title: Do Fukui function maxima relate to sites of metabolism? A critical case study.
abstract: The usefulness of local reactivity descriptors for understanding drug metabolism is investigated. Electrophilic Fukui functions are calculated for 18 drugs and 11 agrochemicals and their relation to experimentally observed metabolites is discussed. Maxima of the Fukui functions correspond to major sites of metabolic attack in many examples, facilitating a posteriori understanding of experimental findings. In the second part of the paper, the nature of the electrophilic oxidant species in cytochromes, called "Compound I" (Cpd I), is investigated within the Fukui framework. Nucleophilic Fukui functions are calculated involving the relevant spin states of Cpd I, allowing a more qualitative, intuitive understanding of its reactivity.
authors.affiliation: Bayer CropScience, Research/Scientific Computing, Agricultural Centre Monheim, D-40789 Monheim, Germany. michael.beck@bayercropscience.com
authors.forename: Michael E
authors.initials: ME
authors.lastname: Beck
mesh_terms: D016573:Agrochemicals / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D004583:Electrons; D006900:Hydroxylation; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D016573:Agrochemicals; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System