Computational modeling of the enzymatic activity of B 12 -dependent enzymes requires a detailed understanding of the factors that influence the strength of the CoAC bond and the limits associated with a particular level of theory. To address this issue, a systematic analysis of the electronic and structural properties of coenzyme B 12 models has been performed to establish the performance of three different functionals including B3LYP, BP86, and revPBE. In particular the cobalt-carbon bond dissociation energies, axial bond lengths, and selected stretching frequencies have been analyzed in detail. Current analysis shows that widely used B3LYP functional significantly underestimates the strength of the CoAC bond while the nonhybrid BP86 functional produces very consistent results in comparison to experimental data. To explain such different performance of these functionals molecular orbital analysis associated with axial bonds has been performed to show differences in axial bonding provided by hybrid and nonhybrid functionals.

Density functional theory has been applied to the investigation of the reductive cleavage mechanism of methylcobalamin (MeCbl). In the reductive cleavage of MeCbl, the Co-C bond is cleaved homolytically, and formation of the anion radical ([MeCbl]*-) reduces the dissociation energy by approximately 50%. Such dissociation energy lowering in [MeCbl]*- arises from the involvement of two electronic states: the initial state, which is formed upon electron addition, has dominant pi*corrin character, but when the Co-C bond is stretched the unpaired electron moves to the sigma*Co-C state, and the final cleavage involves the three-electron (sigma)2(sigma*)1 bond. The pi*corrin-sigma*Co-C states crossing does not take place at the equilibrium geometry of [MeCbl]*- but only when the Co-C bond is stretched to 2.3 A. In contrast to the neutral cofactor, the most energetically efficient cleavage of the Co-C bond is from the base-off form. The analysis of thermodynamic and kinetic data provides a rationale as to why Co-C cleavage in reduced form requires prior departure of the axial base. Finally, the possible connection of present work to B12 enzymatic catalysis and the involvement of anion-radical-like [MeCbl]*- species in relevant methyl transfer reactions is discussed.

The geometric and electronic structures, as well as the thermodynamic properties of trivalent lanthanide hydrates {Ln(H(2)O)(8,9)(3+) and Ln(H(2)O)(8,9)(H(2)O)(12,14)(3+), Ln = La-Lu} have been examined using unrestricted density functional theory (UDFT), unrestricted Möller-Plesset perturbation theory (UMP2), and multiconfigurational self-consistent field methods (MCSCF). While Ln-hydrates with 2-5 unpaired f-electrons have some multiconfigurational character, the correlation energy lies within 5-7 kcal/mol across the period and for varying coordination numbers. As such DFT yields structural parameters and thermodynamic data quite close to experimental values. Both UDFT and UMP2 predict free energies of water addition to the Ln(H(2)O)(8)(3+) species to become less favorable across the period; however, it is a non-linear function of the surface charge density of the ion. UDFT further predicts that the symmetry of the metal-water bond lengths is sensitive to the specific f-electron configuration, presumably because of repulsive interactions between filled f-orbitals and water lone-pairs. Within the Ln(H(2)O)(8,9)(H(2)O)(12,14)(3+) clusters, interactions between solvation shells overrides this orbital effect, increasing the accuracy of the geometric parameters and calculated vibrational frequencies. Calculated atomic charges indicate that the water ligands each donate 0.1 to 0.2 electrons to the Ln(III) metals, with increasing electron donation across the period. Significant polarization and charge transfer between solvation shells is also observed. The relationship between empirical effective charges and calculated atomic charges is discussed with suggestions for reconciling the trends across the period.

The ForceFit program package has been developed for fitting classical force field parameters based upon a force matching algorithm to quantum mechanical gradients of configurations that span the potential energy surface of the system. The program, which runs under UNIX and is written in C++, is an easy-to-use, nonproprietary platform that enables gradient fitting of a wide variety of functional force field forms to quantum mechanical information obtained from an array of common electronic structure codes. All aspects of the fitting process are run from a graphical user interface, from the parsing of quantum mechanical data, assembling of a potential energy surface database, setting the force field, and variables to be optimized, choosing a molecular mechanics code for comparison to the reference data, and finally, the initiation of a least squares minimization algorithm. Furthermore, the code is based on a modular templated code design that enables the facile addition of new functionality to the program.