Hydrolytic Protein Cleavage Mediated by Unusual Mononuclear Copper(II) Complexes: X-ray Structures and Solution Studies

The crystal structures and redox and UV−vis/EPR spectroscopic properties of two new mononuclear copper(II)
complexes, [Cu(HL1)Cl2] (1) and [Cu(L1)Cl] (2), prepared through the reaction between copper(II) chloride and the
ligand 2-[(bis(pyridylmethyl)amino)methyl]-4-methyl-6-formylphenol (HL1) under distinct base conditions, are reported
along with solution studies. Also, we demonstrate that these CuII complexes are able to cleave unactivated peptide
bonds from bovine serum albumin (BSA) and the thermostable enzyme Taq DNA polymerase at micromolar
concentration, under mild pH and temperature conditions. The cleavage activity seems to be specific with defined
proteolytic fragments appearing after protein treatment. The location of the specific cleavage sites was tentatively
assigned to solvent-accessible portions of the protein. These are two of the most active Cu(II) complexes described
to date, since their cleavage activity is detected in minutes and evidence is here presented for a hydrolytic mechanism
mediating protein cleavage by these complexes.