ABSTRACT:The topological analysis of the electron localization function (ELF) provides a convenient mathematical framework enabling an unambiguous characterization of bonds and more particularly in terms of bond types. In this contribution, we present an overview of the applications of this approach to biological and biomimetic systems.

Sulfite oxidase is a mononuclear molybdenum enzyme that oxidises sulfite to sulfate in many organisms, including man. Three different reaction mechanisms have been suggested, based on experimental and computational studies. Here, we study all three with combined quantum mechanical (QM) and molecular mechanical (QM/MM) methods, including calculations with large basis sets, very large QM regions (803 atoms) and QM/MM free-energy perturbations. Our results show that the enzyme is set up to follow a mechanism in which the sulfur atom of the sulfite substrate reacts directly with the equatorial oxo ligand of the Mo ion, forming a Mo-bound sulfate product, which dissociates in the second step. The first step is rate limiting, with a barrier of 39–49 kJ/mol. The low barrier is obtained by an intricate hydrogen-bond network around the substrate, which is preserved during the reaction. This network favours the deprotonated substrate and disfavours the other two reaction mechanisms. We have studied the reaction with both an oxidised and a reduced form of the molybdopterin ligand and quantum-refinement calculations indicate that it is in the normal reduced tetrahydro form in this protein.

Quantum chemistry computations have been used to investigate the possibility of a Pb(2+)/Ca(2+) substitution in the three calcium sites of the synaptotagmin enzyme. Provided explicit cation solvation is taken into account, it is shown that the substitution is energetically feasible and induces a strong reorganization of the Ca(2+)-coordinating sites, which may preclude the enzyme for any efficient role when lead poisoning occurs.