Intramolecular stacking interactions in ternary copper(II) complexes formed by a heteroaromatic amine and 9-[2-(2-phosphonoethoxy)ethyl]adenine, a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine.
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 dianions of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA2-) and (2-phosphonoethoxy)ethane (PEE2-), also known as [2-(2-ethoxy)ethyl]phosphonate, were determined by potentiometric pH titrations in aqueous solution (25 degrees C; I=0.1 M, NaNO3). The ternary Cu(Arm)(PEEA) complexes are considerably more stable than the corresponding Cu(Arm)(R-PO3) species, where R-PO3(2-) represents a phosph(on)ate ligand with a group R that is unable to participate in any kind of interaction within the complexes. The increased stability is attributed to intramolecular stack formation in the Cu(Arm)(PEEA) complexes and also, to a smaller extent, to the formation of 6-membered chelates involving the ether oxygen atom present in the -CH2-O-CH2-CH2-PO3(2-) residue of PEEA2-. This latter interaction is separately quantified by studying the ternary Cu(Arm)(PEE) complexes which can form the 6-membered chelates but where no intramolecular ligand-ligand stacking is possible. Application of these results allows a quantitative analysis of the intramolecular equilibria involving three structurally different Cu(Arm)(PEEA) species; e.g., of the Cu(Bpy)(PEEA) system about 11% exist with the metal ion solely coordinated to the phosphonate group, 4% as a 6-membered chelate involving the ether oxygen atom of the -CH2-O-CH2CH2-PO3(2-) residue, and 85% with an intramolecular stack between the adenine moiety of PEEA2- and the aromatic rings of Bpy. In addition, the Cu(Arm)(PEEA) complexes may be protonated, leading to Cu(Arm)(H;PEEA)+ species for which it is concluded that the proton is located at the phosphonate group and that the complexes are mainly formed (50 and 70%) by a stacking adduct between Cu(Arm)2+ and the adenine residue of H(PEEA)-. Finally, the stacking properties of adenosine 5'-monophosphate (AMP2-), of the dianion of 9-[2-(phophonomethoxy)ethyl]adenine (PMEA2-) and of several of its analogues (=PA2-) are compared in their ternary Cu(Arm)(AMP) and Cu(Arm)(PA) systems. Conclusions regarding the antiviral properties of several acyclic nucleoside phosphonates are shortly discussed.
Fernández-Botello
Alfonso
A
Department of Chemistry, Inorganic Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland.
Holý
Antonín
A
Moreno
Virtudes
V
Sigel
Helmut
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D000838:Anions; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D006509:Hepatitis B / Q000188:drug therapy; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000032:analysis / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry; D011199:Potentiometry; D011522:Protons; D011725:Pyridines / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000588:Amines; D000838:Anions; D000998:Antiviral Agents; D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D010618:Phenanthrolines; D011522:Protons; D011725:Pyridines; D012996:Solutions; D014867:Water; D003300:Copper; D000225:Adenine