Theoretical studies on the chemical decomposition of 5-aza-2′-deoxycytidine: DFT study and Monte Carlo simulation

The decomposition mechanism of 5-Aza-2??-deoxycytidine has been studied by the use of computational techniques. Optimized structures for all of the stationary points in the gas phase were investigated at B3LYP/6-31+G(d,p) level of theory. Single-point energies were determined employing the ab initio MP2 method in conjunction with the 6-311++G(d,p) basis set. Five possible pathways, paths 1?C5, were evaluated. In each pathway, the direct (A-paths 1?C5) and water-assisted (B-paths 1?C5) processes were considered. Meanwhile, the local microhydration model with the direct participation of three water molecules around the reaction centers was adopted to mimic the system for the water-assisted decomposition mechanisms above, where one water molecule is the nucleophilic reactant and the other two are the auxiliary molecules located on each side of the nucleophilic water. The results in the gas phase exhibit that the energy barriers of the water-assisted pathways based on the local microhydration model decrease dramatically by about 15?C20?kcal/mol as compared with those of the direct pathways because of the contribution of the auxiliary water molecules. In addition, bulk solvent effects of water were determined by means of the self-consistent reaction field based on the conductor-like polarized continuum model and Monte Carlo simulation with free energy perturbation (MC-FEP) technique, respectively. Our computational results indicate that B-path 3 in the decomposition reaction of 5-azadC is the most favorable, where the calculated rate constant (1.68?×?10^?3?min^?1) using the MC-FEP method is within the range of the experimentally determined values [(5.89?±?0.54)?×?10^?3?min^?1 by UV and (1.46?±?0.08)?×?10^?3?min^?1 by NMR].     

Theoretical study of mechanism and kinetics for the reaction of hydroxyl radical with 2′-deoxycytidine

The reaction mechanism and kinetics for the abstraction of hydrogen and addition of hydroxyl radical (OH) to 2′-deoxycytidine have been studied using density functional theory at MX06-2X/6-311+G(d,p) level in aqueous solution. The optimized geometries, energies, and thermodynamic properties of all stationary points along the hydrogen abstraction reaction and the addition reaction pathways are calculated. The single-point energy calculations of the main pathways at CCSD(T)/6-31+G(d,p)//MX06-2X/6-311+G(d,p) level are performed. The rate constants and the branching ratios of different channels are evaluated using the canonical variational transition (CVT) state theory with small-curvature tunneling (SCT) correction in aqueous solution to simulate the biological system. The branching ratios of hydrogen abstraction from the C1′ site and the C5′ site and OH radical addition to the C5 site and the C6 site are 57.27% and 12.26% and 23.85% and 5.69%, respectively. The overall calculated rate constant is 4.47?×?10⁹ dm³ mol^?1 s^?1 at 298 K which is in good agreement with experiments. The study could help better understand reactive oxygen species causing DNA oxidative damage.     

Quantum chemical studies on the structures, properties and decomposition of the azido derivatives of trinitrobenzenes

The geometries,heats of formation and electronic structures of 15 azido-derivatives of 1,2,3-TNB (Ⅰ),1,2,4-TNB (Ⅱ) and 1,3,5-TNB (Ⅲ) have been studied using quantum chemical AMI method at HF level.The effect of azido substitution on the structures and properties of TNBs has been discussed and the relative stability of the title compounds has been established.The processes of the decomposition of the title compounds by breaking C-NO2,C-N3 and CN-N2 bonds are investigated at UHF-AM1 level.It is shown that the decomposition of the title compounds may be initiated by the cleavage of both C-NO2 and N-N2 bonds.     

Theoretical study on decomposition of γ-halo allylalkoxide and β-halo acrylate ions

β, γ-Substituted γ-halo allylalkoxide ions decompose to form a halogen ion, formaldehyde, and an alkyne under mild conditions, for example at room temperature. The E isomer does not differ from the Z isomer in terms of activation energy. We attempted to shed light on the mechanism of the reaction by using ab initio molecular orbital calculations. The observed propensity was confirmed by the present calculation on model molecules, γ-chloro allylalkoxide ions. We conducted further calculations and compared the alkoxide results with a similar reaction of β-haloacrylate ions that release carbon dioxide instead of formaldehyde. This similar reaction needs heating as high as 150°C. The activation energy of the acrylate ions (36–39 kcal mol⁻¹) was calculated to be about 10 kcal mol⁻¹ higher than that of the alkoxide ions. The activation energy of the E acrylate ion is smaller by 0.8 kcal mol⁻¹ than that of the Z isomer at the MP2/6-31+G**//RHF/6-31+G* level of theory. This is consistent with experimental results. While the ready deprotonation from the carboxylic group does not activate the acrylate ion very much, the alkoxide ion is destabilized to a great degree in the process of anion formation. The difficulty in deprotonation that proceeds from the neutral molecule is seen in the difference in the activation energies for the decomposition of the corresponding anions. Therefore, the pK _a of a hydroxy or a carboxylic group plays the leading role in determining the magnitude of activation energies of allyl halides with a negatively charged fragment. Received: 2 July 1998 / Accepted: 9 September 1998 / Published online: 8 February 1999     

Theoretical studies on the substitution effect of fluorine on ethylene

The substitution effect of fluorine on ethylene is investigated by means of studyingthe properties of the charge distribution at the bond critical points with the theory of atomsin molecules.It is found that fluorine atom acts not only as a σ electron acceptor,but also asa π electron donor,and these double effects are reflected in the quantity of ellipticity,Lap-lacian and the charge density of charge distribution at the bond critical points.For C—C,C—Fbonds,the major axis of elliptical contours is perpendicular to the molecular plane,but forC—H bond,it is parallel to the molecular plane.Other effects originating from the substi-tution have also been discussed.     

Monte Carlo simulation of the kinetics of the helix—coil transition in a synthetic DNA

Values of the rate at which an alternating copolymeric nucleic acid melts after a temperature jump have been obtained with a Monte Carlo simulation. Using a Glauber—Ising scheme to model the dynamics, the helix—random coil transition shows a pure “monodispersive” relaxation in accord with previous analytical and experimental predictions.     

The simulation of the adsorption of unsaturated cyclic hydrocarbons on the (001)-2 × 1 reconstructed silicon surface by the Monte Carlo and transfer-matrix methods

A model of the adsorption of cyclic unsaturated molecules on the Si(001)-2 × 1 reconstructed surface was developed for the example of 1,4-cyclohexadiene, which can be differently adsorbed on surface adsorption centers. Calculations were performed for a grand canonical ensemble by the Monte Carlo and transfer matrix methods. The structure of the ordered phases formed and the conditions of their appearance were studied in detail. It was shown that the suggested model reproduced all the qualitative special features of the system studied and similar systems.     

Theoretical study on the reaction mechanism of CH2SH + NO2

The mechanisms of CH₂SH with NO₂ reaction were investigated on the singlet and triplet potential energy surfaces (PES) at the BMC-CCSD//B3LYP/6-311 + G(d,p) level. The result shows that the title reaction is more favourable on the singlet PES thermodynamically, and it is less competitive on the triplet PES. On the singlet PES, the initial addition of CH₂SH with NO₂ leads to HSCH₂NO₂ (IM2) without any transition state, followed by a concerted step involving C–N fission and shift of H atom from S to O giving out CH₂S + trans-HONO, which is the major products of the title reaction. With higher barrier height, the minor products are CH₂S + HNO₂, formed by a similar concerted step from the initial adduct HSCH₂ONO (IM1). The direct abstraction route of H atom in SH group abstracted by O atom might be of some importance. It starts from the addition of the reactants to form a weak interaction molecular complex (MC3), subsequently, surmounts a low barrier height leading to another complex (MC2), which gives out CH₂S + trans-HONO finally. Other direct hydrogen abstraction channels could be negligible with higher barrier heights and less stable products.     

Theoretical studies on the mechanism of the thermal decarboxylation and decarbonylation of a number of α-keto-acids

Both processes of decarboxylation and decarbonylation of a number of acids including RCOCO2H,R=H,CH3,CH2F,CF3,CH=CH2,Ph,OH have been studied by semi-empirical MO theory AMI method to verify the reaction mechanism of each process and the effect of different substituents on them.The calculated results are consistent with the experimental reports and can be summed up as follows:(1) The decarboxylation of these acids to form aldehydes and carbon dioxide is concerted and takes place through a 4-membered ring transition state in which a partial negative charge develops on the carbon of the α-carbonyl group,so that the inductive effect of some substituents is favourable for this process.(2) Their decarbonylation into carboxylic acids and carbon monoxide however is the attack of the OH on the carbon of the alkyl portion of the acid,forming a 3-membered ring transition state.(3) The activation energy of decarbonylation is lower than that of decarboxylation,since oxygen is more nucleophilic than hydrogen and als     

Theoretical studies on the photoinduced rearrangement mechanism of α-santonin

α-Santonin is the first organic compound observed to feature a photoinduced rearrangement and is now known to undergo a series of photochemical processes under UV irradiation. On the basis of the considerable interest of this system as a prototype, and of the yet limited insights reached for the basic photo mechanisms, we calculate the high-level electronic structures and explore the potential energy surfaces (PES) of α-santonin in the ground and lowest-lying excited states, their couplings, and the possible photoinduced isomerization pathways. The calculations identify the low-lying singlet excited state (1)(nπ*) accessible under light irradiation, which decays to the low-energy (3)(ππ*) state through an intersystem crossing in the Franck-Condon region to initiate the photoinduced rearrangement. The initial reaction from the C3-C5 bond coupling, which takes place on the (3)(ππ*) state potential energy surface, leads to a three-membered alkyl-ring compound intermediate state INT. The following photochemical reactions have the possibility to arise from two distinct C-C bond cleavages, C4-C5 and C3-C4, denoted as path A and path B. Path A is favored both dynamically on the excited-state PES and thermodynamically on the ground-state PES in vacuo. Experiments show that it also becomes the dominant photoinduced rearrangement process in the crystal, which can be explained by considering the requirement for less space and the stacking effect under the confined environment. Path B is dynamical advantaged both on the ground- and excited-state PESs in a weak polar solvent, such as dioxane. Once the biradical intermediate B-INT is accessible on the ground-state PES, the formation of the product B-P is almost barrier free.     

Theoretical studies on the binding energy of β-sheet models

In this paper, B3LYP and MP2 methods are used to investigate the binding energy of seventeen antiparallel and parallel β-sheet models. The results indicate that the binding energy obtained from B3LYP calculations is weaker than that obtained from MP2 calculations but the relative binding energy yielded by B3LYP is almost the same as that by MP2. For the antiparallel β-sheets in which two N-H⋯O=C hydrogen bonds can form either a large hydrogen-bonded ring or a small hydrogen-bonded ring, the binding energy increases obviously when one large ring unit is added, whereas it only changes slightly when one small ring unit is added because of the secondary electrostatic repulsive interaction existing in the small ring unit which is estimated to be about 20 kJ/mol. For the parallel β-sheet models, the binding energy increases almost exactly linearly with the increase of the chain length.     

Theoretical studies on the potential energy surfaces and vibrational energy levels of HXeF and HXeCl

The potential energy surfaces for the electronic ground state of the HXeCl and HXeF molecules areconstructed by using the internally contracted multi-reference configuration interaction with theDavidson correction(icMRCI Q)method and large basis sets.The stabilities and dissociation barriersare identified from the potential energy surfaces.The three-body dissociation channel is found to bethe dominate dissociation channel for HXeCl,while two dissociation channels are possible and com-petitive for HXeF.Based on the obtained potentials,vibrational energy levels of HXeCl and HXeF arecalculated using the Lanczos algorithm.Our theoretical results are in good agreement with the avail-able observed values.Particularly,the calculated fundamental frequency of the H—Xe stretching vi-bration including the Xe matrix effect of HXeCl is found to be 1666.6 cm-1,which is only 17.6 cm-1higher than the recently observed value of 1649 cm-1.     

Quantum chemical study on the thermal rearrangements of HNCRCR''''CO

MINDO/3 molecular orbital theory has been used to study the thermal rearrangements of HNCRCR'CO.The results obtained show that the activation energy of this rearrangement depends on the migrating group R and the group R'.     

Theoretical studies on the structures and reactivity of stannylenoids I.The structures and isomerization of stannylenoid H_2SnLiF

The structures of singlet stannylenoid H2SnLiF have been examined by ab initio MO theory. Four equilibrium states and three transition states of isomerization reaction are located. The calculation shows that the p-complex 1 is the most stable and experimentally detectable. The other three species, three-membered ring 2, o-complex 3 and tetrahedron 4, are also local minima on the potential energy surface, but are higher in energy.     

Molecular orbital studies on nucleoside antibiotics: Part IX. Conformation of 5-ethynyl- and 5-vinyl-2′-deoxycytidines

5-Substituted deoxycytidines exhibit antiviral and antimetabolic properties and they are selective inhibitors of herpes simplex virus (HSV). Conformational properties of two of the 5-substituted deoxycytidines, namely: 5-ethynyl- and 5-vinyl-2′-deoxycytidines, have been investigated by the PCILO method and compared with those of their parent nucleoside (2′-deoxycytidine). The results indicate striking similarity in their conformational behaviour. This result has important biological significance in terms of their biological activity. The mechanism of their action is discussed.     

Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2′,3′-dideoxy-3′-thiacytidine)formamidine

The hydrolysis mechanisms of N,N-dimethyl-N′-(2′,3′-dideoxy-3′-thiacytidine)formamidine (FA-3TC) in the gas phase and in aqueous solution were studied by use of the density functional theory B3LYP/6-31 G(d, p) method. Two possible reaction pathways in the title reaction were considered. In one pathway water attacks the C=N double bond first (path A) while in the other water attacks the C—N single bond first (path B). The calculated results indicate that the first step in both pathways is the rate-limiting process and path A is more favorable than path B in the gas phase. The effect of solvent water on the title reaction was assessed at the B3LYP/6-31 G(d, p) level of theory based on the po-larizable continuum model (CPCM). In water the first mechanism (path A) is also favored.     

Theoretical study on the mechanism of C2Cl3 + NO2 reaction

The radical-molecule reaction of C₂Cl₃ with NO₂ is explored at the B3LYP/6-311G(d,p) and CCSD(T)/6-311+G(d,p) (single-point) levels. On the singlet potential energy surface (PES), the association between C₂Cl₃ and NO₂ is found to be carbon-to-nitrogen attack forming the adduct C₂Cl₃NO₂ (1) without any encounter barrier, followed by isomerization to C₂Cl₃ONO (2). Starting from 2, the most feasible pathway is the N–O1 bond cleavage which lead to P ₁ (C₂Cl₃O + NO). Much less competitively, 2 transforms to the three-membered ring isomer c-OCCl₂C–ClNO (4 ^a ) which can easily interconvert to c-OCCl₂C–ClNO 4 ^b . Then 4 (4 ^a , 4 ^b ) takes direct C1–C2 and C2–O1 bonds cleavage to give P ₂ (COCl₂ + ClCNO). The lesser competitive channel is the 4 ^a isomerizes to the four-membered ring intermediate O-c-CNClOCCl₂ (5) followed by dissociation to P₃ (CO + ClNOCCl₂). The concerted 1,2-Cl shift along with C1–O1 bond rupture of 4 ^b to form ONC(O)CCl₃ (6) followed by dissociation to P ₄ (ClNO + OCCCl₂) is even much less feasible. Moreover, some of P ₃ and P ₄ can further dissociate to P ₅ (ClNO + CO + CCl₂). Compared with the singlet pathways, the triplet pathways may have less contribution to the title reaction. Our results are in marked difference from previous theoretical studies which showed that two initial adducts C₂Cl₃–NO₂ and C₂Cl₃–ONO are obtained. Moreover, in the present paper we focus our main attentions on the cyclic isomers in view of only the chain-like isomers are considered by previous studies. The present study may be helpful for understanding the halogenated vinyl chemistry.     

Quantum chemical study on the thermal Diels-Alder reaction of cyclohexadiene and methyl crotonate

AM1 molecular orbital method using the unrestricted Hartree-Fock(UHF) calculations has been applied to investigate the thermal reaction of cyclohexadiene and methyl crotonate. The calculated results indicate that the thermal Diels-Alder reaction proceeds to product through the concerted path and two radical pathways.     

DFT study of α-maltose: influence of hydroxyl orientations on the glycosidic bond

The result of DFT geometry optimization of 68 unique α-maltose conformers at the B3LYP/6-311++G** level of theory is described. Particular attention is paid to the hydroxyl group rotational positions and their influence on the glycosidic bond dihedral angles. The orientation of lone pair electrons across the bridging hydrogen bonds are implicated in directing the glycosidic dihedral angles with for example, conformers gg-gg and gt-gt, having different minimum energy conformations for the clockwise (c) and the reverse clockwise (r) forms. Conformers tg-gg, gg-tg, tg-tg, gt-gg, and gg-gt were studied, to understand the intermediate glycosidic bond conformations. The conformation, tg-gg-c, was found to be the lowest energy structure. When the hydroxyl groups on each glucose residue were made to point in opposite directions, i.e., c/r and r/c, the optimized structures were found to have high relative energies. Several optimized ‘kink’ structures were found around (, ψ_H) ∼(−40°, −40°), the lowest relative energy conformation being ∼3 kcal/mol. “Kink” conformations are observed in crystalline CA-10 and CA-14mers. Band-flip conformations, also observed in X-ray structures of CA-26 fragments, were studied with the lowest energy α-maltose conformations ∼4.0 kcal/mol above the global energy minimum. Several trends in geometry resulting from hydroxyl rotamer directions are described. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Names are necessary to report factually on available data; however, the USDA neither guarantees nor warrants the standard of the product, and the use of the name by USDA implies no approval of the product to the exclusion of others that may also be suitable.