Direct Energy Measurement of Short Hydrogen Bonds in Solution by 17O NMR Spectroscopy

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Authors

Toubaei, Abouzar

Date

2019-06-04

Type

thesis

Language

eng

Keyword

Short Hydrogen Bond, 17O NMR, Density Functional Theory

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Abstract

Hydrogen bonding interactions are of paramount importance in many chemical and biological processes. Although the physicochemical parameters to identify hydrogen bonds (HBs) have been established in the literature, direct measurement of HB energies in solution has remained a significant challenge. In this thesis, we report a new 17O NMR method for directly measuring the energetics of intramolecular HBs in solution. The new method is based on determination of the rotational barrier of a carboxylate group in which one of the two oxygen atoms is involved in an intramolecular HB. We have applied this new approach to a variety of carboxylate monoanions that are known to have the shortest, thus the strongest, intramolecular HBs and obtained the HB energetic values between 7.0 ± 0.5 and 10.9 ± 0.5 kcal mol-1 in various protic and aprotic solvents as well as in protic solvents containing various amounts of water. We have also measured the energetics of breaking the elongated O−H covalent bonds in picolinic acid N-oxide (PANO), phenylmaleate, and citraconate in DMF, which were found to be 10.7 ± 0.5, 9.5 ± 0.5, and 10.2 ± 0.5 kcal mol-1, respectively. Since an elongated covalent O−H bond should be stronger than any H···O HB, the experimentally measured energetics of the elongated O−H covalent bond in PANO, 10.7 ± 0.5 kcal mol-1, may represent the upper limit of the HB energetics in solution. To supplement the experimental 17O NMR approach, we have combined density functional theory (DFT) calculations with the integral equation formalism polarized continuum model (IEFPCM) to determine the carboxylate rotational barrier and the corresponding HB energetics. The new experimental results reported in this thesis have significantly advanced our understanding of HB energetics. If one uses the common classification of strong HBs (12–24 kcal mol-1), our results immediately suggest that strong HBs do not exist in solution. Our findings have also put into question whether any HB in the transition state of enzymatic reactions can actually provide 10-20 kcal mol-1 for catalysis as proposed by Gerlt and Gassman.

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