Modeling the active sites of metalloenzymes with thiolate coordination

Abstract

Nitrile Hydratase (NHase) is a bacterial enzyme which catalyzes the hydrolysis of organic nitriles to their corresponding amides. The active site of NHase contains Fe (III) or Co(III) ions in an unusual coordination sphere containing 2 amide N atoms and three S donors. The research described herein is an attempt to model this active site using two different model systems: one that generates metal-coordinated imines, and one that generates metal-coordinated amides. Using 2,2’-dithiodibenzaldehyde and derivatives of 2,2’-dithiodisalicylic acid as reactants, several new and interesting metal coordinated imine and metal coordinated amide complexes have been synthesized. The synthesis and crystallization of several new organic and ligand species is discussed as well. The synthesis of a Co complex that resembles the active site of NHase is reported herein, along with several other new organometallic species. Also, two projects using computational chemistry are reported: one modeling trispyrazolylborate (Tp) complexes of iron and copper, and one modeling iron, manganese, and copper complexes of pentadentate imine/phenolate ligands. Complexes of Tp ligands with relatively bulky substituents in the 3-position are subject to isomerization through a borotropic shift. Computational chemistry has shed light on the energetics behind the borotropic shift. Calculations on the CO stretching frequency of several different TpCu(I)CO complexes have been carried out in an effort to match experimental data and generate predictive values for several other species not yet synthesized. This stretching frequency can generally be directly related to the electron withdrawing/donating character of the Tp ligand attached to the metal center. Pentdentate imine/phenolate ligands can coordinate to transition metals in a number of isomers. Computational chemistry has been used to shed light on the structural preferences of the iron, manganese, and copper species. These calculations were able to match the experimental data for crystallographically characterized species, and the metal complexes were shown to have specific structural preferences depending on the identity of the metal used.