0000000001310868
AUTHOR
ÁLvaro Martínez-camarena
Ditopic Aza-Scorpiand Ligands Interact Selectively with ds-RNA and Modulate the Interaction upon Formation of Zn2+ Complexes
Nucleic acids are essential biomolecules in living systems and represent one of the main targets of chemists, biophysics, biologists, and nanotechnologists. New small molecules are continuously developed to target the duplex (ds) structure of DNA and, most recently, RNA to be used as therapeutics and/or biological tools. Stimuli-triggered systems can promote and hamper the interaction to biomolecules through external stimuli such as light and metal coordination. In this work, we report on the interaction with ds-DNA and ds-RNA of two aza-macrocycles able to coordinate Zn2+ metal ions and form binuclear complexes. The interaction of the aza-macrocycles and the Zn2+ metal complexes with duple…
A step forward in the development of superoxide dismutase mimetic nanozymes: the effect of the charge of the surface on antioxidant activity
Two binucleating hezaaza macrocycles containing a pyridinol spacer have been prepared and characterised. Protonation studies indicate the deprotonation of the phenol group at relatively low pH values with the concomitant occurrence of a keto-enolic equilibrium. These ligands readily form binuclear Cu2+ and Zn2+ complexes as denoted by potentiometric and spectroscopic studies. The binding of the metals yields to the ready deprotonation of the phenol with the stabilisation of the keto form that results in complexes of greater stabilities than the analogous ones containing pyridine as spacer instead of pyridine. Mixed Cu2+–Zn2+-complexes were also detected in aqueous solutions containing equim…
Acid–base behaviour and binding to double stranded DNA/RNA of benzo[g]phthalazine-based ligands
The affinity and the binding mode of two benzo[g]phthalazine compounds, functionalized with one or two 2-(imidazole-4-yl)-ethylamine groups, to DNA and RNA models have been evaluated by means of UV-Vis, fluorescence and circular dichroism (CD) spectroscopies in combination with viscometry and molecular dynamics. Both organic molecules bind strongly to all nucleic acid models via the intercalation mode in the duplex structure, especially compound 1. Intriguingly, 1 exhibits different emission responses depending on the base composition of duplex DNA/RNAs, which points out the possibility of using it as a base selective nucleic acid probe. Moreover, the acid-base behaviour of both compounds h…
Development of Polyamine‐Substituted Triphenylamine Ligands with High Affinity and Selectivity for G‐Quadruplex DNA
Currently, significant efforts are devoted to designing small molecules able to bind selectively to guanine quadruplexes (G4s). These noncanonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, a series of triphenylamine (TPA)-based compounds, including macrocyclic polyamines, that displayed high affinity towards G4 DNA were reported. Following this initial work, herein a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, are presented with the aim of maximising the selectivity towards G4 DNA. The acid-bas…
Heterocyclic Diamines with Leishmanicidal Activity.
Leishmaniasis is one of the world's most neglected diseases with a worldwide prevalence of 12 million people. There are no effective human vaccines for its prevention, and outdated drugs hamper treatment. Therefore, research aimed at developing new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, here, we present 10 new compounds made up by linking alkylated ethylenediamine units to pyridine or quinoline heterocycles with promising in vitro and in vivo efficacy against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani, and Leishmania braziliensis species. Three compounds (2, 4, and 5) showed a selectivity index muc…
Synthesis, Characterization, and Cu(2+) Coordination Studies of a 3-Hydroxy-4-pyridinone Aza Scorpiand Derivative.
The synthesis, acid-base behavior, and Cu(2+) coordination chemistry of a new ligand (L1) consisting of an azamacrocyclic core appended with a lateral chain containing a 3-hydroxy-2-methyl-4(1H)-pyridinone group have been studied by potentiometry, cyclic voltammetry, and NMR and UV-vis spectroscopy. UV-vis and NMR studies showed that phenolate group was protonated at the highest pH values [log K = 9.72(1)]. Potentiometric studies point out the formation of Cu(2+) complexes of 1:2, 2:2, 4:3, 1:1, and 2:1 Cu(2+)/L1 stoichiometries. UV-vis analysis and electrochemical studies evidence the implication of the pyridinone moieties in the metal coordination of the 1:2 Cu(2+)/L1 complexes. L1 shows …
Toward a Rational Design of Polyamine-Based Zinc-Chelating Agents for Cancer Therapies.
In vitro viability assays against a representative panel of human cancer cell lines revealed that polyamines L1a and L5a displayed remarkable activity with IC50 values in the micromolar range. Preliminary research indicated that both compounds promoted G1 cell cycle arrest followed by cellular senescence and apoptosis. The induction of apoptotic cell death involved loss of mitochondrial outer membrane permeability and activation of caspases 3/7. Interestingly, L1a and L5a failed to activate cellular DNA damage response. The high intracellular zinc-chelating capacity of both compounds, deduced from the metal-specific Zinquin assay and ZnL2+ stability constant values in solution, strongly sup…
Methylation as an effective way to generate SOD-activity in copper complexes of scorpiand-like azamacrocyclic receptors
Abstract Methylation of the secondary amine groups of a scorpiand-type ligand consisting of a pyridine spacer connected through methylene groups to a tris(2-aminomethyl) unit with the pendant arm further functionalised with a 3-pyridine unit leads to a ligand whose Cu(II) complex exhibits threefold enhanced SOD activity with respect to the non-methylated ligand. Potentiometric studies indicate the formation of [CuL] 2+ species with a stability three orders of magnitude lower than that formed with the related non-methylated ligand. Kinetic studies indicate that methylation of the secondary nitrogens causes a deceleration of both the complex formation and the acid-induced dissociation of the …
Coordination Chemistry of Cu2+ Complexes of Small N-Alkylated Tetra-azacyclophanes with SOD Activity
A new tetraaza-pyridinophane macrocycle (L1) N-alkylated with two isopropyl and one methyl groups symmetrically disposed has been prepared and its behavior compared with those of the unsubstituted pyridinophane (L3) and the related compound with three methyl groups (L2). The protonation studies show that, first, a proton binds to the central methylated amine group of L1, while, second protonation leads to a reorganization of the protons that are at this stage attached to the lateral isopropylated amines. The X-ray structure of [HL1]+ agrees with the UV–vis and NMR studies as well as with the results of DFT calculations. The stability of the Cu2+ complexes decreases on increasing the bulkine…
Unveiling the reaction mechanism of novel copper N-alkylated tetra-azacyclophanes with outstanding superoxide dismutase activity.
Quantum chemical and multiscale calculations reveal the mechanistic pathway of two superoxide dismutase mimetic N-alkylated tetra-azacyclophane copper complexes with remarkable activity. The arrangement of the binding site afforded by the bulky alkyl substituents and the coordinated water molecule as a proton source play key roles in the reaction mechanism.
Inhibitory Effect of Azamacrocyclic Ligands on Polyphenol Oxidase in Model and Food Systems
[EN] Enzymatic browning is one of the main problems faced by the food industry due to the enzyme polyphenol oxidase (PPO) provoking an undesirable color change in the presence of oxygen. Here, we report the evaluation of 10 different azamacrocyclic compounds with diverse morphologies as potential inhibitors against the activity of PPO, both in model and real systems. An initial screening of 10 ligands shows that all azamacrocyclic compounds inhibit to some extent the enzymatic browning, but the molecular structure plays a crucial role on the power of inhibition. Kinetic studies of the most active ligand (L2) reveal a S-parabolic I-parabolic noncompetitive inhibition mechanism and a remarkab…
Oxidative stress protection by manganese complexes of tail-tied aza-scorpiand ligands.
The Mn2+ coordination chemistry of double scorpiand ligands in which two polyazacyclophane macrocycles have been connected by pyridine, phenanthroline and bipyridine spacers has been studied by potentiometry, paramagnetic NMR and electrochemistry. All ligands show high stability with Mn2+ and the complexes were formed in a wide pH range. DFT calculations support the structures and coordination geometries derived from the study. A remarkable antioxidant activity was evidenced for these systems by the McCord-Fridovich assay and in Escherichiacoli sodAsodB deficient bacterial cells. The three systems were tested as anti-inflammatory drugs in human macrophages measuring the accumulation of cyto…
Assembly of Polyiodide Networks with Cu(II) Complexes of Pyridinol-Based Tetraaza Macrocycles
Polyiodide networks are currently of great practical interest for the preparation of new electronic materials. The participation of metals in the formation of these networks is believed to improve their mechanical performance and thermal stability. Here we report the results on the construction of polyiodide networks obtained using Cu(II) complexes of a series of pyridinol-based tetraazacyclophanes as countercations. The assembly of these crystalline polyiodides takes place from aqueous solutions on the basis of similar structural elements, the [CuL]2+ and [Cu(H–1L)]+ (L = L2, L2-Me, L2-Me3) complex cations, so that the peculiarities induced by the increase of N-methylation of ligands, the …
Enhancement of SOD activity in boehmite supported nanoreceptors
The binuclear Cu2+ complex of a pyridinophane polyamine ligand ranking amongst the fastest SOD mimetics so far reported displays a remarkable SOD activity enhancement when grafted to the surface of boehmite (γ-AlO(OH)) nanoparticles (BNPs).
Stabilisation of Exotic Tribromide (Br3−) Anions via Supramolecular Interaction with A Tosylated Macrocyclic Pyridinophane. A Serendipitous Case.
Tetraaza-macrocyclic pyridinophane L-Ts, decorated with a p-toluenesulfonyl (tosyl
Stabilization of polyiodide networks with Cu(ii) complexes of small methylated polyazacyclophanes: shifting directional control from H-bonds to I⋯I interactions
Ordered polyiodide networks have recently gathered considerable attention as electronic materials, a topic historically dominated by metals. Could we incorporate metal cations into polyiodide frameworks in a controlled manner to simultaneously boost electronic properties and robustness of these materials? Herein we present a first principles study featuring three analogous polyazacyclophanes (L, L-Me, L-Me3), differing only in the extent of N-methylation. We demonstrate (potentiometry, ITC) how they all form the same CuL2+ (L = L, L-Me, L-Me3) complex as prevalent species in solution, so that a level playing field exists where only N-methylation distinguishes them. Then we use them as count…
CCDC 1827335: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Andrea Liberato, Estefanía Delgado-Pinar, Andrés G. Algarra, Javier Pitarch-Jarque, José M. Llinares, M. Ángeles Mañez, Antonio Domenech-Carbó, Manuel G. Basallote, Enrique García-España|2018|Inorg.Chem.|57|10961|doi:10.1021/acs.inorgchem.8b01492
CCDC 1982975: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Pedro A. Sánchez-Murcia, Salvador Blasco, Leticia González, Enrique García-España|2020|Chem.Commun.|56|7511|doi:10.1039/D0CC01926G
CCDC 2017310: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Matteo Savastano, José M. Llinares, Begoña Verdejo, Antonio Bianchi, Enrique García-España, Carla Bazzicalupi|2020|Inorg.Chem.Front.|7|4239|doi:10.1039/D0QI00912A
CCDC 2192965: Experimental Crystal Structure Determination
Related Article: Valeria Dantignana, M. Carmen Pérez-Segura, Pau Besalú-Sala, Estefanía Delgado-Pinar, Álvaro Martínez-Camarena, Joan Serrano-Plana, Andrea Álvarez-Núñez, Carmen E. Castillo, Enrique García-España, Josep M. Luis, Manuel G. Basallote, Miquel Costas, Anna Company|2023|Angew.Chem.,Int.Ed.|62||doi:10.1002/anie.202211361
CCDC 2192964: Experimental Crystal Structure Determination
Related Article: Valeria Dantignana, M. Carmen Pérez-Segura, Pau Besalú-Sala, Estefanía Delgado-Pinar, Álvaro Martínez-Camarena, Joan Serrano-Plana, Andrea Álvarez-Núñez, Carmen E. Castillo, Enrique García-España, Josep M. Luis, Manuel G. Basallote, Miquel Costas, Anna Company|2023|Angew.Chem.,Int.Ed.|62||doi:10.1002/anie.202211361
CCDC 1827337: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Andrea Liberato, Estefanía Delgado-Pinar, Andrés G. Algarra, Javier Pitarch-Jarque, José M. Llinares, M. Ángeles Mañez, Antonio Domenech-Carbó, Manuel G. Basallote, Enrique García-España|2018|Inorg.Chem.|57|10961|doi:10.1021/acs.inorgchem.8b01492
CCDC 2192963: Experimental Crystal Structure Determination
Related Article: Valeria Dantignana, M. Carmen Pérez-Segura, Pau Besalú-Sala, Estefanía Delgado-Pinar, Álvaro Martínez-Camarena, Joan Serrano-Plana, Andrea Álvarez-Núñez, Carmen E. Castillo, Enrique García-España, Josep M. Luis, Manuel G. Basallote, Miquel Costas, Anna Company|2023|Angew.Chem.,Int.Ed.|62||doi:10.1002/anie.202211361
CCDC 2017311: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Matteo Savastano, José M. Llinares, Begoña Verdejo, Antonio Bianchi, Enrique García-España, Carla Bazzicalupi|2020|Inorg.Chem.Front.|7|4239|doi:10.1039/D0QI00912A
CCDC 2017309: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Matteo Savastano, José M. Llinares, Begoña Verdejo, Antonio Bianchi, Enrique García-España, Carla Bazzicalupi|2020|Inorg.Chem.Front.|7|4239|doi:10.1039/D0QI00912A
CCDC 1827336: Experimental Crystal Structure Determination
Related Article: Álvaro Martínez-Camarena, Andrea Liberato, Estefanía Delgado-Pinar, Andrés G. Algarra, Javier Pitarch-Jarque, José M. Llinares, M. Ángeles Mañez, Antonio Domenech-Carbó, Manuel G. Basallote, Enrique García-España|2018|Inorg.Chem.|57|10961|doi:10.1021/acs.inorgchem.8b01492
CCDC 2192962: Experimental Crystal Structure Determination
Related Article: Valeria Dantignana, M. Carmen Pérez-Segura, Pau Besalú-Sala, Estefanía Delgado-Pinar, Álvaro Martínez-Camarena, Joan Serrano-Plana, Andrea Álvarez-Núñez, Carmen E. Castillo, Enrique García-España, Josep M. Luis, Manuel G. Basallote, Miquel Costas, Anna Company|2023|Angew.Chem.,Int.Ed.|62||doi:10.1002/anie.202211361