Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Inorg Chem ; 61(16): 6193-6208, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35394766

RESUMEN

Photoredox catalysis constitutes a very powerful tool in organic synthesis, due to its versatility, efficiency, and the mild conditions required by photoinduced transformations. In this paper, we present an efficient and selective photocatalytic procedure for the aerobic oxidative dehydrogenation of partially saturated N-heterocycles to afford the respective N-heteroarenes (indoles, quinolines, acridines, and quinoxalines). The protocol involves the use of new Ir(III) biscyclometalated photocatalysts of the general formula [Ir(C^N)2(N^N')]Cl, where the C^N ligand is 2-(2,4-difluorophenyl)pyridinate, and N^N' are different ligands based on the 2-(2'-pyridyl)benzimidazole scaffold. In-depth electrochemical and photophysical studies as well as DFT calculations have allowed us to establish structure-activity relationships, which provide insights for the rational design of efficient metal-based dyes in photocatalytic oxidation reactions. In addition, we have formulated a dual mechanism, mediated by the radical anion superoxide, for the above-mentioned transformations.


Asunto(s)
Fármacos Fotosensibilizantes , Quinolinas , Bencimidazoles , Catálisis , Fármacos Fotosensibilizantes/farmacología
2.
Chemistry ; 26(53): 12219-12232, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32301532

RESUMEN

Five new RuII polypyridyl complexes bearing N-(arylsulfonyl)-8-amidoquinolate ligands and three of their biscyclometalated IrIII congeners have been prepared and employed as photocatalysts (PCs) in the photooxidation of benzylamines with O2 . In particular, the new RuII complexes do not exhibit photoluminescence, rather they harvest visible light efficiently and are very stable in solution under irradiation with blue light. Their non-emissive behavior has been related to the low electrochemical energy gaps and rationalized on the basis of theoretical calculations (DFT analysis) that predict low S0 ←T1 energy values. Moreover, the RuII complexes, despite being non-emissive, display excellent activities in the selective photocatalytic transformation of benzylamines into the corresponding imines. The presence of an electron-withdrawing group (-CF3) on the arene ring of the N-(arylsulfonyl)-8-amidoquinolate ligand improves the photocatalytic activity of the corresponding photocatalyst. Furthermore, all the experimental evidence, including transient absorption spectroscopy measurements suggest that singlet oxygen is the actual oxidant. The IrIII analogues are considerably more photosensitive and consequently less efficient photosensitizers (PSs).

3.
Inorg Chem ; 59(19): 14171-14183, 2020 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-32930592

RESUMEN

The importance of ion pairing in different fields of chemistry is widely recognized. In this work, we have synthesized a set of cationic p-cymene ruthenium complexes of general formula [(p-cym)Ru(L')(κ2-O^N-L)]X (p-cym = p-cymene; L' = N-methylimidazole (MeIm), N-ethylpiperidylimidazole (EpipIm), 1,3,5-triaza-7-phosphaadamantane (PTA); L = 2-(1H-benzimidazol-2-yl)phenolato (L1), 2-(1,3-benzothiazol-2-yl)phenolato (L2); X = Cl-, BF4-, OTf-, BPh4-). X-ray diffraction studies on selected complexes revealed relatively strong anion-cation interactions in the solid state mainly based on N-H···X (X = Cl, F, O) and C-H···π interactions, also observed in the DFT-modeled complexes in the gas phase. Moreover, NMR studies showed that they exist as intimate ion pairs in solution and, remarkably, as head-to-tail quadruples in the particular case of the cation [(p-cym)Ru(MeIm)(κ2- O^N-L1)]+ ([1]+) with Cl- and BPh4- as counteranions. Furthermore, a value of ΔG = -2.9 kcal mol-1 at 299 K has been estimated for the equilibrium {[1]BPh4···[1]BPh4} ⇆ 2{[1]+···BPh4-} in concentrated CDCl3 solutions. In addition, preliminary studies concerning the cytotoxic properties against HeLa cell lines of the derivatives suggested a positive effect derived from the presence of the lipophilic BPh4- anion and also from the NH group of the benzimidazolyl fragment.

4.
Chemistry ; 24(42): 10662-10671, 2018 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-29806715

RESUMEN

A new family of heteroleptic bis-cyclometalated IrIII complexes with formula [Ir(CN^ )2 (NN^ )]Cl (CN^ =2-phenylpyridinate and NN^ =2,2'-dipyridylamine or N-benzylated 2,2'-dipyridylamines, were synthesized, characterized, and successfully used as photosensitizers in the catalytic photooxidation of an array of dialkyl, dibenzyl, alkyl aryl, and diaryl sulfides, as well as sulfur-containing amino acids. Furthermore, the reactions proceeded with optimal chemoselectivity, and atom economy under mild conditions. Experimental observations support a dual mechanism in which singlet oxygen and superoxide are the actual oxidants.

5.
Chemistry ; 24(66): 17523-17537, 2018 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-30176086

RESUMEN

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral IrIII biscyclometalated complexes of general formula [Ir(C^N)2 (N^O)], where the N^O ligands are 2-(benzimidazolyl)phenolate-N,O (L1, series a) and 2-(benzothiazolyl)phenolate-N,O (L2, series b), and the C^N ligands are 2-(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy)2 (L1)] (dfppy=2-(4,6-difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for 1 O2 generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited-state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S-containing aminoacids with full selectivity.


Asunto(s)
Complejos de Coordinación/química , Iridio/química , Ligandos , Fármacos Fotosensibilizantes/síntesis química , Azoles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Cristalografía por Rayos X , Estabilidad de Medicamentos , Técnicas Electroquímicas , Humanos , Hidroxibenzoatos/química , Luz , Microscopía Fluorescente , Conformación Molecular , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Teoría Cuántica , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Fluorescencia
6.
Inorg Chem ; 57(3): 970-984, 2018 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-29303596

RESUMEN

Precursors of chelate pyridine-N-heterocyclic carbene (N^C:) ligands with methyl- or benzyl-substituted imidazolylidene fragments were synthesized. They were used to obtain 12 iridium bis-cyclometalated complexes of the type [Ir(C^N)2(N^C:)]+ (C^N = 2-(phenyl)pyridinato-C2,N, ppy, 2-(4,6-difluorophenyl)pyridinato-C2,N, dfppy). The ancillary N^C: ligands contain different structural modifications. The aim of the work was to analyze the effect that changes in the two types of ligands have on the photophysical and electrochemical properties and also on the behavior of these materials as photosensitizers. The X-ray crystal structures of five complexes were determined. The complexes emitted in the blue-green region. It was expected that the frontier orbitals and thus the photophysical and electrochemical properties would be controlled by the main C^N ligands, and it was demonstrated that the effect of the modifications in the N^C: ligand, especially the presence of a nitro group in the pyridine ring or the interruption of conjugation between the two rings, also affected these properties. The quenching with O2 and photostability studies were also performed. Density functional theory calculations were used to explain the behavior of some derivatives. The complexes and other previously reported compounds were employed as photosensitizers (PS) in preliminary studies on the production of H2 from water using [Co(bpy)3]Cl2 (bpy = 2,2'-bipyridine) as catalyst and triethanolamine (TEOA) as the sacrificial reductant. The absence of quenching of the PS with TEOA allowed us to propose an oxidative quenching mechanism.

7.
Inorg Chem ; 57(22): 14186-14198, 2018 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-30395446

RESUMEN

Considering the interest in processes related to hydrogen storage such as CO2 hydrogenation and formic acid (FA) decomposition, we have synthesized a set of Ir, Rh, or Ru complexes to be tested as versatile precatalysts in these reactions. In relation with the formation of H2 from FA, the possible applicability of these complexes in the transfer hydrogenation (TH) of challenging substrates as quinoline derivatives using FA/formate as hydrogen donor has also been addressed. Bearing in mind the importance of secondary coordination sphere interactions, N,N' ligands containing NH2 groups, coordinated or not to the metal center, were used. The general formula of the new complexes are [( p-cymene)RuCl(N,N')]X, X = Cl-, BF4- and [Cp*MCl(N,N')]Cl, M = Rh, Ir, where the N,N' ligands are 8-aminoquinoline (HL1), 6-pyridyl-2,4-diamine-1,3,5-triazine (L2) and 5-amino-1,10-phenanthroline (L3). Some complexes are not active or catalyze only one process. However, the complexes [Cp*MCl(HL1)]Cl with M = Rh, Ir are versatile catalysts that are active in hydrogenation of quinolines, FA decomposition, and also in CO2 hydrogenation with the iridium derivative being more active and robust. The CO2 hydrogenation takes place in mild conditions using only 5 bar of pressure of each gas (CO2 and H2). The behavior of some precatalysts in D2O and after the addition of 9 equiv of HCO2Na (pseudocatalytic conditions) has been studied in detail and mechanisms for the FA decomposition and the hydrogenation of CO2 have been proposed. For the Ru, Ir, or Rh complexes with ligand HL1, the amido species with the deprotonated ligand are observed. In the case of ruthenium, the formate complex is also detected. For the iridium derivative, both the amido intermediate and the hydrido species have been observed. This hydrido complex undergoes a process of umpolung D+↔ Ir-D. All in all, the results of this work reflect the active role of -NH2 in the transfer of H+.

8.
Inorg Chem ; 57(10): 6124-6134, 2018 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-29722534

RESUMEN

Given the potent anticancer properties of cis-diamminedichloroplatinum(II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4'-disubstituted bpy ligands (bpy = 2,2'-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV-vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-"PtCl2" derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.


Asunto(s)
Complejos de Coordinación/química , Platino (Metal)/química , Albúmina Sérica Bovina/química , Células A549 , Rastreo Diferencial de Calorimetría , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/toxicidad , ADN/química , Nucleótidos de Desoxiguanina/química , Estabilidad de Medicamentos , Células HeLa , Humanos , Ligandos , Estructura Molecular , Unión Proteica
9.
Inorg Chem ; 56(22): 13679-13696, 2017 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-29099179

RESUMEN

The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in neoplastic cell lines.


Asunto(s)
Antineoplásicos/farmacología , Ácidos Carboxílicos/farmacología , Complejos de Coordinación/farmacología , Compuestos Organoplatinos/farmacología , Rutenio/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Apoptosis/efectos de los fármacos , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/efectos de la radiación , Línea Celular Tumoral , Cisplatino/farmacología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/efectos de la radiación , ADN/química , Daño del ADN , Humanos , Sustancias Intercalantes/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Sustancias Intercalantes/efectos de la radiación , Luz , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Compuestos Organoplatinos/síntesis química , Compuestos Organoplatinos/química , Compuestos Organoplatinos/efectos de la radiación , Plásmidos
10.
Inorg Chem ; 53(20): 11274-88, 2014 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-25302401

RESUMEN

The ligands 2-pyridin-2-yl-1H-benzimidazole (HL(1)), 1-methyl-2-pyridin-2-ylbenzimidazole (HL(2)), and 2-(1H-imidazol-2-yl)pyridine (HL(3)) and the proligand 2-phenyl-1H-benzimidazole (HL(4)) have been used to prepare five different types of new ruthenium(II) arene compounds: (i) monocationic complexes with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL)]Y [HL = HL(1), HL(2), or HL(3); Y = Cl or BF4; arene = 2-phenoxyethanol (phoxet), benzene (bz), or p-cymene (p-cym)]; (ii) dicationic aqua complexes of the formula [(η(6)-arene)Ru(OH2)(κ(2)-N,N-HL(1))](Y)2 (Y = Cl or TfO; arene = phoxet, bz, or p-cym); (iii) the nucleobase derivative [(η(6)-arene)Ru(9-MeG)(κ(2)-N,N-HL(1))](PF6)2 (9-MeG = 9-methylguanine); (iv) neutral complexes consistent with the formulation [(η(6)-arene)RuCl(κ(2)-N,N-L(1))] (arene = bz or p-cym); (v) the neutral cyclometalated complex [(η(6)-p-cym)RuCl(κ(2)-N,C-L(4))]. The cytototoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (MCR-5, MCF-7, A2780, and A2780cis) in order to establish structure-activity relationships. Three of the compounds with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL(1))]Cl differing in the arene moiety have been studied in depth in terms of thermodynamic dissociation constants, aquation kinetic constants, and DNA binding measurements. The biologically most active compound is the p-cym derivative, which strongly destabilizes the DNA double helix, whereas those with bz and phoxet have only a small effect on the stability of the DNA double helix. Moreover, the inhibitory activity of several compounds toward CDK1 has also been evaluated. The DNA binding ability of some of the studied compounds and their CDK1 inhibitory effect suggest a multitarget mechanism for their biological activity.


Asunto(s)
Antineoplásicos/farmacología , Compuestos Organometálicos/farmacología , Oxadiazoles/química , Inhibidores de Proteínas Quinasas/farmacología , Rutenio/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Proteína Quinasa CDC2 , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ligandos , Células MCF-7 , Modelos Moleculares , Conformación Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA