Intramolecular stacking interactions in ternary copper(II) complexes formed with 2,2′-bipyridine or 1,10-phenanthroline and 9-(4-phosphonobutyl)adenine (dPMEA), the carba relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA)

• Published in: Journal of inorganic biochemistry 2001-03, Vol.84 (1), p.39-46
• Main Authors: Gómez-Coca, Raquel B., Kapinos, Larisa E., Holý, Antonı́n, Vilaplana, Rosario A., González-Vı́lchez, Francisco, Sigel, Helmut
• Format: Article
• Language: English
• Subjects: Adenosine 5′-monophosphate analogues; Intramolecular stack formation; Isomeric complex equilibria; Mixed ligand complexes; Stability constants
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/S0162-0134(00)00194-X

The stability constants of the mixed ligand complexes formed between Cu(Arm) 2+, where Arm=2,2′-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and the monoanion or the dianion of 9-(4-phosphonobutyl)adenine (dPMEA=3′-deoxa-PMEA), which is the carba analogue of the antivirally active 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), were determined by potentiometric pH titrations in aqueous solution at 25°C and I=0.1 M (NaNO 3). Detailed stability constant comparisons reveal that in the monoprotonated ternary Cu(Arm)(H;dPMEA) + complexes the proton is at the phosphonate group and that stacking between Cu(Arm) 2+ and H(dPMEA) − plays a significant role. For the Cu(Arm)(dPMEA) complexes a large increase in complex stability (compared to the stability expected on the basis of the basicity of the phosphonate group) is observed, which is due to intramolecular stack formation between the aromatic ring systems of Phen or Bpy and the purine moiety of dPMEA 2−. The formation degree of the stacked isomer in the Cu(Arm)(dPMEA) systems is on the order of 90%, though it is somewhat more pronounced with Phen than with Bpy. Comparisons of the Cu(Arm)(N) systems, where N=dPMEA 2− and PMEA 2− or adenosine 5′-monophosphate (AMP 2−), reveal that the stacking properties of dPMEA 2− and PMEA 2− resemble closely those of their parent nucleotide AMP 2−.