Molecular recognition of modified nucleobases. Self-complementarity and base-pairing of betainic guanine model compounds

Abstract

Cross-conjugated models 11–14 of the natural modified RNA-nucleobase 7-methylguanosine 2, which is a conjugated mesomeric betaine, were synthesized and their self-complementarity and base-pairing properties were studied. Nucleophilic substitution of heteroaromatics with 2-amino-6-chloropyrimidin-4-ol 6 in 1,2-dichlorobenzene and subsequent treatment of the resulting pyrimidinylheteroarenium salts 7–10 with the anion exchange resin Amberlite IRA-93 in its hydroxy form gave the title compounds 11–14 almost quantitatively. Electrospray ionization mass spectrometry (ESIMS) and ¹H NMR titrations reveal that 11–14 are self-complementary molecules which form homo-intermolecular dimers. Semiempirical as well as ab initio calculations predict analogous geometries of the dimers and lead to considerable stabilization energies in comparison to the monomeric species. In ESI mass spectrometry, the molecular masses of noncovalent 1 ∶ 1 associates between the model compounds and the complementary nucleobase cytosine and the nucleoside cytidine can be detected. An ab initio calculation leads to a stabilization energy of 71.3 kJ mol⁻¹ on base-pairing of the mesomeric betaine 11 with cytosine. Additionally, dimeric 1 ∶ 1 associates can be detected between 11 and the self-complementary d(CpGp) as a DNA model compound.