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 A₁₂-A₁₈. 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 °C are 7.2 (±0.5) × 10^-2 M^-1 s^-1, 6.3 (±0.3) × 10^-2 M^-1 s^-1 and 1.4 (±0.2) × 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(STHP)(CF₃SO₃)₃; binding constants and first-order catalytic rate constants are, respectively, 62 (±9) M^-1 and 9.5 (±0.9) × 10^-4 s^-1, 68 (±9) M^-1 and 1.8 (±0.4) × 10^-4 s^-1, and 130 (±24) M^-1 and 6.6 (±1.0) × 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.