Nucleic Acid Base Pair and Mispair Interactions with Metal IonsA Thermodynamic Aspect

Abstract

Potentiometric equilibrium measurements were made for some metal ions (M(II) = Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Ca(II), Sr(II), and Ba(II)) with guanine (A) in a 1:1 (M(II):A) ratio and with cytosine, cytidine, 5-bromocytosine, 5-azacytosine, and 5-fluorocytosine as primary ligands (L) and guanine as secondary ligand in a 1:1:1 (M(II):L:A) ratio at (25.0, 35.0, and 45.0) °C and I = 0.1 mol·dm-3 NaNO3 in aqueous solution. The experimental pH-titration data were analyzed by using a BEST computer program in order to evaluate the formation constants of various intermediate species and their relative distribution. The experimental conditions were selected in such a way that the self-association of the nucleobases and their complexes due to stacking interaction was negligibly small, so that only the neutral monomeric and hydroxo ternary complexes were studied. The enthalpy (ΔfH°) and entropy (ΔfS°) changes for the formation of binary and ternary complexes were calculated from temperature coefficient data. The δΔfS° values are positive for all the metal ligand systems. The negative δΔfH° values indicate the extra stabilization of most of the ternary complexes by the exothermic enthalpy change (δΔfS° = ΔTS° − ΔBS° and δΔfH° = ΔTH° − ΔBS° where ΔTS°, ΔTH° and ΔBS°, ΔBH° are the entropy and enthalpy values associated with the ternary and binary complexes, respectively). On the basis of IR data for metal complexes with the 5FC−G mispair, it has been proposed that the guanine is bonded to metal ions through N1/C6O and N7, whereas cytosine and its derivatives are bonded through N3 atoms in ternary complexes.