David T. Puerta

[(TpMe,Ph)2Zn2(H3O2)]ClO4: a new H3O2 species relevant to zinc proteinases

Abstract A dinuclear zinc(II) complex has been isolated from the reaction of Zn(ClO4)2 with TpMe,Ph (TpMe,Ph=hydrotris(5,3-methylphenylpyrazolyl)borate). We have characterized this species by a high quality X-ray crystal structure (R1=3.83%), and found it to contain a H3O2 bridge. We discuss the relevance of this structure in terms of hydrolytic zinc enzymes that utilize hydrogen-bond stabilized water nucleophiles to perform peptide bond cleavage.

Synthesis and structure of the hexameric, dodecanuclear metallamacrocycle [(5-methyl-3-phenylpyrazole)2Zn2(OCH2CH2S)]6Electronic supplementary information (ESI) available: crystal structure diagrams. See http://www.rsc.org/suppdata/cc/b3/b300453h/

A metallamacrocycle containing twelve Zn2+ ions, making it the largest member of a family of pyrazole-bridged cyclic metal clusters, has been synthesized and structurally characterized from the reaction of [Zn(ClO4)2] with 5-methyl-3-phenylpyrazole, 2-mercaptoethanol, and NaOH.

Synthesis, structure and spectroscopy of new thiopyrone and hydroxypyridinethione transition-metal complexes

The coordination chemistry of several O,S mixed donor ligands, namely thiopyrone and hydroxypyridinethione chelators, with a variety of middle and late first-row transition-metal ions is described. Complexes of 3-hydroxy-2-methyl-4-thiopyrone (thiomaltol) with cobalt(II), copper(II) and zinc(II); 3-hydroxy-1,2-dimethyl-4(1H)-pyridinethione (3,4-HOPTO) with iron(III), nickel(II), copper(II) and zinc(II); and 3-hydroxy-1-methyl-2(1H)-pyridinethione (3,2-HOPTO) with iron(III), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. The structures, absorbance spectroscopy, cyclic voltammetry and superconducting quantum interferometer device (SQUID) measurements of selected metal complexes, as well as ligand protonation constants, are reported. Most of the metal complexes show coordination geometries indicative of a strong trans influence by the O,S chelators. The data presented herein provide the most detailed study of the transition-metal coordination chemistry of both thiopyrone and hydroxypyridinethione O,S donor ligands to date, and provide the basis for the investigation of these ligands in realm of biological inorganic chemistry.

Inhibition of the Lymphoid Tyrosine Phosphatase: The Effect of Zinc(II) ions and Chelating Ligand Fragments on Enzymatic Activity

A 96-member chelator fragment library (CFL-1.1) was screened to identify inhibitors of the lymphoid tyrosine phosphatase in the absence and presence of zinc acetate. Fragments that inhibit LYP activity more potently in the presence of zinc, fragments that rescue LYP activity in the presence of inhibitory concentrations of zinc, and fragments that inhibit LYP activity independent of zinc concentration were identified. Of these, 1,2-dihydroxynaphthalene was the most potent inhibitor with an IC50 value of 2.52±0.06 μM after 2 h of incubation. LYP inhibition by 1,2-dihydroxynaphthalene was very similar to inhibition by 1,2-naphthoquinone (IC50=1.10±0.03 µM), indicating that the oxidized quinone species is likely the active inhibitor. The inhibition was time-dependent, consistent with covalent modification of the enzyme.