Acyclic nucleoside phosphonates are of medical relevance and deserve detailed chemical characterization. We focus here on (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) and include for comparison 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), as well as the nucleobase-free (phosphonomethoxy)ethane (PME) and (R)-hydroxy-2-(phosphonomethoxy)propane (HPMP). The acidity constants of H 3 (HPMPA) + were determined and compared with those of the related phosph(on)ate derivatives; they are also needed to understand the properties of the metal ion complexes. Given that in vivo nucleotides and their analogues participate in reactions typically as divalent metal ion (M 2+ ) complexes, the stability constants of the M(H;HPMPA) + and M(HPMPA) species with M 2+ = Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ , Mn 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ , and Cd 2+ were measured. Comparisons between the results for HPMPA 2and the previous data for PMEA 2-, HPMP 2and PME 2revealed that for most M(HPMPA) complexes the enhanced stability (the enhancement relative to the stability of a simple [a]