Phosphoryl Transfer Processes Promoted by a Trifunctional Calix[4]arene Inspired by DNA Topoisomerase I

The cone-calix[4]arene derivative (1H(3))(2+), decorated at the upper rim with two guanidinium units and a phenolic hydroxyl in an ABAH functionalization pattern, effectively promotes the cleavage of the DNA model compound bis(p-nitrophenyl) phosphate (BNPP) in 80% DMSO solution at pH values in the range 8.5-12.0. The pH dependence of the kinetics was found to be fully consistent with the results of the potentiometric titration of the triprotic acid (1H(3))(2+). At pH 9.5, the rate enhancement of p-nitrophenol liberation from BNPP relative to background hydrolysis is 6.5 x 10(4)-fold at 1 mM concentration of the calix[4]arene derivative. Experimental data clearly point to the effective cooperation of the three active units and to the involvement of the phenolate moiety as a nucleophile in the phosphoryl transfer step. Subsequent liberation of a second equivalent of p-nitrophenol from the phosphorylated calixarene intermediate is conceivably promoted by the "built-in" guanidine/guanidinium catalytic dyad.