Hydrotris borate, zinc complexes

Pyridyl functionalized tris(pyrazolyl)borate ligands show some interesting properties including the formation of polynuclear zinc complexes.23,1 Some of these contain extensive H bonding and have potential as models for multinuclear zinc enzymes such as phospholipase C or PI nuclease.235 A bis-ligand complex of the hydrotris(5-methyl-3-(3-pyridyl)pyrazolyl)borate ligand (23) shows octahedral coordination of all six pyrazole nitrogen donors despite the steric bulk. 

Trispyrazolylborates are models for tris-histidine active sites in zinc enzymes, e.g., the matrix metalloproteinases involved in breakdown of extracellular matrices. Inhibition of these metalloproteinases may prove valuable in the treatment of, inter alios, cancer and arthritis, so efforts are being made to find appropriate ligands to block the zinc active site. The search has recently moved on from hydroxamates to hydroxypyridinones - l-hydroxy-2-pyridinone is a cyclic analogue of hydroxamic acid. As reported in Section II.B.2 earlier, hydroxypyridinones form stable five-coordinate complexes on reaction with hydrotris(3,5-phenylmethylpyrazolyl)borate zinc hydroxide. Modeling studies suggest that hydroxypyridinonate ligands should be able to access the active site in the enzyme with ease (110). 

Reaction of the hydrotris(pyrazolyl)borate zinc alkoxide complex [TpCum,Me]Zn-OiPr with the NAD + mimic A-benzylnicotinamide chloride in isopropanol yielded a... 

Synthesis of functional models of carbonic anhydrase has been attempted with the isolation of an initial mononuclear zinc hydroxide complex with the ligand hydrotris(3-t-butyl-5-methyl-pyrazolyl)borate. Vahrenkamp and co-workers demonstrate the functional as well as the structural analogy to the enzyme carbonic anhydrase. A reversible uptake of carbon dioxide was observed, although the unstable bicarbonate complex rapidly forms a dinuclear bridged complex. In addition, coordinated carbonate esters have been formed and hydrolyzed, and inhibition by small ions noted.462 A number of related complexes are discussed in the earlier Section 6.8.4. 

Deprotonation of the zinc alcohol complexes shown in Fig. 12 to produce zinc alkoxide species has not been reported. Instead, mononuclear, tetrahedral zinc alkoxide complexes, supported by hydrotris(pyrazolyl)borate ligands, ([TpBut,Me or Tpph,Me, Scheme 8), have been generated via treatment of zinc hydride precursor complexes with aliphatic alcohols.68-70 A zinc ethoxide complex, [TpBut,Me]Zn-OEt, was also prepared via decarboxylation of the ethyl carbonate complex, [TpBut,Me]Zn-0C(0)0Et.49 X-ray crystallographic studies of [Tpph Me] Zn-OCH3 and [TpBut,Me]Zn-OEt revealed Zn-O bond lengths of 1.874(2) and 1.826(2) A, respectively.68,71 These bond distances are 0.1 A shorter than found for the alcohol complexes shown in Fig. 12. 

The new ligand hydrotris(3-(2/-furyl)-5-methylpyrazolyl)borate TpFl, Me reacts with zinc salts forming complexes [ZnX(TpFu,Me)] (X = Cl, Br, I, NCS, CH3COO, CF3COO). When zinc(II) perchlorate was employed, however, [Zn(TpFu,Me)2] afforded preferably. Careful control of the reaction conditions allows the formation of the enzyme model [Zn-OH(TpFu Me)], which mimics carbonic... 

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