ENANTIOSELECTIVITY IN ENZYME-CATALYZED ELECTRON-TRANSFER TO AND FROM PLANAR CHIRAL ORGANOMETALLIC COMPOUNDS

Asymmetric cyclopalladation of dimethylaminomethylferrocene in the pre sence of N-acetyl-(R)- or (S)-leucine afforded enantiomerically enrich ed palladacycles (S)- and (R)-[Pd{C5H3(CH2NMe2)FeC5H5}(mu-Cl)](2), res pectively. Carbonylation of each enantiomer followed by iodomethylatio n and reduction by sodium amalgam gave (S)- and (R)-2-methylferrocene carboxylic acid (1) with an optical purity of 80 and 93%, respectively . (S)- and (R)-1 readily undergo one-electron (1e) oxidation to form t he corresponding ferricenium cations by hydrogen peroxide, catalyzed b y horseradish peroxidase (HRP) and chloroperoxidase (CLP) from Caldari omyces fumago (25 degrees C, pH 5-8 and 2.75, respectively). In the ca se of HRP, the reaction is strictly first-order with respect to (S)- a nd (R)-1 (rate=k[HRP][1]), whereas Michaelis-Menten kinetics are obser ved for CLP. The strongly pH-dependent kinetic enantioselectivity is, however, only observed in the case of HRP. HRP-generated cations (S)-1 (-) and (R)-1(+) have been used to demonstrate that their enzymatic re duction by reduced glucose oxidase (GO) is also enantioselective; the (S)-1(-) enantiomer is more reactive than (R)-1(+) by a factor of 1.54 . The existence of the planar chiral enantioselectivity in the GO cata lysis was also confirmed by the cyclic voltammetry study of (S)-1 and (R)-1 in the presence of GO and beta-D-glucose with glassy carbon and pyrolytic graphite electrodes, The corresponding enantioselectivity fa ctors k(S)-1(+)/k(R)-1(+) are 1.7 and 1.6, respectively, Based on the known X-ray structural data for the active site of GO, it has been ten tatively suggested that the enantioselectivity originates from the hyd rophobic contact between the enzyme tyr-68 residue and the eta(5)-C5H5 ring of 1(+), and a hydrogen bond network formed by his-516 and/or hi s-559 residues and the carboxylic group of the ferrocene derivative, T he findings reported confirm the existence of enantioselective electro n transfer between oxidoreductases and organometallic compounds with a planar chirality. The lack of kinetic enantioselectivity may be a res ult of i) the incorrect rate-limiting step, ii) unfavorable pH region. and iii) the deficit of charged groups attached to ferrocenes.