H-Bonding in Alcohols Is Reflected in the Cα−H Bond Strength:  Variation of C−D Vibrational Frequency and Fractionation Factor

• Published in: Journal of the American Chemical Society 2000-11, Vol.122 (47), p.11660-11669
• Main Authors: Gawlita, Ewa, Lantz, Marily, Paneth, Piotr, Bell, Alasdair F, Tonge, Peter J, Anderson, Vernon E
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja001891d

The variation of the C−D vibrational stretching frequency in primary and secondary alcohols containing the D−C−O−H functionality has been examined for cases in which the alcohol functions as a proton donor in an H-bond. The C−D stretching frequency is a function of the H-bond enthalpy of formation determined by Hartree−Fock calculations, decreasing by approximately 5 cm-1 per kcal/mol. This decrease in frequency is attributed to the increase in the overlap of the O−H bonding electrons with the C−D antibonding orbital as the H-bond is strengthened. The Raman spectra of [1-D]trifluoroethanol and [1-D]trifluoroethoxide in aqueous solution serve as an example; the alcohol has two separate C−D stretches that differ by 45 cm-1 and deprotonation results in an average 78 cm-1 decrease in the C−D stretching frequency. A measured deuterium equilibrium isotope effect on the acid ionization constant of [1-D2]trifluoroethanol of 1.13 is consistent with a decreased fractionation factor of the C-1 protons due to the decrease in the C−D stretching frequency. A model nucleoside complexed with the H-bonding residues at the active site of nucleoside hydrolase indicates that H-bond formation can explain the anomalous secondary isotope effects reported for the hydrolysis of [5‘-3H]inosine (Horenstein et al. Biochemistry 1991, 30, 10788−10795). The correlations of both the C−D stretching frequency and the fractionation factor with the conformation and H-bond strength with primary and secondary alcohols as donors should serve as tools for the characterization of these important interactions in biological systems.