Recognition and Self... In Metal Directed Assembly of Palindromic Artificial Oligopeptides

Open Access
Gallagher, Joy Ann
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
July 01, 2013
Committee Members:
  • Mary Elizabeth Williams, Dissertation Advisor
  • Thomas E Mallouk, Committee Member
  • Squire J Booker, Committee Member
  • Michael Anthony Hickner, Committee Member
  • Self-Assembly
  • Supramolecular
  • Copper
  • Palindromic
  • Biomimetic
  • Artificial Oligopeptide
  • Inorganic Architectures
Nature provides a framework for self-assembly via molecular recognition: the sequence of modular small units (e.g. nucleobases and amino acids) direct higher order assemblies capable of performing the functions necessary for life, including information storage and processing, catalysis, and photosynthesis. Supramolecular chemistry has evolved to create artificial receptors which self-organize via molecular recognition, largely directed via metal-coordination chemistry; however synthesis of sizable structures approaching natural systems has proved synthetically daunting. Combining the synthetic versatility of peptide coupling chemistry with coordination chemistry provides a platform for the facile expansion of multimetallic systems that have implications in catalysis, artificial photosynthesis, molecular wires, and sensing. This thesis describes the development of a new route for the synthesis of symmetric, palindromic ligand-substituted artificial oligopeptides designed to eliminate geometric isomers upon metal binding. A central monomeric unit with dicarboxylic acid termini substituted with bipyridine (bpy) or pyridine (py) is reacted with amine terminated aminoethylglycine (aeg) monomers substituted with pyridyl based ligands: bpy, py, or terpyridine (tpy) under standard peptide coupling conditions to produce novel homo- and hetero-functional tripeptides in a one-pot synthesis. The streamlined synthetic route allows for rapid interchange of tripeptide functionality as well as the potential for stream-lined expansion to oligopeptide length of 5-mer, 7-mer, 9-mer, etc. Tripeptide sequences were designed to contain molecular recognition codes, whereby in the presence of a tetracoordinate metal (Cu2+, Zn2+), a bidentate bpy ligand will be self-complementary forming a [2 x 2] complex [M(bpy)2]2+, and a tridentate tpy will be complementary to monodentate py forming a [3 x 1] complex [M(tpy)(py)]2+. Studies included self-assembling monofunctional bpy-tripeptide, which formed a duplex upon addition of Cu2+ . iv Addition of a series of monovalent anions showed large, polarizable coordinating anions, (I-, Br-) and tuned the metal center environment, perturbating the Cu2+ geometry from a distorted square planar environment, to tetragonal. Heterotopic ligand sequences, py-bpy-py (pbp) and tpy-bpy-tpy (tbt), were synthesized to form duplex structures from dissimilar strands, extending the metal-directed assembly and molecular recognition properties to more sophisticated behaviors present in natural systems. Additional tripeptides (py-py-py, ppp; bpy-py-bpy, bpb) were synthesized and used in addition to previously synthesized tripeptides to explore binding selectivity in the presence of the Cu-saturated tbt complex. The final body of work focused on developing a functional, photoswitchable artificial oligopeptide scaffold. Azobenzene, a reversible, photoswitchable molecule, was inserted into the artificial oligopeptide backbone. A series of artificial oligopeptides containing bpy- and acetyl (ac-) substituted aeg monomers connected via an azobenzene diamide (b(azo)b, ac(azo)ac, bb(azo)bb) were synthesized. Reversible photoswitching behavior was observed for the single strand. Addition of metal (M= Zn2+, Cu2+) resulted in two switchable structures: mono-metallic hairpin [M(b(azo)b)]2+ and dimetallic duplex [M2(b(azo)b)]4+. Irradiation to promote isomerization reversibly controlled the conformation.