nearly planar with torsion angles of 0.54 and 1.16 °C between the planes of two terminal phenyl groups for (1) and (2), respectively. π-Stacks were observed in both structures with interplanar distances of 3.367 and 3.454 Å for the bromo- and chloro- compounds, respectively. Hirshfeld surface analysis confirms quantitively a picture of the inter- and intra-molecular interactions in both compounds compared with polymorph I (the most common form) of curcumin. UV–Vis absorption spectra are shifted to higher wavelengths with l_max of 475 and 477 nm for compounds 1 and 2, respectively, compared with 442 nm in dichloromethane solutions. The newly synthesized molecules will open the door for numerous possible synthetic modifications of the α-carbon to prepare valuable analogues of curcumin with more favorable solubility profiles. Full article

In the past few years, there has been an increasing interest in mycosporines—UV-absorbing molecules—bringing important insights into their intrinsic properties as natural sunscreens. Herein, mycosporine-serinol and gadusol (enolate form)/gadusolate were exposed to UV radiation via a solar simulator and the photostability was assessed in pure water and different natural matrices like river, estuary and ocean water. In general, this study revealed that the photodegradation of gadusolate and mycosporine-serinol was higher in natural matrices than in pure water due to the generation of singlet oxygen on UV irradiation. In pure water, in terms of photostability, both gadusolate and mycosporine-serinol were found to offer good protection and high performance in terms of photodegradation quantum yield ((0.8 ± 0.2) × 10⁻⁴ and (1.1 ± 0.6) × 10⁻⁴, respectively). Nonetheless, the photostability of mycosporine-serinol was found to be superior to that of gadusolate in natural water, namely, ocean, estuary and river. The present work highlights how mycosporine-serinol and gadusolate resist photodegradation, and supports their role as effective and stable UV-B sunscreens. Full article

Succinimide residues formed spontaneously from aspartic acid (Asp) and asparagine (Asn) residues in proteins and peptides are stereochemically unstable, undergoing partial l-to-d stereoinversion, and this is responsible for the d-Asp and d-β-Asp residues found in long-lived proteins. These stereoinverted abnormal amino acid residues are believed to be related to aging and some age-related diseases such as cataracts. Although the succinimide stereoinversion is nonenzymatic, a catalyst is required for it to occur at physiological temperature. In this study, it was found by density functional theory (DFT) calculations that a hydrogen phosphate ion (HPO₄²⁻) can effectively catalyze the stereoinversion of the succinimide intermediate. The HPO₄²⁻ ion abstracts a proton from the asymmetric carbon atom of the succinimide residue to form an enolate intermediate. Then, while the resultant dihydrogen phosphate ion (H₂PO₄⁻) remains bound to the enolate ion, a water molecule donates a proton to the enolate intermediate on the opposite side from the phosphate (which is the rate-determining step) to produce the inverted carbon atom. The calculated activation barrier (ca. 90 kJ mol⁻¹) is consistent with a slow in vivo reaction. The present found mechanism can be termed the “unsymmetrical S_E1” or “pseudo-S_E2” mechanism. Full article

Excited-state intramolecular proton transfer (ESIPT) reactions are crucial in photoresponsive materials and fluorescent markers. The fluorescent compound 4-aminophthalimide (4-AP) has been reported to exhibit solvent-assisted ESIPT in protic solvents, such as methanol, wherein the solvent interacts with 4-AP to form a six-membered hydrogen-bonded ring that is strengthened upon excitation. Although the controversial observation of ESIPT in 4-AP has been extensively studied, the molecular mechanism has yet to be fully explored. In this study, femtosecond infrared spectroscopy was used to investigate the dynamics of 4-AP in methanol and acetonitrile after excitation at 350 and 300 nm, which promoted 4-AP to the S₁ and S₂ states, respectively. The excited 4-AP in the S₁ state relaxed to the ground state, while 4-AP in the S₂ state relaxed via the S₁ state without the occurrence of ESIPT. The enol form of 4-AP (Enol 4-AP) in the S₁ state was calculated to be ~10 kcal/mol higher in energy than the keto form in the S₁ state, indicating that keto-to-enol tautomerization was endergonic, ultimately resulting in no observable ESIPT for 4-AP in the S₁ state. Upon the excitation of 4-AP to the S₂ state, the transition to Enol-4-AP in the S₁ state was found to be exergonic; however, ESIPT must compete with an internal conversion from the S₂ to the S₁ state. The internal S₂ → S₁ conversion was significantly faster than the solvent-assisted ESIPT, resulting in a negligible ESIPT for the 4-AP excited to the S₂ state. The detailed excitation dynamics of 4-AP clearly reveal the molecular mechanism underlying its negligible ESIPT, despite the fact that it forms a favorable structure for solvent-assisted ESIPT. Full article

This study investigates the chemical structure of profoxydim, focusing on its E–isomer, the main commercial form. The research aimed to determine the predominant tautomeric forms under various environmental conditions. Using proton and carbon–13 NMR spectroscopy alongside theoretical modeling, we examined tautomers and their conformers in different solvents (MeOD, DMSO, CDCl₃, benzene) to mimic gas and aqueous phases. The findings reveal that the enolic form dominates in the gas phase, while the ketonic form prevails in aqueous environments, providing key insights into the herbicide’s environmental behavior. We also observed an isomeric transition from E to Z under acidic conditions, which could affect profoxydim’s reactivity in natural environments. The theoretical calculations indicated that in acidic conditions, the E and Z forms are nearly degenerate, with the E form remaining dominant in neutral environments. Additionally, QSAR models assessed the toxicity of various tautomers, revealing significant differences that could impact bioactivity and environmental fate. This research offers crucial insights into the structural dynamics of profoxydim, contributing to cyclohexanedione chemistry and the development of more effective herbicides. Full article

A simple protocol for the preparation of O-acylated enol form (R/S)-ethyl-2-acetoxy-4-phenyl-4H-chromene-3-carboxylate 5 was presented. The compound was characterized by ¹H-, ¹³C-and DEPT135 NMR spectra, including {¹H,¹H} COSY, {¹H,¹³C} HSQC, {¹H,¹³C} HMBC, and 2D-NOESY spectra. The preferred regioselectivity for O-acylation of 3,4-dihydrocoumarin 5 in the presence of substituent in the 4th position in the chroman ring and accounting for the steric hindrance of the ester group in the 3rd place was confirmed. Full article

A new curcuminoid molecule (3) has been designed and synthesized, containing a central -(CH₂)₂-COOH chain at the α carbon of the keto-enol moiety in the structure. The carboxylic acid group is added to react with exposed amino groups on silica oxide nanoparticles (nSiO₂), forming an amide bond to attach the curcuminoid moiety to the nSiO₂ covalently. The Kaiser test quantifies the functionalization degree, yielding 222 μmol of curcuminoid per gram of nanoparticles. The synthesized hybrid nanosystem, nSiO₂-NHCO-CCM, displays significant emission properties, with a maximum emission at 538 nm in dichloromethane, similar to curcuminoid 1 (without the central chain), which emits at 565 nm in the same solvent. Solvent-induced spectral effects on the absorption and emission bands of the new hybrid nanosystem are confirmed, similar to those observed for the free curcuminoid (1). The new nanosystem is evaluated in the presence of kerosene in water, showing an emission band at 525 nm as a detection response. The ability of nSiO₂-NHCO-CCM to change its fluorescence when interacting with kerosene in water is notable, as it overcomes the limitation caused by the insolubility of free curcuminoid 1 in water, allowing for the exploitation of its properties when connected to the water-stable nanosystem for future detection studies. Full article