The stability constants of the 1:1 complexes formed between Mg 2 + , Ca 2 + , Sr 2 + , Ba 2 + , Mn 2 + , CO 2 + , Ni 2 + , Cu 2 + , Zn 2 + , or Cd 2 + and (phosphonomethoxy)ethane (PME 2 - ) or 9-[2-(phosphonomethoxy)ethyl] adenine (PMEA 2 - ), an adenosine monophosphate (AMP 2 - )) analogue, are used in combination with log K M M ( R - P O 3 ) versus pK H ( R - P O 3 ) straight-line plots (where R in R-PO 2 - 3 is a non-coordinating residue) to demonstrate that for all the M(PME) and M(PMEA) complexes with the mentioned metal ions a stability higher than expected for a sole phosphonate coordination of the metal ion occurs. This increased stability is due to the formation of five-membered chelates involving the ether oxygen present in the -O-CH 2 -PO 2 - 3 residue of PME 2 - ; the same is true to a large extent also for the M(PMEA) complexes. However, e.g., for the complex formed between Cu 2 + and (PMEA 2 - ), an additional stability increase is observed which has to be attributed to a metal ion-adenine interaction thus giving rise to equilibria between three different M(PMEA) isomers. A procedure, which is generally applicable, for the analysis of such intramolecular equilibria is summarized. For Cu(PMEA) it is calculated that 17 (+/-3)% exist as an isomer with a sole Cu 2 + -phosphonate coordination, 34 (+/-10)% form the mentioned five-membered chelate involving the ether oxygen, and the remaining 49 (+/-10)% are due to an isomer, designated Cu(PMEA) c l / A d , which also contains a Cu 2 + -adenine interaction. Based on various arguments it is suggested that this latter isomer probably contains two chelate rings which result from a metal ion coordination to the phosphonate group, the ether oxygen, and N-3 of the adenine residue. Interestingly, the formation degree of Cu(PMEA) c l / A d passes through a minimum upon addition of 1,4-dioxane to the aqueous solution; i.e., small amounts of dioxane inhibit the Cu 2 + -adenine interaction, while larger amounts favor it again. This solvent effect is analogous to an observation made with the macrochelate of Cu(5'-AMP) in which the metal ion is bound to the phosphate group and N-7 of the adenine residue. Moreover, ternary Cu(arm)(PMEA) systems, where arm = 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen), are analyzed. It is shown that also in these systems three isomeric species form intramolecular equilibria; e.g., of Cu(bpy)(PMEA) about 3% exist with the metal ion solely coordinated to the phosphonate group, 10% as a five-membered chelate involving the -O>-CH 2 -PO 2 - 3 residue of (PMEA 2 - ), and 87% with an intramolecular stack between the adenine moiety of (PMEA 2 - ), and the aromatic rings of bpy. Finally, the properties of (PMEA 2 - ), and 5'-AMP 2 - are compared, and it is emphasized that the ether oxygen, which influences the stability and especially the structure of the M(PMEA) complexes in solution, is crucial for the antiviral properties of PMEA. The properties of a related compound, i.e., (S)-9-[3-hydroxy-2-(phosphonomethoxy)-propyl]adenine (HPMPA 2 - ), which differs from (PMEA 2 - ), by the additional presence of a -CH 2 OH group in the chain bound to the adenine moiety, i.e., in the -CH 2 -CH(CH 2 OH)-O-CH 2 -PO 2 - 3 residue, are also shortly indicated and some general aspects of enzymic reactions with nucleotides are considered.