Chemical Reactivity of Oxo‐ and Aza‐γ‐lactam Rings

Different mechanisms for the alkaline hydrolysis of oxo and aza‐γ‐lactam rings have been studied by ab initio calculations at the MP2/6‐31+G*//MP2/6‐31+G* and B3LYP/6‐31+G*//B3LYP/6‐31+G* levels. The tetrahedral intermediate can undergo two different reactions, the cleavage of the C₂−N₂ bond (the classical mechanism) and the cleavage of the C₂−X₆ bond (X=O, N). Both compounds present similar energy barriers for the classical fragmentation, and show considerably lower barriers for the alternative mechanism. Because of this reactivity, the compounds studied are expected to be β‐lactamase inhibitors.     

Struktur und Eigenschaften des Hydridomethyltetrafluorphosphatanions, [CH3PF4H]—

Structure and Properties of the Hydridomethyltetrafluorophosphate Anion, [CH₃PF₄H]^— Methyltrifluorphosphorane reacts with strong fluoride donors like CsF, (CH₃)₄NF and (CH₃)₄PF with formation of the corresponding hydridomethyltetrafluorophosphates. The salts are characterized by NMR, IR and Raman spectroscopy. The experimental results show that only the trans isomer is formed. For both isomers theoretical calculations (B3LYP/6‐31+G* and RHF/6‐31+G*) were carried out. The difference for the Gibbs free energy between the isomers was calculated to be 35.4 kJ/mol (B3LYP/6‐31+G*). The RHF/6‐31+G* calculation yields, for the almost octahedral trans isomer, bond distances of r(PF) = 167 pm, r(PC) = 184.5 pm and r(PH) = 138.1 pm.     

AB initio study of thermodynamic stability and structure of cage molecules B4N4H8 and Be4O4H8

Stable molecular structures of heterocubane systems B₄N₄H₈ 2 and Be₄O₄H₈, isoelectronic to the cubane molecule, are investigated by ab initio (RHF/6-31G**, MP2(full)/6-31C**, and MP2(full)/6-311+ + G**) methods and are shown to be highly thetmodynamically stable. Decomposition of structure 2 into two 1,3,2,4-diazadiboroethidine molecules 6 or four iminobomne NBNH molecules 11 is an endothermal process taking 10.1 (RHF/6-31G**), 39.6 (MP2(full)/6-31G**) kcaUmole and 140.6 (RHF/6-31G**), 161.4 (MP2(full)/6-31G**) kcal/mole, respectively. Decomposition of structure 3 into two 1,3,2,4-dioxydi-beryllothidine molecules 12 or four molecules 13 is also an endothermal reaction taking 22.1 (RHF/6-31G**), 39.8 (MP2(full)/6-31G**) kcal/mole and 127.1 (RHF/6-31G**), 155.2 (MP2(full)/631G**) kcal/mole, respectively. The geometrical characteristics of simple molecules BeH₂ 15, Be₂ 16 and 17, Be₂H₂ 18, Be₂H₄ 19, BeO 20, and Be₂O₂ 21 are calculated. Translated from Zhumal Struktumoi Khim ii, Vol. 41, No. 1, pp. 3-13, January–February, 2000     

Mismatch base pairing of the mutagen 8‐oxoguanine and its derivatives with adenine: A theoretical search for possible antimutagenic agents

Molecular geometries of 8‐oxoguanine (8OG), those of its substituted derivatives with the substitutions CH₂, CF₂, CO, CNH, O, and S in place of the N7H7 group, adenine (A), and the base pairs of 8OG and its substituted derivatives with adenine were optimized using the RHF/6‐31+G* and B3LYP/6‐31+G* methods in gas phase. All the molecules and their hydrogen‐bonded complexes were solvated in aqueous media employing the polarized continuum model (PCM) of the self‐consistent reaction field (SCRF) theory using the RHF/6‐31+G* and B3LYP/6‐31+G* methods. The optimized geometrical parameters of the 8OG‐A base pair at the RHF/6‐31+G* and B3LYP/6‐31+G* levels of theory agree satisfactorily with those of an oligonucleotide containing the base pair found from X‐ray crystallography. The pattern of hydrogen bonding in the CF₂‐ and O‐substituted 8OG‐A base pair is of Watson–Crick type and that in the unsubstituted and CH₂‐, CNH‐, and S‐substituted base pairs is of Hoogsteen type. In the CO‐substituted base pair, the hydrogen bonding pattern is of neither Watson–Crick nor Hoogsteen type. The CF₂‐substitution appears to introduce steric hindrance for stacking of DNA bases. On the basis of these results, it appears that among all the substituted 8OG molecules considered here, the O‐substituted derivative may be useful as an antimutagenic drug. It is, however, subject to experimental verification. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

OPLS all-atom force field for carbohydrates

The OPLS all-atom (AA) force field for organic and biomolecular systems has been expanded to include carbohydrates. Starting with reported nonbonded parameters of alcohols, ethers, and diols, torsional parameters were fit to reproduce results from ab initio calculations on the hexopyranoses, α,β-d -glucopyranose, α,β-d -mannopyranose, α,β-d -galactopyranose, methyl α,β-d -glucopyranoside, and methyl α,β-d -mannopyranoside. In all, geometry optimizations were carried out for 144 conformers at the restricted Hartree–Fock (RHF)/6–31G* level. For the conformers with a relative energy within 3 kcal/mol of the global minima, the effects of electron correlation and basis-set extension were considered by performing single-point calculations with density functional theory at the B3LYP/6–311+G** level. The torsional parameters for the OPLS-AA force field were parameterized to reproduce the energies and structures of these 44 conformers. The resultant force field reproduces the ab initio calculated energies with an average unsigned error of 0.41 kcal/mol. The α/β ratios as well as the relative energies between the isomeric hexopyranoses are in good accord with the ab initio results. The predictive abilities of the force field were also tested against RHF/6–31G* results for d -allopyranose with excellent success; a surprising discovery is that the lowest energy conformer of d -allopyranose is a β anomer. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1955–1970, 1997     

A Complete Active Space Self‐Consistent Field (CASSCF) Study of the Reaction Mechanism of the α‐Alkynone Rearrangement

The pyrolytic rearrangement of α‐alkynones has been discovered by Karpf and Dreiding [1] in 1979. The mechanism of this reaction, which involves an acetylene‐vinylidene rearrangement followed by cyclization of the intermediate vinylidene carbene by insertion into a β‐C−H bond, has been debated in a couple of theoretical investigations. Restricted Hartree‐Fock (RHF) and single‐point Møller‐Plesset 2 (MP2) calculations at the RHF geometries apparently indicate the carbene cyclization to be the rate‐determining step, contrary to chemical intuition. However, larger‐scale correlated calculations with completely optimized molecular geometries ((8,8) CASSCF/6‐311G**), augmented with a perturbative account for the dynamic correlation contribution to the electronic energy, show vanishing energy barriers to the cyclization step and large activation energies for the acetylene‐vinylidene rearrangement, which is thus confirmed as the rate‐determining step of the title reaction.     

Comparison of ground and excited state polarizabilities of thiophene,cyclopentadiene, and fulvene oligomers and their cyano substituted derivatives—Ab initio study

Ab Initio study of the ground and excited state polarizabilities of thiophene, fulvene, and cyclopentadiene based conducting oligomers and their cyano derivatives have been performed using the restricted Hartree–Fock (RHF) and the configuration interaction singles (CIS) approaches, respectively, with 3‐21G* basis set. For comparison purposes, for some small oligomers (monomers and dimers), higher basis sets (6‐31G*, 6‐31+G*, aug‐cc‐pVTZ) were also employed in the computations of polarizabilities. The trends in polarizability as a function of oligomer length were investigated. For all systems, the RHF polarizability increases as n^1.2–1.3 as n gets larger and the CIS polarizability increases as n^1.4–1.6 for n less than seven or eight rings and then increases approximately linearly with n for larger n. For the thiophene based systems the dependence of the polarizability on bond length alternation (BLA) along the backbone of the oligomers was also investigated using the RHF, density functional (DFT), and CIS theories (with 3‐21G* basis set). For thiophene dimer, we also performed RHF/aug‐cc‐pVTZ calculations of polarizabilities versus BLA. We found that the polarizability is largest when BLA is near zero (for both ground and excited states), which correlates with the lowest excitation energy. Comparison with experimental results has been made where possible. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1983–1995, 2007     

Double Bond Migration Mechanism in Allyl Systems Involving the Hydroxide Ion. 2. Polarizable Continuum Model (PCM)

Isomerization processes of a double bond site in propene and methylthiopropene molecules with the hydroxide ion were studied in the framework of the RHF/6-31+G*, MP2/6-31+G*, and B3LYP/6-31+G* (density functional) ab initio methods. The solvent effect was taken into account using PCM in its IEFPCM and SCIPCM versions. It is shown that to construct a reaction profile for propene rearrangement, it suffices to perform geometry optimization of stationary points within the Born–Onsager model with further refinement of the energy using IEFPCM. The reaction profiles obtained display that the multiple bond migration mechanism involving the hydroxide ion proton is energetically preferable to the two-stage mechanism forming a solvated carbanion for the propene molecule and for the methylthiopropene molecule that forms a much more stable carbanion.     

Effect of basic set quality and electron correlation on the scale factors of a harmonic force field

The completely optimized structure and harmonic force field of s-trans-buta-1,3-diene are reported at the MP2/6-31G and MP2/6-31G* levels of computation. Sets of empirical scale factors for the calculated force fields are derived and compared with the corresponding values computed at the RHF/4-31G and RHF/6-31G levels. Changes in the scale factors for this series of force fields are discussed. The vibrational frequencies are also reported for thirteen isotopomers of s-trans-buta-1,3-diene using the MP2/6-31G* force field. Some characteristics of the gauche and cis forms of buta-1,3-diene are also given.     

Conformational analysis of 2,4-dialkyl-1,3,2-dioxaborinanes

Computer modeling using the quantum-chemical empirical MM+ method and nonempirical RHF//6-31G(d), MP2//6-31G(d), and, in individual cases, RHF//3-21G methods was employed to study the potential energy surface of 2,4-dialkyl-1,3,2-dioxaborinanes. The optimal geometry and ¹H NMR spectral data gave values for ∆G ⁰ of the methyl and hexyl substituents at C-4 of the heterocyclic ring equal to 0.6 and 1.6 kcal/mol, respectively.     

Approximate transferability in alkanenitriles

The atomic and bond properties of a series of alkanenitriles were calculated in order to analyze the transferability of the CN, methyl, and methylene groups. The calculations were carried out using the atoms in molecules (AIM) theory on RHF/6‐31++G**// RHF/6‐31G** wave functions obtained for compounds CN–R (R ranging from H to C₁₁H₂₃). Linear correlations between L(Ω) and N(Ω) were used to establish N(CH₂) and N(CH₃) nearly transferable values. Average values and maximum differences to the mean value of several properties were used for classifying the CN group. It shows a transferable behavior along the CN–R series for R>Et. The methyl group presents specific properties when R<Pr. The methylene groups can be classified considering both their position with respect to the end of the chain and the position with respect to the CN group. The atomic energy displays a dependence on the molecular size. Although this behavior does not allow to consider this property as transferable, both the ab initio total electronic molecular energies and the experimental heats of formation can be fitted, by linear regression analysis, as a function of the number of methylene groups. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

Electronic effects of conjugated enones on their reactivity in transformations of ADDN type

Using RHF/3-21G, RHF/6-31G(d, p), MP2/6-31G(d, p), B3LYP/6-31G(fd, p) approximations the structure and ¹³C NMR spectra of 2-alkylsubstituted cyclohexene-2-ones and 2-alkylacroleins are studied and calculated. In the series of 2-alkylcyclohexene-2-ones the effect of the substituent on a deviation from coplanarity of the C=C-C=O fragment is more expressed in comparison with 2-alkylacroleins. This deviation (5°) is not enough to explain the observed properties of 2-alkylcyclohexene-2-ones due to disturbed conjugation. The particular behavior of (R)-4-mentenone in reactions of 1,4-addition and ozonolysis is explained by a more expressed +I-effect of the alkyl substituent in α-position.     

Theoretical Study of Ammonolysis of Monobactams: Kinetic Role of the N‐Sulfonate Group

The ammonolysis reaction of 3‐(formylamino)‐4‐methyl‐2‐oxoazetidine‐1‐sulfonate is investigated by quantum‐chemical methods (B3LYP/6‐31+G*) as a model system of the aminolysis reaction of monobactam antibiotics involved in the allergic reaction to these drugs. The influence of the N‐sulfonate group on the β‐lactam ring, reaction intermediates, and transition states is characterized in terms of the geometries and relative energies of the corresponding critical structures located on the B3LYP/6‐31+G* potential‐energy surface. It is shown that the N‐sulfonate group, which has only a moderate impact on the structure and charge distribution of the β‐lactam ring, reduces the rate‐determining ΔG barrier by ca. 20 kcal/mol with respect to a purely uncatalyzed ammonolysis of the unsubstituted system, azetidin‐2‐one. This intramolecular catalytic effect occurs through a −NH−SO↔[−N−SO₃H]⁻ isomerization process, which is involved in the proton relay from the attacking ammonia molecule to the β‐lactam N‐atom. Our theoretical results predict that, in aqueous solution, monobactams will show an intrinsic reactivity against amine nucleophiles more important than that of penicillins.     

Study of the Alkaline Hydrolysis of the Azetidin-2-one Ring by ab initio Methods: Influence of the solvent

A comprehensive study of the alkaline hydrolysis of the β-lactam ring of azetidin-2-one was carried out using ab initio molecular-orbital calculations at the RHF/6-31 + G* level. The influence of the solvent on this reaction was investigated by using the reaction field method (SCRF); the solvent was found to suppress the interference of some gas-phase reactions and allow the presence of a transition state to be detected as the nucleophile approaches the β-lactam ring. The transition state corresponds to a structure where the OH^? group lies at a distance of 1.927 Å from the C?O group of the β-lactam ring and exhibits a potential barrier of 13.6 kcal/mol.     

Ab initio study of reactions of 1‐halogen‐3‐methoxy‐1‐propynes with Grignard reagent

The structures of coordination complexes of methylmagnesium chloride with 1‐halogen‐3‐methoxy‐1‐propynes have been studied by means of ab initio methods (RHF/3‐21G*, RHF/6‐31G* and RHF/6‐31G**), taking into account the electron correlation by Møller‐Plesset perturbation theory (MP2). Two pathways of the nucleophilic halogen substitution reaction between the reagents have been considered. The calculations predict the addition–elimination mechanism as advantageous for the reaction. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

乙烯醇钠的从头算研究(英文)

在ＲＨＦ／３－２１Ｇ和ＲＨＦ／６－３１＋Ｇ水平上优化了乙烯醇钠的的平衡构型及过渡态，比较了不同构型的稳定性。在ＲＨＦ／６－３１＋Ｇ水平上探讨了气相中由乙醛和氢氧化钠生成乙烯醇钠的机理。并在ＭＰ２（ｆｕｌ）／６－３１＋Ｇ／／ＭＰ２（ｆｕｌ）／６－３１＋Ｇ水平下计算了反应热     

Quantum Chemical Model of a Lysozyme+Substrate Complex and a Cooperative Process in It

This paper presents an ab initio (RHF/6-31G** and MP2(full)6-31G**) and density functional (DFT) study of the structure and energetics of formation of an intermolecular complex which is the simplest model of an active center lysozyme with a substrate. The calculated energy of complex formation is 41.4 (RHF), 53.4 (MP2), and 52.7 kcal/mole (DFT). The proton transfer reaction is a concerted reaction having an energy barrier of 41.1 (RHF), 31.6 (MP2), and 25.3 (DFT) kcal/mole.     

Multistep conformational interconversion mechanism of cyclododecane. A simple and fast analysis using potential energy curves

An ab initio and Density Functional Theory (DFT) study of the conformational properties of cyclododecane was carried out. The energetically preferred equilibrium structures, their relative stability, and some of the transition state (TS) structures involved in the conformational interconversion pathways were analyzed from RHF/6‐31G(d), B3LYP/6‐31G(d,p) and B3LYP/6311++G(d,p) calculations. Aug‐cc‐pVDZ//B3LYP/6311++G(d,p) single point calculations predict that the multistep conformational interconversion mechanism requires 11.07 kcal/mol, which is in agreement with the available experimental data. These results allow us to form a concise idea about the internal intricacies of the preferred forms of cyclododecane, describing the conformations as well as the conformational interconversion processes in the conformational potential energy hypersurface. Our results indicated that performing an exhaustive analysis of the potential energy curves connecting the most representative conformations is a valid alternate tool to determine the principal conformational interconversion paths for cyclododecane. This methodology represents a satisfactory first approximation for the conformational analysis of medium‐ and large‐size flexible cyclic compounds. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Multiple bond migration with participation of a protophilic agent

Ab initio study of the pathways of migration of the double bond in the 3-methylthioprop-1-ene (1) and 3-methoxyprop-1-ene (2) molecules with participation of hydroxide ion was carried out by the RHF/6-31+G^* and MP2/6-31+G//RHF/6-31+G^* methods. Conformational isomerism of the initial molecules and reaction products was considered. The distinctions are discussed in the spatial and electronic structure of intermediate carbanions stabilized (for1) due to the negative hyperconjugation. Stationary points corresponding to complexes between the molecules under study and the hydroxide ion and between the corresponding carbanion and water molecule were localized on the potential energy surfaces of the proton transfer reactions. For2, the single-stage mechanism of prototropic rearrangement involving the H atom of the hydroxide ions was found to be more energetically preferable than the two-stage mechanism, whereas both mechanisms are expected to be equiprobable for1. For Parts 1–3, see Refs. 1–3. Translated fromIzvestiya Akademii Nauk. Seriya Kimicheskaya, No. 3, pp. 407–413, March, 2000.     

The Hartree-Fock dissociation of F2

We examine the stability of the restricted Hartree-Fock (RHF) wave function for F₂ in the vicinity of the equilibrium internuclear distance (R=R _e ) and the shape of the unrestricted Hartree-Fock (UHF) potential energy curve for the same system. The results depend on the basis set: With a split valence plus polarization basis, 6-31G(d), the RHF wave function is unstable at R _e , and the UHF potential curve is purely dissociative. When the basis is extended to 6-311+G(3d) or 6-311+G(3df), the RHF wave function becomes stable, and the UHF potential curve acquires a local maximum for R slightly (0.02 å) greater than R _e . The local maximum, however, is only 0.1 kcal/mol higher than the local minimum at R=R _e .