Modeling the spin-dependent properties of open-shell Fe(III)-containing systems: towards a computational description of nitrile hydratase

The role of metalloenzyme structure in modulating transition metal reactivity is often difficult to assess using experimental approaches. For example, the structural features of the protein that underpin the low-spin preference of the non-heme Fe(III) in nitrile hydratase (NHase), and the importance of this spin-state to the catalytic mechanism, are unlikely to be determined solely by site-directed mutagenesis and/or characterization of model Fe(III) complexes. Density functional theory (DFT) calculations represent a method for determining the electronic structure of metal centers in enzymes, investigating the properties of hypothetical intermediates in the reaction mechanism, and probing the importance of specific protein residues in controlling metal chemistry. In particular, DFT methods are becoming widely used for delineating effects associated with the spin-dependent reactivity of transition metal complexes. The application of DFT calculations to the study of open-shell systems is, however, fraught with difficulties in both the technical aspects of performing such calculations and the interpretation of results. So as to illustrate these issues for the non-expert, we provide a brief overview of the theoretical basis, performance and limitations of recent DFT studies on a series of Fe(III) complexes that are models for the unusual non-heme Fe(III) center in NHase. (C) 2002 Elsevier Science B.V. All rights reserved.