1H NMR study of the hydrogen bonding of modified nucleosides

Douglas Arthur Klewer, Purdue University

Abstract

The purpose of the present work was to use 1H NMR to determine the strength and specificity of the hydrogen bonding of several azole nucleosides with the natural bases. The 5 and 3 hydroxyl groups were protected with triisopropylsilyl groups to eliminate hydrogen-bonding competition from the hydroxyl protons and to increase the solubility of the nucleosides in chloroform. The chemical shifts of the protons involved in hydrogen bonding were determined by NMR in a series of titration experiments. The concentration dependence of the chemical shifts were then used to calculate the association constant (Ka). The results indicate that the steric bulk of the TIPS groups inhibits the association of the bases compared to the smaller derivatized bases used in the literature. The association constants of control titrations between G:C and A:T are an order of magnitude lower than the values previously reported. The azoles that contain an amide functional group have association constants of about 3–5M –1 which is typical for amides. With the amides studied, only the proton that is cis to the carbonyl is involved in hydrogen bonding. The only exception to this is when imidazole-4-carboxamide binds with T (K trans = 9.01 M–1; Kcis = 4.28 M–1). The strongest association measured in this work is between pyrrole-3-carboxamide and C (K = 10.38 M–1). The proton involved in hydrogen bonding of pyrrole-3- carboxamide could not be determined. This is because only one resonance was observed for the amide protons due to rapid rotation about the amide bond at room temperature. ^

Degree

Ph.D.

Advisors

Major Professor: Donald E. Bergstrom, Purdue University.

Subject Area

Chemistry, Biochemistry|Chemistry, Organic

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