Hydroxamate-Bridged Dinuclear Nickel Complexes as Models for Urease Inhibition

Abstract

Facile reaction of the model urease complex [Ni2(OAc)3(urea)(tmen)2][OTf] (A) with acetohydroxamic acid (AHA) gives the monobridged hydroxamate complex (I) [Ni2(OAc)2(AA)(urea)(tmen)2][OTf] with a Ni−Ni distance of 3.434(1) Å compared to that of 3.5 Å in urease (OAc, CH3COO-; tmen, N,N,N‘,N‘-tetramethylethylenediamine; OTf, CF3SO3; AHA, acetohydroxamic acid; AA, acetohydroxamate anion). I is a close model of one proposed mode of urease inhibition by hydroxamic acids, recently observed in the acetohydroxamate-inhibited C319A variant of Klebsiella aerogenes urease. Reaction of [Ni2(OH2)(OAc)4(tmen)2] (B) with AHA gives the dibridged hydroxamate complex (II) [Ni2(OAc)(AA)2(tmen)2][OAc] with a Ni−Ni distance of 3.005(1) Å. Infrared spectroscopic studies provide evidence for the bridging acetate groups undergoing carboxylate shifts thereby assisting replacement of acetate by hydroxamate. Both I and II show ferromagnetic exchange coupling.

Hydroxamic Acids − An Intriguing Family of Enzyme Inhibitors and Biomedical Ligands

“…Molecular structure of [Ni 7 (2-dmAphaH Ϫ1 ) 2 (2-dmApha) 8 with salicylhydroxamic acid). [77] The double hydroxamate bridging of Ni1ϪNi2 and Ni6ϪNi7 by ligands A and B and F and H, respectively, is similar to that observed in some dinickel model systems for urease inhibition, [28,78] which also contain two hydroxamate bridges and for which inter nickel distances of 3.016 and 3.005 Å have been reported. These values are very similar to the values of 2.958(3) and 2.944(2) Å in the present case.…”

Mandelohydroxamic Acid as Ligand for Copper(II) 15‐Metallacrown‐5 Lanthanide(III) and Copper(II) 15‐Metallacrown‐5 Uranyl Complexes

“…[35] The ESI-MS spectra did not show any evidence for the presence of metallacrown species, so it is likely that the complex formed in solution is the mononuclear Cu(MHA) 2 complex in which the coordination to copper() occurs by the deprotonated hydroxamate and carbonyl oxygen donors. This finding is in sharp contrast to the analogous reaction between α-aminohydroxamic acids and copper(), in which exclusively the [Cu 5 (α-aha) 4 ] 2+ (aha = aminohydroxamic acid) 12-metallacrown-4 complex is formed in solution. [12] In that metallacrown complex the coordination of aminohydroxamic acid occurs also by the deprotonated hydroxamate and carbonyl oxygen atoms; however, the second five-membered ring is also formed through the coordination of hydroximato nitrogen and amino nitrogen to copper().…”

“…[2] In recent years it has become evident that these weak acids possess other types of biological activities. [3][4][5][6][7] Their role as potent and selective inhibitors of a range of metalloenzymes has been of special interest to inorganic chemists, because the biological activities of hydroxamic acids have been mainly attributed to their complexing properties toward transition-metal ions. [8] As a result, the transition-metal complexes of hydroxamic acids are frequently used as bioinorganic model compounds to investigate the enzymatic interactions and binding properties of these bioligands.…”

Electrochemical oxidation of salicylhydroxamic acid on Pt electrode

“…These compounds possess antibacterial and antifungal properties and are selective inhibitors for a variety of enzymes such as peroxidases [2,3], ureases [4], matrix metalloproteases [5,6], hydrolases [7], and peptide deformylases [8]. This makes hydroxamic acids ideal candidates for drug design.…”