Substrate Specificity in Ester Hydrolysis by a New Water-Soluble Heterocyclophane

Article abstract of DOI:10.1021/ja00411a037

A new water-soluble heterocyclophane, N,N,N',N',N'',N'',N''',N'''-octamethyl-2,11,20,29-tetraaza<3.3.3.3>paracyclophanetetrammonium tetrafluoroborate (1), was found to catalyze the hydrolysis reaction of three aromatic chloroacetates, ClCH2CO2R , very effectively and specifically.The rate accelerations judged from the rate constant ratio of k₂/k₀ were 25+/-3 (7c), 6+/-0.5 (7b), or 2.6 (7a) at pH 8.10 in phosphate buffer and 18+/-2 (7c), 11+/-1 (7b), or 2.4 (7a) at pH 6.96 in phosphate buffer, strongly indicating that the "inclusion-electrostatic" catalyst 1 is more effective and discriminating than any of CTAB micelle, simple cyclodextrin inclusion, or an open-chain analogue (9).Very interestingly, however, a unique inhibition by 1 was found with a substrate of the α-chloro-β-naphthyl type (14), showing a rate constant ratio of k_inh/k₀=0.084+/-0.023 (1/12 deceleration).In order to elucidate the basis of this interesting discriminative catalysis or inhibition by 1, mechanistic studies were carried out.Temperature-jump experiments by the use of a model compound for substrate, sodium hydroxynaphthalenecarboxylate (11,12), had shown that the present host-guest inclusions are satisfactorily fast (k_A=1.8E7 to 4.4E7 s^-1 M^-1; k_D=1.6E4 to 3.8E4 s^-1), allowing the host and guest to search for the most appropriate arrangement for the slow subsequent hydrolysis.The absence of any systematic correlation between log (k₂/k₀) vs. pK_a of the leaving phenol or naphthol or a small basicity dependence of the N⁺-aryloxyl interaction leads to the conclusion that the very discriminative catalysis by 1 was developed mostly from specific substrate binding, in a sense that the N⁺-oxyanion interaction, at the transition state for the tetrahedral intermediate formation, remarkably depends on the substrate structure.The one-twelfth deceleration observed for 14 was, therefore, attributed to the inhibition of this N⁺-oxyanion interaction due to either the mechanism of "reverse binding" of the substrate or the "induced disfit".