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 NH<sub>2</sub>−KL(Pen)EGG·(Pen)<b>IG</b>(Pen)G<b>A</b>(Pen)·GGW−CONH<sub>2</sub>. For comparison, we have studied Co(II) binding to the analogous sequence with Cys ligands, the ferredoxin maquette ligand <b>IGA</b> that was originally designed to bind a [4Fe-4S] cluster. The Co(II) affinity and UV−vis spectroscopic properties of <b>IGA</b> indicate formation of a pseudotetrahedral tetrathiolate ligated Co(II). In contrast, <b>IGA-Pen</b> showed formation of a pseudotetrahedral complex with Co(II) bound by three Pen ligands and an exogenous H<sub>2</sub>O. EXAFS data on both Co(II) complexes confirms not only the proposed primary coordination spheres but also shows six Co(II)-C<sub>β</sub> methyl group distances in Co(II)-<b>IGA-Pen</b>. 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.