Molecular interpretation of the structure, dynamics and reactivity of metal complexes and enzymes

This thesis focuses on the development of molecular mechanical (MM) methods and force fields to model hyper-valent molecules, transition metal complexes and ultimately, the study of enzymatic reactions. Metal specialized VALBOND force fields are developed for transition metals Cu and Fe containing metal complexes and applied to study the structural dynamics of aqueous [Fe(bpy)3] complexe and the solvation shell around them. In particular, structural rearrangement of solvation shell around the metal complexes during the electronic excitation/redox and spin cross over process were investigated in detail using the VALBOND method. Over the last 30 years, with the advent of ultrafast spectroscopy, particularly time-resolved X-ray absorption spectroscopy (XANES), it is possible to capture the sub-picosecond solvation dynamics around metal ions, providing a basis not only to validate our model but also complementing experimental findings. Specifically, this is done for the Cu ion with bioactive ligands eg. imidazole, i.e the [Cu(Imd)4]2+ complex, where control of hydration around the metal center was studied thoroughly and it is observed that the intra-molecular degrees of freedom i.e planarity in the Cu-Imd plane controls the hydration around the Cu center. A new Multi-State VALBOND (MS-VALBOND) method was developed for modeling transition metal-containing and hypervalent molecules. This approach is particularly suited for molecules with unusual shapes and systems that need to be described by a superposition of resonance structures, each of which satisfies the octet rule. The implementation is based on the original VALBOND force field and allows smooth switching between resonance structures, each of which can be characterized by its own force field,including varying charge distributions, and coupling terms between the states. Successful implementation of MS-VALBOND in one of the most popular molecular dynamics MD packages CHARMM was tested using a hypervalent molecule ClF3, the metal complex cisplatin and the SN2 reaction BrMe + Cl- ---> Br- + MeCl in aqueous solution. Finally, an enzymatic reaction the nitric oxide dioxygenation in truncated hemoglobin (TrHbN) and its active site mutant Y33A was explored using advanced multi-surface adiabatic reactive molecular dynamics (MS-ARMD). The ligand exchange reaction, FeNO+O2 ---> FeO2 + NO (starting from a HbNO state), which is the very first step of the NO3- formation was studied and found to be the rate determining step. The computed kinetics agrees very well with experiment