0000000001305953
AUTHOR
Mario Inclán
Modulation of DNA binding by reversible metal-controlled molecular reorganizations of scorpiand-like ligands.
DNA interaction with scorpiand azamacrocycles has been achieved through modulation of their binding affinities. Studies performed with different experimental techniques provided evidence that pH or metal-driven molecular reorganizations of these ligands regulate their ability to interact with calf thymus DNA (ctDNA) through an intercalative mode. Interestingly enough, metal-driven molecular reorganizations serve to increase or decrease the biological activities of these compounds significantly.
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…
Synthetic single and double aza-scorpiand macrocycles acting as inhibitors of the antioxidant enzymes iron superoxide dismutase and trypanothione reductase in Trypanosoma cruzi with promising results in a murine model
The anti-chagasic activity of a series of eleven derivatives of aza-scorpiand-like macrocycles, some of them newly synthesised, was assayed. The four compounds with the best selectivity indices in vitro were subjected to in vivo assays. Tests in a murine model of the acute phase of Chagas disease showed a two-fold reduction in parasitaemia compared to that with benznidazole. Furthermore, compounds 7 and 11, with 4-pyridine and phenanthroline substituents in the lateral chain, caused a remarkable decrease in parasitaemia reactivation during the chronic phase after inducing immunosuppression in mice. These activity studies were complemented by measuring their inhibitory effect towards the ant…
A Metal-Based Receptor for Selective Coordination and Fluorescent Sensing of Chloride
A scorpionate Zn2+ complex, constituted by a macrocyclic pyridinophane core attached to a pendant arm containing a fluorescent pyridyl-oxadiazole-phenyl unit (PyPD), has been shown to selectively recognize chloride anions, giving rise to changes in fluorescence emission that are clearly visible under a 365 nm UV lamp. This recognition event has been studied by means of absorption, fluorescence, and NMR spectroscopy, and it involves the intramolecular displacement of the PyPD unit by chloride anions. Moreover, since the chromophore is not removed from the system after the recognition event, the fluorescence can readily be restored by elimination of the bound chloride anion.
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…
Efficient two-step synthesis of water soluble BODIPY–TREN chemosensors for copper(II) ions
Two simple fluorescent sensors for Cu(II) ions were synthesized in two reaction steps, using recently developed C–H functionalization reactions for boron dipyrrins, starting from a standard 8-aryl-BODIPY dye and a tris(2-aminoethyl)amine (TREN) ligand. At pH 5, the resulting BODIPY–TREN conjugates are demonstrated to be promising, highly selective, water soluble, Cu(II) sensors that can permeate the cell membrane. crosscheck: This document is CrossCheck deposited related_data: Supplementary Information identifier: Bram Verbelen (ORCID) identifier: Wim Dehaen (ORCID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: Thi…
In vitro antileishmanial activity of aza-scorpiand macrocycles. Inhibition of the antioxidant enzyme iron superoxide dismutase
The in vitro leishmanicidal activity of a series of nine aza-scorpiand-like macrocycles, recently synthesized, was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, using promastigotes and intracellular amastigotes forms. The cytotoxicity of the tested compounds on J774.2 macrophage cells was also measured. Four of the tested compounds (1, 2, 8 and 9) showed selectivity indexes higher than those of the reference drug Glucantime for the three Leishmania species. Moreover, the data on infection rates and on amastigotes showed that compounds 1, 2, 8 and 9 are the most active against the three Leishmania species. The changes in the excretion product profi…
Voltammetry of microparticles, scanning electrochemical microscopy and scanning tunneling microscopy applied to the study of dsDNA binding and damage by scorpiand-like polyamine receptors
Abstract Microparticulate deposits of scorpiand-like azamacrocyclic receptors (L1–L4) attached to graphite electrodes provide distinctive voltammetric features in contact with aqueous DNA solutions at biological pH, denoting the formation of DNA surface complexes. This voltammetry allows for screening dsDNA, ssDNA and G-Quadruplex DNA using L4-modified electrodes. Scanning electrochemical microscopy and scanning tunneling microscopy examination of dsDNA fibers attached to the substrate electrode in contact with DMSO solutions containing ferrocene and receptor indicate that a synergic effect is exerted between electrochemically generated ferrocenium ion and the receptors so that they increas…
Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin
The enantioselectivity of β-cyclodextrin (β-CD) towards L- and D-N-acetyltryptophan (NAcTrp) has been studied in aqueous solution and the crystalline state. NMR studies in solution show that β-CD forms complexes of very similar but not identical geometry with both L- and D-NAcTrp and exhibits stronger binding with L-NAcTrp. In the crystalline state, only β-CD–L-NAcTrp crystallizes readily from aqueous solutions as a dimeric complex (two hosts enclosing two guest molecules). In contrast, crystals of the complex β-CD–D-NAcTrp were never obtained, although numerous conditions were tried. In aqueous solution, the orientation of the guest in both complexes is different than in the β-CD–L-NAcTrp …
A hybrid catalyst for decontamination of organic pollutants based on a bifunctional dicopper(II) complex anchored over niobium oxyhydroxide
Abstract This article describes the preparation and characterization of a hybrid oxidation catalyst for decontamination of organic pollutants which involves a bifunctional dicopper(II) complex and the niobium(V) oxyhydroxide as the active species, the later one being also a solid support. The pH range for the existence of the active species was determined by potentiometric and UV–vis spectroscopy at 25 °C and 0.15 M NaCl in a H 2 O/EtOH (70:30 v/v) solvent mixture containing copper(II) and the ligand N , N -2,2′-ethylenediphenylenebis(oxamic acid) (H 4 L). As far as the hybrid material is concerned, FTIR, FT-Raman, TEM and SEM images, surface area and TG/DTA analyses showed the occurrence o…
Solution and solid state studies with the bis-oxalato building block [Cr(pyim)(C2O4)2]− [pyim = 2-(2′-pyridyl)imidazole]
The preparation, X-ray structure, and variable temperature magnetic study of the new compound {Ba(H2O)3/2[Cr(pyim)(C2O4)2]2}n·9/2nH2O (1) [pyim = 2-(2′-pyridyl)imidazole and C2O42− = dianion of oxalic acid], together with the potentiometric and spectrophotometric studies of the protonation/deprotonation equilibria of the pyim ligand and the ternary complex [Cr(pyim)(C2O4)2]−, are reported herein. The crystal structure of 1 consists of neutral chains, with diamond-shaped units sharing barium(II), with the two other corners occupied by chromium(III). The two metal centers are connected through bis(bidentate) oxalate. Very weak antiferromagnetic interactions between the chromium(III) ions occu…
MWCNTs-Supported Pd(II) Complexes with High Catalytic Efficiency in Oxygen Reduction Reaction in Alkaline Media
We report here the remarkable catalytic efficiency observed for two Pd(II) azamacrocyclic complexes supported on multiwalled carbon nanotubes (MWCNTs) toward oxygen reduction reactions. Beyond a main (90%) 4e
Dicopper(II) Metallacyclophanes with N,N'-2,6-Pyridinebis(oxamate): Solution Study, Synthesis, Crystal Structures, and Magnetic Properties.
The complexing ability of copper(II) in solution by the ligand N,N'-2,6-pyridinebis(oxamic acid) (H4mpyba, H4L) was determined through potentiometric and UV-vis spectroscopy at 25 °C and 0.15 M NaCl. The logarithms of the equilibrium constants for its copper(II) complexes according to the eqs 2H2L + 2Cu ⇆ [Cu2(H2L)2], 2H2L + 2Cu ⇆ [Cu2(H2L) (HL)] + H, 2H2L + 2Cu ⇆ [Cu2(HL)2] + 2H, 2H2L + 2Cu ⇆ [Cu2(HL)(L)] + 3H, and 2H2L + 2Cu ⇆ [Cu2L2] + 4H were 12.02(7), 8.04(5), 1.26(6), -7.51(6), and -16.36(6), respectively. The knowledge of the solution behavior has supported the synthesis of three new compounds bearing the common building block Cu2L2(4-). Their formulas are (Me4N)4[Cu2(mpyba)2(H2O)2]·…
Zn2+ and Cu2+ complexes of a fluorescent scorpiand-type oxadiazole azamacrocyclic ligand: crystal structures, solution studies and optical properties
A ligand comprised of a macrocyclic pyridinophane core having a pendant arm containing a secondary amine group linked through a methylene spacer to a pyridyl–oxadiazole–phenyl (PyPD) fluorescent system has been prepared (L). The crystal structures of [ZnL](ClO4)2 and [CuL](ClO4)2 show that M2+ is coordinated to all the nitrogen atoms of the macrocyclic core, the secondary amine of the pendant arm and the nitrogen atom of the pyridine group of the fluorescent moiety, the latter bond being clearly weaker than the one with the pyridine of the macrocycle. Solution studies showed the formation of a highly stable Cu2+ complex with 1 : 1 stoichiometry, whereas with Zn2+ least stable complexes were…
A New Heterogeneous Catalyst Obtained via Supramolecular Decoration of Graphene with a Pd2+ Azamacrocyclic Complex
A new G-(H2L)-Pd heterogeneous catalyst has been prepared via a self-assembly process consisting in the spontaneous adsorption, in water at room temperature, of a macrocyclic H2L ligand on graphene (G) (G + H2L = G-(H2L)), followed by decoration of the macrocycle with Pd2+ ions (G-(H2L) + Pd2+ = G-(H2L)-Pd) under the same mild conditions. This supramolecular approach is a sustainable (green) procedure that preserves the special characteristics of graphene and furnishes an efficient catalyst for the Cu-free Sonogashira cross coupling reaction between iodobenzene and phenylacetylene. Indeed, G-(H2L)-Pd shows an excellent conversion (90%) of reactants into diphenylacetylene under mild conditio…
Aza-macrocyclic triphenylamine ligands for G-quadruplex recognition
A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pendant aza-macrocycle(s) (TPA3PY) has been synthesised and studied by means of pH-metric titrations, UV/Vis spectroscopy and fluorescence experiments. The affinity of these ligands for G-quadruplex (G4) DNA and the selectivity they show for G4s over duplex DNA were investigated by Forster resonance energy transfer (FRET) melting assays, fluorimetric titrations and circular dichroism spectroscopy. Interestingly, the interactions of the bi- and especially the tri-branched ligands with G4s lead to a very intense redshifted fluorescence emission band that may be associated with intermolecular aggregation betw…
Binding Mode and Selectivity of a Scorpiand-Like Polyamine Ligand to Single- and Double-Stranded DNA and RNA: Metal- and pH-Driven Modulation
The interaction of a polyazacyclophane ligand having an ethylamine pendant arm functionalized with an anthryl group (L), with the single-stranded polynucleotides polyA, polyG, polyU, and polyC as well as with the double-stranded polynucleotides polyA-polyU, poly(dAT)(2), and poly(dGC)(2) has been followed by UV/Vis titration, steady state fluorescence spectroscopy, and thermal denaturation measurements. In the case of the single-stranded polynucleotides, the UV/Vis and fluorescence titrations permit to distinguish between sequences containing purine and pyrimidine bases. For the double-stranded polynucleotides the UV/Vis measurements show for all of them hypochromicity and bathochromic shif…
Construction of green nanostructured heterogeneous catalysts via non-covalent surface decoration of multi-walled carbon nanotubes with Pd(II) complexes of azamacrocycles
Abstract Green nanostructured heterogeneous catalysts were prepared via a bottom-up strategy. Designed ligands were synthesized joining covalently an electrondeficient pyrimidine residue and a scorpiand azamacrocycle. The desired molecular properties were easily transferred to nanostructured materials in two steps: first, exploiting their spontaneous chemisorption onto multi-walled carbon nanotubes (MWCNTs) via the pyrimidinic moiety in water at room temperature, then, taking advantage of the easy coordination of Pd(II) to the azamacrocycle in the same conditions. An evenly distribution of catalytic centres was obtained on the MWCNTs surface. Catalytic properties of these materials were ass…
Manganese(II) complexes of scorpiand-like azamacrocycles as MnSOD mimics.
Mn(II) complexes of scorpiand-type azamacrocycles constituted by a tretrazapyridinophane core appended with an ethylamino tail including 2- or 4-quinoline functionalities show very appealing in vitro SOD activity. The observed behaviour is related to structural and electrochemical parameters.
Molecular recognition of nucleotides in water by scorpiand-type receptors based on nucleobase discrimination.
Abstract: The detection of nucleotides is of crucial impor-tance because they are the basic building blocks of nucleicacids. Scorpiand-based polyamine receptors functionalizedwith pyridine or anthracene units are able to form stablecomplexes with nucleotides in water, based on coulombic,p–p stacking, and hydrogen-bonding interactions. This be-havior has been rationalized by means of an explorationwith NMR spectroscopy and DFT calculations. Binding con-stants were determined by potentiometry. Fluorescencespectroscopy studies have revealed the potential of these re-ceptors as sensors to effectively and selectively distinguishguanosine-5’-triphosphate (GTP) from adenosine-5’-triphos-phate (ATP…
Homo- and Heterobinuclear Cu2+ and Zn2+ Complexes of Ditopic Aza Scorpiand Ligands as Superoxide Dismutase Mimics
Two polytopic aza-scorpiand-like ligands, 6-[7-(diaminoethyl)-3,7-diazaheptyl]-3,6,9-triaza-1-(2,6-pyridina)cyclodecaphane (L1) and 6-[6′-[3,6,9-triaza-1-(2,6-pyridina)cyclodecaphan-6-yl]-3-azahexyl]-3,6,9-triaza-1-(2,6-pyridina)cyclodecaphane (L2), have been synthesized. The acid–base behavior and Cu2+, Zn2+, and Cu2+/Zn2+ mixed coordination have been analyzed by potentiometry, cyclic voltammetry, and UV–vis spectroscopy. The resolution of the crystal structures of [Cu2L2Cl2](ClO4)2·1.67H2O (1), [Cu2HL2Br2](ClO4)3·1.5H2O (2), and [CuZnL2Cl2](ClO4)2·1.64H2O (3) shows, in agreement with the solution data, the formation of homobinuclear Cu2+/Cu2+ and heterobinuclear Cu2+/Zn2+ complexes. The m…
CCDC 1952561: Experimental Crystal Structure Determination
Related Article: Gianluca Ambrosi, M. Paz Clares, Isabel Pont, Mauro Formica, Vieri Fusi, Angela Ricci, Paola Paoli, Patrizia Rossi, Enrique García-España, Mario Inclán|2020|Dalton Trans.|49|1897|doi:10.1039/C9DT04764F
CCDC 1507631: Experimental Crystal Structure Determination
Related Article: Lluís Guijarro, Mario Inclán, Javier Pitarch-Jarque, Antonio Doménech-Carbó, Javier U. Chicote, Sandra Trefler, Enrique García-España, Antonio García-España, Begoña Verdejo|2017|Inorg.Chem.|56|13748|doi:10.1021/acs.inorgchem.7b01756
CCDC 946980: Experimental Crystal Structure Determination
Related Article: Francisco R. Fortea-Pérez, Julia Vallejo, Mario Inclán, Mariadel Déniz, Jorge Pasán, Enrique García-España and Miguel Julve|2013|J.Coord.Chem.|66|3349|doi:10.1080/00958972.2013.837460
CCDC 1531987: Experimental Crystal Structure Determination
Related Article: Spyros D. Chatziefthimiou, Mario Inclán, Petros Giastas, Athanasios Papakyriakou, Konstantina Yannakopoulou and Irene M. Mavridis|2017|Beilstein J.Org.Chem.|13|1572|doi:10.3762/bjoc.13.157
CCDC 1053439: Experimental Crystal Structure Determination
Related Article: Tamires S. Fernandes, Ramon S. Vilela, Ana K. Valdo, Felipe T. Martins, Enrique García-España, Mario Inclán, Joan Cano, Francesc Lloret, Miguel Julve, Humberto O. Stumpf, and Danielle Cangussu|2016|Inorg.Chem.|55|2390|doi:10.1021/acs.inorgchem.5b02786
CCDC 1531988: Experimental Crystal Structure Determination
Related Article: Spyros D. Chatziefthimiou, Mario Inclán, Petros Giastas, Athanasios Papakyriakou, Konstantina Yannakopoulou and Irene M. Mavridis|2017|Beilstein J.Org.Chem.|13|1572|doi:10.3762/bjoc.13.157
CCDC 1529591: Experimental Crystal Structure Determination
Related Article: Gianluca Ambrosi, M. Paz Clares, Isabel Pont, Mauro Formica, Vieri Fusi, Angela Ricci, Paola Paoli, Patrizia Rossi, Enrique García-España, Mario Inclán|2020|Dalton Trans.|49|1897|doi:10.1039/C9DT04764F
CCDC 1053438: Experimental Crystal Structure Determination
Related Article: Tamires S. Fernandes, Ramon S. Vilela, Ana K. Valdo, Felipe T. Martins, Enrique García-España, Mario Inclán, Joan Cano, Francesc Lloret, Miguel Julve, Humberto O. Stumpf, and Danielle Cangussu|2016|Inorg.Chem.|55|2390|doi:10.1021/acs.inorgchem.5b02786
CCDC 1053437: Experimental Crystal Structure Determination
Related Article: Tamires S. Fernandes, Ramon S. Vilela, Ana K. Valdo, Felipe T. Martins, Enrique García-España, Mario Inclán, Joan Cano, Francesc Lloret, Miguel Julve, Humberto O. Stumpf, and Danielle Cangussu|2016|Inorg.Chem.|55|2390|doi:10.1021/acs.inorgchem.5b02786
CCDC 1507632: Experimental Crystal Structure Determination
Related Article: Lluís Guijarro, Mario Inclán, Javier Pitarch-Jarque, Antonio Doménech-Carbó, Javier U. Chicote, Sandra Trefler, Enrique García-España, Antonio García-España, Begoña Verdejo|2017|Inorg.Chem.|56|13748|doi:10.1021/acs.inorgchem.7b01756
CCDC 1507630: Experimental Crystal Structure Determination
Related Article: Lluís Guijarro, Mario Inclán, Javier Pitarch-Jarque, Antonio Doménech-Carbó, Javier U. Chicote, Sandra Trefler, Enrique García-España, Antonio García-España, Begoña Verdejo|2017|Inorg.Chem.|56|13748|doi:10.1021/acs.inorgchem.7b01756