Amide group hydrogen bonding ability

As a p hydroxy derivative of phenylalanine tyrosine has properties similar to those of phenylalanine plus the ability to engage m hydrogen bonding via its —OH group Asparagine and glutamine are not amines they are amides The side chains of both O... 

Coleman et al. have performed a preliminary structure/activity study for a series of analogues of 77 [149]. They found that removal of the naphthoate moiety (88 Scheme 11.11) dramatically reduced the yield of DNA alkylation, while replacement of the NH2 group with O-benzyl (89 and 90) abolished DNA alkylation completely. Compound 91 alkylated DNA with reduced efficiency, so this effect is not simply due to a requirement for a hydrogen bond donor at this position. Perhaps the amide is required at this position to increase the ability of the C=0 to act as a hydrogen bond acceptor. Importantly, they found a strong correlation between the extent of in vitro DNA alkylation and cell culture cytotoxicity. 

They are of interest in studies on the thermodynamic behavior of nonionic compounds in aqueous media because they have the ability of forming hydrogen bonds with the solvent (through the two r/j-amide groups in the cyclic dipeptide ring), and give rise to hydrophobic interactions. ... 

Use of a hydrocarbon solvent such as cyclohexane can discriminate these compounds either as the only measured value or as a value to be subtracted from the octanol value (Alog P) [19-21]. Unfortunately, cyclohexane is a poor solvent for many compounds and does not have the utility of octanol. Groups which hydrogen bond and attenuate actual membrane crossing compared to their predicted ability based on octanol are listed in Figure 1.4. The presence of two or more amide, carboxyl functions in a molecule will significantly impact on membrane crossing ability and will need substantial intrinsic lipophilicity in other functions to provide sufficient hydrophobicity to penetrate the lipid core of the membrane. 

As Table 1.2 shows, m, values tend to increase with the ability of a group to form hydrogen bonds, its dipole moment, and its molecular size (polarizability). Thus, the amide and... 

Other neutral hosts have also been prepared based upon the hydrogen-bond donating ability of appropriately arranged amide groups,71-74 highly fluorinated macrocycles,75 or even +S=08- and 8+P=Os- dipoles.76... 

Our next optimization step consisted in introduction of substituents in the 4-position of the aromatic peptide subunits of 3 [18]. These substituents should affect the rotation of neighboring amide groups by steric effects. More importantly, if they can form hydrogen bonds to the amide protons they should stabilize peptide conformations in which all NH groups point away from the cavity center. This effect would not only affect the flexibility but also the anion-binding ability of 3, because, for the latter, a conformation with converging NH groups is required. To... 

---