Synthesis, electrochemistry and metal binding properties of monosubstituted ferrocenoyl peptides with thioether-containing sidechains

Ferrocenoyl peptides incorporating thioether functionality respond more strongly to mercury(II) than to other heavy metal ions in solution. Compounds reported previously in this context are all 1,1′-disubstituted, and all include two or more sulfur-containing amino acids. To test whether two thioether groups are required for effective mercury binding by these systems, we have prepared a series of singly-substituted ferrocenoyl peptides from ferrocenecarboxylic acid and l-methionine, S-methyl-l-cysteine or S-trityl-l-cysteine, and tested them as electrochemical probes for mercury(II). Nine ferrocenoyl peptides have been synthesised using a Boc-protecting group strategy and HBTU-mediated peptide coupling. The electrochemical properties of these compounds have been determined using cyclic voltammetry, and all show fully reversible one electron oxidation steps. Forward sweep half wave peaks (E_F), reverse sweep half wave peaks (E_R), peak separations (ΔE_P) and half wave potentials (E_1/2) are reported. Changes in the potential of the iron(II)/iron(III) redox couple of the ferrocene core have been used to quantify heavy metal-peptide interactions, revealing that these monotopic systems also respond more strongly to mercury(II) than to zinc(II), cadmium(II), silver(I) and lead(II). NMR experiments to characterise the peptide-mercury interaction implicate the thioether sulfur as the site of mercury binding and indicate 1:1 stoichiometry. The crystal structure of ferrocenoyl-S-methyl-l-cysteine methyl ester is also reported. The greater responsiveness of these systems to mercury(II) makes them interesting leads for the development of biologically inspired sensors for this toxic heavy metal.