Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

James A. Wisner

Abstract

The design of artificial or synthetic strands that self-assemble to form double-helical complexes have been of great interest to chemists and researchers since the discovery of the double helical DNA structure in 1953 by Watson and Crick. Most of the complexes were self-complementary double-helical homodimers and while few heterodimer complexes are also known. The present thesis describes the design, synthesis and characterization of complementary and self-complementary hydrogen bond arrays built from heterocycles such as pyridine, thiazine dioxide and indole connected in different sequences. The sequence-based stabilities, insolubility issues, substitution and preorganization effects in these arrays have been studied in detail.

The design and syntheses of four self-complementary oligomers that contain an underlying AADD hydrogen bond Donor/Acceptor sequence are presented and their self-association examined in the solution and solid states. Substitution with electron donating and withdrawing groups and the influence of preorganization had a large effect on the overall stabilities of the complexes studied. A wide range (>105 M-1) of stabilities were demonstrated and in the most extreme case, the dimerization constant measured (Kdimer ≥ 4.5 x 107 M-1) is comparable to the most stable homodimers of neutral coplanar AADD arrays reported to date.

Two sets of DDD hydrogen bond arrays were synthesized that form triply hydrogen bonded double helical complexes with an AAA array when combined in CDCl3 solution. In contrast to the detrimental effect of appended alkyl chain arrays containing tethers between donor heterocycles displayed an increased stability in their association constants (Ka).

The effect of introduction of a hexyl chain on the solubility of an originally insoluble (in CDCl3) DDD array based on three thiazine dioxides was studied. The association constants measured based on NMR titrations and ITC titrations demonstrate formation of a highly stable double-helical pair with a Ka valueof 1.4 x 105 M-1. A self-complementary double helical complex based on six hydrogen bond AAADDD array was also synthesized and displays very strong dimerization (Kdimer > 4.5 x 107 M-1 in CDCl3) examined by NMR dilution and mixed solvent studies. These findings establish the high potential of the DDD array and the AAADDD array as monomer components to build supramolecular architectures or polymers.


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