Extent of intramolecular pi stacks in aqueous solution in mixed-ligand copper(II) complexes formed by heteroaromatic amines and the anticancer and antivirally active 9[2-(phosphonomethoxy)ethyl]guanine (PMEG). A comparison with related acyclic nucleotide analogues

0458528 - ÚOCHB 2017 RIV GB eng J - Článek v odborném periodiku
Blindauer, C. A. - Sigel, A. - Operschall, B. P. - Griesser, R. - Holý, Antonín - Sigel, H.
Extent of intramolecular pi stacks in aqueous solution in mixed-ligand copper(II) complexes formed by heteroaromatic amines and the anticancer and antivirally active 9[2-(phosphonomethoxy)ethyl]guanine (PMEG). A comparison with related acyclic nucleotide analogues.
Polyhedron. Roč. 103, Jan 8 (2016), s. 248-260. ISSN 0277-5387. E-ISSN 1873-3719
Institucionální podpora: RVO:61388963
Klíčová slova: anticancer activity * antivirals * aromatic-ring stacking * isomeric equilibria * nucleotide analogues
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 1.926, rok: 2016

The acyclic nucleoside phosphonate (ANP(2-))9-[2-(phosphonomethoxy)ethyliguanine (PMEG) is anticancer and antivirally active. The acidity constants of the threefold protonated H-3(PMEG)(+) were determined by potentiometric pH titrations (aq. sol.; 25 degrees C; I = 0.1 M, NaNO3). Under the same conditions and by the same method, the stability constants of the binary Cu(H;PMEG)(+) and Cu(PMEG) complexes as well as those of the ternary ones containing a heteroaromatic N ligand (Arm), that is, of Cu(Arm)(H;PMEG)(+) and Cu(Arm)(PMEG), where Arm = 2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen), were measured. The corresponding equilibrium constants, taken from our earlier work for the systems with 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP) as well as those for Cu(PME) and Cu(Arm)(PME), where PME2- = (phosphonomethoxy)ethane = (ethoxymethyl)phosphonate, were used for comparisons. These reveal that in the monoprotonated ternary Cu(Arm)(H;PE)(+) complexes, the proton and Cu(Arm)(2+) are at the phosphonate group; the ether oxygen of the -CH2-O-CH2-P(O)(2)(-)(OH) residue also participates to some extent in Cu(Arm)(2+). coordination. Furthermore, the coordinated Cu(Arm)(2+) forms a bridge with the purine moiety undergoing pi-pi stacking which is more pronounced with H center dot PMEDAP(-) than with H center dot PMEA(-). Most intense is pi stack formation (st) with the guanine residue of H center dot PMEG(-); here the bridged form Cu(Arm)(H.PMEG)(st)(+) occurs next to an open (op), unbridged (binary) stack, formulated as Cu(Arm)(2+)/(H.PMEG)(op)(-). The unprotonated and neutral ternary Cu(Arm)(PE) complexes are considerably more stable than the corresponding Cu(Arm)(R-PO3) species, where R-PO32- represents a phosph(on)ate ligand with a group R that is unable to participate in any intramolecular interaction.
Trvalý link: http://hdl.handle.net/11104/0258789