Synthesis and luminescence properties of a trinucleotide–europium(III) complex conjugate

Abstract

Two trinucleotide conjugates of the macrocyclic ligand 1,4,7-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane are prepared. One contains only DNA (1) and the second is a chimeric RNA/DNA conjugate (2). The synthetic methodology used to prepare the trinucleotide macrocyclic ligand conjugates is based on the introduction of a convertible nucleoside which has an electrophilic function to facilitate the attachment of any nucleophilic ligand to the 5′-position of the 3′-nucleoside unit. The convertible nucleoside is first treated with the macrocyclic ligand, 1,4,7,10-tetraazacyclododecane, followed by alkylation of the three remaining amine groups to give a conjugated macrocyclic ligand with three pendent amide groups. Addition of an equivalent of EuCl₃ to trinucleotide (1) or (2) yields the complexes Eu(1) and Eu(2), respectively. Studies using time-resolved and steady state direct excitation luminescence spectroscopy show that Eu(III) binds to the macrocyclic moiety in 1 and in 2. The excitation peak frequency for the ⁷F_o→⁵D_o transition and the unexpectedly low number of water ligands in Eu(1) and Eu(2) are consistent with additional interactions of the Eu(III) macrocycle with one of the phosphate diester groups. Studies show that Eu(2) undergoes cleavage at the uridine nucleotide. The unique point of attachment of the macrocyclic complex will enable the preparation of new lanthanide nucleic acid conjugates with useful properties.