p<i>K</i>_a Determination of d‑Ribose by Raman Spectroscopy

Determination of the p<i>K</i>_a of OH groups present in d-ribose is crucial in order to elucidate the origin and mechanism of many catalytic processes that involve the ribose unit. However, there is hardly any reports about the experimental p<i>K</i>_a of the OH group due to the lack of an appropriate method. In this study we investigated the protonation state of OH groups in d-ribose by introducing C–D labeling and measuring the changes in the isolated C–D frequency in several isotopologues of the compound with pH. The large shift in the ν_C–D of d-ribose-C1-D in ionized condition compared to other deuterium-substituted d-riboses (e.g., d-ribose-C2-D, d-ribose-C3-D, etc.) confirmed that the C1–OH group preferred ionization, and the ionization p<i>K</i>_a was 11.8. Both the ionized and the unionized structures of d-ribose preferred the pyranose conformation, which was supported by ¹³C NMR experiments. Electronic redistribution via resonance and intramolecular hydrogen-bond formation were proposed to account for the stabilization of the ionized structure

C_α–H Carries Information of a Hydrogen Bond Involving the Geminal Hydroxyl Group: A Case Study with a Hydrogen-Bonded Complex of 1,1,1,3,3,3-Hexafluoro-2-propanol and Tertiary Amines

Experimental measurement of the contribution of H-bonding to intermolecular and intramolecular interactions that provide specificity to biological complex formation is an important aspect of macromolecular chemistry and structural biology. However, there are very few viable methods available to determine the energetic contribution of an individual hydrogen bond to binding and catalysis in biological systems. Therefore, the methods that use secondary deuterium isotope effects analyzed by NMR or equilibrium or kinetic isotope effect measurements are attractive ways to gain information on the H-bonding properties of an alcohol system, particularly in a biological environment. Here, we explore the anharmonic contribution to the C–H group when the O–H group of 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) forms an intermolecular H-bond with the amines by quantum mechanical calculations and by experimentally measuring the H/D effect by NMR. Within the framework of density functional theory, ab initio calculations were carried out for HFP in its two different conformational states and their H-bonded complexes with tertiary amines to determine the ¹³C chemical shielding, change in their vibrational equilibrium distances, and the deuterium isotope effect on ¹³C2 (secondary carbon) of HFP upon formation of complexes with tertiary amines. When C2–OH was involved in hydrogen bond formation (O–H as hydrogen donor), it weakened the geminal C2–H bond; it was reflected in the NMR chemical shift, coupling constant, and the equilibrium distances of the C–H bond. The first derivative of nuclear shielding at C2 in HFP was −48.94 and −50.73 ppm Å^–1 for anti and gauche conformations, respectively. In the complex, the values were −50.28 and −50.76 ppm Å^–1, respectively. The C–H stretching frequency was lower than the free monomer, indicating enhanced anharmonicity in the C–H bond in the complex form. In chloroform, HFP formed a complex with the amine; δC2 was 69.107 ppm for HFP–triethylamine and 68.766 ppm for HFP-<i>d</i>₂–triethylamine and the difference in chemical shift, the ΔδC2 was 341 ppb. The enhanced anharmonicity in the hydrogen-bonded complex resulted in a larger vibrational equilibrium distance in C–H/D bonds. An analysis with the Morse potential function indicated that the enhanced anharmonicity encountered in the bond was the origin of a larger isotope effect and the equilibrium distances. Change in vibrational equilibrium distance and the deuterium isotope effect, as observed in the complex, could be used as parameters in monitoring the strength of the H-bond in small model systems with promising application in biomacromolecules