H. Sigel, Dong Chen, N. A. Corfù
Dec 16, 1992
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Journal
Helvetica Chimica Acta
Abstract
The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, (in part) Zn2+, or Cd2+ and (phosphonylmethoxy)ethane (PME2−) or 9−[2−(phosphonylmethoxy)ethyl]adenine (PMEA2−) were determined by potentiometric pH titration in aqueous solution (I = 0.1M, NaNO3; 25°). The experimental conditions were carefully selected such that self-association of the adenine derivative PMEA and of its complexes was negligibly small; i.e., it was made certain that the properties of the monomeric [M(PMEA)] complexes were studied. Recent measurements with simple phosphate monoesters, R–MP2– (where R is a non-coordinating residue; S. S. Massoud, H. Sigel, Inorg. Chem.1988, 27, 1447), were used to show that analogously simple phosphonates (RPO) – we studied now the complexes of methyl phosphonate and ethyl phosphonate – fit on the same log K/logKvs. pK/ pK straight-line plots. With these reference lines, it could be demonstrated that for all the [M(PME)] complexes with the mentioned metal ions an increased complex stability is measured; i.e., a stability higher than that expected for a sole phosphonate coordination of the metal ion. This increased stability is attributed to the formation of five-membered chelates involving the ether oxygen present in the OCH2PO residue of PME2− (and PMEA2−); the formation degree of the five-membered [M(PME)] chelates varies between ca. 15 and 40% for the alkaline earth ions and ca. 35 to 65% for 3d ions and Zn2+ or Cd2+. Interestingly, for the [M(PMEA)] complexes within the error limits exactly the same observations are made indicating that the same five-membered chelates are formed, and that the adenine residue has no influence on the stability of these complexes, with the exception of those with Ni2+ and Cu2+. For these two metal ions, an additional stability increase is observed which has to be attributed to a metal ion-adenine interaction giving thus rise to equilibria between three different [M(PMEA)] isomers. These equilibria are analyzed, and for [Cu(PMEA)] it is calculated that 17(±3)% exist as an isomer with a sole Cu2+-phosphonate coordination, 34(±10)% form the mentioned five-membered chelate involving the ether oxygen, and the remaining 49(±10)% are due to an isomer containing also a Cu2+-adenine interaction. Based on various arguments, it is suggested that this latter isomer contains two chelate rings which result from a metal-ion coordination to the phosphonate group, the ether oxygen, and to N(3) of the adenine residue. For [Ni(PMEA)], the isomer with a Ni2+-adenine interaction is formed to only 22(±13)%; for [Cd(PMEA)] and the other [M(PMEA)] complexes if at all, only traces of such an isomer are occurring. In addition, the [M(PMEA)] complexes may be protonated leading to [M(H·PMEA)]+ species in which the proton is mainly at the phosphonate group, while the metal ion is bound in an adenosine-type fashion to the nucleic base residue. Finally, the properties of [M(PMEA)] and [M(AMP)] complexes are compared, and in this connection it should be emphasized that the ether oxygen which influences so much the stability and structure of the [M(PMEA)] complexes in solution is also crucial for the antiviral properties of PMEA.