Metal-ion-governed molecular recognition: extent of intramolecular stack formation in mixed-ligand--copper(II) complexes containing a heteroaromatic N base and an adenosine monophosphate (2'AMP, 3'AMP, or 5'AMP). A structuring effect of the metal-ion bridge.

Stability constants of mixed-ligand Cu(Arm)(AMP) complexes [where Arm = 2,2'-bipyridyl (Bpy) or 1,10-phenanthroline (Phen) and AMP2- = 2'AMP2-, 3'AMP2- or 5'AMP2-] were determined by potentiometric pH titrations in aqueous solution at I = 0.1 M (NaNO3) and 25 degrees C. The ternary Cu(Arm)(AMP) complexes are more stable than corresponding Cu(Arm)(R-MP) complexes, where R-MP2- represents a phosphate monoester with a group R that is unable to participate in any kind of interaction within the complexes as, for example, D-ribose 5'-monophosphate. This increased stability is attributed, in agreement with previous results, to intramolecular stack formation in the Cu(Arm)(AMP) complexes between the purine residue of the AMPs and the aromatic rings of Bpy or Phen. Based on correlation lines (previously obtained from log K versus pKa plots) for Cu(Arm)(R-MP) complexes without a ligand-ligand interaction, a quantitative evaluation was carried out. The degree of formation of the species with the intramolecular stacks increases for the Cu(Arm)(AMP) complexes in the series: 3'AMP2- less than 5'AMP2- less than 2'AMP2-; e.g. in Cu(Bpy)(3'AMP) the stack reaches a formation degree of 45 +/- 11% and in Cu(Bpy)(2'AMP) one of 96.1 +/- 0.7% is obtained. It must be emphasized that these differences are due to the different steric orientations of the bridging metal ion, which result from the varying position of the phosphate group on the ribose ring. As shown by 1H-NMR shift measurements, there is no significant effect of the position of the phosphate group on the stability of the binary (Phen)(AMP)2- adducts (K approximately 36 M-1 in D2O); such an effect is seen only if a metal-ion bridge is formed between the moieties forming the stack, i.e. metal-ion coordination imposes individual properties on the AMPs. By also taking into account some recent results on other nucleoside 5'-monophosphate complexes, the following trend for an increasing stacking tendency of the nucleic base moieties can be established: uracil approximately less than cytosine approximately less than thymine much less than adenine less than 7-deazaadenine. Some additional conclusions of general importance are given and the relevance of the results with regard to bio-systems is indicated.