Chromium(V) peptide complexes: Synthesis and spectroscopic characterization

A series of stable Cr(V) model complexes that mimic the binding of Cr(V) to peptide backbones at the C-terminus of proteins have been prepared for NN-dimethylurea derivatives of the tripeptides Aib(3)-DMF, AibLAlaAib-DMF, and AibDAlaAib-DMF (Aib = 2-amino-2-methylpropanoic acid, DMF = N,N-dimethylformamide). The Cr(II) precursor complexes were synthesized by the initial deprotonation of the amide and acid groups of the peptide ligands in DMF with potassium tert-butoxide in the presence of CrCl(2). The Cr(II) intermediates thus formed were then immediately oxidized to Cr(V) using tert-butyl hydroperoxide. Spectroscopic and mass-spectrometric analyses of the Cr(V) complexes showed that a new metal-directed organic transformation of the ligand had occurred. This involved a DMF solvent molecule becoming covalently bound to the amine group of the peptide ligand, yielding a urea group, and a third coordinated deprotonated urea nitrogen donor. A metal-directed oxidative coupling has been proposed as a possible mechanism for the organic transformation. The Cr(V/IV) reduction potential was determined for the three Cr(V) complexes using cyclic voltammetry, and in all cases it was quasi-reversible. These are the first isolated and fully characterized Cr(V) complexes with non-sulfur-containing peptide ligands.