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 (EF), reverse sweep half wave peaks (ER), peak separations (ΔEP) and half wave potentials (E1/2) 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.

A series of monosubstituted ferrocenoyl peptides has been prepared from ferrocenecarboxylic acid and l-methionine, S-methyl-l-cysteine or S-trityl-l-cysteine, and tested as electrochemical probes for mercury(II). These compounds incorporate the thioether-containing amino acids as metal binding agents, and ferrocene as an electrochemical reporter. How do they respond to mercury(II) and other heavy metal ions?.Figure optionsDownload as PowerPoint slideResearch highlights
► Nine singly-substituted ferrocenoyl peptides with thioether side chains synthesised.
► Electrochemical properties (EF, ER, EP, E1/2) determined using cyclic voltammetry.
► Metal binding properties investigated electrochemically: more responsive to mercury(II) than to other metal ions.
► NMR experiments indicate 1:1 stoichiometry for peptide: mercury binding.
► The crystal structure of ferrocenoyl-S-methyl-L-cysteine methyl ester is reported.