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We propose and examine a comprehensive mechanism of the [(η 5 -C 5 H 5 )Rh]-catalyzed [2+2+2] cycloadditions of acetylene to benzene and of acetylene and acetonitrile to 2-methylpyridine, based on an extensive and detailed exploration of the potential energy surfaces using density functional theory. Both processes involve the formation of a coordinatively unsaturated 16-electron metallacycle, occurring after the replacement of the ancillary ligands L of the catalyst precursor of general formula [(η 5 -C 5 H 5 )-RhL 2 ] (typically L ) C 2 H 4 , CO, PH 3 or L 2 ) 1,5-cyclooctadiene) by two acetylene molecules. The facile coordination of a third acetylene molecule, and its subsequent addition to the π electron system of the rhodacycle, leads to the formation of an intermediate, which is characterized by a six-membered arene ring coordinated to the metal in η 4 fashion. The release of benzene occurs by stepwise addition of two acetylene molecules, which regenerates the catalyst. In the presence of acetonitrile, a nitrile molecule coordinates to the rhodacycle, and different stages are outlined for the process, leading to the eventual release of 2-methylpyridine. The steric and electronic effects of the π ligand coordinated to the metal are also included in our exploration by addressing the whole mechanism of the [(η 5 -C 9 H 7 )Rh]-catalyzed alkyne self-trimerization to benzene. The kinetic parameters, i.e., the energies in vacuum and in different solvents, and the geometries of the intermediates and of the transition states are analyzed in detail.

A valence-only ͑V͒ dipole moment surface ͑DMS͒ has been computed for water at the internally contracted multireference configuration interaction level using the extended atom-centered correlation-consistent Gaussian basis set aug-cc-pV6Z. Small corrections to these dipole values, resulting from core correlation ͑C͒ and relativistic ͑R͒ effects, have also been computed and added to the V surface. The resulting DMS surface is hence called CVR. Interestingly, the C and R corrections cancel out each other almost completely over the whole grid of points investigated. The ground-state CVR dipole of H 2 16 O is 1.8676 D. This value compares well with the best ab initio one determined in this study, 1.8539Ϯ 0.0013 D, which in turn agrees well with the measured ground-state dipole moment of water, 1.8546͑6͒ D. Line intensities computed with the help of the CVR DMS shows that the present DMS is highly similar to though slightly more accurate than the best previous DMS of water determined by Schwenke and Partridge ͓J. Chem. Phys. 113, 16 ͑2000͔͒. The influence of the precision of the rovibrational wave functions computed using different potential energy surfaces ͑PESs͒ has been investigated and proved to be small, due mostly to the small discrepancies between the best ab initio and empirical PESs of water. Several different measures to test the DMS of water are advanced. The seemingly most sensitive measure is the comparison between the ab initio line intensities and those measured by ultralong pathlength methods which are sensitive to very weak transitions.

Thioredoxins (Trx) are enzymes with a characteristic CXYC active-site motif that catalyze the reduction of disulfide bonds in other proteins. We have theoretically explored this reaction mechanism, both in the gas phase and in water, using density functional theory. The mechanism of disulfide reduction involves two consecutive thiol-disulfide exchange reactions, that is, nucleophilic substitutions at sulfur (S(N)2@S): first, by one Trx cysteine-thiolate group (Cys-32) at a sulfur atom of the disulfide substrate and, second, by the other Trx cysteine-thiolate group (the buried thiol of Cys-35) at the sulfur atom of the first Trx cysteine. We have investigated the intrinsic nature of such S(N)2@S substitution using the simple CH3S(-) + CH3SSCH3 model and how it is affected by solvation in aqueous solution. Next, we have examined how the behavior of the elementary S(N)2@S steps changes in the more realistic enzyme-substrate model CGPC + CH3SSCH3, which contains the active-site of Trx. In all model reactions, solvation turns the hypervalent trisulfide anion (i.e., the S(N)2@S transition species) from a stable complex into a transition state. Importantly, our analyses suggest that the deprotonation of the buried thiol (which is required before the latter can enter into the second S(N)2@S step) is done by the leaving group evolving from the first S(N)2@S step. Finally, molecular dynamics (MD) simulations, in the gas phase and in water, of CGPC, CGGC, and the corresponding wild-type Trx and P34G Trx show that the activity of the thioredoxin active-site motif (CXYC) is determined not only by the structural rigidity associated with the particular variable residues (XY) but also by the number of amide N-H groups. The latter are involved in the stabilization of the Cys-32 thiolate and thus affect the acidity and nucleophilicity of this residue.