title: Phosphoryl Transfer Processes Promoted by a Trifunctional Calix[4]arene Inspired by DNA Topoisomerase I.
abstract: The cone-calix[4]arene derivative (1H3)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 (1H3)2+. At pH 9.5, the rate enhancement of p-nitrophenol liberation from BNPP relative to background hydrolysis is 6.5 × 104-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.
authors: Dipartimento di Chimica and IMC - CNR Sezione Meccanismi di Reazione, Universitá La Sapienza , 00185 Rome, Italy.
authors: Riccardo
authors: R
authors: Salvio
authors: Dipartimento di Chimica, Universitá degli Studi di Parma , Viale delle Scienze 17/A, 43124 Parma, Italy.
authors: Stefano
authors: S
authors: Volpi
authors: Dipartimento di Chimica and IMC - CNR Sezione Meccanismi di Reazione, Universitá La Sapienza , 00185 Rome, Italy.
authors: Roberta
authors: R
authors: Cacciapaglia
authors: Dipartimento di Chimica, Universitá degli Studi di Parma , Viale delle Scienze 17/A, 43124 Parma, Italy.
authors: Francesco
authors: F
authors: Sansone
authors: Dipartimento di Chimica and IMC - CNR Sezione Meccanismi di Reazione, Universitá La Sapienza , 00185 Rome, Italy.
authors: Luigi
authors: L
authors: Mandolini
authors: Dipartimento di Chimica, Universitá degli Studi di Parma , Viale delle Scienze 17/A, 43124 Parma, Italy.
authors: Alessandro
authors: A
authors: Casnati
mesh_terms: D047250:Calixarenes / Q000737:chemistry*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010636:Phenols / Q000737:chemistry*; D010758:Phosphorus / Q000737:chemistry*; D011199:Potentiometry; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D010758:Phosphorus; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human