Pyridine-Substituted Oligopeptides as Scaffolds for the Assembly of Multimetallic Complexes:  Variation of Chain Length

Abstract

This paper presents the synthesis and characterization of pyridine-substituted artificial oligopeptides with an aminoethylglycine backbone of varying length, which are designed to act as scaffolds for the self-assembly of multimetallic structures. The identities and purities of the oligopeptides are confirmed with mass spectrometry, (1)H NMR, HPLC, and pH titrations. The acid dissociation constants for the oligopeptides were determined and were found to decrease with increasing pyridine units. Titrations of the oligopeptides with Cu(II) and Pt(II) complexes containing the tridentate ligands 2,2':6',2''-terpyridine and pyridine 2,6-dicarboxylic acid were monitored using UV-visible absorption spectroscopy and showed stoichiometric binding based on the number of pyridines on the peptide strand. Metal titrations performed using an analogous oligopeptide with methyl substituents (in place of the pyridine ligands) showed very weak or no binding. In the case of the oligopeptides containing bound Pt(terpyridine)(2+) complexes, cyclic voltammetry reveals two sequential one-electron reductions at formal potentials that do not vary as a function of oligopeptide length. The measured diffusion coefficients were measured with chronoamperometry and were found to decrease with increasing oliopeptide length.

Synthesis and Characterization of a (Dipyridylthiophene)platin Complex of a Pyridyl‐Substituted Aminoethylglycine Artificial Dipeptide

“…In comparison with our previous report of artificial pyridyl aeg peptides,2b this dipeptide was prepared in higher yield (34.8 % vs. 29 % by solid‐phase synthesis) and in much larger scale (590 mg vs. 43 mg by solid phase). To confirm the identity and purity of the dipeptide, analysis by electrospray ionization mass spectrometry (ESI+ MS) and 1 H NMR was performed.…”

“…Our group has used solid‐phase peptide synthesis to prepare artificial aeg peptides by efficient separation of peptide‐coupling reagents from the oligomers 2a,2b,2d. However, we have been limited by the small quantities that are afforded by solid‐phase synthesis, which is largely determined by the loading of functional groups on the resin support 2a,2b,2d. To increase the quantities of material that are available for electrochemical and spectroscopic investigations, we have recently turned to purely solution‐phase peptide syntheses.…”

“…We have previously described the synthesis and characterization of artificial oligopeptides with an aminoethylglycine (aeg) backbone that contain heterocyclic pendant ligands 2,5. These compounds rely on metal coordination to form the single‐stranded,2a,2b duplex,2a,2c,2d and hairpin5 geometries shown in Scheme . These structures self‐assemble on the basis of the denticity of the attached ligand and coordination chemistry of the added metal ions.…”

Square-Planar Pd(II), Pt(II), and Au(III) Terpyridine Complexes: Their Syntheses, Physical Properties, Supramolecular Constructs, and Biomedical Activities

“…171,172 It was assumed that the four-tethered Pt-terpyridine complexes on the backbone of the peptide chain, as in 234, which resemble nucleic acids on the DNA sugar-phosphate backbone, would increase binding affinity of 234. To this extent, a doublestranded (ds) DNA fragment with 12 base pairs (bp) was chosen as a model for binding studies (Figure 102).…”

Nucleic Acid Mimetics

“…Structures using the [3 × 3] binding motif were studied using phenyl terpyridine ( -tpy)-substituted oligopeptides of varying length, which formed duplex structures in the presence of Co(II) and Fe(II), forming [Co( -tpy) 2 ] 2+ and [Fe( -tpy) 2 ] 2+ cross-links, respectively. 92 More recent studies with these bioinspired inorganic structures focus on the control of the relative orientation of the oligopeptide strands to eliminate the formation of parallel versus antiparallel isomers, alternative registers, and polymers. One strategy involves mimicking the hairpin form of RNA by substituting a [Ru(bpy) 3 ] 2+ with aeg so that the tethered ligandosides are forced in a complementary position (Figure 23b).…”