Intramolecular π-stacks in mixed-ligand copper(II) complexes formed by heteroaromatic amines and antivirally active acyclic nucleotide analogs carrying a hydroxy-2-(phosphonomethoxy)propyl residue‡

AbstractAcyclic nucleoside phosphonates (ANPs) are of medical relevance and deserve detailed chemical characterization. We focus here on 1-[2-(phosphonomethoxy)ethyl]cytosine (PMEC), (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC), 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), and (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) and include for comparison the nucleobase-free (phosphonomethoxy)ethane (PME) and (R)-hydroxy-2-(phosphonomethoxy)propane (HPMP). The acidity constants of H3(ANP)+ and H2(NP) (NP2– = nucleoside phosph(on)ate derivative) are needed to understand the properties of the ternary neutral Cu(Arm)(ANP/NP) [Arm = 2,2′-bipyridine (Bpy) or 1,10-phenanthroline (Phen)] and the monoprotonated Cu(Arm)(H;ANP)+ complexes. The Cu(Arm)(ANP) species are considerably more stable than the corresponding Cu(Arm)(R-PO3), where R- represents a phosph(on)ate ligand with a non-coordinating group R. The observed stability enhancements are due to intramolecular stack formation (st) betwe...