Synthesis, Characterization, and Assembly of Shape-Persistent Aromatic Oligoamide Macrocycles with a Backbone of Reduced Constraint
Kline, Mark A.
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The synthesis, characterization, and assembly of a new class of aromatic oligoamide macrocycles with a backbone of reduced constraint is presented in this thesis. The modification of our initially reported six-membered oligoamide macrocycle has led to three generations of aromatic oligoamide macrocycles, of which the third-generation is elaborated upon in Chapters 2-4. The properties of the third-generation macrocycles allow for as of yet unprecedented self-assembly by a rationally designed system. The synthesis of these macrocycles required deviation from our highly efficient one-pot synthetic methods and the difficulty of their purification has led to the use of techniques considered non-standard within our own laboratory. Chapter 1 is a review of supramolecular chemistry and the intermolecular interactions deemed most critical to the synthesis and properties of aromatic oligoamide macrocycles. The study of macrocycles and their intrinsic properties has laid the foundations of this vast and broad field of chemistry. Various classes of shape-persistent macrocycles are presented, including the important relationship between our oligoamide macrocycles and the work and systems developed by others. A descriptive presentation of the three-generations of aromatic oligoamide macrocycles begins Chapter 2. Study of the three generations has offered a tunable system by which the properties of aggregation and the function of macrocyclic assemblies can be controlled rationally. The synthesis of generation three was accomplished by the step-wise coupling of oligomeric precursors after the unsuccessful attempts to produce macrocycles by the one-pot condensation of acid chlorides and amines. Their separation was probed by multiple methods, of which HPLC was found to be the most effective means to isolate macrocycles in high purity. Chapter 3 discusses the conclusions drawn from experiments probing the exceptionally strong anisotropic aggregation of generation three macrocycles in both solution and solid states. Unusual and unexpected observations found include: (1) backbone-mediated association, (2) ground-state aggregation at very low (sub-pM) concentrations, (3) high sensitivity of the aggregation to solvent polarity, (4) extremely strong intermolecular association, with an estimated association constant in the 10 13 M -1 range in chloroform, (5) time courses of the aggregation that point to two growth phases, and (6) existence of individually dispersed, cylindrical stacks of the macrocyclic molecules in solution. This aggregation was investigated using 1 H NMR, FTIR, SEM, XRD, GPC, DLS, fluorescence spectroscopy, steady-state fluorescence anisotropy, UV-Vis, CD, and computation modeling. This new class of oligoamide macrocycles with a backbone of reduced constraint failed to bind the guanidinium ion, unlike the first- and second-generation of oligoamide macrocycles. Chapter 4 explores the conformational flexibility of these macrocycles in relation to those with a fully rigidified backbone containing six introverted amide bonds. A qualitative investigation of backbone conformation using two-dimensional NMR suggests the existence of backbone conformations in which some proportion of the amide bonds have become extroverted. Additional evidence of conformational freedom is provided by single crystal X-ray diffraction studies in which two different macrocycle conformations nucleated different crystal batches to provide unit cells of different parameters.