Extent of Intramolecular pi Stacks in Aqueous Solution in Mixed-Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and 1-[2-(Phosphonomethoxy)ethyl]cytosine (PMEC), a Relative of Antivirally Active Acyclic Nucleotide Analogues (Part 72)

0424812 - ÚOCHB 2014 RIV DE eng J - Journal Article
Blindauer, C. A. - Sigel, A. - Operschall, B. P. - Holý, Antonín - Sigel, H.
Extent of Intramolecular pi Stacks in Aqueous Solution in Mixed-Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and 1-[2-(Phosphonomethoxy)ethyl]cytosine (PMEC), a Relative of Antivirally Active Acyclic Nucleotide Analogues (Part 72).
Zeitschrift für anorganische und allgemeine Chemie. Roč. 639, 8-9 (2013), s. 1661-1673. ISSN 0044-2313. E-ISSN 1521-3749
Institutional support: RVO:61388963
Keywords : nucleotide analogues * antivirals * complex stabilities * isomers * equilibria * mixed ligand complexes
Subject RIV: CC - Organic Chemistry
Impact factor: 1.251, year: 2013

Stability constants of the ternary Cu(Arm)(H;PMEC)(+) and Cu(Arm)(PMEC) complexes were measured by potentiometric pH titrations and compared with those of Cu(Arm)(H;PMEA)(+) and Cu(Arm)(PMEA) {PMEA(2-)} and related species. The basicity of the terminal phosphonate group is similar in PMEC2- and PMEA(2-). Stability-constant comparisons reveal, that in the monoprotonated ternary u(Arm)(H;PMEC)(+) complexes H+ is at the phosphonate group, that the ether oxygen atom of the -CH2-O-CH2-P(O)(2)(-) (OH) residue participates, next to the P(O)(2)(-)(OH) group, in Cu(Arm)(2+) coordination. The Cu(Arm)(PMEC) complexes are considerably more stable than the corresponding Cu(Arm)(R-PO3) species. The stability enhancements are mainly attributed to intramolecular stacks and to the formation of five-membered chelates involving the ether oxygen atom of the -CH2-O-CH2-P(O)(3)(2-) residue of PMEC2-. Analysis of the intramolecular equilibria reveals that ca. 10% of the isomeric ternary complexes exist with Cu(Arm)(2+) solely coordinated to the phosphonate group, ca. 25% as a five-membered chelate involving the ether oxygen, and ca. 65% with an intramolecular pi-pi stack between the pyrimidine moiety of PMEC2- and the rings of Bpy or Phen. It seems feasible that the reduced stacking intensity of PMEC2- and a different hydrogen bonding, leads to a different orientation of the cytosine (compared to adenine) in the active site of the nucleic acid polymerases, resulting in a reduced antiviral activity of PMEC compared to PMEA.
Permanent Link: http://hdl.handle.net/11104/0230843