Chiroptical, ESMS and NMR spectroscopic study of the interaction of enantiopure lanthanide complexes with selected self-complementary dodecamer oligonucleotides

Abstract

The interaction of Δ- and Λ-Eu and Yb cationic complexes bearing an N-methylphenanthridinium chromophore with [(CG)₆]₂, [(AT)₆]₂ and [CGCGAATTCGCG]₂ has been interrogated by ESMS, ¹H NMR, absorption, difference circular dichroism, fluorescence quenching and Ln luminescence emission spectroscopy. Stepwise complexation occurs with up to 3 ∶ 1 limiting stoichiometry for [(CG)₆]₂ and 2 ∶ 1 for [CGCGAATTCGCG]₂, as indicated by absorption measurements and direct ESMS observation of the non-covalent duplex adducts. Binding to [(CG)₆]₂ occurred with an affinity of 8.7 × 10⁶ M⁻¹ duplex⁻¹ for the Δ-Eu isomer which was 50 times greater than to [(AT)₆]₂. A primary component of the free energy of binding has been linked to an intercalative interaction, supported by absorption, ICD and fluorescence quenching characteristics. The lanthanide coordination environment and local helicity remain unchanged but the oligonucleotide underwent distinctive changes in local helicity and pitch which were sensitive to the handedness of the Ln complex and in certain cases to the nature of the Ln ion (Yb vs. Eu). With [CGCGAATTCGCG]₂¹H NMR TOCSY and NOESY analysis in the presence of increasing concentrations of the Gd analogues revealed that the most avid complex binding site was located in the centre of the oligonucleotide, with the Δ-isomer binding more strongly.