Mechanistic studies using antihydrophobic agents

Abstract: The hydrophobic effect-that decreases the solubilities of organic compounds in water and leads to aggregation of such species in water solution+an be diminished by various additives that we have termed antihydrophobic agents. When relatively small amounts are used, this may be the principal effect of such additives on solubilities and reaction rates. If so, quantitative studies can reveal the amount of hydrophobic surface that becomes isolated from the water solvent in a transition state; this is a direct guide to transition state structure. This paper describes the evidence for this new approach to elucidating transition state structures for some reactions in water, and the relevance of this information to the situation in other solvents. Introduction. Molecules with apolar surfaces tend to aggregate in water solution because of the hydrophobic effect. This-the tendency of non-polar surfaces to avoid contact with water-is often ascribed to the strong self-association of water, but a quantitative study reveals that the major factor is the superior solvation of hydrocarbons by other hydrocarbons, rather than by water (1). Regardless of its cause, the hydrophobic effect can be invoked as a major determinant of the solubility of many organic compounds in water. Thus agents that increase the hydrophobic effect cause a decreased solubility of hydrocarbons in water, while agents that we have termed antihydrophobic cause an increase on hydrocarbon solubility. Such antihydrophobic agents are also denaturants of proteins and nucleic acids, whose three-dimensional structures are in large part the result of hydrophobic interactions between amino acid sidechains or nucleotide bases