title: Studies on the mechanism of aldehyde oxidase and xanthine oxidase.
abstract: DFT calculations support a concerted mechanism for xanthine oxidase and aldehyde oxidase hydride displacement from the sp(2) carbon of 6-substituted 4-quinazolinones. The variations in transition state structure show that C-O bond formation is nearly complete in the transition state and the transition state changes are anti-Hammond with the C-H and C-O bond lengths being more product-like for the faster reactions. The C-O bond length in the transition state is around 90% formed. However, the C-H bond is only about 80% broken. This leads to a very tetrahedral transition state with an O-C-N angle of 109 degrees. Thus, while the mechanism is concerted, the antibonding orbital of the C-H bond that is broken is not directly attacked by the nucleophile and instead hydride displacement occurs after almost complete tetrahedral transition state formation. In support of this the C=N bond is lengthened in the transition state indicating that attack on the electrophilic carbon occurs by addition to the C=N bond with negative charge increasing on the nitrogen. Differences in experimental reaction rates are accurately reproduced by these calculations and tend to support this mechanism.
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington 99164, USA.
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Alfaro
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Jones
mesh_terms: D042931:Aldehyde Oxidase / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods*; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D052999:Quinazolinones / Q000737:chemistry; D013816:Thermodynamics; D014969:Xanthine Oxidase / Q000737:chemistry*
chemical_list: D052999:Quinazolinones; D014969:Xanthine Oxidase; D042931:Aldehyde Oxidase; D009584:Nitrogen; D010100:Oxygen