Vanadate, vanadium compounds and selected other transition metal complexes are known inhibitors for phosphorylases and phosphatases.1-7 The hydrolysis of phosphate esters and phosphate anhydrides can follow an associative five-coordinate transition state geometry of the general formula VO4X, which for the phosphate systems is generally considered to be trigonal bipyramidal.  A range of vanadium complexes and other transition metal complexes have been shown to inhibit phosphatases, including a range of metal complexes, some which have been found to keep the ligand associated with the metal ion as the enzymes are inhibited. Five coordinate geometries for transition metal complexes, however, are often found to be between the idealized square planar and trigonal bipyramidal geometries.  Other coordination geometries and other metal complexes have also been characterized as inhibitors, suggesting that the structural features are not the sole reason for the observed potency in the complexes. Many model complexes have been synthesized to model the VO4X geometry.  Here we present an analysis of the structural parameters from X-ray crystallography of five-coordinate vanadium complexes with a VO4X core geometry (X = C, N, O, Cl, F, S, N, O) and compare this to the vanadium-based inhibitors crystalized inside various phosphorylases.  We will compare each structure to the ideal transition state geometry for hydrolysis, to evaluate the importance of the structural perturbation in small molecule structures and inside a protein, respectively.  We expect that these studies will provide some information about the nature of the coordination geometry and possible why vanadium and other transition metal complexes are excellent transition state analogs.References  1 Cantley, Jr., L. C.; Resh, M. D.; Guidotti, G. Nature 1978 , 272, 552-554.2. Posner, B. I.; Faure, R.; Burgess, J. W.; Bevan, A. P.; Lachance, D.; Zhang-Sun, G.; Fantus, I. G.; Ng, J. B.; Hall, D. A.; Lum, B. S. J. Biol. Chem. 1994,  269, 4596-4604.3. Crans, D.C.; Keramidas, A.D.; Drouza,C. Phosphorus, Sulphur, and Silicon 1996 , 109-110, 245-248.4. McLauchlan, C.C.; Hooker, J.D.; Jones, M.A.; Dymon, Z.; Backhus, E.A.; Greiner, B.A.; Dorner, N.A.; Youkhana, M.A.; Manus, L.M. J. Inorg. Biochem. 2010 , 104, 274-281.5.  Lu, L.; Yue, J.; Yuan, C.; Zhu, M.; Han, H.; Liu, Z.; Guo, M. J. Inorg. Biochem. 2011 , 105, 1323-1328.6. Lu, L.; Gao, X.; Zhu, M.; Wang, S.; Wu, Q.; Xing, S.; Fu, X.; Liu, Z.; Guo, M. BioMetals 2012,  25 (3), 599-610.7. Yang, X.-G.; Wang, K. In Biomedical Inorganic Polymers, M�ller, W. E. G.; Wang, X.; Schr�der, H. C., Eds. Springer Berlin Heidelberg: 2013; Vol. 54, pp 1-18.

Phosphorylase and phosphatase inhibition by transition metal inhibitors: Are trigonal bipyramidal complexes better inhibitors than square planar complexes?

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.