Effect of Solvation on Ozonolysis Reaction Intermediates and Transition States

Electrostatic solvent effects on the ozonolysis of ethylene have been investigated using correlated ab initio and density functional approaches. We use a simple polarizable continuum model for the solvent. It allows us to evaluate the medium effect on both the electronic and nuclear structure of the chemical species involved in the reaction. The computations confirm that basically the reaction proceeds through the Criegee mechanism. However, formation of the van der Waals complexes ethyl-ene/ozone and carbonyl oxide/formaldehyde also appears to play a role. All the calculated species are stabilized with respect to the reactants except the transition state corresponding to the primary ozonide formation. In general, electrostatic solvent effects are relatively small for activation barriers of single reaction steps and more substantial for the corresponding reaction energies. Moreover, the medium significantly modifies the structure of some species for which polarization effects are crucial.     

A study on the structures of the substituted (aminomethyl)lithium and (thiomethyl)lithium compounds

The structures of substituted (aminomethyl)lithium and (thiomethyl)lithium compounds have been examined. Geometric parameters, charge densities, bond orders, dipole moments and heats of formation for all the members of the two series of monomers and dimers of the units LiCN(R)2 and LiCSR where R=H, CH3(Me), C6H5(Ph) have been calculated. The structures of the three complex compounds containing the same units; [[Li(CH2SMe)(THF)]X], [Li2(CH2SPh)2(THF)4] and [Li2(CH2NPh2)2(THF)3] have also been modeled. Geometry optimizations have been performed with the semiempirical PM3 method. The molecular orbital calculations have been carried out by a self-consistent field method using the restricted Hartree-Fock formalism. Comparisons have been made with the corresponding properties of methyl lithium monomer and dimer. The results show that in all of the nitrogen-containing monomers, the C-Li bonds weaken and the Li-C-H(N) angles decrease due to the coordination of lithium with nitrogen. Substitution of hydrogen atoms by methyl or phenyl groups decreases the Li-N coordination. In the sulfur-containing compounds, sulfur behaves similarly to nitrogen but the changes are smaller because the 3p lone-pair orbital of sulfur is higher in energy than the 2p lone-pair of nitrogen. All the dimers of nitrogen/sulfur-containing methyl lithium derivatives form six-membered rings in which the Li-N(S) coordination is greater than the one in the corresponding monomers. Dimerization reactions have been found to be exothermic and the formation of all the dimers is favored. The results obtained for the three complex structures are comparable to the experimental results reported in the literature.Keywords:     

Coupling of structural fluctuations to deamidation reaction in triosephosphate isomerase by Gaussian network model

We study the structural fluctuations of triosephosphate isomerase (TIM) by an elastic model, namely, the Gaussian network model (GNM), to identify a network of coupled motions in the allosteric communication between its deamidation and catalytic sites, and the promoting motions for the deamidation activity. For this, three TIM structures have been studied: one crystal structure and two model structures designed to describe different putative models for the deamidation reaction taking place at the subunit interface. The structural fluctuations have been mapped on the functional properties; then the differences in the fluctuations between the two models in relation to the deamidation reaction have been considered. The results demonstrate that the qualitative picture of the mean-square fluctuations and the correlations between the fluctuations are similar in both, but the differences may affect the observed barrier height of the deamidation reaction. The higher packing density at regions close to deamidation sites, reflected by the high-frequency fluctuating residues in the respective regions, the stronger positive correlation between the fluctuations of the deamidation sites, and enhanced positive correlation of the primary deamidation site with the extended vicinity of the catalytic region on the juxtaposed unit promote the probability of the deamidation reaction. The results in general emphasize the importance of structural fluctuations in enzyme reactions, as well as proposing the present methodology as a plausible approach for studies on the network of coupled promoting motions in protein functions.     

Understanding the mode of action of ThDP in benzoylformate decarboxylase

The mechanism of all elementary steps involved in the catalytic cycle of benzoylformate decarboxylase (BFD, E.C. 4.1.1.7) to generate the acyloin linkage is investigated by extensive molecular dynamics simulations. Models involving different charge states of amino acids and/or mutants of critical residues were constructed to understand the involvement of the catalytically active residues and the reactivity differences between different substrates in this reaction. Our calculations confirm that H70, S26, and H281 are catalytically active amino acids. H281 functions as a base to accept H_donor in the first nucleophilic attack and as an acid in the second, to donate the proton back to O_acceptor. S26 assists H281 in deprotonation of the donor aldehyde and protonation of the acceptor aldehyde. In both the first and second nucleophilic attacks, H70 interacts with O_aldehyde and aligns it toward the nucleophilic center. H70 has been found to have an electrostatic effect on the approaching aldehyde whose absence would block the initiation of the reaction. The reactivity difference between benzaldehyde (BA) and acetaldehyde (AA) is mainly explained by the steric interactions of the acceptor aldehyde with the surrounding amino acids in the active center of the enzyme. © 2009 Wiley Periodicals, Inc. Biopolymers 93: 32–46, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

An ab initio study of the formation of alkoxy radicals by reactions of simple alkenes with the OH radical

The formation of ethoxy, propoxy and butoxy radicals in the reactions of ethene, propene, cis- and trans-2-butene with the OH radical has been modeled in the gaseous phase at the MP2/6-31+G(d) level. All the possible reaction pathways have been investigated, and the structures as well as the energetics have been determined. The reactants, prereaction complexes, transition states and products located along the alkene-OH radical reaction coordinates have been discussed thoroughly. The rate determining step for these reactions is the conversion of hydroxyalkyl radicals to alkoxy radicals. The reaction barriers and exothermicities for these small alkenes are more or less identical for the compounds studied. Nevertheless, addition of OH to the central carbon atom of propene is slightly favored kinetically and thermodynamically (1 kcal mol^-1) over the others.     

A computational approach to the synthesis of dirithromycin

Dirithromycin is a macrolide antibiotic derived from erythromycin A. Dirithromycin is synthesized by the condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)-acetaldehyde. To gain insight into the synthesis, the condensation mechanism has been analyzed computationally by the AM1 method in the gas phase. First, the formation of the Schiff bases of dirithromycin and epidirithromycin from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)-acetaldehyde were modeled. Then, the tautomerization of the Schiff bases to dirithromycin and epidirithromycin were considered. Finally, the epimerization of the Schiff base of epidirithromycin to the Schiff base of dirithromycin was investigated. Our results show that, even though carbinolamine forms faster for epidirithromycin than the corresponding structure for dirithromycin, dirithromycin is the major product of the synthesis. Figure Synthesis of dirithromycin     

A computational approach to the polymerizabilities of diallylamines

Some selected diallylamine monomers have been studied with the semiempirical PM3 method as model compounds for N,N-dialkyl-N-2-(alkoxycarbonyl)allylammonium salts, in order to build up a quantitative and qualitative relationship between the experimental cyclopolymerizabilities of the monomers and calculated parameters such as charge, energy, geometrical features, bond orders, local softness values and HOMO-LUMO gaps. The charges on nitrogen, vinyl and allyl carbons, the activation barriers, the local softness values and the HOMO-LUMO gaps are found to represent the polymerizability trend of the monomers in general. Three-dimensional structures have been proposed for the reactants and their transition states by geometry optimizations with PM3.     

Modeling the deamidation of asparagine residues via succinimide intermediates

Density functional theory (B3LYP/6-31G*) has been used to study the cyclization, deamidation and hydrolysis reactions of a model peptide. Single point energy calculations with the polarized continuum model drastically lower the activation energy for cyclization in a basic medium. Confirmation of the experimental results that cyclization is slower than deamidation in acidic media and the opposite is true in basic media has enabled us to propose mechanisms for both processes.     

Electrostatic solvent effects on the conversion of substituted carbonyl oxides to dioxiranes

The effects of substituents (H, CH₃, CN, OCH₃, di-CH₃, and di-CN) on the conversion of carbonyl oxides to dioxiranes have been examined in the gas phase and in solution, with B3LYP/6-31G(d,p). The solvent has been modeled with the SCIPCM method. Optimizations in solution have shown that the geometry of carbonyl oxides and the reaction barriers for their conversion to dioxiranes depend on the characteristics of the substituents. The syn isomers of CH₃ and OCH₃ carbonyl oxides are more stable than their anti counterparts, whereas the conversion of anti substituted carbonyl oxides into dioxiranes is easier for all the substituents. Disubstitution favors the ring-opening reaction of dioxiranes.