title: Alkaline phosphatase inhibition by vanadyl-beta-diketone complexes: electron density effects.
abstract: A series of systematically modified vanadyl-beta-diketone complexes, VO(beta-diketone)(2), bearing substituent groups with different electron inductive properties were synthesized and evaluated as inhibitors against calf-intestine alkaline phosphatase (APase). A combination of biochemical and quantum mechanical techniques were employed to identify structure-activity relationships relevant for rational design of phosphatase inhibitors. Kinetic parameters and activation free energy, enthalpy, and entropy for calf-intestine APase-catalyzed dephosphorylation of para-nitrophenylphosphate were also determined along with the inhibition constants (K(i)) for the VO(beta-diketone)(2) complexes. Increased positive charge on the vanadyl group increases the inhibition potency of the complex while the absence of an available coordination site on the complex decreases its inhibition potency. These findings correlate well with the results of ab initio electron density calculations for the complexes.
authors.affiliation: Department of Chemistry, Loyola University Chicago, Chicago, IL, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Ziegler
authors.forename: Jan
authors.initials: J
authors.lastname: Florian
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ballicora
authors.forename: Albert W
authors.initials: AW
authors.lastname: Herlinger
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D004583:Electrons; D007659:Ketones / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014638:Vanadates / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D007659:Ketones; D014638:Vanadates; D000469:Alkaline Phosphatase