Computational studies hydrogen bonds

The models discussed previously by no means represent an exhaustive list. In addition to the solubility models, approaches using molecular orbital computations have been used to study hydrogen-bonding mechanisms and to compare the results with SAW sensor data [187]. These ab-initio computations have been used successfully, but can currently only be applied to molecules of limited size because of the high cost and long computing time involved. 

Klebe, G. and Abraham, U. (1999) Comparative molecular similarity index analysis (CoMSIA) to study hydrogen-bonding properties and to score combinatorial libraries, f. Comput. Aid. Mol. Des., 13, 1-10. 

In Table 17, we compare the computed results of water dimer, which is probably the most extensively studied hydrogen-bonded system, The predicted dipole moment fj. of water dimer from DFT and MP2 approaches agree quite well with the experimental fj. of water dimer. Rq-q is the distance between two oxygen atoms as shown in Figure 2, while the donor proton resides in between and forms a near linear O-H-0 bonding, Gradient-corrected functionals and MP2 predict very accurately for this geometrical parameter, while local S-VWN predicts a value for Rq-q that is much too short 0.27 A shorter than the experimental observation. 

The ideas of Frank, Evans and Kauzmann had a profound influence on the way chemists thought about hydrophobic effects in the decades that followed However, after the study of the hydrophobic hydration shell through computer simulations became feasible, the ideas about the hydrophobic hydration gradually changed. It became apparent that the hydrogen bonds in the hydrophobic hydration shell are nof or only to a minor extent, stronger than in normal water which is not compatible with an iceberg character of the hydration shell. 

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

BW Beck, Q Xie, T Ichiye. Computational study of S—H S hydrogen bonds m [4Ee-4S]-type ferredoxm x-ray and NMR structures Characterization and implications for redox potentials. Protein Sci, submitted. 

Water has physical hemical properties that are very different from those of other solvents [1] and its role in enhancing the reactivity and selectivity of some organic reactions is still a debated question. Recent experimental studies [3e, 9] and computer simulations [10] seem to indicate, at least with respect to the rate enhancement of aqueous Diels Alder reactions, that the main effects are due to the enforced hydrophobic interactions and hydrogen bond interactions. 

Levy (Chapter 6) has also explored the use of supercomputers to study detailed properties of biological macromolecule that are only Indirectly accessible to experiment, with particular emphasis on solvent effects and on the Interplay between computer simulations and experimental techniques such as NMR, X-ray structures, and vltratlonal spectra. The chapter by Jorgensen (Chapter 12) summarizes recent work on the kinetics of simple reactions In solutions. This kind of calculation provides examples of how simulations can address questions that are hard to address experimentally. For example Jorgensen s simulations predicted the existence of an Intermediate for the reaction of chloride Ion with methyl chloride In DMF which had not been anticipated experimentally, and they Indicate that the weaker solvation of the transition state as compared to reactants for this reaction In aqueous solution Is not due to a decrease In the number of hydrogen bonds, but rather due to a weakening of the hydrogen bonds. 

There have been a number of computational studies of the epoxidation reaction. These studies have generally found that the hydrogen-bonded peroxy acid is approximately perpendicular to the axis of the double bond, giving a spiro structure.75 Figure 12.8 shows TS structures and Ea values based on B3LYP/6-31G computations. The Ea trend is as expected for an electrophilic process OCH3 < CH3 CH = CH2 < H < CN. Similar trends were found in MP4/6-31G and QCISD/6-31G computations. 

Detection of the dA N1 and dC N3 adducts may not in one sense be particularly important for DNA based on their central position within the helical conformation and hydrogen bonding network.37,38 Still, the deoxynucleoside studies helped to focus attention on the reversibility of alkylation by QM and provided insight into the reactions of duplex DNA described below in Section 9.3. Reaction at the deoxynucleoside level also provided an essential system for developing a theoretical treatment of QM reaction.50-52 Computations based on density functional theory well rationalized the published results on d A and correctly anticipated the results on dG and dC reviewed above and described in more detail in Chapter 2 (Freccero). 

Jeong, H. Y., Han, Y., Comment on A Computational Study of the Structures of Van der Waals and Hydrogen Bonded Complexes of Ethene and Ethyne Chem. Phys. Lett., 263, 345. 

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