Ferrocinnamic acid

Czamieki and Breslow (22) have studied the rate of acyl transfer from a substrate that is bound by the acyl part rather than by the leaving group. Having shown that ferrocene binds strongly to -cyclodextrin, Czamiecki and Breslow employed the p-nitrophenyl ester of ferrocinnamic acid in kinetic studies using DMSO-buffer mixtures. A rate acceleration of 51,000 times background was observed for acylation of /i-cyclodextrin. 

One structure that seemed attractive was ferrocinnamic acid, a ferrocene derivative carrying an acrylic acid chain. The substrate examined was the p-nitrophenyl ester of this acid (I) (12). It was clear from the known binding constants of ferrocene (4) and of p-nitrophenyl acetate that the ferrocene nucleus should be the one... 

Acylation of fl-cyclodextrin. The acylation of /5-cyclodextrin is modestly accelerated by bound m-nitrophenyl acetate, m-N02C6H40C0CH3. Recently acylation of /3-cyclodextrin at a rate comparable to acylation of chymotrypsin has been reported. The acylating reagent is the p-nitrophenyl ester (1) of ferrocinnamic acid. This reagent was chosen because ferrocene is strongly bound within the cavity of /3-cyclodextrin. The acylation is accelerated by > 50,000-fold compared to hydrolysis of 1 in DMSO-HjO alone buffered at pH 6.8. Thus cyclodextrins can behave as artificial enzymes. 

The acylation of the cyclohepta-amylose anion in 60% DMSO 40% water by the 4-nitrophenyl ester of ferrocinnamic acid (1) is accelerated over 50 000-foId compared with the hydrolysis by buffer alone. The actual rate achieved is similar to that for the acylation of -chymotrypsin by 4-nitrophenyl acetate. This is the greatest acceleration observed for cycloamylose catalysis, but at the same time highlights one of the difficulties of using this class of compounds as general catalysts. The optimum substrate structure has to be found for the catalyst. According to molecular models, (1) fits snugly into the preformed cavity. 

The reason for interest in the details is that the acceleration with I was very large compared with that which had been observed previously with cyclodextrin reactions. In fact, in a system with 60% DMSO-40% H20 and hydroxide supplied by a buffer that in H20 would have a pH of 6.8, the Vmax was 0.18 sec-1. This represented an acceleration 750,000-fold compared with hydrolysis by the hydroxide ion alone in this same buffered medium in the absence of cyclodextrin. The product of this reaction was the ferrocinnamate ester of cyclodextrin, which then hydrolyzed slowly in a second step to the salt of the free acid. 

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