Search Results (20)

In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. Full article

A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves an easy modification of quinine (in general, any cinchona alkaloid) toward clickable 9-azide that reacts with N-propargyl-cis-5-norbornene-exo-2,3-dicarboxylic imide in Cu(I)-catalyzed Huisgen cycloaddition (click chemistry). The resulting monomers undergo a controllable ROMP reaction that leads to novel polymers of a desired length and solubility. This sequence allows for the facile preparation of a regularly decorated polymeric material having one quinine moiety per single mer of the polymer chain inaccessible using typical immobilization methods. A poly(norbornene-5,6-dicarboxyimide) type of polymeric matrix was selected due to the high reactivity of the exo-norbornene motif in Ru(II)-catalyzed ROMP and its chemical and thermal stability as well as convenient, scalable access from inexpensive cis-5-norbornene-exo-2,3-dicarboxylic anhydride (‘one-pot’ Diels–Alder reaction of dicyclopentadiene and maleic anhydride). An appropriate combination of a Grubbs catalyst, Ru(II) (G1, G2), and ROMP conditions allowed for the efficient synthesis of well-defined soluble polymers with mass parameters in the range Mn = 2.24 × 10⁴ – 2.26 × 10⁴ g/mol and Mw = 2.90 × 10⁴–3.05 × 10⁴ g/mol with good polydispersity, Đ_M = 1.32–1.35, and excellent thermal stability (up to 309°C T_d10). Spectroscopic studies (NMR and electronic circular dichroism (ECD)) of these products revealed a linear structure with the slight advantage of a trans-configuration of an olefinic double bond. The resulting short-chain polymer discriminates mandelic acid enantiomers with a preference for the (R)-stereoisomer in spectrofluorimetric assays. This concept seems to be rather general with respect to other molecules dedicated to incorporation into the poly(norbornene-5,6-dicarboxyimide) chain. Full article

N-Heterocyclic carbenes (NHCs) have been widely utilized over the past three decades due to their broad applications, yet synthetic methods for their preparation remain limited. A promising approach for NHC generation involves the thermolysis of NHC adducts. Herein, we report the synthesis of NHC pentafluorobenzene adducts featuring an o-carboranyl group in the backbone (2), which, unlike previously studied systems, resists thermal decomposition. Density functional theory (DFT) calculations were used to investigate the discrepancy, revealing that the decomposition reaction is kinetically controlled. For widely studied NHC systems like IMes and SIMes, the activation barriers were calculated to be 246.3 kJ/mol and 267.3 kJ/mol, respectively, aligning with reactions requiring heating. In contrast, the o-carborane system exhibited a significantly higher barrier of 320.5 kJ/mol, primarily due to the structural influence of the o-carborane backbone. Further analysis indicates that delocalization of π-electrons from the backbone into the NHC’s p-orbitals lowers the activation barrier, whereas delocalization into an exo-NHC ring increases it. These findings provide new insights into the thermal generation of NHCs and we hope it can offer guidance for future NHC design and synthesis. Full article

The production of microbial metabolites such as (exo)polysaccharides, lipids, or mannitol through the cultivation of microorganisms on sustainable, low-cost carbon sources is of high interest within the framework of a circular economy. In the current study, two non-extensively studied, non-conventional yeast strains, namely, Cutaneotrichosporon curvatus NRRL YB-775 and Papiliotrema laurentii NRRL Y-3594, were evaluated for their capability to grow on semi-defined lactose-, glycerol-, or glucose-based substrates and produce value-added metabolites. Three different nitrogen-to-carbon ratios (i.e., 20, 80, 160 mol/mol) were tested in shake-flask batch experiments. Pretreated secondary cheese whey (SCW) was used for fed-batch bioreactor cultivation of P. laurentii NRRL Y-3594, under nitrogen limitation. Based on the screening results, both strains can grow on low-cost substrates, yielding high concentrations of microbial biomass (>20 g/L) under nitrogen-excess conditions, with polysaccharides comprising the predominant component (>40%, w/w, of dry biomass). Glucose- and glycerol-based cultures of C. curvatus promote the secretion of mannitol (13.0 g/L in the case of glucose, under nitrogen-limited conditions). The lipids (maximum 2.2 g/L) produced by both strains were rich in oleic acid (≥40%, w/w) and could potentially be utilized to produce second-generation biodiesel. SCW was nutritionally sufficient to grow P. laurentii strain, resulting in exopolysaccharides secretion (25.6 g/L), along with dry biomass (37.9 g/L) and lipid (4.6 g/L) production. Full article

This study aims to investigate the structural, spectroscopic, and electronic properties of the synthetic missile fuel exo- and endo-tetrahydrodicyclopentadiene (THDCPD, JP-10) using density functional theory (DFT). It is to understand the dominance of the liquid exo-isomer (96%) of the jet fuel from the subtle differences between the isomers. The present DFT calculations reveal that the exo-isomer is 15.51 kJ/mol more stable than the endo-isomer, attributed to the flipping of the triangular ΔC8-C10-C9 ring in its norbornane skeleton. Calculated nuclear magnetic resonance (¹³C-NMR) and infrared (IR) spectra, validated by experimental data, reveal larger chemical shifts for junction carbons (C1/C2 and C3/C4) due to reduced electron shielding and show distinct vibrational patterns. Charge analysis indicates that all carbon atoms are negatively charged except for the C1/C2 carbons which are positively charged in both isomers. While overall IR spectra of the isomers appear similar, bands near 3000 cm⁻¹ correspond to distinctly different vibrational modes. The exo-isomer’s electronic structure features a more delocalized HOMO and a larger HOMO-LUMO gap (7.63 eV) than the endo-isomer (7.37 eV). All such differences contribute to the properties of exo-THDCPD and, therefore, why the exo-isomer dominates JP-10 fuel. Full article

One-component or bifunctional organocatalysts are some of the most capable compounds to perform the synthesis of cyclic carbonates from epoxides and carbon dioxide (CO₂) since the presence of a co-catalyst is not required. In this study, we designed, synthesized, and evaluated five halogenated compounds as bifunctional organocatalysts for this catalytic transformation. Among them, 1,3-dimethylimidazolium iodide (1) exhibited the highest catalytic efficiency, enabling the synthesis of a broad range of monosubstituted cyclic carbonates with diverse functional groups under mild conditions (80 °C, 20 bar CO₂) within 1 h, using only 1 mol% catalyst loading. Remarkably, this organocatalyst also facilitated the synthesis of five internal cyclic carbonates and a carvone-derived exo-cyclic carbonate, which was obtained for the first time without the use of a metal catalyst, under more demanding conditions. A mechanistic proposal was developed through a combination of ¹H-NMR studies and density functional theory (DFT) simulations. Styrene oxide and cyclohexene oxide were used as model substrates to investigate the reaction pathway, which was computed using an optimized climbing-image nudged elastic band (CI-NEB) method. The results revealed the critical role of 1,3-dimethylimidazolium iodide in key reaction steps, particularly in facilitating the epoxy ring opening process. These findings highlight the potential use of bifunctional compounds as efficient and versatile catalysts for CO₂ valorization. Full article

Homogeneous catalysis involving a transition metal agostic interaction (TM^…H^…C) is an attractive strategy for C–H bond activation, in which the transition metal agostic intermediates serve as the critical component. To investigate the roles of manganese agostic intermediates in the unusual migration of the Mn(CO)₃ fragment in the (exo-phenyl)(η³-cyclohexenyl)manganese tricarbonyl [(Ph)(η³-C₆H₈)Mn(CO)₃] (complex 1) under the protonation of tetrafluoroboric acid–diethyl ether (HBF₄.Et₂O), a comprehensive density functional theory (DFT) theoretical study was performed. The computational results showed that formation of the [(cyclohex-3-enyl)-η⁶-benzene]manganese tricarbonyl complex [(C₆H₉)(η⁶-Ph)Mn(CO)₃⁺][BF₄] (complex 2) was achieved via a series of mono-agostic and di-agostic intermediates. The overall rate-limiting step for this unusual migration of the Mn(CO)₃ fragment is the formation of the di-agostic (η²-phenyl)manganese complex 8 (4 → 5 → 8) with a Gibbs barrier of 15.4 kcal mol⁻¹. The agostic intermediates with TM^…H^…C agostic interactions were well-characterized by geometry parameters, Atoms-In-Molecules (AIM) analyses, and the Natural Adaptive Orbitals (NAdOs). The located pathways in the current study successfully explained the experimental observations, and the findings on the TM^…H^…C agostic interaction provided a new aspect of the catalytic reaction with the manganese complex. Full article

Contact lens-mediated microbial keratitis caused by Pseudomonas aeruginosa and Streptococcus pneumoniae provokes corneal damage and vision loss. Recently, natural phytochemicals have become complementary medicines for corneal destruction. Herein, we aimed to identify multi-targeting Aloe vera-derived phytochemicals capable of inhibiting bacterial and host targets of keratitis through ADME (absorption, distribution, metabolism, and excretion), docking, molecular dynamics (MD) simulation, MMGBSA (molecular mechanics generalized Born surface area) and density functional theory (DFT) investigations. An extensive literature search revealed ExoU, ExoS, ExoT, ExoY, and PLY as virulent bacterial targets. Simultaneously, differential gene expression (DGE) and pathway enrichment analysis-specified host transcription factor (SPI1) influences keratitis pathogenesis. Molecular docking analysis uncovered aloeresin-A as a promising inhibitor against bacterial and host targets, demonstrating strong binding energies ranging from −7.59 to −6.20 kcal/mol. Further, MMGBSA and MD simulation analysis reflect higher binding free energies and stable interactions of aloeresin-A with the targets. In addition, DFT studies reveal the chemical reactiveness of aloeresin-A through quantum chemical calculations. Hence, our findings show aloeresin-A to be a promising candidate for effectively inhibiting keratitis. However, additional research is imperative for potential integration into lens care solutions. Full article

This work discusses diatomic molecular spectroscopy of laser-induced plasma and analysis of data records, specifically signatures of cyanide, CN. Line strength data from various databases are compared for simulation of the CN, $B{}^2{\Sigma }^{+}⟶X{}^2{\Sigma }^{+}$, $\Delta \mathrm{v}=0$ sequence. Of interest are recent predictions using an astrophysical database, i.e., ExoMol, a laser-induced fluorescence database, i.e., LIFBASE, and a program for simulating rotational, vibrational, and electronic spectra, i.e., PGOPHER. Cyanide spectra that are predicted from these databases are compared with line-strength data that have been in use by the author for the last three decades in the analysis of laser–plasma emission spectra. Comparisons with experimental laser–plasma records are communicated as well for spectral resolutions of 33 and 110 picometer. The accuracy of the CN line-strength data is better than one picometer. Laboratory experiments utilize 308 nm, 35 picosecond bursts within an overall 1 nanosecond pulse-width, and 1064 nm, 6 ns pulse-width radiation. Experimental results are compared with predictions. Differences of the databases are elaborated for equilibrium of rotational and vibrational modes and at an internal, molecular temperature of the order of 8,000 Kelvin. Applications of accurate CN data include, for example, combustion diagnosis, chemistry, and supersonic and hypersonic expansion diagnosis. The cyanide molecule is also of interest in the study of astrophysical phenomena. Full article

Inter- and intra-molecular proton-transfers between functional groups in nucleobases play a principal role in their interactions (pairing) in nucleic acids. Although prototropic rearrangements (intramolecular proton-transfers) for neutral pyrimidine bases are well documented, they have not always been considered for their protonated and deprotonated forms. The complete isomeric mixtures in acid-base equilibria and in acidity–basicity parameters have not yet been examined. Taking into account the lack of literature and data, research into the question of prototropy for the ionic (protonated and deprotonated) forms has been undertaken in this work. For the purposes of this investigation, two isomeric pyrimidine bases (C—cytosine and iC—isocytosine) were chosen. They exhibit analogous (symmetrical) general acid-base equilibria (intermolecular proton-transfers). Being similar polyfunctional tautomeric systems, C and iC possess two labile protons and five conjugated tautomeric sites. However, positions of exo groups are different. Consequently, structural conversions such as prototropy, rotational, and geometrical isomerism of exo groups (=O/−OH and =NH/−NH₂) and their intramolecular interactions with endo groups (=N−/>NH) possible in neutral C and iC and in their ionic forms lead to some differences in compositions of isomeric mixtures. By application of quantum–chemical methods to the isolated (in vacuo) species, stability of all possible neutral and ionic isomers has been examined and the candidate isomers selected. The complete isomeric mixtures have been considered for the first time for di-deprotonated, mono-deprotonated, mono-protonated, and di-protonated forms. Protonation–deprotonation reactions have been analyzed in the gas phase that models non-polar environment. The gas-phase microscopic (kinetic) and macroscopic (thermodynamic) acidity–basicity parameters have been estimated for each step of acid-base equilibria. When proceeding from di-anion to di-cation in four steps of protonation–deprotonation reaction, the macroscopic proton affinities for C and iC differ by less than 10 kcal mol⁻¹. Their DFT-calculated values are as follows: 451 and 457, 340 and 339, 228 and 224, and 100 and 104 kcal mol⁻¹, respectively. Differences between the microscopic proton affinities for analogous isomers of C and iC seem to be larger for the exo than endo groups. Owing to variations of relative stabilities for neutral and ionic isomers, in some cases they are even larger than 10 kcal mol⁻¹. Full article

Polymerization of isobutylene (IB) for synthesizing highly reactive polyisobutylene (HRPIB) is characterized by a complicated fast intrinsic reaction rate; therefore, the features of its products exhibit a strong dependence on mixing efficiency. To provide uniform and efficient mixing, a rotating packed bed was employed as a reactor for polymerization of IB. The effects of operating parameters including polymerization temperature (T), rotating speed (N) and relative dosage of monomers and initiating systems ([M]₀/[I]₀) on number-average molecular weight (M_n) of HRPIB were studied. HRPIB with M_n of 2550 g·mol⁻¹ and exo-olefin terminal content of 85 mol% were efficiently obtained at suitable conditions as T of 283 K, N of 1600 rpm and [M]₀/[I]₀ of 49. Moreover, the M_n can be regulated by changing T, N and [M]₀/[I]₀. Based on the presumptive-steady-state analysis method and the coalescence–redispersion model, a model for prediction of the M_n was developed and validated, and the calculated M_n values agreed well with experimental results, with a deviation of ±10%. The results demonstrate that RPB is a promising reactor for synthesizing HRPIB, and the given model for M_n can be applied for the design of RPB and process optimization. Full article

The intramolecular ionic Diels–Alder (IIDA) reactions of two dieniminiums were studied within the Molecular Electron Density Theory (MEDT) at the ωB97XD/6-311G(d,p) computational level. Topological analysis of the electron localization function (ELF) of dieniminiums showed that their electronic structures can been seen as the sum of those of butadiene and ethaniminium. The superelectrophilic character of dieniminiums accounts for the high intramolecular global electron density transfer taking place from the diene framework to the iminium one at the transition state structures (TSs) of these IIDA reactions, which are classified as the forward electro density flux. The activation enthalpy associated with the IIDA reaction of the experimental dieniminium, 8.7 kcal·mol⁻¹, was closer to that of the ionic Diels–Alder (I-DA) reaction between butadiene and ethaniminium, 9.3 kcal·mol⁻¹. However, the activation Gibbs free energy of the IIDA reaction was 12.7 kcal·mol⁻¹ lower than that of the intermolecular I-DA reaction. The strong exergonic character of the IIDA reaction, higher than 20.5 kcal·mol⁻¹, makes the reaction irreversible. These IIDA reactions present a total re/exo and si/endo diastereoselectivity, which is controlled by the most favorable chair conformation of the tetramethylene chain. ELF topological analysis of the single bond formation indicated that these IIDA reactions take place through a non-concerted two-stage one-step mechanism. Finally, ELF and atoms-in-molecules (AIM) topological analyses of the TS associated with the inter and intramolecular processes showed the great similarity between them. Full article

The copolymerization of ethylene‒diene conjugates (butadiene (BD), isoprene (IP) and nonconjugates (5-ethylidene-2-norbornene (ENB), vinyl norbornene VNB, 4-vinylcyclohexene (VCH) and 1, 4-hexadiene (HD)), and terpolymerization of ethylene-propylene-diene conjugates (BD, IP) and nonconjugates (ENB, VNB, VCH and HD) using two traditional catalysts of C₂-symmetric metallocene—silylene-bridged rac-Me₂Si(2-Me-4-Ph-Ind)₂ZrCl₂ (complex A) and ethylene-bridged rac-Et(Ind)₂ZrCl₂ (complex B)—with a [Ph₃C][B(C₆F₅)₄] borate/TIBA co-catalyst, were intensively studied. Compared to that in the copolymerization of ethylene diene, the catalytic activity was more significant in E/P/diene terpolymerization. We obtained a maximum yield of both metallocene catalysts with conjugated diene between 3.00 × 10⁶ g/mol_Mt·h and 5.00 × 10⁶ g/mol_Mt·h. ENB had the highest deactivation impact on complex A, and HD had the most substantial deactivation effect on complex B. A ¹H NMR study suggests that dienes were incorporated into the co/ter polymers’ backbone through regioselectivity. ENB and VNB, inserted by the edo double bond, left the ethylidene double bond intact, so VCH had an exo double bond. Complex A’s methyl and phenyl groups rendered it structurally stable and exhibited a dihedral angle greater than that of complex B, resulting in 1, 2 isoprene insertion higher than 1, 4 isoprene that is usually incapable of polymerization coordination. High efficiency in terms of co- and ter- monomer incorporation with higher molecular weight was found for complex 1. The rate of incorporation of ethylene and propylene in the terpolymer backbone structure may also be altered by the conjugated and nonconjugated dienes. ¹³C-NMR, ¹H-NMR, and GPC techniques were used to characterize the polymers obtained. Full article

A series of exo-methylene 6-membered ring conjugated dienes, which are directly or indirectly obtained from terpenoids, such as β-phellandrene, carvone, piperitone, and verbenone, were radically polymerized. Although their radical homopolymerizations were very slow, radical copolymerizations proceeded well with various common vinyl monomers, such as methyl acrylate (MA), acrylonitrile (AN), methyl methacrylate (MMA), and styrene (St), resulting in copolymers with comparable incorporation ratios of bio-based cyclic conjugated monomer units ranging from 40 to 60 mol% at a 1:1 feed ratio. The monomer reactivity ratios when using AN as a comonomer were close to 0, whereas those with St were approximately 0.5 to 1, indicating that these diene monomers can be considered electron-rich monomers. Reversible addition fragmentation chain-transfer (RAFT) copolymerizations with MA, AN, MMA, and St were all successful when using S-cumyl-S’-butyl trithiocarbonate (CBTC) as the RAFT agent resulting in copolymers with controlled molecular weights. The copolymers obtained with AN, MMA, or St showed glass transition temperatures (T_g) similar to those of common vinyl polymers (T_g ~ 100 °C), indicating that biobased cyclic structures were successfully incorporated into commodity polymers without losing good thermal properties. Full article

We define a new inversion in a cage isomerism (ic): X@C⋯Y₪_icY@C⋯X, (₪ is the isomerism relation) as an isomerism in the three-component system of molecules X, Y, and a cage C, in which one of the molecules is located inside and the other outside the cage. The ic isomerism is similar to the endo-exo one, which occurs only if either the interior or exterior of C is empty. By contrast, ic occurs only if neither the interior nor the exterior of C is empty. We also discuss the other closely related types of isomerisms are also discussed. Calculations of the XH⋯NH₃@C₆₀ and NH3⋯HX@C₆₀ic isomers were performed at the ωB97XD/Def2TZVP level. The calculated energies demonstrated that the systems with the HX acid outside (X = F, Cl) and the NH₃ base inside the cage, XH⋯NH₃@C₆₀, are more stable than their ic isomers, NH₃⋯HX@C₆₀, by about 4–8 kcal/mol. This is because NH₃ is more stabilized inside the cage than HX (a matter of 6.5 kcal/mol). In the studied systems and subsystems, the HX molecules are Lewis acids and the NH₃ molecule is always a Lewis base. The C₆₀ molecule with HX inside or outside the cage is also an acid for the NH₃ base positioned outside or inside the cage. On the other hand, the C₆₀ cage is truly amphoteric because it is simultaneously an acid and a base. Full article