Phosphodiester cleavage by trivalent lanthanides in the presence of native cyclodextrins

Abstract

Testing phosphodiesterase activity of Eu(III) in the presence of native cyclodextrins revealed capacity of β-cyclodextrin (β-CD) to stabilize catalytically active metal hydroxocomplexes in mildly basic solutions. Kinetics of the hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) and transesterification of 2-hydroxypropyl 4-nitrophenyl phosphate (HPNP) as models of DNA and RNA respectively has been studied with La(III), Pr(III), Nd(III), Eu(III), Gd(III) and Dy(III) cations in the presence of β-CD in the range of pH 7.0–9.0. The overall catalytic effect with 2mM lanthanide–β-CD complexes was up to 105 for HPNP and 108 for BNPP at pH 8 demonstrating the highest catalytic activity among so far reported artificial phosphodiesterases. Analysis of concentration and pH-dependences of observed rate constants for different lanthanides showed that active species are binuclear polyhydroxocomplexes of general type [M2(β-CD)(OH)n]6−n with n=3–5. The metal–β-CD and phosphodiester–β-CD interactions were studied by 1H NMR spectroscopy. Mechanistic implications of much higher catalytic efficiency in BNPP hydrolysis as compared to HPNP transesterification are discussed.