Extent of Intramolecular p-Stacks in Aqueous Solution in Mixed-Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and Several 2-Aminopurine Derivatives of the Antivirally Active Nucleotide Analog 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA)

0385302 - ÚOCHB 2013 RIV DE eng J - Journal Article
Gómez-Coca, R. B. - Blindauer, C. A. - Sigel, A. - Operschall, B. P. - Holý, Antonín - Sigel, H.
Extent of Intramolecular p-Stacks in Aqueous Solution in Mixed-Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and Several 2-Aminopurine Derivatives of the Antivirally Active Nucleotide Analog 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA).
Chemistry & Biodiversity. Roč. 9, č. 9 (2012), s. 2008-2034. ISSN 1612-1872. E-ISSN 1612-1880
R&D Projects: GA MŠMT 1M0508
Institutional research plan: CEZ:AV0Z40550506
Keywords : copper complexes * nucleotides * acyclic nucleoside phosphonates * ANPs * antiviral activity
Subject RIV: CE - Biochemistry
Impact factor: 1.808, year: 2012

The acidity constants of twofold protonated, antivirally active, acyclic nucleoside phosphonates (ANPs), 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), 2-amino-9-[2-(phosphonomethoxy)ethyl]purine (PME2AP), 2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (PMEDAP), or 2-amino-6-(dimethylamino)-9-[2-(phosphonomethoxy)ethyl]purine (PME(2A6DMAP), as well as the stability constants of the corresponding ternary Cu complexes are compared. The constants for the systems containing PMEDAP and PME(2A6DMAP) have been determined now by potentiometric pH titrations in aqueous solution at I=0.1M (NaNO3) and 25 degrees; the corresponding results for the other ANPs were taken from our earlier work. The basicity of the terminal phosphonate group is very similar for all the ANP species, whereas the addition of a second amino substituent at the pyrimidine ring of the purine moiety significantly increases the basicity of the N(1) site. Detailed stability-constant comparisons for mixed-ligand Cu(II) complexes and the role of pi-pi stacking between the aromatic rings and the purine moiety are discussed. There are indications that ternary Cu(Arm)(2+)-bridged stacks as well as unbridged (binary) stacks are formed. The 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 kind of intramolecular interaction within the complexes. The observed stability enhancements are mainly attributed to intramolecular-stack formation in the Cu(Arm)(PE) complexes and also, to a smaller extent, to the formation of five-membered chelates involving the ether O-atom present in the -CH2-O-CH2-PO3 residue. Comparison of the various formation degrees of the species formed reveals that, in the Cu(phen)(PE) complexes, intramolecular-stack formation is more pronounced than in the Cu(bpy)(PE) species.
Permanent Link: http://hdl.handle.net/11104/0214602