Specific Oxidation of Peptides via Their Copper Complexes

The oxidation of the copper(II) complex of tetra-l-alanine with 2 equiv of chloroiridate at pH 6–9 yields equimolar quantities of di-l-alanine amide and pyruvoyl-l-alanine. Similarly, di-l-alanine amide and pyruvoyl-di-l-alanine are obtained from penta-l-alanine. The copper(II) complexes of other peptides showed similar fragmentation in which the third amino acid residue (from the amino end) is destroyed. The mechanism proposed for this reaction involves oxidation of the Cu^II to Cu^III, the intramolecular reduction of Cu^III to give a free-radical intermediate; in a subsequent step the Cu^II which remains bound to this radical is again oxidized to Cu^III by a second molecule of IrCl₆²⁻ leading to oxidation of the peptide group and ultimately to the formation of a carbonylic group. The possibility of using this or similar reactions for locating complexed copper atoms in peptides and protein is discussed.