COMPARISON OF THE EXTENT OF MACROCHELATE FORMATION IN COMPLEXES OF DIVALENT METAL-IONS WITH GUANOSINE (GMP(2-)), INOSINE (IMP(2-)), AND ADENOSINE 5'-MONOPHOSPHATE (AMP(2-)) - THE CRUCIAL ROLE OF N-7 BASICITY IN METAL ION-NUCLEIC BASE RECOGNITION

The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ and IMP(2-) or GMP(2-) were determined by potentiometric pH titration in aqueous solution (25 degrees C; I = 0.1 M, NaNO3) and evaluated together with the constants previously determined for the corresponding AMP(2-) complexes. The experimental conditions were selected such that self-association of the nucleotides (NMP(2-)) and their complexes was negligibly small; i.e., the monomeric M(NMP) and M(NMP-H) complexes were studied. On the basis of recent measurements with simple phosphate monoesters and phosphonate derivatives, R-MP(2-), where R is a noncoordinating residue (Sigel, H. et al. Helv. Chim. Acta 1992, 75, 2634), it is shown that in all the M(NMP) complexes of IMP(2-) and GMP(2-) a base interaction of the phosphate-coordinated metal ion occurs. The various formation degrees of the resulting M(NMP) and M(NMP-H) macrochelates are determined. To be able to relate the formation degree of the M(NMP) macrochelates with the basicity of N-7, the acidity constants of monoprotonated inosine and guanosine were also measured and the microacidity constant scheme for H-3(IMP)(+) was elaborated. Plots of the log stability increases determined for the M(NMP) complexes by comparison with calculated data for a sole metal ion-phosphate coordination versus the negative log of the microacidity constants of the H+(N-7) site of the monoprotonated nucleosides, including adenosine, reveal that the extent of macrochelate formation is mainly determined by the basicity of N-7. However, these same plots also indicate that in the M(IMP) and M(GMP) complexes formed with Co2+, Ni2+, and Cd2+ an additional outer-sphere coordination to 0-6 is likely. Macrochelation with the alkaline earth ions (formation degree <30%) is suggested to be largely of an outer-sphere type. The structures of the mentioned macrochelates, the evidence for inner-sphere versus outer-sphere binding of the metal ions, and the various intramolecular equilibria are discussed. Finally, it is emphasized that this kind of knowledge also improves our understanding of the selective recognition of metal ions by nucleic acids.