Year of Publication

2006

Document Type

Dissertation

College

Arts and Sciences

Department

Chemistry

First Advisor

Arthur Cammers

Abstract

Mimicking the structure and even the function of an ??-peptide with artificial chainmolecules such as ??-peptides, ??-peptides and other unnatural oligomers has shown early success.The structural similarities between natural peptides and oligoureas lead to the belief that C2-symmetric oligoureas could be a good candidate for peptidomimicry. Molecular modelingindicates that both homochiral (all monomers have the same absolute configuration) andalternate chiral (absolute configuration of the residues alternate) C2-symmetric oligoureas canform helix- and sheet-like structures in solution conditionally.Several C2-symmetric 1,2-diamines were chosen as the building blocks for the synthesisof chiral oligoureas, and all diamines except for one were prepared in lab. Homochiral andheterochiral oligoureas based on the same diamine or mixed diamines were synthesized in thesolution phase, growing a chain by adding one unit at a time to one terminus or two units at atime to both termini with 4-nitrophenoxycarbonyl (PNP)- activated and t-butoxycarbonyl (Boc)- protected diamines as the intermediates. All the chiral oligoureas were purified by eitherrecrystallization and /or column chromatography and/ or HPLC and characterized by NMR andMALDI-MS. For some oligoureas, crystal structures were obtained. Fragment condensation wasattempted to improve the efficiency of the synthesis, but this approach led to cyclized oligoureasinstead of the desired concatenated residues.Conformational studies of chiral oligoureas were done in both the solid state and thesolution state. The crystal structures of some homochiral oligoureas and some alternate chiraloligoureas indicate that both helix-like structures and extended structures exist for these C2-symmetric oligoureas. NMR and Circular Dichroism (CD) were used to study the conformationof oligoureas in solution, but the conformational study by NMR was not conclusive. CD studyshowed that these oligoureas have multiple conformations in solution and that some of theconformations are sensitive to solvents and temperature. Also, short homochiral and alternatechiral oligoureas based on trans-1,2-diaminocyclohexane (DACH) exhibit signs of cooperativebehavior in solution as gauged by a series of experiments.

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