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

0496372 - ÚOCHB 2019 RIV GB eng J - Článek v odborném periodiku
Blindauer, C. A. - Griesser, R. - Holý, Antonín - Operschall, B. P. - Sigel, A. - Song, B. - Sigel, H.
Intramolecular pi-stacks in mixed-ligand copper(II) complexes formed by heteroaromatic amines and antivirally active acyclic nucleotide analogs carrying a hydroxy-2-(phosphonomethoxy)propyl residue.
Journal of Coordination Chemistry. Roč. 71, 11/13 (2018), s. 1910-1934. ISSN 0095-8972. E-ISSN 1029-0389
Institucionální podpora: RVO:61388963
Klíčová slova: antivirals * aromatic-ring stacking * ether oxygen coordination * intramolecular isomeric equilibria * nucleotide analogs
Obor OECD: Organic chemistry
Impakt faktor: 1.685, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0289166