Chiral Selectivity in Inter-reactant Recognition and Electron Transfer of the Oxidation of Horse Heart Cytochrome c by Trioxalatocobaltate(III)

Outer-sphere electron transfer (ET) between optically active transition-metal complexes and either other transition-metal complexes or metalloproteins is a prototype reaction for kinetic chirality. Chirality as the ratio between bimolecular rate constants of two enantiomers mostly amounts to 1.05-1.2 with either the Λ or Δ form the more reactive, but the origin of chirality in ET parameters such as work terms, electronic transmission coefficient, and nuclear reorganization free energy has not been addressed. We report a study of ET between the Λ-/Δ-[Co(Ox)3](3-) pair (Ox = oxalate) and horse heart cytochrome c (cyt c). This choice is prompted by strong ion-pair formation that enables separation into inter-reactant interaction (chiral "recognition") and ET within the ion pair ("stereoselectivity"). Chiral selectivity was first addressed experimentally. Λ-[Co(Ox)3](3-) was found to be both the more strongly bound and faster reacting enantiomer expressed respectively by the ion-pair formation constant KX and ET rate constant kET(X) (X = Λ and Δ), with KΛ/KΔ and kET(Λ)/kET(Δ) both ≈1.1-1.2. rac-[Co(Ox)3](3-) behavior is intermediate between those of Λ- and Δ-[Co(Ox)3](3-). Chirality was next analyzed by quantum-mechanical ET theory combined with density functional theory and statistical mechanical computations. We also modeled the ion pair K(+)·[Co(Ox)3](3-) in order to address the influence of the solution ionic strength. The complex structure of cyt c meant that this reactant was represented solely by the heme group including the chiral axial ligands L-His and L-Met. Both singlet and triplet hemes as well as hemes with partially deprotonated propionic acid side groups were addressed. The computations showed that the most favorable inter-reactant configuration involved a narrow distance and orientation space very close to the contact distance, substantiating the notion of a reaction complex and the equivalence of the binding constant to a bimolecular reaction volume. The reaction is significantly diabatic even at these short inter-reactant distances, with electronic transmission coefficients κel(X) = 10(-3)-10(-2). The computations demonstrated chirality in both KX and κel(X) but no chirality in the reorganization and reaction free energy (driving force). As a result of subtle features in both KX and κel(X) chirality, the "operational" chirality κET(Λ)KΛ/κET(Δ)KΔ emerges larger than unity (1.1-1.2) from the molecular modeling as in the experimental data.