Adenosine 5′-triphosphate (ATP⁴⁻) and related nucleoside 5′-triphosphates (NTP⁴⁻) serve as substrates in the form of metal ion complexes in enzymic reactions taking part thus in central metabolic processes. With this in mind, the coordination chemistry of NTPs is critically reviewed and the conditions are defined for studies aiming to describe the properties of monomeric complexes because at higher concentrations (>1 mM) self-stacking may take place. The metal ion (M²⁺) complexes of purine–NTPs are more stable than those of pyrimidine–NTPs; this stability enhancement is attributed, in accord with NMR studies, to macrochelate formation of the phosphate-coordinated M²⁺ with N7 of the purine residue and the formation degrees of the resulting isomeric complexes are listed. Furthermore, the formation of mixed-ligand complexes (including also those with buffer molecules), the effect of a reduced solvent polarity on complex stability and structure (giving rise to selectivity), the use of nucleotide analogues as antiviral agents, and the effect of metal ions on group transfer reactions are summarized.

The acidity constants of protonated 7,9-dimethylguanine, 7-methylguanosine, 7,9-dimethylhypoxanthine, 7-methylinosine, 9-methyladenine, 1,9-dimethyladenine, 7,9-dimethyladenine and 1-methyladenosine were determined in aqueous solution at 25 °C and I = 0.1 M (NaNO₃). In those instances where pK_a > 2 potentiometric pH titrations were used for the determinations; when pK_a < 2, UV spectrophotometric and ¹H-NMR shift measurements were employed (25 °C). In these latter instances, where I is often larger than 0.1 M, the H₀ scale was applied to define the H⁺ activity of the strong acid (HClO₄; HNO₃). A combination of the present results with values taken from our earlier work allowed us to quantify the intrinsic acidic properties in aqueous solution of the (N1)H^{0 or +} and (N7)H⁺ sites via micro acidity constant schemes for seven purine derivatives and to calculate the tautomeric ratios regarding the monoprotonated species, that is N7–N1·H versus H·N7–N1 meaning that in one isomer H⁺ is at the N1 site and in the other at N7. A plot of the micro acidity constants pk^N7–N1 _H·N7–N1, which quantify the acidity of the (N7)H⁺ site, versus the macro acidity constants pK_a/(N1)H, which largely refer to the release of the proton from the (N1)H unit, results in a straight line for the guanine and hypoxanthine derivatives. This fact allows estimation of the micro acidity constant for any related derivative provided a value for pK_a/(N1)H is known. The presented results are also meaningful for nucleic acids because they quantify the acid–base properties of their individual sites.

Acyclic nucleoside phosphonates (ANPs), i.e., analogues of (2′-deoxy)nucleoside 5′-monophosphates, have been studied during the past 15 years for their potential as antiviral drugs. One of these compounds, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; Adefovir) was recently approved in the form of its bis(pivaloyloxymethyl)ester (Adefovir dipivoxil) for use in hepatitis B therapy, a disease evoked by a DNA virus. Diphosphorylated PMEA²⁻, i.e., PMEApp⁴⁻, is initially recognized by nucleic acid polymerases as an excellent substrate, but after insertion in the growing nucleic acid chain, this is terminated due to the lack of a 3′-hydroxy group. Based on the metal ion-binding properties of PMEApp⁴⁻ it can be explained why the ether oxygen in the aliphatic chain, R–CH₂–O–CH₂–PO₃pp⁴⁻, is compulsory for a useful biological activity. Consequently, this critical review presents an overview on the coordination chemistry of various ANPs and correlates this to their biological properties.