Investigations of Metal-Coordinated Peptides as Supramolecular Synthons

This article describes the synthesis and controlled assembly of four model biological-hybrid scaffolds
via coordination of a metal complex to four new tripeptides. Each model tripeptide investigated has
either a central pyridyl glycyl or a pyridyl alanyl residue between two terminally protected glycines. All
tripeptides were coordinated to their complementary recognition unit, a p-methoxy SCS−Pd pincer
complex. The assembly events were fully characterized and investigated by 1H NMR, ES-MS, and
isothermal titration calorimetry (ITC) to elucidate how the substitution and spatial distance of the pyridyl
moiety to the peptide backbone affects the metal coordination. Using these characterization techniques,
we have shown that the metal-coordination events in all cases are fast and quantitative and that the
peptide backbones do not interfere with the self-assembly. The ITC analyses showed that the 4-pyridyl
tripeptides are the tightest binding ligands toward the palladated pincer complexes with the alanyl derivative
being the strongest overall, demonstrating the superiority of the 4-pyridyl peptides over their 3-pyridyl
analogues. The measured association constants are comparable to other pincer−pyridine systems in DMSO
suggesting that the controlled coordination of the metalated pincer/pyridine interaction is an interesting
biological synthon and will allow for the future development of important noncovalent peptide-based
hybrid materials.