Hydrogen bonds structural physical effects

Effect of hydrogen bonds on the properties of liquids— The effect of hydrogen bonded structures is to produce certain anomalies in the physical properties of... 

The structure of the boundary layers of water depends on the nature of the surface. Near a hydrophilic surface this stmcture must be essentially different from that on a hydrophobic substrate because of the absence of hydrogen bonds between water and the surface in the latter case. When the surface is chemically and physically inert, the inability of the water molecules to extend their hydrogen bond structure into such a surface could have the same effect as heating. If the surface interacts with water, the inability of those molecules forcibly oriented near the surface to maintain normal hydrogen bonding with their neighbors creates the same type of perturbation [172]. 

The most frequently encountered hydrolysis reaction in drug instability is that of the ester, but curtain esters can be stable for many years when properly formulated. Substituents can have a dramatic effect on reaction rates. For example, the tert-butyl ester of acetic acid is about 120 times more stable than the methyl ester, which, in turn, is approximately 60 times more stable than the vinyl analog [16]. Structure-reactivity relationships are dealt with in the discipline of physical organic chemistry. Substituent groups may exert electronic (inductive and resonance), steric, and/or hydrogen-bonding effects that can drastically affect the stability of compounds. A detailed treatment of substituent effects can be found in a review by Hansch et al. [17] and in the classical reference text by Hammett [18]. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

In order to understand these extreme changes in physical and chemical properties of hydrogen-bonded systems, first attempts to model their dynamics were related to rather simple structures, as exhibited by the KDP family or squaric acid and its analogues. The isotope effects on their ferro- or anti-ferroelectric transition temperatures are listed in Table 1 together with the corresponding isotope exponent. 

Hydrogen-bonding interactions are considerably weaker than ionic interactions and covalent bonds but have a profound effect on many chemical and physical properties [221] and determine the shapes of large molecules such as proteins and nucleic acids. Protein secondary structure is determined by H bonding between the carbonyl oxygen of one amide unit and the N—H bond of another. The two strands of the double helix of... 

Other energetic components associated widi the solvation process include non-electrostatic aspects of hydrogen bonding and solvent-structural rearrangements like the hydrophobic effect. Despite many years of study, the fundamental physics associated with both of these processes remains fairly controversial, and physically based models have not been applied with any regularity in the context of continuum solvation models. 

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