3 - Multiple pathways in cyclodextrin-catalyzed hydrolysis of perfluoro-alkylamides

ALEJANDRO M. GRANADOS; RITA H. DE ROSSI

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Lugar: Washington; Año: 1995 vol. 117 p. 3690 - 3696

0002-7863

The hydrolysis of p-nitroanilide of perfluoroalkanoic acids, CF3(CF2),,CO-, with n = 1, 2, 3, 5, 6, and 7, la-f, was studied in the presence of P-cyclodextrin (CD). All reactions were catalyzed by CD through the formation of a 1:l and 1:2 inclusion complexes. The association equilibrium constants for the 1:l complexes were dependent on the number of carbons of the fluoroalkyl chain, whereas those of the 1:2 complexes were almost independent. These results indicate that, in the former case, the perfluoroalkyl chain is included, while in the latter, the CD unit encloses the aryl ring. For compounds la,b both complexes were more reactive than the substrate itself. The ratio of the reaction of complexed to uncomplexed substrate had its highest value for la in the case of the 1:l complex, and for lb, the 1:2 complex. This is attributed to the geometry of the complexes. Although compounds lc-e reacted at the same rates in the free or 1: 1 complexed form, CD accelerated the reactions because of an increase of the pKa of the substrate, which results in a higher concentration of the neutral reactive substrate at the same pH. Compound If formed aggregates even at 1 0-6 M concentration, and CD-induced deaggregation resulted in catalysis of the reaction. and for lb, the 1:2 complex. This is attributed to the geometry of the complexes. Although compounds lc-e reacted at the same rates in the free or 1: 1 complexed form, CD accelerated the reactions because of an increase of the pKa of the substrate, which results in a higher concentration of the neutral reactive substrate at the same pH. Compound If formed aggregates even at 1 0-6 M concentration, and CD-induced deaggregation resulted in catalysis of the reaction. Introduction Cyclodextrins are cyclic oligomers of a-D-glucose which are produced by enzymatic hydrolysis of starch. Compounds with 6, 7, and 8 glucose units are called a-, ,6-, and y-cyclodextrin.2 These compounds have been used as enzyme models for proteases and have proved to be good catalysts for the hydrolysis of ester^.^ On the other hand, the hydrolysis of amides has been little studied in the presence of cycl~dextrins.~-~ The effect of cyclodextrins on the hydrolysis of p-nitrophenyl alkanoates of different chain length has been studied in several lab~ratories,´-~a nd it was found that the kinetic parameters varied, as the acyl chain length changed, consistent with the change in the mode of binding of the ester from aryl to alkyl group incl~sion.~ The hydrolysis of m-nitrotrifluoroacetanilide and trifluoroacetanilide is inhibited by P-cyclodextrin @-CD) and hydroxypropyl-, 6-cyclodextrin (HPCD), whereas the reaction of p-nitrotrifluoroacetanilide is catalyzed. l o This contrasting behavior of amides and esters is attributed to different rate-limiting steps in the mechanism of product formation of the catalyzed pathway,