Internal hydrogen bonding

Ot-HehcalBundles. The a-helix is the most extensively studied protein stmctural motif. Because a-hehces form internal hydrogen bonds between the C=0 of residue i and the N—H of residue i + 4 (see Fig. 2), the individual helix is stabili2ed and can exist in isolation. Individual heUces can be manipulated as independent stmctural modules designed to associate in some predetermined manner. Often, a minimalist approach to the design of a-hehces has been taken. In this approach the goal is to obtain the desired stmctural motif using the simplest possible constmction. 

The configuration was assigned after oxidation of (43) and (44) to the corresponding 3,20-diketones. The diketone obtained from (44) showed an intramolecular bonded hydroxyl absorption at 3450 cm h Inspection of molecular models indicates that only a 12 -hydroxyl function can form an internal hydrogen bond to the 20-carbonyl group. 

However, not all such proton transfers are diffusion controlled. For example, if an internal hydrogen bond exists in a molecule, reaction with an external acid or base is often much slower. In the following case ... 

L. P. Kuhn pointed out that, if hydroxyl groups of an a-dihydroxy compound are sufficiently close, they will form an internal hydrogen-bond. 

SCHEME 7.20 Cyclopent[6]indole analogues. Quinone methide structure shown with internal hydrogen bonding. 

The results of AE calculations shown in Scheme 7.26 show that internal hydrogen bonds can influence the thermodynamics of quinone methide tautomerization in some instances. For the prekinamycin quinone methide without internal hydrogen bonds... 

Lemus, R. H. Skibo, E. B. Design of pyritnido[4.5-s quinazoline-based anthraquinone mimics, structure-activity relationship for quinone methide formation and the influence of internal hydrogen bonds on quinone methide fate. J. Org. Chem. 1992, 57, 5649-5660. 

Internal hydrogen bonding promotes imidazole transfer in the reaction of primary and secondary benzyl alcohols with CDI (A) or ImSOIm (B) [15],[16]... 

Upon deuteration (exchange of the H in the internal hydrogen bond for D) we get... 

The internal hydrogen bond is the origin of the rapid deactivation. 

Aformamide-water complex109 was studied by Sim et al. by means of the DFT(SVWN), DFT(PW86/P86), and DFT(B88/P86) calculations. The LDA led to qualitatively wrong results for conformational energies of this hydrogen-bonded complex. Furthermore, the poor performance of the LDA calculations was observed in studies of conformational equilibria in malonaldehyde, a molecule with the internal hydrogen bond. 

Caminati, W., A. C. Fantoni, B. Velino, K. Siam, L. Schafer, J. D. Ewbank, and C. Van Alsenoy. 1987a. Conformational Equilibrium and Internal Hydrogen Bonding in 2-Methylallyl Alcohol Detection of a Second Conformer by Microwave Spectroscopy on the Basis of Ab Initio Structure Calculations. J. Mol. Spectrosc. 124, 72-81. 

Most PARPi are based upon nicotinamide (1), the by-product of the PARylation reaction, which itself is a micromolar PARPi. PARPi have been developed using three design approaches constraining the amide using an internal hydrogen bond, forming a lactam, and incorporation of the amide into a heterocycle [3,15]. 

Figure 18. Conformations of diol epoxides of BP. (a) Diagrams of the anti- and syn-isomers of a diol epoxide showing the possibility for internal hydrogen-bonding in the syn-diol epoxide.

C. J. Cramer and D. G. Truhlar, Quantum chemical conformational analysis of 1,2-ethanediol Correlation and solvation effects on the tendency to form internal hydrogen bonds in the gas phase and aqueous solution, J. Am. Chem. Soc. 116 3892 (1994). 

TMDs usually consist of a helix. The peptide bond is intrinsically polar and can form internal hydrogen bonds... 

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