title: Hydrolysis of DNA model substrates catalyzed by metal-substituted Wells-Dawson polyoxometalates.
abstract: In this study we report the first example of phosphoester bond hydrolysis in 4-nitrophenyl phosphate (NPP) and bis-4-nitrophenyl phosphate (BNPP), two commonly used DNA model substrates, promoted by metal-substituted polyoxometalates (POMs). Different transition metal and lanthanide ions were incorporated into the Wells-Dawson polyoxometalate framework and subsequently screened for their hydrolytic activity towards the cleavage of the phosphoester bonds in NPP and BNPP. From these complexes, the Zr(iv)-substituted POM showed the highest reactivity. At pD 7.2 and 50 °C a NPP hydrolysis rate constant of 7.71 × 10(-4) min(-1) (t(1/2) = 15 h) was calculated, representing a rate enhancement of nearly two orders of magnitude in comparison with the spontaneous hydrolysis of NPP. The catalytic (k(c) = 1.73 × 10(-3) min(-1)) and formation constant (K(f) = 520.02 M(-1)) for the NPP-Zr(iv)-POM complex were determined from kinetic experiments. The reaction proceeded faster in acidic conditions and (31)P NMR experiments showed that faster hydrolysis is proportional to the presence of the 1 : 1 monosubstituted Zr(iv)-POM at acidic pD values. The strong interaction of the 1 : 1 monosubstituted Zr(iv)-POM with the P-O bond of NPP was evidenced by the large chemical shift and the line broadening of the (31)P nucleus in NPP observed upon addition of the metal complex. Significantly, a ten-fold excess of NPP was fully hydrolyzed in the presence of the Zr(iv)-POM, proving the principles of catalysis. The NMR spectra did not show sign of any paramagnetic species, excluding an oxidative cleavage mechanism and suggesting purely hydrolytic cleavage.
authors.affiliation: KU Leuven, Department of Chemistry, Celestijnenlaan 200F, B-3001 Heverlee, Belgium.
authors.forename: Stef
authors.initials: S
authors.lastname: Vanhaecht
authors.forename: Gregory
authors.initials: G
authors.lastname: Absillis
authors.forename: Tatjana N
authors.initials: TN
authors.lastname: Parac-Vogt
mesh_terms: D002384:Catalysis; D004247:DNA / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D009596:Nitrophenols / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D017973:Tungsten Compounds / Q000737:chemistry*; D000099294:Polyoxometalates
chemical_list: D004247:DNA; D008670:Metals; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates; C008644:nitrophenylphosphate; C002887:bis(4-nitrophenyl)phosphate