COMBINED QUANTUM-MECHANICAL MOLECULAR MECHANICS MODELING FOR LARGE ORGANOMETALLIC AND METALLOBIOCHEMICAL SYSTEMS - APPLICATION TO VITAMIN-B-12

For modeling targe organometallic and metallobiochemical systems where neither quantum mechanical (QM) nor molecular mechanics (MM) calculat ions, applied separately, can solve the problem, we worked out a metho d of combined QM/MM calculations with an electronically transparent in terface which allows charge transfers between the quantum and classica l fragments. The necessary conditions of fragmentation, interfragment self-consistency, and QM-MM continuity are formulated and satisfied by cutting the system on a 2s2p atom (border atom) that participates wit h its hybridized orbitals in both fragments and does not serve as a pi bridge between them, and using a special iferative procedure of doubl e (intrafragment and interfragment) self-consistent (DSC) calculations which realizes the electronically transparent interface and charge tr ansfers between the fragments. The method is implemented in a package of computer programs and applied successfully to modeling a series of large metallobiochemical systems. In developing the previous results o btained for picket-fence iron porphyrin, a more complicated system, Co beta-Cyanoimidazolylcobamide (Vitamin B-12) is reported here. The sys tem with 180 atoms is divided into eight fragments; the central (cobal t) fragment is treated by QM, while the others and the system as a who le are optimized by MM. The geometry obtained is in good agreement wit h the experimental data. The DSC procedure reveals significant charge transfers between the fragments.