Ester Hydrolysis by a Cyclodextrin Dimer Catalyst with a Tridentate N,N ',N ''-Zinc Linking Group

A new beta-cyclodextrin dimer, 2,6-dimethylpyridine-bridged-bis(6-monoammonio-beta-cyclodextrin) (pyridyl BisCD, L), is synthesized. Its zinc complex (ZnL) is prepared, characterized, and applied as a catalyst for diester hydrolysis. The formation constant (log L-ML=7.3 +/- 0.04) of the complex and deprotonation constant (pK(a1) = 8.14 +/- 0.03, pK(a2) = 9.24 +/- 0.01) of the coordinated water molecule were determined by a potentiometric pH titration at (25 +/- 0.1)degrees C, indicating a tridentate N,N',N ''-zinc coordination. Hydrolysis kinetics of carboxylic acid esters were determined with bis(4-nitrophenyl)carbonate (BNPC) and 4-nitrophenyl acetate (NA) as the substrates. The resulting hydrolysis rate constants show that ZnL has a very high rate of catalysis for BNPC hydrolysis, yielding an 8.98 x 10(3) fold rate enhancement over uncatalyzed hydrolysis at pH 7.00, compared to only a 71.76-fold rate enhancement for NA hydrolysis. Hydrolysis kinetics of phosphate esters catalyzed by ZnL are also investigated using bis(4-nitrophenyl)phosphate (BNPP) and disodium 4-nitrophenyl phosphate (NPP) as the substrates. The initial first-order rate constant of catalytic hydrolysis for BNPP was 1.29 x 10(-7)s(-1) at pH8.5, 35 degrees C and 0.1 mm catalyst concentration, about 1600-fold acceleration over uncatalyzed hydrolysis. The pH dependence of the BNPP cleavage in aqueous buffer was shown as a sigmoidal curve with an inflection point around pH 8.25, which is nearly identical to the pK(a) value of the catalyst from the potentiometric titration. The k(BNPP) of BNPP hydrolysis promoted by ZnL is found to be 1.68 x 10(-3)M(-1)s(-1), higher than that of NPP, and comparatively higher than those promoted by its other tridentate N,N',N ''-zinc analogues.