Piano-Stool Ruthenium(II) complexes with delayed cytotoxic activity: origin of the lag time

We have recently reported a series of piano-stool ruthenium(II) complexes of the general formula [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] showing excellent cytotoxic activities (particularly when R2 = R3 = methyl). In the present study, new members of this family of compounds have been prepared with the objective to investigate the effect of the steric hindrance of a bulky phosphane ligand, namely diisopropyl(1-pyrenyl)phosphane (L), on exchange reactions involving the coordinated halides (X = Cl, I). Two η6-arene rings were used, i.e. η6-methyl benzoate (mba) and η6-p-cymene (p-cym), and four complexes were synthesized, namely [RuCl2(mba)(L)] (1Cl2iPr), [RuI2(mba)(L)] (1I2iPr), [RuCl2(p-cym)(L)] (2Cl2iPr), and [RuI2(p-cym)(L)] (2I2iPr). Unexpectedly, all of the complexes exhibited poor cytotoxic activities after 24 h of incubation with cells, in contrast to the related compounds previously reported. However, it was observed that aged DMSO solutions of 2I2iPr (from 2 to 7 days) exhibited better activities in comparison to freshly prepared solutions and that the activity improved over "aging" time. Thorough studies were therefore performed to uncover the origin of this lag time in the cytotoxicity efficiency. The data achieved clearly demonstrated that compounds 2I2iPr and 2Cl2iPr were undergoing a series of transformation reactions in DMSO (with higher rates for the iodido complex 2I2iPr), ultimately generating cyclometalated species through a mechanism involving DMSO as a coordinated proton abstractor. The cyclometalated complexes detected in solution were subsequently prepared; hence, pure [RuCl(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3CliPr), [RuI(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3IiPr), and [Ru(p-cym)(κS-dmso)(κ2C-diisopropyl(1-pyrenyl)phosphane)]PF6 (3dmsoiPr) were synthesized and fully characterized. Remarkably, 3CliPr, 3IiPr, and 3dmsoiPr are all very efficient cytotoxic agents, exhibiting slightly better activities in comparison to the chlorido noncyclometalated complexes [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] described in an earlier report. For comparison purposes, the iodido compounds [RuI2(mba)(dimethyl(1-pyrenyl)phosphane)] (1I2Me) and [RuI2(p-cym)(dimethyl(1-pyrenyl)phosphane)] (2I2Me), bearing the less hindered dimethyl(1-pyrenyl)phosphane ligand, have also been prepared. The cytotoxic and chemical behaviors of 1I2Me and 1I2Me were comparable to those of their chlorido counterparts reported previously

Piano-stool ruthenium(II) complexes with delayed cytotoxic activity: Origin of the lag time

We have recently reported a series of piano-stool ruthenium(II) complexes of the general formula [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] showing excellent cytotoxic activities (particularly when R2 = R3 = methyl). In the present study, new members of this family of compounds have been prepared with the objective to investigate the effect of the steric hindrance of a bulky phosphane ligand, namely diisopropyl(1-pyrenyl)phosphane (L), on exchange reactions involving the coordinated halides (X = Cl, I). Two η6-arene rings were used, i.e. η6-methyl benzoate (mba) and η6-p-cymene (p-cym), and four complexes were synthesized, namely [RuCl2(mba)(L)] (1Cl2iPr), [RuI2(mba)(L)] (1I2iPr), [RuCl2(p-cym)(L)] (2Cl2iPr), and [RuI2(p-cym)(L)] (2I2iPr). Unexpectedly, all of the complexes exhibited poor cytotoxic activities after 24 h of incubation with cells, in contrast to the related compounds previously reported. However, it was observed that aged DMSO solutions of 2I2iPr (from 2 to 7 days) exhibited better activities in comparison to freshly prepared solutions and that the activity improved over “aging” time. Thorough studies were therefore performed to uncover the origin of this lag time in the cytotoxicity efficiency. The data achieved clearly demonstrated that compounds 2I2iPr and 2Cl2iPr were undergoing a series of transformation reactions in DMSO (with higher rates for the iodido complex 2I2iPr), ultimately generating cyclometalated species through a mechanism involving DMSO as a coordinated proton abstractor. The cyclometalated complexes detected in solution were subsequently prepared; hence, pure [RuCl(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3CliPr), [RuI(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3IiPr), and [Ru(p-cym)(κS-dmso)(κ2C-diisopropyl(1-pyrenyl)phosphane)]PF6 (3dmsoiPr) were synthesized and fully characterized. Remarkably, 3CliPr, 3IiPr, and 3dmsoiPr are all very efficient cytotoxic agents, exhibiting slightly better activities in comparison to the chlorido noncyclometalated complexes [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] described in an earlier report. For comparison purposes, the iodido compounds [RuI2(mba)(dimethyl(1-pyrenyl)phosphane)] (1I2Me) and [RuI2(p-cym)(dimethyl(1-pyrenyl)phosphane)] (2I2Me), bearing the less hindered dimethyl(1-pyrenyl)phosphane ligand, have also been prepared. The cytotoxic and chemical behaviors of 1I2Me and 1I2Me were comparable to those of their chlorido counterparts reported previously.Financial support from the Spanish Ministerio de Ciencia Innovación, y Universidades (Project Nos. CTQ2015-65040-P, RED2018-102471-T, PID2019-107006GB-C21, PGC2018-098630-B-I00, and CTQ2017-88446-R AEI/FEDER, UE) and from the Instituto de Salud Carlos III (ISCIIIFIS PI18/00441, FEDER) is acknowledged. A.G. thanks the Royal Society of Chemistry for financial support (RSC Research Fund grant RF19-7147). J.C. thanks the Spanish MICINN for a Ramoń y Cajal research contract (RYC2018-024692-I) and the Spanish Structures of Excellence María de Maeztu program (MDM-2017-0767). P.G. acknowledges the Institució Catalana de Recerca i Estudis Avançats (ICREA).Peer reviewe

Impacto positivo del capital social en la gobernanza forestal comunitaria: Un análisis cuantitativo

Social capital is unobservable but can be inferred from its effects on society. We evaluated the influence of cognitive and structural social capital on deforestation rates in community forests in Mexico using surveys and statistical modeling. We examined predictions concerning the influence of demography, education, ethnicity, gender, and geography on community-based forest governance outcomes. Results revealed lower deforestation rates in remote forests managed by majority indigenous communities with above-average education levels and a higher proportion of female-headed households. Our findings support the main hypothesis, which proposed that sustainable forest governance is determined by social capital and cohesion. Our methodology constitutes a transferrable analytical framework and the results serve as a point of reference for the design of agrarian, conservation, and rural development policies. We recommend additional studies to reduce sampling uncertainty and increase the explanatory power of the models.El capital social es inobservable, pero se infiere por sus efectos en la sociedad. En un contexto de manejo forestal comunitario, evaluamos la influencia del capital social cognitivo y estructural sobre la deforestación en México empleando estudios en terreno y modelación estadística. Examinamos predicciones acerca del efecto de la demografía, educación, etnicidad, género, y geografía sobre el desempeño de la gobernanza comunitaria. Los resultados revelaron que la deforestación disminuyó en bosques aislados, manejados por comunidades mayoritariamente indígenas, con escolaridad superior al promedio, y mayor proporción de hogares con jefatura femenina. Nuestros hallazgos sustentan la hipótesis principal, la cual sostiene que la cohesión y el capital social son determinantes para la gobernanza forestal sustentable. Nuestra metodología aporta un marco analítico transferible, y los resultados fundamentos para diseñar políticas agrarias, de conservación, y desarrollo rural. Recomendamos estudios adicionales para aumentar la certidumbre muestral y el poder explicativo de los modelos

Ingreso y calidad del aire en ciudades. ¿Existe una curva de Kuznets para las emisiones del transporte en la Zona Metropolitana del Valle de México?

Antecedentes: La contaminación atmosférica proveniente del transporte en las urbes y sus impactos a la salud y el bienestar de las personas son preocupaciones crecientes en la región de América Latina. Existen muy pocos análisis que esclarezcan la relación entre los niveles de ingreso y contaminación proveniente del transporte a nivel microeconómico, con un gran vacío en ciudades de países en desarrollo.Metodología: Se corrió un modelo de mínimos cuadrados ordinarios (MCO) lineal, cuadrático y cúbico del modelo típico de Kuznets para conocer la relación existente entre el ingreso y las variables de contaminación atmosférica. Se construyó una base de datos con información de 2010, 2012 y 2014, con datos del Módulo de Condiciones Socioeconómicas (MCS) del Instituto Nacional de Estadística, Geografía e Informática (INEGI) para una muestra representativa de 1 582 hogares, con datos de ingreso anual e ingreso per cápita por hogar, así como sobre la ubicación del hogar, el número y modelo de los vehículos que éste posee y un estimado propio sobre distancias recorridas, para ponderar las emisiones con el modelo MOVES-México, que utiliza las mediciones de monitoreo atmosférico existentes en la Zona Metropolitana del Valle de México (ZMVM).Resultados: Existe una relación monotónica (lineal positiva) entre el monóxido de carbono (CO) y el dióxido de carbono equivalente (CO2eq), y cuadrática (Uinvertida) para los óxidos de nitrógeno (NOx), por mucho, los menos abundantes de los tres gases.Conclusiones: Inclusive a niveles de ingreso por encima de los puntos de inflexión observados en la literatura, los hogares más ricos siguen sin internalizar el costo social de contaminar. Los resultados sugieren el diseño urgente de políticas públicas que promuevan un cambio en los modos de transporte en la ZMVM

Ingreso y calidad del aire en ciudades: ¿Existe una curva de Kuznets para las emisiones del transporte en la Zona Metropolitana del Valle de México?

Antecedentes: La contaminación atmosférica proveniente del transporte en las urbes y sus impactos a la salud y el bienestar de las personas son preocupaciones crecientes en la región de América Latina. Existen muy pocos análisis que esclarezcan la relación entre los niveles de ingreso y contaminación proveniente del transporte a nivel microeconómico, con un gran vacío en ciudades de países en desarrollo.Metodología: Se corrió un modelo de mínimos cuadrados ordinarios (MCO) lineal, cuadrático y cúbico del modelo típico de Kuznets para conocer la relación existente entre el ingreso y las variables de contaminación atmosférica. Se construyó una base de datos con información de 2010, 2012 y 2014, con datos del Módulo de Condiciones Socioeconómicas (MCS) del Instituto Nacional de Estadística, Geografía e Informática (INEGI) para una muestra representativa de 1 582 hogares, con datos de ingreso anual e ingreso per cápita por hogar, así como sobre la ubicación del hogar, el número y modelo de los vehículos que éste posee y un estimado propio sobre distancias recorridas, para ponderar las emisiones con el modelo MOVES-México, que utiliza las mediciones de monitoreo atmosférico existentes en la Zona Metropolitana del Valle de México (ZMVM).Resultados: Existe una relación monotónica (lineal positiva) entre el monóxido de carbono (CO) y el dióxido de carbono equivalente (CO2eq), y cuadrática (Uinvertida) para los óxidos de nitrógeno (NOx), por mucho, los menos abundantes de los tres gases.Conclusiones: Inclusive a niveles de ingreso por encima de los puntos de inflexión observados en la literatura, los hogares más ricos siguen sin internalizar el costo social de contaminar. Los resultados sugieren el diseño urgente de políticas públicas que promuevan un cambio en los modos de transporte en la ZMVM

Economic spillover from Natural Protected Areas to conventional tourist destinations

En este artículo examinamos el papel de las Áreas Naturales Protegidas (ANPs) como fuente de derrama económica en México atrayendo turistas que no llegarían en ausencia de estas. Para ello, planteamos un modelo econométrico que explica el número de cuartos ocupados de destinos turísticos en función de la proximidad a ANPs, controlado por otras características del sitio. Un estimado conservador indica que 17.7% de los cuartos ocupados por turistas extranjeros estarían explicados por la proximidad a ANPs. Estos resultados plantean posibilidades como un mecanismo de compensación por parte del turismo convencional, propuesta económicamente eficiente y que contribuye al desarrollo sostenible

Piano-Stool Ruthenium(II) Complexes with Delayed Cytotoxic Activity: Origin of the Lag Time

We have recently reported a series of piano-stool ruthenium(II) complexes of the general formula [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] showing excellent cytotoxic activities (particularly when R2 = R3 = methyl). In the present study, new members of this family of compounds have been prepared with the objective to investigate the effect of the steric hindrance of a bulky phosphane ligand, namely diisopropyl(1-pyrenyl)phosphane (L), on exchange reactions involving the coordinated halides (X = Cl, I). Two η6-arene rings were used, i.e. η6-methyl benzoate (mba) and η6-p-cymene (p-cym), and four complexes were synthesized, namely [RuCl2(mba)(L)] (1Cl2iPr), [RuI2(mba)(L)] (1I2iPr), [RuCl2(p-cym)(L)] (2Cl2iPr), and [RuI2(p-cym)(L)] (2I2iPr). Unexpectedly, all of the complexes exhibited poor cytotoxic activities after 24 h of incubation with cells, in contrast to the related compounds previously reported. However, it was observed that aged DMSO solutions of 2I2iPr (from 2 to 7 days) exhibited better activities in comparison to freshly prepared solutions and that the activity improved over “aging” time. Thorough studies were therefore performed to uncover the origin of this lag time in the cytotoxicity efficiency. The data achieved clearly demonstrated that compounds 2I2iPr and 2Cl2iPr were undergoing a series of transformation reactions in DMSO (with higher rates for the iodido complex 2I2iPr), ultimately generating cyclometalated species through a mechanism involving DMSO as a coordinated proton abstractor. The cyclometalated complexes detected in solution were subsequently prepared; hence, pure [RuCl(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3CliPr), [RuI(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3IiPr), and [Ru(p-cym)(κS-dmso)(κ2C-diisopropyl(1-pyrenyl)phosphane)]PF6 (3dmsoiPr) were synthesized and fully characterized. Remarkably, 3CliPr, 3IiPr, and 3dmsoiPr are all very efficient cytotoxic agents, exhibiting slightly better activities in comparison to the chlorido noncyclometalated complexes [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] described in an earlier report. For comparison purposes, the iodido compounds [RuI2(mba)(dimethyl(1-pyrenyl)phosphane)] (1I2Me) and [RuI2(p-cym)(dimethyl(1-pyrenyl)phosphane)] (2I2Me), bearing the less hindered dimethyl(1-pyrenyl)phosphane ligand, have also been prepared. The cytotoxic and chemical behaviors of 1I2Me and 1I2Me were comparable to those of their chlorido counterparts reported previously.Financial support from the Spanish Ministerio de Ciencia Innovación, y Universidades (Project Nos. CTQ2015-65040-P, RED2018-102471-T, PID2019-107006GB-C21, PGC2018-098630-B-I00, and CTQ2017-88446-R AEI/FEDER, UE) and from the Instituto de Salud Carlos III (ISCIIIFIS PI18/00441, FEDER) is acknowledged. A.G. thanks the Royal Society of Chemistry for financial support (RSC Research Fund grant RF19-7147). J.C. thanks the Spanish MICINN for a Ramoń y Cajal research contract (RYC2018-024692-I) and the Spanish Structures of Excellence María de Maeztu program (MDM-2017-0767). P.G. acknowledges the Institució Catalana de Recerca i Estudis Avançats (ICREA).Peer reviewe

Values of our Ecosystemic Health Index for all ecosystem types (IGBP).

<p>The color of each data point corresponds to the type of noise (white, pink and brown).</p