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

Pérez-Toro, Inmaculada; Domínguez‐Martín, Alicia; Choquesillo-Lazarte, Duane; Vílchez-Rodríguez, Esther; González‐Pérez, Josefa María; Castiñeiras, Alfonso; Niclós‐Gutiérrez, Juan

doi:10.1016/j.jinorgbio.2015.03.006

Cited by 19 publications

(20 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The all-trans centrosymmetric anions (Figures 2 and A2) have symmetry-related pairs of O-aqua, N7-acv, and O-sulfate donor atoms featuring a rather typical elongated-octahedral Cu(II) coordination, type 4 + 2, with bond lengths of Cu-O(aqua) of 1.963(2) Å, of Cu-N7(acv) of 2.018(2) Å, and of Cu-O(sulfate) of 2.427(2) Å, respectively (Table A2). It seems clear that the, shortest strongly-bound Cu-O(aqua) favor the cooperation of each Cu-N7(acv) bond with an intra-molecular interligand (aqua)O1-H1B···O6(acv) interaction (2.615(3) Å, 157.3 • ) (Table A3), thus leading to the most common MBP of the acv ligand [2][3][4][5][6][7][8][9]12]. This fact imposes the coordination of O-sulfate atoms towards the apical/distal sites of the copper(II) surrounding.…”

Section: Resultsmentioning

confidence: 99%

“…This acyclic guanine nucleoside analog has proved to bind nucleoside phosphorylases [1] as well as several metal ions. Structural knowledge on mixed-ligand metal-acv complexes (see selected reference [2][3][4][5][6][7][8][9][10][11][12]) supports a variety of metal binding patterns (MBPs) and interesting molecular recognition features. So far, the reported MBPs can be summarized as follows: (a) the formation of the M-N7 bond, with [2][3][4][5][6][7][8][9]12] or without [8,10] the cooperation of an intra-molecular interligand A-H···O6(acv) interaction (A=O or N acceptor); (b) the N7,O6-chelation mode [11]; (c) the µ 2 -N7,O(ol) (see Figure 1) bridging role [3]; and finally, (d) a multi-functional role featured by the µ 3 -N7,O6,O(e)+O(ol), which comprises the bridging, chelating, and tetradentate modes of acv [12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural and Theoretical Evidence of the Depleted Proton Affinity of the N3-Atom in Acyclovir

et al. 2016

Self Cite

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural and Theoretical Evidence of the Depleted Proton Affinity of the N3-Atom in Acyclovir

et al. 2016

Self Cite

View full text Add to dashboard Cite

“…The role of purines in this context is—to some extent—controversial. Albeit there seems to be no doubt that purines are excellent metal chelators, this feature alone may not be enough for them to act as protectors against metal‐induced OD. One of the earliest studies on the subject showed that purines are capable of protecting ascorbate from copper‐catalyzed oxidation, provided that the N atoms at positions 3 and 9 (Scheme ) are unsubstituted .…”

Section: Introductionmentioning

confidence: 99%

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Castañeda‐Arriaga

Pérez-González

Álvarez-Idaboy

et al. 2017

Int J of Quantum Chemistry

View full text Add to dashboard Cite

Oxidative damage to biomolecules is a serious health-threatening issue, which leads to the development of several diseases. Oxidative conditions are frequently catalyzed by metal ions. In this study, the role of purines in the copper-catalyzed oxidative stress was investigated using the density functional theory. The obtained results indicate that purines can have a dual behavior, acting as both protectors and promoters of oxidative stress. Their protection role arises from their known radical scavenging activity, as well as their ability to chelate Cu(II) leading to complexes that areto some extent-harder to reduce than free Cu(II). Conversely, their pro-oxidant role is a consequence of their reductant behavior, when deprotonated. Thus, the purines' anions can reduce Cu (II) to Cu(I), making the latter available to be involved in Fenton-like reactions. Consequently, mixtures of purines and Cu(II), at pHs where the fraction of deprotonated purines is rather significant, would yield • OH radicals. In turn, these very reactive radicals would damage biological targets such as lipids, proteins, and DNA.antioxidants, kinetics, pro-oxidants, rate constants, reaction mechanism 1 | I N TR ODU C TI ON Oxidative damage (OD) to biological targets such as lipids, proteins, and DNA is a serious health-threatening phenomenon. It has been held responsible, at least in part, for the onset and development of several diseases including cancer [1][2][3] ; rheumatoid arthritis [4][5][6] ; neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, depression, multiple sclerosis, and memory loss [7][8][9][10][11][12][13] ; cardiovascular diseases such as atherosclerosis, ischemia, hypertension, cardiac hypertrophy, heart failure, and cardiomyopathy [14][15][16][17] ; as well as renal [18][19][20] and pulmonary failure. [21][22][23] OD arises as a consequence of a chemical imbalance between the production and consumption of oxidants, known as oxidative stress (OS). [24] One of the most damaging oxidants in biological systems is the hydroxyl radical ( • OH). It can be produced, in the presence of metal ions such as Fe(II) or Cu(I), by Fenton or Fenton-like reactions (M q 1 H 2 O 2 ! M q11 1OH -1 • OH). However, the most stable and abundant forms of these two metals, under physiological conditions, are Fe(III) and Cu(II). Thus, • OH production would actually involve the metal-catalyzed Haber-Weiss recombination (HWR). It comprises two chemical steps. The first one is the reduction of the metal ions (M q11 1 O •2 2 ! M q 1 3 O 2 ) and the second one is the Fenton reaction. Consequently, redox active metal ions are of particular interest for the chemistry of living systems. These ions cannot only bind to DNA, but they can also promote OD to DNA by mediating the production of oxygen reactive species (ROS). [25] In fact metal-mediated OD to DNA has become an important topic in metal toxicity and carcinogenesis. [26][27][28][29]

show abstract

“…Curiously the O-carboxylate(btc) acceptor involved in such interligand H-bonding interaction implies an un-bonded to the Zn(II) O atom. This is certainly a relevant fact because of the common cooperation of metal-N(purine-like) bonds with (purine-like)N-H···O(carboxylate) intra-molecular interligand interactions was built with a metal-O(coordinated) H-acceptor atom [53].…”

Section: Discussionmentioning

confidence: 99%

“…This review emphasizes the relevance of the N(heterocyclic)-H tautomeric possibilities in neutral and protonated forms of such kinds of natural or synthetic closely related N-heterocyclic ligands. Recent reports from our groups extend these points of view to the guanine-synthetic acyclovir as a ligand [52][53][54]. Now we have the opportunity to deep into the relevance of these factors on the basis of the available crystallographic results related to cationic forms of Hdap, its salts and inner-or out-sphere metal complexes.…”

Section: Structural Insides On N(heterocyclic)-proton Affinities H-tmentioning

confidence: 98%

Anion–Cation Recognition Pattern, Thermal Stability and DFT-Calculations in the Crystal Structure of H2dap[Cd(HEDTA)(H2O)] Salt (H2dap = H2(N3,N7)-2,6-Diaminopurinium Cation)

et al. 2020

Self Cite

View full text Add to dashboard Cite

The proton transfer between equimolar amounts of [Cd(H 2 EDTA)(H 2 O)] and 2,6-diaminopurine (Hdap) yielded crystals of the out-of-sphere metal complex H 2 (N3,N7)dap [Cd(HEDTA)(H 2 O)]·H 2 O (1) that was studied by single-crystal X-ray diffraction, thermogravimetry, FT-IR spectroscopy, density functional theory (DFT) and quantum theory of "atoms-in-molecules" (QTAIM) methods. The crystal was mainly dominated by H-bonds, favored by the observed tautomer of the 2,6-diaminopurinium(1+) cation. Each chelate anion was H-bonded to three neighboring cations; two of them were also connected by a symmetry-related anti-parallel π,π-staking interaction. Our results are in clear contrast with that previously reported for H 2 (N1,N9)ade [Cu(HEDTA) (H 2 O)]·2H 2 O (EGOWIG in Cambridge Structural Database (CSD), Hade = adenine), in which H-bonds and π,π-stacking played relevant roles in the anion-cation interaction and the recognition between two pairs of ions, respectively. Factors contributing in such remarkable differences are discussed on the basis of the additional presence of the exocyclic 2-amino group in 2,6-diaminopurinium(1+) ion. Crystals 2020, 10, 304 2 of 15 reported analog of adenine, [Cu(HEDTA)(H 2 O)]·2H 2 O [5,32], was also performed. The H-bonding networks that are established at both faces of H 2 dap were also studied using DFT calculations and the relative strength of each H-bond was estimated using the QTAIM theory. The antiparallel π,π-stacking interactions that were formed between the cations were also studied, focusing on the effect of the counter-ions. Materials and Methods ReagentsH 4 EDTA acid (TCI), Hdap (Alfa Aesar) and CdCO 3 (Alfa Aesar) were used as received. CrystallographyA colorless needle crystal of H 2 dap[Cd(HEDTA)(H 2 O)]·H 2 O (1) was mounted on a glass fiber and used for data collection. Crystal data were collected at 100(2) K, using a Bruker D8 VENTURE PHOTON III-14 diffractometer. Graphite-monochromated MoK(α) radiation (λ = 0.71073 Å) was used throughout. The data were processed with APEX2 [33] and corrected for absorption using SADABS (transmissions factors: 1.000-0.962) [34]. The structure was solved by direct methods using the program SHELXS-2013 [35] and refined by full-matrix least-squares techniques against F 2 using SHELXL-2013 [35]. Positional and anisotropic atomic displacement parameters were refined for all non-hydrogen atoms. Hydrogen atoms were located in difference maps and included as fixed contributions riding on attached atoms with isotropic thermal parameters 1.2/1.5 times those of their carrier atoms. Criteria of a satisfactory complete analysis were the ratios of 'rms' shift to standard deviation less than 0.001 and no significant features in final difference maps. Atomic scattering factors were taken from the International Tables for Crystallography [36]. Molecular graphics were plotted with PLATON [37]. A summary of the crystal data, experimental details and refinement results are listed in Table 1. Crystallographic data for 1 has been deposited in the Cambridg...

show abstract

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

Cited by 19 publications

References 67 publications

Structural and Theoretical Evidence of the Depleted Proton Affinity of the N3-Atom in Acyclovir

Structural and Theoretical Evidence of the Depleted Proton Affinity of the N3-Atom in Acyclovir

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Anion–Cation Recognition Pattern, Thermal Stability and DFT-Calculations in the Crystal Structure of H2dap[Cd(HEDTA)(H2O)] Salt (H2dap = H2(N3,N7)-2,6-Diaminopurinium Cation)

Contact Info

Product

Resources

About