RNA CLEAVAGE AND PHOSPHATE DIESTER TRANSESTERIFICATION BY ENCAPSULATED LANTHANIDE IONS - TRAVERSING THE LANTHANIDE SERIES WITH LANTHANUM(III), EUROPIUM(III), AND LUTETIUM(III) COMPLEXES OF 1,4,7,10-TETRAKIS(2-HYDROXYALKYL)-1,4,7,10-TETRAAZACYCLODODECANE

Lanthanide(III) complexes of two related Ligands, 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane (THED) and(1S,4S,7S,10S)-1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (S-THP) promote transesterification of the 4-nitrophenyl phosphate ester of propylene glycol (1) and cleavage of RNA oligomers A(12)-A(18) The pH-rate profiles for the transesterification of 1 or cleavage of RNA oligomers by lanthanide(III) complexes suggest that a lanthanide-bound hydroxide (Ln(OH)(2+)) or lanthanide-bound alkoxide (Ln(OR)(2+)) complex is the catalytically active species. Second-order rate constants for the transesterification of 1 by Ln(OH)(2+) or Ln(OR)(2+) at 37 degrees C are 7.2 (+/- 0.5) x 10(-2) M(-1) s(-1), 6.3 (+/- 0.3) x 10(-2) M(-1) s(-1) and 1.4 (+/- 0.2) x 10(-2) M(-1) s(-1) for the THED complex of europium(III) and for the S-THP complexes of lanthanum(III) and europium-(III), respectively. A second-order rate constant of 1.1 M(-1) s(-1) is obtained for the cleavage of RNA oligomers by the Eu(OH)2+ or Eu(OR)2+ form of the europium(III) THED complex. At higher concentrations of lanthanide(III) complex (>1.00 mM) at pH values where Ln(OH)(2+) or Ln(OR)(2+) are the predominent species, saturation kinetics are observed for the transesterification of 1 by Eu(THED)(CF3SO3)(3), Eu(S-THP)(CF3SO3)(3), or La(S-THP)(CF3SO3)(3); binding constants and first-order catalytic rate constants are, respectively, 62 (+/- 9) M(-1) and 9.5 (+/- 0.9) x 10(-4) s(-1), 68 (+/- 9) M(-1) and 1.8 (+/- 0.4) x 10(-4) s(-1), and 130 (+/- 24) M(-1) and 6.6 (+/- 1.0) x 10(-4) s(-1). As determined by potentiometric titrations, pK(a), values for lanthanide-bound water or lanthanide-bound hydroxyalkyl decrease on traversing the lanthanide series: La(S-THP(CF3SO3)(3), 8.40 (+/- 0.05); Eu(THED)(CF3SO3)(3), 7.50 (+/- 0.05); Eu(S-THP)(CF3SO3)(3) 7.80 (+/- 0.1); Lu(S-THP)(CF3SO3)(3), 6.40 (+/- 0.1) and 9.30 (+/- 0.1). Conductivity measurements suggest that the europium(III) complexes exist as 3:1 electrolytes in water at pH 6.5.