MECHANISM OF LACTIC-ACID FORMATION CATALYZED BY A MACROCYCLIC CHROMIUM(III) COMPLEX - A COMPARISON WITH THE GLYOXALASE-I ENZYME

The transformation of methylglyoxal and of 1,3-dihydroxyacetone and glyceraldehyde into lactic acid can be catalyzed by metal complexes, and chromium(III) complexes of the macrocyclic 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane tetraamine ligand, with two coordination sites in the cis position available for substrate coordination, are reasonably effective for the production of coordinated lactate. The detailed stoichiometry of this process, including stereoselectivity studies using optically active complexes, has been investigated by a combination of H-1 and C-13 NMR, ion-exchange chromatography, deuterium labelling studies, and a single-crystal structure determination of one of the diastereomers formed from 1,3-dihydroxyacetone: cis-[Cr(cycb)(C3H4O3)]ClO4, which crystallizes in the orthorhombic space group Fdd2 with a = 31.663(15), b = 9.650(5), c = 15.848(7) Angstrom and Z = 8. The suggested mechanism of the methylglyoxal transformation process involves bidentate substrate coordination followed by protonation, dehydration and carbocation formation, intramolecular 1,2-hydride shift, and deprotonation. This mechanism is discussed in relation to the zinc(II)-containing glyoxalase I enzyme, which performs an analogous substrate transformation in natural systems. The transformations of 1,3-dihydroxyacetone and glyceraldehyde are stoichiometrically more complicated, and result for both substrates in coordinated lactate in which one hydrogen atom in the methyl group originates from solvent water.