Journal
JOURNAL OF COORDINATION CHEMISTRY
Volume 71, Issue 11-13, Pages 1910-1934Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/00958972.2018.1490019
Keywords
Antivirals; aromatic-ring stacking; ether oxygen coordination; intramolecular isomeric equilibria; nucleotide analogs
Categories
Funding
- Department of Chemistry of the University of Basel
- University of Warwick
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Acyclic 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 H-3(ANP)(+) and H-2(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-PO32- represents a phosph(on)ate ligand with a non-coordinating group R. The observed stability enhancements are due to intramolecular stack formation (st) between the aromatic rings of Arm and the nucleobase residues and also to the formation of five-membered chelates involving the ether oxygen of the -CH(R)-O-CH2-PO32- residue (cl/O) (R=H or CH2-OH). In intramolecular equilibria, three structurally different Cu(Arm)(ANP) isomers occur; for example, of Cu(Phen)(HPMPA) about 5% exist as an open (op) Cu(Phen)(HPMPA)(op) isomer, 17% as Cu(Phen)(HPMPA)(cl/O), and 78% as Cu(Phen)(HPMPA)(st). In Cu(Arm)(ANP) the stacking tendency decreases in the order PMEA(2-)>HPMPA(2-)>PMEC2->HPMPC2-. In monoprotonated Cu(Arm)(H;ANP)(+) both H+ and Cu(Arm)(2+) are at PO32- undergoing similar intramolecular equilibria as indicated above.
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