Ternary Copper(II) Complexes in Solution Formed With 8-Aza Derivatives of the Antiviral Nucleotide Analogue 9-[2-(Phosphonomethoxy)Ethyl]Adenine (PMEA).
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-(phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA) and 8-[2-(phosphonomethoxy)ethyl]-8-azaadenine (8,8aPMEA) (both also abbreviated as PA(2-)) were determined by potentiometric pH titrations in aqueous solution (25 ( degrees )C; I = 0.1 M, NaNO(3)). All four ternary Cu(Arm)(PA) complexes are considerably more stable than corresponding Cu(Arm)(R-PO(3)) species, where R-PO(3) (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)(PA) complexes and also to the formation of 5-membered chelates involving the ether oxygen present in the -CH(2)-O-CH(2)-PO(3) (2-) residue of the azaPMEAs. A quantitative analysis of the intramolecular equilibria involving three structurally different Cu(Arm)(PA) species is carried out. For example, about 5% of the Cu(Bpy)(8,8aPMEA) system exist with the metal ion solely coordinated to the phosphonate group, 14% as a 5-membered chelate involving the -CH(2)-O-CH(2)-PO(3) (2-)residue, and 81% with an intramolecular stack between the 8-azapurine moiety and the aromatic rings of Bpy. The results for the other systems are similar though with Phen a formation degree of about 90% for the intramolecular stack is reached. The existence of the stacked species is also proven by spectrophotometric measurements. In addition, the Cu(Arm)(PA) complexes may be protonated, leading to Cu(Arm)(H;PA)(+) species for which it is concluded that the proton is located at the phosphonate group and that the complexes are mainly formed by a stacking adduct between Cu(Arm)(2+) and H(PA)(-). Conclusions regarding the biological properties of these azaPMEAs are shortly indicated.
Gómez-Coca
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Institute of Inorganic Chemistry University of Basel Spitalstrasse 5 l Basel CH-4056 Switzerland.
Kapinos
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Holý
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Vilaplana
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González-Vílchez
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Sigel
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