Diastereoselective multicomponent synthesis of dihydroisoindolo[2,1-a]quinolin-11-ones mediated by eutectic solvents.

In this contribution, a series of dihydroisoindolo[2,1-a]quinolin-11-ones was synthesized by a one-pot multicomponent Povarov reaction starting from anilines, alkenes (trans-anethole, methyl eugenol and indene) and 2-formylbenzoic acid. Different eutectic solvents bearing Lewis or Brønsted acids were evaluated as reaction media and catalysts for the model reaction employing p-toluidine and trans-anethole finding that the eutectic mixture ChCl/ZnCl2 (1/2) allowed the obtention of the target compound in 77% isolated yield. Under the optimized reaction conditions, 20 derivatives were obtained in good to moderated yields using meta- and para-susbstituted anilines, while the corresponding ortho-analogs followed a different pathway affording isoindolinones. In addition, the eutectic mixture was reused in six cycles without observing a detrimental catalytic activity. This methodology features mild reaction conditions, short reaction time, simple work-up, and utilization of a reusable solvent; and provides straightforward and diastereoselective access to these alkaloid-like heterocyclic molecules.

Tin(ii) chloride dihydrate/choline chloride deep eutectic solvent: redox properties in the fast synthesis of N-arylacetamides and indolo(pyrrolo)[1,2-a]quinoxalines.

In this contribution a physicochemical, IR and Raman characterization for the tin(ii) chloride dihydrate/choline chloride eutectic mixture is reported. The redox properties of this solvent were also studied by cyclic voltammetry finding that it can be successfully used as an electrochemical solvent for electrosynthesis and electroanalytical processes and does not require negative potentials as verified by the reduction of nitrobenzene. The potential use of this eutectic mixture as a redox solvent was further explored in obtaining aromatic amines and N-arylacetamides starting from a wide variety of nitroaromatic compounds. In addition, a fast synthetic strategy for the construction of a series of indolo(pyrrolo)[1,2-a]quinoxalines was developed by reacting 1-(2-nitrophenyl)-1H-indole(pyrrole) with aldehydes. This simple protocol offers a straightforward method for the construction of the target quinoxalines in short reaction times and high yields where the key step involves a tandem one-pot reductive cyclization-oxidation.

Tariquidar-Related Chalcones and Ketones as ABCG2 Modulators.

ABC transporters, including ABCG2, play a vital role in defending the human body against the vast range of xenobiotics. Even though this is beneficial for human health, these protein transporters have been implicated in the emerging resistance of cancer cells to a variety of structurally and functionally diverse anticancer drugs. In order to investigate their role in resistance, potent and selective ABCG2 modulators have been described in the literature. A leading class of modulators are the tariquidar analogues; however, their susceptibility to hydrolysis limits their applicable use. To overcome this, we synthesized a novel series of chalcone- and ketone-based compounds inspired by reported tariquidar analogues. Compounds were characterized and evaluated for their ABCG2 modulatory activity and ABC transporter selectivity. When compared to transporters ABCB1 and ABCC1, the chalcone-based compounds exhibited selectivity for ABCG2, while the ketone-based compounds showed only a slight preference for ABCG2. From the former series, chalcone 16d (UR-DP48) displayed similar activity to the reference fumitremorgin C, both producing comparable maximal effects. The compound exhibited marked antiproliferative activity, while cytotoxicity was less pronounced for the most active compound 17f from the ketone series. Chalcone-containing tariquidar analogues are promising modulators to aid in functional investigations of ABCG2 transporters.

Synthesis, characterization, X-ray crystal structure and DFT calculations of 4-([2,2':6',2 '' -terpyridin]-4'-yl)phenol / Síntesis, caracterización, estructura cristalina y cálculos DFT para el 4-([2,2':6',2 '' -terpiridin]-4'-il)fenol / Síntese, caracterização, estrutura de cristal e cálculos DFT para o 4-([2,2':6',2 '' -terpiridina]-4'-il)fenol

Abstract The synthesis of new terpyridine (Tpy) derivatives has been subject of extensive research due to its potential as functional materials for solar energy conversion, among other applications. In this contribution, the 4-([2,2':6',2"-terpyndm]-4'-yl)phenol (TpyOH) was synthesized, characterized and studied through several methods, including X-ray crystallography and computational approaches. Single crystal X-ray structure analysis shows that TpyOH is essentially planar, with dihedral angles of about 5.03° between the central pyridinyl and the phenolic ring, and also 6.05 and 12.2° in the terpyridine moiety. In the crystal, molecules are linked by intermolecular hydrogen bonds and through П- П stacking interactions. Using a time dependent density functional theory approach and taking into account bulk solvent effects, the absorption and fluorescence spectra of TpyOH were investigated and compared. The TD-DFT S0→Sn and S1 →S0 transition energies are in good agreement with experimental results. The frontier molecular orbitals analysis showed that the low-energy absorption band has an intraligand charge transfer character (ICT), while the high-energy band is a common feature of П- П* transitions of the Tpy moiety. The S1→S0 emission transition also has an ICT character, with a 90% contribution from the HOMO→LUMO transitions.

Resumen La síntesis de derivados terpiridinicos (Tpy) se ha investigado ampliamente debido a su potencial para la conversión de energía solar En este artículo se sintetizó y caracterizó el 4-([2,2':6',2"-terpiridin]-4'-il)fenol (TpyOH), a través de varias metodologías como la cristalografía de rayos X y herramientas computacionales. El análisis de rayos X de monocristal mostró que el TpyOH es plano, con ángulos diedros de 5,03° entre el piridinilo central y el anillo fenólico, con presencia de ángulos de 6,05 y 12,2° en la porción terpiridínica. En el cristal, las moléculas están unidas por enlaces de hidrógeno intermoleculares y mediante interacciones de apilamiento n-n. Utilizando cálculos DFT dependientes del tiempo (TD-DFT) y teniendo en cuenta el efecto de los disolventes, se investigaron y compararon los espectros de absorción y fluorescencia de TpyOH. Las energías de transición TD-DFT de S0→Sn y S1→S0 concuerdan con los resultados experimentales. El análisis de orbitales moleculares de frontera mostró que la banda de absorción de baja energía corresponde a transferencia de carga intraligando (ICT); mientras que la banda de alta energía es común en las transiciones П-П* del resto Tpy. La emisión debido a la transición S1→S0 corresponde a ICT, con una contribución del 90% proveniente de transiciones HOMO→LUMO.

Resumo A síntese de derivados de terpiridina (Tpy) tem sido estudada devido ao seu potencial para a conversão de energia solar. Nesta contribuição, o 4-([2,2':6',2"- terpindina]-4'-il) fenol (TpyOH) foi sintetizado, caracterizado e estudado por vários métodos A análise de estrutura de raios X de cristal único mostra que o TpyOH é plano, com Ångulos diedros de 5,03 ° entre o piridinilo central e o anel fenólico, e também 6,05 e 12,2 ° na porção de terpiridina No cristal, as moléculas são ligadas por ligações intermoleculares de hidrogênio e através de interações de empilhamento n-n. Usando uma abordagem da teoria funcional da densidade dependente do tempo e levando em consideração os efeitos do solvente em massa, foram investigados e comparados os espectros de absorção e fluorescência do TpyOH As energias de transição TD-DFT S0→Sn e S1→S0 estão de acordo com os resultados experimentais A análise de orbitários moleculares de fronteira mostrou que a banda de absorção de baixa energia possui um caráter de transferência de carga intraligando (TIC), enquanto a banda de alta energia é uma característica comum das transições П-П* da fração Tpy. A transição de emissão S1→S0 também tem um caráter TIC, com uma contribuição de 90% das transições HOMO→LUMO.

Crystal structure of ethyl (E)-2-cyano-3-(thio-phen-2-yl)acrylate: two conformers forming a discrete disorder.

In the title compound, C10H9NO2S, all the non-H atoms, except for the ethyl fragment, lie nearly in the same plane. Despite the mol-ecular planarity, the ethyl fragment presents more than one conformation, giving rise to a discrete disorder, which was modelled with two different crystallographic sites for the eth-oxy O and eth-oxy α-C atoms, with occupancy values of 0.5. In the crystal, the three-dimensional array is mainly directed by C-H⋯(O,N) inter-actions, giving rise to inversion dimers with R22(10) and R22(14) motifs and infinite chains running along the [100] direction.

Crystal structures of three N-(3-acetyl-phen-yl)quinoline-2-carboxamides.

In the title compounds, N-(5-acetyl-2-methyl-phen-yl)quinoline-2-carboxamide [C19H16N2O2, (I)], N-(5-acetyl-2-bromo-phen-yl)quinoline-2-carboxamide [C18H13BrN2O2, (II)] and N-(5-acetyl-2-ethynylphen-yl)quinoline-2-carboxamide [C20H14N2O2, (III)], the quinoline ring system is essentially planar and forms a dihedral angles of 3.68 (5) (I), 5.59 (7) (II) and 1.87 (6)° (III) with the acetyl-substituted ring. The mol-ecular structures of (I) and (III) each feature an intra-molecular N-H⋯N hydrogen bond, forming an S(5) ring, while in (II) an intra-molecular bifurcated N-H⋯(N,Br) hydrogen bond forms two S(5) rings. In the crystals, weak C-H⋯O hydrogen bonds link mol-ecules of (I) into C(7) chains long [010], mol-ecules of (II) into chains of R22(8) rings along [110] and mol-ecules of (III) into C(8) chains along [010]. In (I), there are no significant π-π stacking inter-actions under 4 Å, but in both (II) and (III), π-π inter-actions link the weak hydrogen-bonded chains into layers parallel to (001) [centroid-centroid disttances of 3.748 (1) Šin (II) and 3.577 (1), 3.784 (1) and 3.780 (1) Šin (III)].

Crystal structure of N-(2-benzoyl-5-ethynylphen-yl)quinoline-2-carboxamide.

In the title compound, C25H16N2O2, the quinoline ring system is essentially planar, with a maximum deviation of 0.030 (1) Å, and forms a dihedral angle of 20.9 (1)° with benzoyl benzene ring. The unsubstituted phenyl ring forms dihedral angles of 52.7 (1)° with the quinoline ring system and 54.1 (1)° with the ethynyl-substituted benzene ring. The mol-ecule contains an intra-molecular bifurcated N-H⋯(O,N) hydrogen bond, forming S(5) and S(6) rings, which may influence the conformation of the mol-ecule. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network. In addition, the three-dimensional structure contains π-π stacking inter-actions, with centroid-centroid distances of 3.695 (1) and 3.751 (1) Å.

Magnetita (Fe 3 O 4 ): Una estructura inorgánica con multiples aplicaciones en catálisis heterogénea / Magnetite (Fe 3 O 4 ): An inorganic structure with many applications for heterogeneous catalysis / Magnetita (Fe 3 O 4 ): Uma estrutura inorgânica com múltiplas aplicações em catálise heterogénea

Resumen Se describió la intervención del mineral magnetita como catalizador o como soporte catalitico, un material inorgánico con una estructura de espinela inversa (FeFe204), en el desarrollo de un número importante de reacciones quimicas de interes cientifico, tecnológico y ambiental. Debido a la necesidad actual de generar procesos quimicos eficientes y favorables ambientalmente, la magnetita se ha convertido en un material promisorio en los contextos de la quimica verde, la quimica fina y la catálisis heterogénea. Este óxido de hierro se ha estudiado en diversas reacciones: catalizador másico, soporte catalitico de metales y de óxidos metálicos, núcleo de catalizadores tipo core-shell, o modificado mediante el anclaje de organocatalizadores y complejos metálicos. Se discute el desempeno catalitico de estos sistemas basados en magnetita, en reacciones de catálisis asimetrica, ambiental, ácido-base, de óxido-reducción, de sintesis multicomponente y de acoplamiento C-C. Particularmente, dichos catalizadores han mostrado enorme importancia en ciertas reacciones de tipo Sonogashira, Sonogashira-Hagihara, Mannich, Ullman, Knoevenagel, Suzuki-Miyaura y Fenton heterogénea, entre otras. Finalmente, se detallaron algunos usos tecnológicos de la magnetita en el contexto nacional (Colombia) y se intentó localizar geográficamente los depósitos importantes.

Abstract This manuscript contains a review on the mediation of magnetite, an inorganic material with an inverse spinel structure (FeFe204), being used as either catalyst or catalytic support in many chemical reactions of scientific, technological and environmental interest. Because of current awareness on the efficient and environmentally friendly chemical processes, magnetite has become as a promising material in contexts such as green chemistry, fine chemistry, and heterogeneous catalysis. This iron oxide has been used in several reactions as bulk catalyst, catalytic support of either metals or metal oxides, core in catalysts type core-shell, or as solid modified by grafting with organocatalysts and metal complexes. The catalytic performance of these systems has been described in some chemical processes such as: asymmetric catalysis, environmental catalysis, acid-base catalysis, redox reactions, multicomponent synthesis reactions, and those of C-C coupling. Particularly, these catalysts have shown large importance in a variety of reactions: Sonogashira, Sonogashira-Hagihara, Mannich, Ullman, Knoevenagel, Suzuki-Miyaura, and the Fenton heterogeneous reaction, among others. Finally, some technological uses of magnetite in the national context (Colombia) are detailed, and localizing geographically the most important deposits of this mineral in the Colombian region was intended.

Resumo Foi descrita uma intervenção da mineral magnetita, um material inorgânico com estrutura de espinela inversa (FeFe204), como catalisador ou como suporte catalitico no desenvolvimento de um número importante de reações quimicas de interesse cientifico, tecnológico e ambiental. Devido à necessidade atual de gerar processos quimicos eficientes e favoráveis ambientalmente, a magnetita surge como um material promissório nos contextos da quimica verde, da quimica fina e da catálise heterogénea. Este óxido de ferro e objeto de estudo em diversas reações: catalizador mássico, suporte catalitico de metais e de óxidos metálicos, núcleo de catalizadores tipo core-shell, ou modificado mediante a ancoragem de organocatalizadores e complexos metálicos. E descrito o desempenho catalitico deste tipo de sistemas em algumas reacóes de catálise assimetrica, ambiental, ácido-base, de óxido-redução, de sintese multicomponente y de acoplamento C-C. Particularmente, ditos catalisadores tem mostrado enorme importáncia em certas reações do tipo Sonogashira, Sonogashira-Hagihara, Mannich, Ullman, Knoevenagel, Suzuki-Miyaura e a reação Fenton heterogénea, entre outras. Finalmente, são detalhados alguns usos tecnológicos da magnetita no contexto nacional (Colômbia) e realiza-se um esforço por localizar geograficamente os depósitos mais importantes do mineral no território colombiano.

ABCG2/BCRP: Specific and Nonspecific Modulators.

Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2). The first two transporters have been widely studied already and reviews summarized the results. The ABCG2 protein has been a subject of intense study since its discovery as its overexpression has been detected in resistant cell lines in numerous types of human cancers. To date, a long list of modulators of ABCG2 exists and continues to increase. However, little is known about the clinical consequences of ABCG2 modulation. This makes the design of novel, potent, and nontoxic inhibitors of this efflux protein a major challenge to reverse MDR and thereby increase the success of chemotherapy. The aim of the present review is to describe and highlight specific and nonspecific modulators of ABCG2 reported to date based on the selectivity of the compounds, as many of them are effective against one or more ABC transport proteins.

Quinoline carboxamide-type ABCG2 modulators: indole and quinoline moieties as anilide replacements.

ABC, it's easy as 1 2 3! Bioisosteric replacement of the anilide core by an indole moiety considerably increased stability and gave potent and selective ABCG2 (BCRP) inhibitors. Some compounds are superior to the reference substances fumitremorgin C and Ko143 in terms of potency and efficacy and are the most potent ABCG2 modulators reported so far.

Aqueous citric acid as green reaction media for the synthesis of octahydroxanthenes / Ácido citrico acuoso como medio de reacción "verde" en la síntesis de octahidroxantenos / Ácido cítrico aquoso como meio de reação verde para a síntese de octaidroxantenos

A simple, convenient and environmentally friendly one-pot procedure for the synthesis of 1,8-dioxo-octahydroxanthenes by the reaction of dimedone and aromatic aldehydes in aqueous citric acid is described. In this green synthetic protocol promoted by the reaction media, the use of any other catalysts and hazardous organic solvents are avoided, making the work up procedure greener and easier. The isolation of the products, obtained in good yields, is readily performed by filtration and crystallization from ethanol when required and the aqueous acidic media can be easily recycled and reused several times without significant loss of catalytic activity.

En esta contribución se describe un procedimiento one-pot simple, conveniente y medioambientalmente amigable para la síntesis de 1,8-dioxo-octahidroxantenos por la reacción de dimedona y aldehídos aromáticos en ácido cítrico acuoso. En este protocolo de síntesis "verde" promovido por el medio de reacción, el uso de otros catalizadores y solventes orgánicos peligrosos es eliminado, haciendo el tratamiento final de la reacción más fácil y "verde". El aislamiento de los productos, obtenidos en buenos rendimientos, se lleva a cabo mediante filtración y recristalización en etanol cuando es necesario, y el medio acuoso ácido puede ser reciclado y reutilizado varias veces sin pérdida significativa de la actividad catalítica.

É descrito um procedimento simples, conveniente, e ambientalmente amigável para a síntese de 1,8-dioxo-octaidroxantenes pela reação de dimedona e aldeídos aromáticos em ácido cítrico aquoso em uma só etapa. Em este protocolo de síntese verde, promovido pelo meio de reação, a utilização de algum outro catalisador e solvente orgânico perigoso é evitada, fazendo o procedimento mais fácil e mais "verde". O isolamento dos produtos, obtidos em grande rendimento, é feito por meio de filtração e cristalização a partir de etanol quando é requerido e o meio aquoso ácido pode ser facilmente recuperado e reutilizado várias vezes sem perder significativamente sua atividade catalítica.

Benzanilide-Biphenyl Replacement: A Bioisosteric Approach to Quinoline Carboxamide-Type ABCG2 Modulators.

Recently reported compounds such as UR-COP78 (6) are among the most potent and selective ABCG2 modulators known so far but are prone to rapid enzymatic cleavage at the central benzanilide moiety. In search for more stable analogues, according to a bioisosteric approach, a series of N-(biphenyl-3-yl)quinoline carboxamides was prepared by solid phase and solution phase synthesis. The biphenyl moiety was constructed by Suzuki coupling. Inhibition of ABCB1 and ABCG2 was determined in a calcein-AM and a Hoechst 33342 microplate assay, respectively. Most synthesized compounds selectively inhibited the ABCG2 transporter at submicromolar concentrations with a maximal inhibitory effect (I max) over 90% (e.g., UR-COP228 (22a), IC50 591 nM, I max 109%; UR-COP258 (31), IC50 544 nM, I max 112%), though with lower potency and selectivity than 6. The biphenyl analogues are considerably more stable and demonstrate that the benzanilide core is not a crucial structural feature of quinoline carboxamide-type ABCG2 modulators.

Photoinduced energy transfer in bichromophoric pyrene-PPV oligomer systems: the role of flexible donor-acceptor bridges.

In this contribution, we report on the electronic energy transfer dynamics of bichromophoric systems incorporating two pyrene chromophores tethered by variable-length flexible alkyloxy chains to p-phenylenevinylene oligomers. These were studied using UV-vis absorption and both steady state and time-resolved fluorescence spectroscopy. Time-resolved emission measurements showed an efficient photoinduced energy transfer process in all the multichromophoric systems, which occurs on the time scale of tens of picoseconds after excitation at 265 nm. The energy transfer process is especially efficient in systems where the linker is formed by eight atoms (up to k(ET) ≈ 2.7 × 10(10) s(-1)), which, despite not being the shortest bridge studied, allows the approach of the donor and acceptor chromophores due to an appropriate number of flexible single bonds. Using Förster theory, we calculated the donor-acceptor distance in each triad from the experimental energy transfer rate, finding them to be in the range 8.8-10 Å.

New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental results to a great extent because a correct classification for both models of 95.24% (20 of 21) of the chemicals was obtained. Of the 21 compounds that were screened and synthesized, 2 molecules (chemicals G-1, UC-245) showed high to moderate cytocidal activity at the concentration of 10 microg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 microg/ml, and the remaining chemicals (from CRIS-105 to CRIS-153, except CRIS-148) were inactive at these assayed concentrations. Finally, the best candidate, G-1 (cytocidal activity of 100% at 10 microg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound.