Comparison of Cysteine and Penicillamine Ligands in a Co(II) Maquette

l-Penicillamine (Pen) has been investigated as a ligand for metalloprotein design by examining the binding of Co(II) to the sequence NH₂−KL(Pen)EGG·(Pen)IG(Pen)GA(Pen)·GGW−CONH₂. For comparison, we have studied Co(II) binding to the analogous sequence with Cys ligands, the ferredoxin maquette ligand IGA that was originally designed to bind a [4Fe-4S] cluster. The Co(II) affinity and UV−vis spectroscopic properties of IGA indicate formation of a pseudotetrahedral tetrathiolate ligated Co(II). In contrast, IGA-Pen showed formation of a pseudotetrahedral complex with Co(II) bound by three Pen ligands and an exogenous H₂O. EXAFS data on both Co(II) complexes confirms not only the proposed primary coordination spheres but also shows six Co(II)-C_β methyl group distances in Co(II)-IGA-Pen. These results demonstrate that ligand sterics in simple peptides can be designed to provide asymmetric coordination spheres such as those commonly observed in natural metalloproteins.