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 gl yceraldehyde into lactic acid can be catalyzed by metal complexes, and chromium(III) complexes of the macrocyclic 12,14-hexamethyl-1,4,8,11- tetraazacyclotetradecane tetraamine ligand, with two coordination site s in the cis position available for substrate coordination, are reason ably effective for the production of coordinated lactate. The detailed stoichiometry of this process, including stereoselectivity studies us ing 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 d iastereomers formed from 1,3-dihydroxyacetone: cis-[Cr(cycb)(C3H4O3)]C lO4, 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 sugges ted mechanism of the methylglyoxal transformation process involves bid entate substrate coordination followed by protonation, dehydration and carbocation formation, intramolecular 1,2-hydride shift, and deproton ation. This mechanism is discussed in relation to the zinc(II)-contain ing glyoxalase I enzyme, which performs an analogous substrate transfo rmation in natural systems. The transformations of 1,3-dihydroxyaceton e and glyceraldehyde are stoichiometrically more complicated, and resu lt for both substrates in coordinated lactate in which one hydrogen at om in the methyl group originates from solvent water.