Experimental Atom-by-Atom Dissection of Amide-Amide and Amide-Hydrocarbon Interactions in HO.

Quantitative information about amide interactions in water is needed to understand their contributions to protein folding and amide effects on aqueous processes and to compare with computer simulations. Here we quantify interactions of urea, alkylated ureas, and other amides by osmometry and amide-aromatic hydrocarbon interactions by solubility. Analysis of these data yields strengths of interaction of ureas and naphthalene with amide spO, amide spN, aliphatic spC, and amide and aromatic spC unified atoms in water. Interactions of amide spO with urea and naphthalene are favorable, while amide spO-alkylurea interactions are unfavorable, becoming more unfavorable with increasing alkylation. Hence, amide spO-amide spN interactions (proposed n-σ* hydrogen bond) and amide spO-aromatic spC (proposed n-π*) interactions are favorable in water, while amide spO-spC interactions are unfavorable. Interactions of all ureas with spC and amide spN are favorable and increase in strength with increasing alkylation, indicating favorable spC-amide spN and spC-spC interactions. Naphthalene results show that aromatic spC-amide spN interactions in water are unfavorable while spC-spC interactions are favorable. These results allow interactions of amide and hydrocarbon moieties and effects of urea and alkylureas on aqueous processes to be predicted or interpreted in terms of structural information. We predict strengths of favorable urea-benzene and N-methylacetamide interactions from experimental information to compare with simulations and indicate how amounts of hydrocarbon and amide surfaces buried in protein folding and other biopolymer processes and transition states can be determined from analysis of urea and diethylurea effects on equilibrium and rate constants.