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We determined the optical profiles of a molecular system coupled with a thermal bath in presence of intramolecular coupling. Solvent effects were explicitly considered as a random variable by model...

The topological profiles of the nonlinear optical properties of a two-level molecular system involving simplified versions of intramolecular coupling immersed in a thermal reservoir have been studied in four-wave mixing (FWM) spectroscopy. Solvent effects have been explicitly considered by modeling the nonradiative interaction with the solute as a random variable. To formulate a solution, it is necessary to introduce stochastic considerations. We assume that system–solvent interactions induce random shifts in the Bohr frequency of the adiabatic states, and their manifestation corresponds to the broadening of the upper level. The Born–Oppenheimer (BO) electronic energy curves for this molecular model consist of two intertwined harmonic oscillator potentials shifted in both their position and their minimum equilibrium energy. The critical quantities for this analysis are the transition and permanent dipole moments, which depend strongly on intramolecular coupling. Our results show how absorption and refractive index are affected by vibronic coupling and solvent stochasticity.

The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior., Graphical abstract Unlabelled Image

The COVID-19 pandemic has accelerated the study of the potential of multi-target drugs (MTDs). The mixture of homologues called ivermectin (avermectin-B1a + avermectin-B1b) has been shown to be a MTD with potential antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the effect of each homologue on the flexibility and stiffness of proteins associated with COVID-19, described as ivermectin targets. We observed that each homologue was stably bound to the proteins studied and was able to induce detectable changes with Elastic Network Models (ENM). The perturbations induced by each homologue were characteristic of each compound and, in turn, were represented by a disruption of native intramolecular networks (interactions between residues). The homologues were able to slightly modify the conformation and stability of the connection points between the Cα atoms of the residues that make up the structural network of proteins (nodes), compared to free proteins. Each homologue was able to modified differently the distribution of quasi-rigid regions of the proteins, which could theoretically alter their biological activities. These results could provide a biophysical-computational view of the potential MTD mechanism that has been reported for ivermectin.

In the present study, the most favourable reaction mechanism in the flash vacuum pyrolysis of 2-[(2E)-2-benzylidenehydrazinyl]pyridine and analogous was theoretically studied using B3LYP-D3/6-311G(d,p) level. The influence of different substituents on the phenyl ring in the para position is evaluated at 500 K. A deep analysis of the mechanisms reveals the influence of the substituents in the activation energy, where the reactivity order OCH3 > CH3 > H > Cl > NO2 is found, following Hammet parameters (σp). To reach the transition state, geometric changes contribute more than 70% of the energy in agreement with the reaction force analysis. A recent independent gradient model (IGM) is also applied to establish an influence between the substituent and the strength of the bonds involved in the mechanism, through an intrinsic bond strength index (IBSI). Furthermore, the influence of the substituent was also evaluated in terms of interatomic distances and evolution percentages, finding high correlations with Hammet σp values.

Theoretical calculations of the gas-phase thermal decomposition kinetics of 2-thiomethyl-1-chloroethane and 4-thiomethyl-1-chlorobutane have been carried out by using Density Functional Theory (DFT), composite CBS-Q3, and Moller-Plesset second-order (MP2) methods in order to elucidate a reasonable reaction mechanism of these compounds. The enhanced reactivities of these two substrates, when compared with their parent compounds, attributed to neighboring group participation (NGP) or anquimeric assistance in the literature, were investigated. For 2-thiomethyl-1-chloroethane two dehydrochlorinaton pathways, with and without NGP were studied. The results of quantum chemical estimations of 2-thiomethyl-1-chloroethane in the gas phase show good agreement with experimental values at B3LYP/6-31++G(2d,p) level, and suggest the 1,2-elimination through non-synchronous four-membered cyclic transition state is the preferred mechanism. For 4-thiomethyl-1-chlorobutane, the significant increase in rate compared to 2-thiomethyl-1-chloroethane, together with the formation of a cyclic product tetrahydrothiophene suggest the anchimeric assistance by the CH3S group in the transition state. Best calculated parameters were obtained with CAM-B3LYP/6-31G++(2d,p). Results support the NGP of the thiomethyl group, through cyclic ion-pair type of intermediate. The bond polarization of the C–Cl, in the direction of Cδ+⋯Clδ−, appears to be the rate determining step of these decompositions.

The mechanism for the thermal isomerization reactions of 2-methyl-4,5-dihydrofuran was investigated using quantum chemical calculations at B3LYP/6-31G(d,p), B3LYP/6-31++G(d,p), MPW1PW91/6-31G(d,p), MPW1PW91/6-31++G(d,p), and [PBE/6-31G(d,p), PBE/6-31++G(d,p)] levels of theory. It was found that 2-methyl-4,5-dihydrofuran isomerizes to acetylcyclopropane, and by a parallel reaction a slower isomerization to give 3-pentene-2-one. The acetylcyclopropane formation occurs through unimolecular electrocyclic mechanism. The 3-penten-2-one formation also takes place through electrocyclic mechanism, involving [1,2] hydrogen migration. The isomerization reaction of acetylcyclopropane to 3-penten-2-one occurs by step-wise mechanism, with the formation of an intermediate product 2-hydroxy-2,4-pentadiene, which subsequently isomerizes to the keto form, 3-penten-2-one. The step-wise acetylcyclopropane isomerization to 3-penten-2-one has lower energy of activation than the direct conversion of 2-methyl-4,5-dihydrofuran to 3-penten-2-one. Reasonable agreement was found between experimental and calculated energies of activation using B3PW91/6-311G(d,p) and MPW1PW91/6-311G(d,p) methods. Results suggest that both isomerization reactions pathways are possible under the experimental conditions reported. However, the lower energy of activation of the rate determining step of the step-wise mechanism favors this process over the single step mechanism.

The unimolecular gas-phase elimination kinetics of 2-methoxy-1chloroethane, 3-methoxy-1-chloropropane, and 4-methoxyl-1chloroburane has been studied by using density functional theory (DFT) methods to propose the most reasonable mechanisms of decomposition of the aforementioned compounds. Calculation results of 2-methoxy-1-chloroethane and 3-methoxy-1-chloropropane suggest dehydrochlorination through a concerted nonsynchronous four-centered cyclic transition state (TS) to give the corresponding olefin. In the case of 4-methoxyl-1-chloroburane, in addition to the 1,2-elimination mechanism, the anchimeric assistance by the methoxy group, through a polar five-centered cyclic TS, provides additional pathways to give 4-methoxy-butene, tetrahydrofuran and chloromethane. The bond polarization of the CACl, in the direction of C dþ ��� Cl d� , is the limiting step of these elimination reactions. The significant increase in rate together with the formation of a cyclic product tetrahydrofuran in the gas-phase elimination of 4-methoxyl-1-chloroburane is attributed to neighboring group participation of the oxygen of the methoxy group in the TS. The theoretical calculations show a good agreement with the reported experimental results. V C 2011 Wiley

The mechanisms for the acid-catalyzed gas-phase dehydration of the tertiary alcohols 2-methyl-2-propanol, 2-methyl-2-butanol, and 2-methyl-2-pentanol were examined at B3LYP/6-31G(d), B3LYP/6-31G(d,p), B3LYP/6-31G(2d,p), B3LYP/6-31G(2d,2p), B3PW1/6-31G(d), B3PW1/6-31G(d,p), B3PW1/6-31G(2d,p), B3PW1/6-31G(2d,2p), MPW91PW91/6-31G(d), MPW91PW91/6-31G(d,p), MPW91PW91/6-31G(2d,p), and MPW91PW91/6-31G(2d,2p) levels of theory. Calculation results suggest that the dehydration processes catalyzed by hydrogen chloride to give the corresponding olefin and water occur with the formation of Van der Waals complexes between the alcohol and hydrogen chloride. The transition states are six-membered cyclic structures involving one molecule of HCl and one of the alcohol. These reactions appear to be molecular in nature. Analysis of the progress along the reaction coordinate, in terms of bond orders, NBO charges, and geometrical parameters suggest these reactions to be moderately polar and nonsynchronous and are dominated by the breaking of the HCl bond, together with an important cleavage of CO bond in the transition state. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2012

The kinetics and mechanisms of the dehydrochlorination of 2-chloro-1- phenylethane, 3-chloro-1-phenylpropane, 4-chloro-1-phenylbutane, 5-chloro-1-phenylpentane, and their corresponding chloroalkanes were examined by means of electronic structure calculation using density functional theory methods B3LYP/6–31G(d,p), B3LYP/6–31++G(d,p), MPW1PW91/6–31G(d,p), MPW1PW91/6–31++G(d,p), PBEPBE/6–31G(d,p), and PBEPBE/6–31++G(d,p). The potential energy surface was investigated for the minimum energy path. Calculated enthalpies and energies of activation are in good agreement with experimental values using the MPW1PW91 and B3LYP methods. The transition state of these reactions is a four-centered cyclic structure. The reported experimental results proposing neighboring group participation by the phenyl group was not supported by theoretical calculations. The rate-determining process in these reactions is the breaking of ClC bond. The reactions are described as concerted moderately polar and nonsynchronous. © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 292–302, 2011

Theoretical calculation of the kinetics and mechanisms of gas-phase elimination of 2-hydroxyphenethyl chloride and 2-methoxyphenethyl chloride has been carried out at the MP2/6-31G(d,p), B3LYP/6-31G(d,p), B3LYP/6-31 + G(d,p), B3PW91/6-31G(d,p) and CCSD(T) levels of the theory. The two substrates undergo parallel elimination reactions. The first process of elimination appears to proceed through a three-membered cyclic transition state by the anchimeric assistance of the aromatic ring to produce the corresponding styrene product and HCl. The second process of elimination occurs through a five-membered cyclic transition state by participation of the oxygen of o-OH or the o-OCH3 to yield in both cases benzohydrofuran. The B3PW91/6-31G(d,p) method was found to be in good agreement with the experimental kinetic and thermodynamic parameters for both substrates in the two reaction channels. However, some differences in the performance of the different methods are observed. NBO analysis of the pyrolysis of both phenethyl chlorides implies a CCl bond polarization, in the sense of Cδ+…Clδ−, which is a rate-determining step for both parallel reactions. Synchronicity parameters imply polar transition states of these elimination reactions. Copyright © 2009 John Wiley & Sons, Ltd.

The theoretical study of the gas-phase pyrolysis kinetics of several tert -nitroalkanes, 2-methyl-2-nitropropane, 2-methyl-2-nitrobutane, and 2, 3-dimethyl-2-nitrobutane, has been carried out at the MP2/6-31G(d), B3LYP/6-31G(d), B3PW91/6-31G(d), levels of theory. The nitroalkanes yield the corresponding alkene and HNO 2 gas in a rate determining step. The B3PW91/6-31G(d) method was found to give a reasonable good agreement with the experimental kinetic and thermodynamic parameters. The elimination of these reactions suggest a concerted non-synchronous five-membered cyclic transition state type of mechanism.

The mechanisms of the gas phase elimination of N,N-dimethylglycine, picolinic acid, and N-phenylglycine and their ethyl esters have been examined at Moller–Plesset MP2/6-31G (d, p) level of theory. The ethyl esters of these 2-amino carboxylic acids produce the corresponding amino carboxylic acid and ethylene in a rate-determining step. However, the unstable intermediate amino carboxylic acid rapidly decarboxylate to give the corresponding amino compound. These calculations imply a concerted, semi-polar six-membered cyclic transition state type of mechanism for the ethyl esters, and a non-synchronous five-membered cyclic transition state for the amino acids decarboxylation. The present results support previous mechanistic consideration of the elimination of the above-mentioned compounds in the gas phase. Copyright © 2008 John Wiley & Sons, Ltd.

The gas-phase elimination kinetics of 2-arylethyl N , N -dimethylcarbamates, (CH 3 ) 2 NCOOCH 2 CH 2 Ar, has been studied at the ab initio MP2/6-31G and MPW1PW91/6-31G(d,p) levels of theory. These carbamates produce N , N -dimethylcarbamic acid and the corresponding 4-substituted styrene in a rate determining step. The unstable intermediate N , N -dimethylcarbamic acid rapidly decarboxylate through a four-membered cyclic transition state to give dimethylamine . These calculations imply a concerted, non-synchronous six-membered cyclic transition state type of mechanism. The present results support the fact that the acidity of the benzylic hydrogen as an important factor for faster elimination rates.

The gas-phase elimination of ethyl N,N-dimethylcarbamates substituted with electron-withdrawing groups at the 2-position of the ethyl were studied by using the Moller–Plesset MP2/6-31G method. Calculations suggest a concerted non-synchronous six-membered cyclic transition state type of mechanism of the above-mentioned carbamates. These substrates undergo thermal elimination to produce the N,N-dimethylcarbamic acid and the corresponding substituted olefin in the rate-determining step. The unstable intermediate, N,N-dimethylcarbamic acid rapidly decomposes through a four-membered cyclic transition state to dimethylamine and CO2 gas. The logarithm of relative theoretical rate coefficients when plotted against original Taft's σ* values gave an approximate straight line (ρ*=−0.137±0.023, r=0.9610 at 360 °C). In addition to this fact, plotting experimental log krel. against the theoretical log krel. for 2-substituted ethyl N,N-dimethylcarbamates an approximate straight line (r=0.9578 at 360 °C) is obtained, which means similar mechanism.

The theoretical studies on the elimination kinetics of 2-substituted ethyl N , N -dimethylcarbamates [(CH 3 ) 2 NCOOCH 2 CH 2 Z, Z=CH 2 C 6 H 5 , C 6 H 5 , C(CH 3 ) CH 2 ] in the gas phase were carried out using the ab initio MP2/6-31G and DFT RMPWP91/6-31G(d,p) levels of theory. These carbamates produce N , N -dimethylcarbamic acid and the corresponding substituted olefin in a rate determining step. On the basis of these calculations, the mechanism appears to be concerted, asynchronous, through a six-membered cyclic transition state structure. The acidity of the benzylic and allylic β-hydrogen is believed to be responsible for faster elimination rates.

Theoretical studies of the gas-phase elimination kinetics of title compounds were performed by using “ab initio” methods at MP2/6-31G, MP2/6-31G(d,p) and ONIOM [MP2/6-31G (d,p) // MP2/6-31G]. Ethyl Oxamate and ethyl oxanilate undergo a rapid decarbonylation to give the corresponding carbamates. These intermediates proceed to a parallel decomposition to give the corresponding unstable carbamic acid and ethylene through six-membered cyclic transition state (path 1) and isocyanate and ethanol through a four-membered cyclic transition state (path 2). Ethyl N,N-dimethyloxamate elimination reaction yields in one step, through a six-membered cyclic transition state, dimethyl oxamic acid and ethylene gas. The calculated bond orders, NBO charges and synchronicity indicate that these reactions are concerted and slightly asynchronous. The estimated kinetic and thermodynamic parameters are in good agreement with the reported experimental values. Copyright © 2006 John Wiley & Sons, Ltd.

Moller-Plesset MP2/6-31G method was used to examine the gas-phase elimination of 2-substituted alkyl ethyl N,N-dimethylcarbamates. The results of these calculations support a concerted non-synchronous six-membered cyclic transition state mechanism for carbamates containing a Cβ–H bond at the alkyl side of the ester. These substrates produce the N,N-dimethylcarbamic acid and the corresponding olefin. The unstable intermediate, N,N-dimethylcarbamic acid, rapidly decomposes through a four-membered cyclic transition state to dimethylamine and CO2 gas. Correlation of the logarithm of theoretical rate coefficients against original Taft's σ* values gave an approximate straight line (ρ*=−1.39, r=0.9558 at 360 °C). In addition to this fact, when log krel is plotted against the theoretical log krel for 2-substituted ethyl N,N-dimethylcarbamates a reasonable straight line (r=0.9919 at 360 °C) is obtained, suggesting similar mechanism.

Metal(II) coordination compounds of a hydrazone ligand (HL) derived from the condensation of cephalexin antibiotic with 2,6-diacetylpyridine bis(hydrazone) were synthesized. The hydrazone ligand and mononuclear [ML(H2O)2][PF6] (M(II)=Mn, Co, Ni, Zn) complexes were characterized by several techniques, including elemental and thermal analysis, molar conductance and magnetic susceptibility measurements, electronic, FT-IR, EPR and (1)H NMR spectral studies. The cephalexin 2,6-diacetylpyridine bis(hydrazone) ligand HL behaves as a monoanionic tetradentate NNNO chelating agent. The biological applications of complexes have been studied on two bacteria strains (Escherichia coli and Staphylococcus aureus) by agar diffusion disc method.

Structural parameters, harmonic frequencies, and force constants of B2F4 were obtained in internal coordinates from ab initio RHF calculations with the 6-311G* basis set. The results obtained are used to calculate the Coriolis coupling constants and the inertial defect for 10B2F4 and 11B2F4 and to compare these values with those obtained by using the autoconsistency method. Both the ab initio and the iterative force fields, despite some significant differences, reproduce the vibrational wave numbers equally well and yield nearly the same Coriolis coupling constants and inertial defects. The calculated inertial defects for 10B2F4 and 11B2F4 are -0.942 and -0.919 amu Å2, respectively.Key words: Coriolis coupling constants, inertial defect, B2F4, harmonic frequencies, force constants.

A reliable set of harmonic force constants was calculated for BF 3 , BCl 3 , BBr 3 , BI 3 , BF 2 Cl, BF 2 Br, BCl 2 F, BCl 2 Br, BBr 2 F, and BBr 2 Cl using the observed vibrational frequencies of these compounds (containing 10 B or 11 B isotopes) and the iterative consistency method. The final force field reproduces quite satisfactorily the experimental frequencies. Some of the principal stretching force constants were found to vary systematically with the electronegativity of the halogen.