Total enantioselectivity in the DNA binding of the dinuclear ruthenium(ii) complex [{Ru(Me2bpy)2}2(μ-bpm)]4+ {bpm = 2,2′-bipyrimidine; Me2bpy = 4,4′-dimethyl-2,2′-bipyridine}

Abstract

The binding of the three stereoisomers (ΔΔ-, ΛΛ- and ΔΛ-) of the dinuclear ruthenium(II) complex [{Ru(Me₂bpy)₂}₂(μ-bpm)]⁴⁺ {Me₂bpy = 4,4′-dimethyl-2,2′-bipyridine; bpm = 2,2′-bipyrimidine} to a tridecanucleotide containing a single adenine bulge has been studied by ¹H NMR spectroscopy. The addition of the ΔΔ-isomer to d(CCGAGAATTCCGG)₂ induced significant chemical shift changes for the base and sugar resonances of the residues at the bulge site (G₃A₄G₅/C₁₁C₁₀), whereas small shifts were observed upon addition of the enantiomeric ΛΛ-form. NOESY spectra of the tridecanucleotide bound with the ΔΔ-isomer revealed intermolecular NOE's between the metal complex and the nucleotide residues at the bulge site, while only weak NOE's were observed to terminal residues to the ΛΛ-form. Competitive binding studies were performed where both enantiomers were simultaneously added to the tridecanucleotide, and for all ratios of the two stereoisomers the ΔΔ-isomer remained selectively bound at the bulge site with the ΛΛ-enantiomer localised at the terminal regions of the tridecanucleotide. The meso-diastereoisomer (ΔΛ) was found to bind to the tridecanucleotide with characteristics intermediate between the ΔΔ- and ΛΛ-enantiomers of the rac form. Two distinct sets of metal complex resonances were observed, with one set having essentially the same shift as the free metal complex, whilst the other set of resonances exhibited significant shifts. The NOE data indicated that the meso-diastereoisomer does not bind as selectively as the ΔΔ-isomer, with NOE's observed to a greater number of nucleotide residues compared to the ΔΔ-form. This study provides a rare example of total enantioselectivity in the binding of an inert transition metal complex to DNA, produced by the shape recognition of both ruthenium(II) centres.