(a
OH
o
OH
H Η
H
> (A) Major;
+(B) : 41
A
12.
Sum of a-hydrogens in A+B is :
(a) 18
(b) 19
(c) 20
(d) 21
IT
Answers
Answer:
The exact knowledge of hydrogen atomic positions of O–H···O hydrogen bonds in solution and in the solid state has been a major challenge in structural and physical organic chemistry. The objective of this review article is to summarize recent developments in the refinement of labile hydrogen positions with the use of: (i) density functional theory (DFT) calculations after a structure has been determined by X-ray from single crystals or from powders; (ii) 1H-NMR chemical shifts as constraints in DFT calculations, and (iii) use of root-mean-square deviation between experimentally determined and DFT calculated 1H-NMR chemical shifts considering the great sensitivity of 1H-NMR shielding to hydrogen bonding properties.
Keywords: chemical shifts, hydrogen bonding, DFT, X-ray diffraction, NMR
1. Introduction
Hydrogen bonding is a fundamental aspect in the determination of three-dimensional structures, reactivity, and functions of biological macromolecules, for encoding genetic information, in crystal engineering and in material sciences [1,2,3,4,5,6,7,8]. Although detection of hydrogen bonds remains an area of active research and the characterization of hydrogen bond interactions has been the subject of numerous experimental and theoretical studies, the detailed understanding of the nature of hydrogen bonding and its structural, energetic, and dynamic properties are still limited. This is due to the fact that the strength of the hydrogen bond depends on several factors, such as the X–H and H···Y lengths, the X–H···Y–Z dihedral angle, the nature of the microenvironment [8,9], the pKa/pKb values of the participating components [10,11,12], and molecular electrostatic potential surfaces [13,14].
X-ray and neutron diffraction of single crystals and, in some cases, of powder samples are the most widespread and popular methods for investigating hydrogen bonding interactions in the solid state, often in conjunction with structural indicators such as bond lengths and bond angles [15,16]. However, the unequivocal determination of hydrogen atomic positions is not straightforward particularly with systems exhibiting proton disorder [1,7,17]. Furthermore, since the X-ray diffraction experiments determine electron density distributions, in a covalent X–H bond with an electronegative atom X, the average position of the electron charge density of the hydrogen atom is displaced towards the X atom. As a result, numerous X-ray structures yielded unrealistic OH bond lengths (~0.8–0.9 Å, compared to a typical value of 1.0 Å), ambiguous conclusions with respect to the molecular ionization states (resulted from proton transfer processes), and the hydrogen bonding network in the crystal lattice. Neutron diffraction, on the other hand, locates the nuclei because neutrons are scattered by nuclei [7]. The results of the two techniques for hydrogen atoms often differ by more than 0.1 Å [18]. It has become a practice in the analysis of X-ray diffraction results to normalize the X–H bonds [19] by increasing the position of hydrogen atoms by a relaxed amount [20] or restraint to a common value from highly accurate neutron diffraction experiments [21]. In addition, significant efforts have been made in assigning the positions of hydrogen atoms from X-ray diffraction experiments with the use of quantum chemical methods [22,23,24].
NMR spectroscopy is among the primary methods for investigating hydrogen bonding interactions both in solution and in the solid states [25]. The existence of hydrogen bond is inferred from several NMR methods, such as chemical shifts [26,27,28,29,30,31,32,33], temperature dependence of chemical shifts [32,33], solvent accessibility [34], the NOE phenomenon [35,36], direct spin-spin scalar coupling between nuclei on both sides of the hydrogen bonds [37,38], isotope effects [4,9,39], REDOR experiments [40], and NMR dipolar coupling in the solid states [41,42]. Developments in quantum chemical methods for calculating NMR chemical shifts [43,44,45] have led to an increasing number of studies which focus on the assignment or reassignment of individual protons and carbons [40], including hydrogen bonding effects [46,47,48], in the elucidation of chemical structures [45] and in the refinement of labile hydrogen positions [49,50]. Such calculations have also played an important role in the new field of NMR crystallography where NMR spectroscopy is combined with X-ray diffraction to aid structural information [51,52,53].
In the present review, we will summarize recent developments in the determination of labile hydrogen atomic positions in O–H···O hydrogen bonds with the combined use of DFT calculations after a structure has been determined by X-ray from single crystals or from powders, and the use of root-mean-square deviation of experimental 1H-NMR chemical shifts with DFT calculated chemical shifts. Finally, we will comment on the future