Life Science Applications of Fukui Functions

摘要

24.1 Introduction Understanding the metabolic fate and behavior of a drug or agro-chemical is of crucial importance for the development of such chemicals, as metabolism in conjunction with absorption, distribution, and excretion determines bio-availability, effect, and adverse reactions as well as toxicology of a drug or agro-chemical. Many computational approaches exist for understanding metabolism and/or toxicology a posteriori as well as prospectively. These typically use statistical modeling based on (often topological) molecular descriptors [1--4]. Cytochrome P450 enzymes play an important role in metabolism, as most oxidative metabolic reactions are mediated by these enzymes (see [5] and [6] for reviews on experimental and theoretical work). With the availability of X-ray structures of cytochrome P450 enzymes, 3D-QSAR models have been developed (for example [7-10]). Another approach is ligand based, predicting the preferred sites of hydrogen abstraction by quantum chemistry (for example [10-12]).