Metal Ion‐Coordinating Properties in Aqueous Solutions of the Antivirally Active Nucleotide Analogue (S)‐9‐[3‐Hydroxy‐2‐(phosphonomethoxy)propyl]adenine (HPMPA) – Quantification of Complex Isomeric Equilibria

摘要: 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) include for comparison 9‐[2‐(phosphonomethoxy)ethyl]adenine (PMEA), as well the nucleobase‐free (phosphonomethoxy)ethane (PME) R )‐hydroxy‐2‐(phosphonomethoxy)propane (HPMP). The acidity constants H 3 + were determined compared with those related phosph(on)ate derivatives; they also needed to understand properties metal ion complexes. Given that in vivo nucleotides their analogues participate reactions typically divalent (M 2+ ) complexes, stability M(H;HPMPA) M(HPMPA) species M = Mg , Ca Sr Ba Mn Co Ni Cu Zn Cd measured. Comparisons between results HPMPA 2- previous data PMEA HPMP PME revealed most complexes enhanced (the enhancement relative a simple phosphonate‐M coordination), can solely be explained by formation 5‐membered chelates involving ether oxygen. These occur equilibrium ′open′ species, phosphonate group being primary binding site. only exceptions which show an additional enhancement; these instances not indicated formed, but coordinates addition N3 adenine residue forming 7‐membered chelate ring. This observation regarding is important because it emphasizes affinity this site (which often ignored). Note DNA double helix exposed solvent minor groove. monoprotonated suggest carry at whereas partly nucleobase group. ratios isomers depend involved, e.g., Cu(H;HPMPA) ratio about 1:1.