Self-assemblies of Metal Cross-Linked Artificial Oligopeptides Substituted with Hydroxyquinoline Ligands

Open Access
Zhang, Meng
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
October 01, 2014
Committee Members:
  • Mary Elizabeth Williams, Dissertation Advisor
  • Mary Elizabeth Williams, Committee Chair
  • Thomas E Mallouk, Committee Member
  • Benjamin James Lear, Committee Member
  • Robert Martin Rioux Jr., Committee Member
  • inorganic chemistry
  • self-assembly
  • metallic oligopeptide
  • electron and energy transfer
  • cooperativity
  • heterometallic complex
Nature utilizes self-assembly to create molecular machines that are capable of performing biological processes necessary for life, including information storage and processing, catalysis, and photosynthesis. A molecular machine is constructed by small units that are directed to assemble through non-covalent interactions, such as hydrogen bonding, metal coordination and π-π stacking. Supramolecular chemistry based on metal-ligand coordination has evolved to create highly organized structures via molecular recognition, and the construction of structures is more programmable using biopolymers with repeating units (e.g., nucleic acids and peptides). This dissertation describes the synthesis and characterization of compounds that combine peptide coupling chemistry with metal-ligand coordination chemistry to design metallated oligopeptide self-assemblies. The factors affecting self-assembly of metallated oligopeptides are investigated in this dissertation, leading to more precise geometrical control and site-selectivity for potential application in molecular electronics, photo-induced catalysts, and artificial enzymes. Artificial tripeptides containing three pendant ligands, hydroxyquinoline (hq) and/or bipyridine (bpy), were synthesized with three different sequences, hq-hq-hq, hq-bpy-hq and bpy-hq-bpy. Separate reaction of these tripeptides with Zn(II) was quantitatively analyzed, and the formed Zn(II)-linked tripeptide duplex was confirmed by analysis with UV-visible spectroscopy, emission spectroscopy, and mass spectrometry. Titrations monitoring formation of the Zn(II) hq tripeptide duplex had an equilibrium constant larger than the monomeric analogue, and a Hill coefficient larger than 1, indicating positive cooperativity. Comparison of the photophysical behaviors of these duplexes indicated sequence-dependent properties. A decrease of emission intensity was observed in Zn tripeptide duplexes containing bpy compared to the hq-hq-hq tripeptide. Electron transfer and/or Dexter energy transfer between metal centers is hypothesized to be the fluorescence quenching mechanism, and is supported by electrochemical, variable-temperature, solvent studies and DFT calculations. The three artificial tripeptides mentioned above have been reacted with Cu(II) to form tripeptide duplexes with three Cu(II) coordinative cross-links. NMR spectroscopy, elemental analysis, and mass spectrometry confirmed the identity of products. The stoichiometry of binding was examined using spectrophotometric absorbance titrations; positive cooperativity was observed during the binding and quantified using the Hill equation. Electron paramagnetic resonance data indicated coupling interactions between Cu(II) centers, and the Cu-Cu distance was calculated to be ~ 5 Å. A negative shift of the reduction potential of [CuII(bpy)2]2+ was observed in the cyclic voltammograms of [CuII3(hq-bpy-hq)2]2+ and [CuII3(bpy-hq-bpy)2]4+ compared to the Cu(II) bpy monomer duplex. We hypothesize that it is caused by the geometry change in reduced [CuI(bpy)2]+ : in the duplex, the close packing of Cu-ligand layers flatten the tetrahedral geometry of [CuI(bpy)2]+, increasing the energy level of the LUMO of the Cu(II). This hypothesis was supported by spectroelectrochemical experiments and DFT calculations. The stabilities of these three tripeptides and their Zn(II) and Cu (II) duplexes were investigated using pH-dependent and sulfide spectrophotometric titrations, and equilibrium constants were calculated. The stability of tri-metallic complexes is higher compared to the monometallic analogues, confirming that the cooperative formation of multiple metal-ligand linkages results in a higher binding affinity. For the Zn(II) complexes of tripeptides containing bpy ligands, the data suggested that the protonation-induced dissociation is less favored because of the repulsion between protons and positive-charged metal-bpy centers. Artificial pentapeptide containing five pendant ligands was synthesized with a sequences hq-bpy-bpy-bpy-hq. The binding selectivities of the pentapeptide and tripeptide hq-bpy-hq with Cu(II) were determined with pH-dependent absorption spectroscopy. The reaction of partially Cu(II)-saturated peptides with Zn(II) was quantitatively analyzed with absorption titration, and the formed Cu(II)Zn(II) cross-linked duplex structures were confirmed by analysis with absorption spectroscopy and mass spectroscopy. EPR and DEER data indicated coupling interactions between Cu(II) centers, and the Cu-Cu distance is calculated to be ~ 9 Å in the Cu(II)Zn(II) cross-linked tripeptide duplex, and ~ 22 Å in the Cu(II)Zn(II) cross-linked pentapeptide duplex. We have expanded the choice of metal species and incorporated Fe(II), Co(II) and Cu(II) ions into tripeptide hq-bpy-hq to create heterometallic complexes. Spectrophotometric titrations suggested the formation of [Fe(bpy)2]2+ and [Co(bpy)2]2+ in the middle of two Cu(hq)2 centers, instead of the thermodynamically favored [Fe(bpy)3]2+ and [Co(bpy)2]2+ complexes. Future studies move to utilize the active catalytic [Fe(bpy)2]2+ and [Co(bpy)2]2+ centers in the duplex structures to catalyze reactions including thermal water oxidation to dioxygen, alkene oxidation with dioxygen, and alkane oxidation with hydroperoxide.