Molecular Recognition of Substituted Aromatic Carboxylic Acids

Interestingly, the minor substitution changes of these three positional isomers showed dramatically different CICS values and their interrelated and AG values, by both n-n and hydrophobic interactions with 1. The largest CICS values for o-(Hc) and m- (He) are 14 and 7 times larger, respectively, than that ofp- (Ha). This observation can be explained by the steric effects of the guests, since the two hydrophilic functional groups which form H-bonds with the bulk H2O need to avoid unfavorable interactions with the hydrophobic cavity of 1. Moreover, these 

H-bonds with the bulk H2O determine the orientations of o-, m-, and p-amino-benzoic acids as they approach host 1 the hydrophobic end of guests o-, m-, and p-aminobenzoic acids must enter 1 more favorably. Therefore, guests with the most exposed hydrophobic portions, such as Ar3, should have the largest CICS values, as was observed. Molecular modeling studies confirm that the distances between the amino H atom and carboxylate O atom for 0-, m-, andp-aminobenzoic acids are 1.85 A, 4.98 A, and 6.87 A, respectively. With the increasing distances between these the two hydrophilic functional groups, from 0-, m-, to p-amino-benzoic acids the steric hindrance also dramatically increases and, at the same time, the exposed hydrophobic portions decrease. 

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