Enantioselectivity in Enzyme-Catalyzed Electron Transfer to and from Planar Chiral Organometallic Compounds

Abstract

Asymmetric cyclopalladation of dimethylaminomethylferrocene in the presence of N-acetyl-(R)- or (S)- leucine afforded enantiomerically en- riched palladacycles (S)- and (R)- (Pd{C5H3(CH2NMe2)FeC5H5}(m-Cl))2, respectively. Carbonylation of each enantiomer followed by iodomethyla- tion 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 the corresponding ferricenium cations by hydrogen perox- ide, catalyzed by horseradish peroxidase (HRP) and chloroperoxidase (CLP) from Caldariomyces fumago (258C, pH 5 - 8 and 2.75, respectively). In the case of HRP, the reaction is strictly first- order with respect to (S)- and (R)-1 (ratea k(HRP)(1)), whereas Michae- lis - Menten kinetics are observed for CLP. The strongly pH-dependent kinetic enantioselectivity is, however, only ob- served in the case of HRP. HRP-gener- ated cations (S)-1 a and (R)-1 a have been used to demonstrate that their enzymat- ic reduction by reduced glucose oxidase (GO) is also enantioselective; the (S)-1 a enantiomer is more reactive than (R)-1 a by a factor of 1.54. The existence of the planar chiral enantioselectivity in the GO catalysis was also confirmed by the cyclic voltammetry study of (S)-1 and (R)-1 in the presence of GO and b-d- glucose with glassy carbon and pyrolytic graphite electrodes. The corresponding enantioselectivity factors k(S)-1 a /k(R)- 1 a are 1.7 and 1.6, respectively. Based on the known X-ray structural data for the active site of GO, it has been tentatively suggested that the enantioselectivity originates from the hydrophobic contact between the enzyme tyr-68 residue and the h 5 -C5H5 ring of 1 a , and a hydrogen bond network formed by his-516 and/or his-559 residues and the carboxylic group of the ferrocene derivative. The findings reported confirm the existence of enantioselective electron transfer be- tween oxidoreductases and organome- tallic compounds with a planar chirality. The lack of kinetic enantioselectivity may be a result of i) the incorrect rate- limiting step, ii) unfavorable pH region, and iii) the deficit of charged groups attached to ferrocenes.