Influence of Water on the Oxidation of Dimethyl Sulfide by the ^·OH Radical

Oxidative stress of sulfur-containing biological molecules in aqueous environments may lead to the formation of adduct intermediates that are too short-lived to be experimentally detectable. In this study we have modeled the simplest of such oxidative reactions: the attack of dimethyl sulfide (DMS) by a hydroxyl radical (^·OH) to form a radical adduct, whose subsequent heterolytic dissociation leads to a radical cation (DMS⁺) that is important for further reactions. We have modeled the aqueous environment with a limited number of discrete water molecules, selected after an original multistep procedure, and further embedded in a polarizable continuum model, to observe the impact of the water configuration on the heterolytic dissociation of the radical adduct. Molecular dynamics and quantum chemical methods (DFT, MP2, and CCSD) were used to elucidate the lowest energy structures resulting from the ^·OH attack on DMS. Subsequent high level <i>ab initio</i> valence bond (BOVB) calculations revealed the possibility for the occurrence of subsequent heterolytic dissociation

Multicenter Bonding in Ditetracyanoethylene Dianion: A Simple Aromatic Picture in Terms of Three-Electron Bonds

The nature of the multicenter, long bond in ditetracyanoethylene dianion complex [TCNE]₂^2– is elucidated using high level <i>ab initio</i> Valence Bond (VB) theory coupled with Quantum Monte Carlo (QMC) methods. This dimer is the prototype of the general family of pancake-bonded dimers with large interplanar separations. Quantitative results obtained with a compact wave function in terms of only six VB structures match the reference CCSD­(T) bonding energies. Analysis of the VB wave function shows that the weights of the VB structures are not compatible with a covalent bond between the π* orbitals of the fragments. On the other hand, these weights are consistent with a simple picture in terms of two resonating bonding schemes, one displaying a pair of interfragment three-electron σ bonds and the other displaying intrafragment three-electron π bonds. This simple picture explains at once (1) the long interfragment bond length, which is independent of the countercations but typical of three-electron (3-e) CC σ bonds, (2) the interfragment orbital overlaps which are very close to the theoretical optimal overlap of 1/6 for a 3-e σ bond, and (3) the unusual importance of dynamic correlation, which is precisely the main bonding component of 3-e bonds. Moreover, it is shown that the [TCNE]₂^2– system is topologically equivalent to the square C₄H₄^2– dianion, a well-established aromatic system. To better understand the role of the cyano substituents, the unsubstituted diethylenic Na⁺₂[C₂H₄]₂^2– complex is studied and shown to be only metastable and topologically equivalent to a rectangular C₄H₄^2– dianion, devoid of aromaticity

Coupled Valence-Bond State Molecular Dynamics Description of an Enzyme-Catalyzed Reaction in a Non-Aqueous Organic Solvent

Enzymes are widely used in nonaqueous solvents to catalyze non-natural reactions. While experimental measurements showed that the solvent nature has a strong effect on the reaction kinetics, the molecular details of the catalytic mechanism in nonaqueous solvents have remained largely elusive. Here we study the transesterification reaction catalyzed by the paradigm subtilisin Carlsberg serine protease in an organic apolar solvent. The rate-limiting acylation step involves a proton transfer between active-site residues and the nucleophilic attack of the substrate to form a tetrahedral intermediate. We design the first coupled valence-bond state model that simultaneously describes both reactions in the enzymatic active site. We develop a new systematic procedure to parametrize this model on high-level <i>ab initio</i> QM/MM free energy calculations that account for the molecular details of the active site and for both substrate and protein conformational fluctuations. Our calculations show that the reaction energy barrier changes dramatically with the solvent and protein conformational fluctuations. We find that the mechanism of the tetrahedral intermediate formation during the acylation step is similar to that determined under aqueous conditions, and that the proton transfer and nucleophilic attack reactions occur concertedly. We identify the reaction coordinate to be mostly due to the rearrangement of some residual water molecules close to the active site