title: Lights and shadows in the challenge of binding acyclovir, a synthetic purine-like nucleoside with antiviral activity, at an apical-distal coordination site in copper(II)-polyamine chelates.
abstract: Several nucleic acid components and their metal complexes are known to be involved in crucial metabolic steps. Therefore the study of metal-nucleic acid interactions becomes essential to understand these biological processes. In this work, the synthetic purine-like nucleoside acyclovir (acv) has been used as a model of guanosine recognition with copper(II)-polyamine chelates. The chemical stability of the N9-acyclic arm in acv offers the possibility to use this antiviral drug to deepen the knowledge of metal-nucleoside interactions. Cu(II) chelates with cyclam, cyclen and trien were used as suitable receptors. All these copper(II) tetraamine chelates have in common the potential ability to yield a Cu-N7(apical) bond assisted by an appropriate (amine)N-H⋯O6(acv) intra-molecular interligand interaction. A series of synthesis afforded the following compounds: [Cu(cyclam)(ClO4)2] (1), {[Cu(cyclam)(μ2-NO3)](NO3)}n (2), {[Cu(cyclam)(μ2-SO4)]·MeOH}n (3), {[Cu(cyclam)(μ2-SO4)]·5H2O}n (4), [Cu(cyclen)(H2O)]SO4·2H2O (5), [Cu(cyclen)(H2O)]SO4·3H2O (6), [Cu(trien)(acv)](NO3)2·acv (7) and [Cu(trien)(acv)]SO4·0.71H2O (8). All these compounds have been characterized by X-ray crystallography and FT-IR spectroscopy. Our results reveal that the macrochelates Cu(cyclen)(2+) and Cu(cyclam)(2+) are unable to bind acv at an apical site. In contrast, the Cu(trien)(2+) complex has proved to be an efficient receptor for acv in compounds (7) and (8). In the ternary complex [Cu(trien)(acv)](2+), the metal binding pattern of acv consists of an apical Cu-N7 bond assisted by an intra-molecular (primary amino)N-H⋯O6(acv) interligand interaction. Structural comparisons reveal that this unprecedented apical role of acv is due to the acyclic nature of trien together with the ability of the Cu(trien)(2+) chelate to generate five-coordinated (type 4+1) copper(II) complexes.
authors: Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
authors: Inmaculada
authors: I
authors: Pérez-Toro
authors: Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain. Electronic address: alicia.dominguez@chem.uzh.ch.
authors: Alicia
authors: A
authors: Domínguez-Martín
authors: Laboratorio de Estudios Cristalográficos, IACT, CSIC-Universidad de Granada, Av. de las Palmeras 4, E-18100 Armilla, Granada, Spain.
authors: Duane
authors: D
authors: Choquesillo-Lazarte
authors: Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
authors: Esther
authors: E
authors: Vílchez-Rodríguez
authors: Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
authors: Josefa María
authors: JM
authors: González-Pérez
authors: Department of Inorganic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Alfonso
authors: A
authors: Castiñeiras
authors: Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
authors: Juan
authors: J
authors: Niclós-Gutiérrez
mesh_terms: D000212:Acyclovir / Q000737:chemistry* / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry* / Q000378:metabolism; D011687:Purines / Q000737:chemistry / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014266:Trientine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D000080027:Cyclams; D006571:Heterocyclic Compounds; D009705:Nucleosides; D011073:Polyamines; D011687:Purines; C024560:cyclam; D003300:Copper; C038072:cyclen; D014266:Trientine; C030985:purine; D000212:Acyclovir
keywords: Acyclovir; Copper(II); Crystal structure; Metal binding pattern; Mixed-ligand complex; Polyamine