Synthesis and electrochemical studies of disubstituted ferrocene/dipeptide conjugates with sulfur-containing side chains

A series of 1,1'-disubstituted ferrocenoyl peptides incorporating dipeptide sidearms has been synthesized and studied electrochemically. The target peptides include ferrocene as an electrochemical reporter, sulfur-containing amino acids (L-methionine, S-methyl-L-cysteine, S-trityl-L-cysteine, S-benzhydryl-L-cysteine) as metal binding agents, and amino acids with non-polar side chains (L-alanine, L-valine, L-phenylalanine) as spacers between reporter and metal binding groups. Ferrocene/dipeptide conjugates were prepared using solution phase peptide synthesis methods employing a BOC-protecting group strategy and HBTU- (O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate) mediated peptide coupling. The electrochemical properties of these 1,1'-substituted ferrocenoyl peptides have been characterized using cyclic voltammetry. All exhibit fully reversible one electron oxidation steps; forward sweep half wave peaks (E-F), reverse sweep half wave peaks (E-R), peak separations (Delta E-P) and half wave potentials (E-1/2) are reported. Finally, towards the goal of utilizing ferrocenoyl peptides to detect heavy metals in solution, the response of these ferrocene/dipeptide conjugates to metal cations (zinc(II), mercury(II), cadmium(II), lead(II), silver(I)) has been examined. Monitoring changes in the potential of the Fe(II)/Fe(III) redox couple to follow peptide/metal interactions, we have probed the influence of the spacer unit between the redox reporter and the metal-binding amino acid, and shown that these systems respond to mercury(II) more strongly than to other heavy metal ions. (C) 2010 Elsevier Ltd. All rights reserved.