2017 |
Sierpe, R; Noyong, M; Simon, U; Aguayo, D; Huerta, J; Kogan, M J; Yutronic, N Construction of 6-Thioguanine and 6-Mercaptopurine Carriers Based on Βcyclodextrins and Gold Nanoparticles Artículo de revista Carbohydrate Polymers, 177 , pp. 22-31, 2017, ISSN: 0144-8617. Resumen | Enlaces | BibTeX | Etiquetas: Antineoplastic, complexes, delivery dqcauchile, Drug Nanotechnology, sputtering @article{RN351, title = {Construction of 6-Thioguanine and 6-Mercaptopurine Carriers Based on Βcyclodextrins and Gold Nanoparticles}, author = { R. Sierpe and M. Noyong and U. Simon and D. Aguayo and J. Huerta and M.J. Kogan and N. Yutronic}, url = {http://www.sciencedirect.com/science/article/pii/S0144861717309785}, doi = {10.1016/j.carbpol.2017.08.102}, issn = {0144-8617}, year = {2017}, date = {2017-01-01}, journal = {Carbohydrate Polymers}, volume = {177}, pages = {22-31}, abstract = {As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in βcyclodextrin (βCD) to form the complexes βCD-TG and βCD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: βCD-TG-AuNPs and βCD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages. The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto βCD-TG and βCD-MP via sputtering was confirmed by UV\textendashvis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA).}, keywords = {Antineoplastic, complexes, delivery dqcauchile, Drug Nanotechnology, sputtering}, pubstate = {published}, tppubtype = {article} } As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in βcyclodextrin (βCD) to form the complexes βCD-TG and βCD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: βCD-TG-AuNPs and βCD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages. The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto βCD-TG and βCD-MP via sputtering was confirmed by UV–vis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA). |
Sierpe, R; Noyong, M; Simon, U; Aguayo, D; Huerta, J; Kogan, M J; Yutronic, N Construction of 6-Thioguanine and 6-Mercaptopurine Carriers Based on Beta Cyclodextrins and Gold Nanoparticles Artículo de revista Carbohydrate Polymers, 177 , pp. 22-31, 2017, ISSN: 0144-8617. Resumen | Enlaces | BibTeX | Etiquetas: anisotropic antineoplastic, applications, cancer, complex, complexes, cytotoxicity delivery, dielectrics, drug drug-delivery, enhanced inclusion ionic-solutions, nanotechnology, permeability, pharmaceutical photothermal solid-state, sputtering, therapy @article{RN352, title = {Construction of 6-Thioguanine and 6-Mercaptopurine Carriers Based on Beta Cyclodextrins and Gold Nanoparticles}, author = { R. Sierpe and M. Noyong and U. Simon and D. Aguayo and J. Huerta and M.J. Kogan and N. Yutronic}, url = {/brokenurl#<Go to ISI>://WOS:000411876200003}, doi = {10.1016/j.carbpol.2017.08.102}, issn = {0144-8617}, year = {2017}, date = {2017-01-01}, journal = {Carbohydrate Polymers}, volume = {177}, pages = {22-31}, abstract = {As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in beta cyclodextrin (beta CD) to form the complexes beta CD-TG and beta CD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: beta CD-TG-AuNPs and beta CD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages., The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto beta CD-TG and beta CD-MP via sputtering was confirmed by UV-vis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA).}, keywords = {anisotropic antineoplastic, applications, cancer, complex, complexes, cytotoxicity delivery, dielectrics, drug drug-delivery, enhanced inclusion ionic-solutions, nanotechnology, permeability, pharmaceutical photothermal solid-state, sputtering, therapy}, pubstate = {published}, tppubtype = {article} } As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in beta cyclodextrin (beta CD) to form the complexes beta CD-TG and beta CD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: beta CD-TG-AuNPs and beta CD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages., The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto beta CD-TG and beta CD-MP via sputtering was confirmed by UV-vis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA). |
Asela, I; Noyong, M; Simon, U; Andrades-Lagos, J; Campanini-Salinas, J; Vasquez-Velasquez, D; Kogan, M; Yutronic, N; Sierpe, R Gold Nanoparticles Stabilized with Beta Cyclodextrin-2-Amino-4-(4-Chlorophenyl)Thiazole Complex: A Novel System for Drug Transport Artículo de revista Plos One, 12 (10), 2017, ISSN: 1932-6203. Resumen | Enlaces | BibTeX | Etiquetas: activity, beta-cyclodextrin, complexes, delivery-systems, inclusion organophosphorus pesticides, photodegradation rates, thiazoles @article{RN353, title = {Gold Nanoparticles Stabilized with Beta Cyclodextrin-2-Amino-4-(4-Chlorophenyl)Thiazole Complex: A Novel System for Drug Transport}, author = { I. Asela and M. Noyong and U. Simon and J. Andrades-Lagos and J. Campanini-Salinas and D. Vasquez-Velasquez and M. Kogan and N. Yutronic and R. Sierpe}, url = {/brokenurl#<Go to ISI>://WOS:000412754400038}, doi = {10.1371/journal.pone.0185652}, issn = {1932-6203}, year = {2017}, date = {2017-01-01}, journal = {Plos One}, volume = {12}, number = {10}, abstract = {While 2-amino-4-(4-chlorophenyl)thiazole (AT) drug and thiazole derivatives have several biological applications, these compounds present some drawbacks, such as low aqueous solubility and instability. A new complex of beta CD-AT has been synthesized to increase AT solubility and has been used as a substrate for the deposit of solid-state AuNPs via magnetron sputtering, thus forming the beta CD-AT-AuNPs ternary system, which is stable in solution. Complex formation has been confirmed through powder X-ray diffraction and 1D and 2D nuclear magnetic resonance. Importantly, the amine and sulfide groups of AT remained exposed and can interact with the surfaces of the AuNPs. The complex association constant (970 M-1) has been determined using phase solubility analysis. AuNPs formation (32 nm average diameter) has been studied by UV-Visible spectroscopy, transmission/scanning electron microscopy and energy-dispersive X-ray analysis. The in vitro permeability assays show that effective permeability of AT increased using beta CD. In contrast, the ternary system did not have the capacity to diffuse through the membrane. Nevertheless, the antibacterial assays have demonstrated that AT is transferred from beta CD-AT-AuNPs, being available to exert its antibacterial activity. In conclusion, this novel beta CD-AT-AuNPs ternary system is a promising alternative to improve the delivery of AT drugs in therapy.}, keywords = {activity, beta-cyclodextrin, complexes, delivery-systems, inclusion organophosphorus pesticides, photodegradation rates, thiazoles}, pubstate = {published}, tppubtype = {article} } While 2-amino-4-(4-chlorophenyl)thiazole (AT) drug and thiazole derivatives have several biological applications, these compounds present some drawbacks, such as low aqueous solubility and instability. A new complex of beta CD-AT has been synthesized to increase AT solubility and has been used as a substrate for the deposit of solid-state AuNPs via magnetron sputtering, thus forming the beta CD-AT-AuNPs ternary system, which is stable in solution. Complex formation has been confirmed through powder X-ray diffraction and 1D and 2D nuclear magnetic resonance. Importantly, the amine and sulfide groups of AT remained exposed and can interact with the surfaces of the AuNPs. The complex association constant (970 M-1) has been determined using phase solubility analysis. AuNPs formation (32 nm average diameter) has been studied by UV-Visible spectroscopy, transmission/scanning electron microscopy and energy-dispersive X-ray analysis. The in vitro permeability assays show that effective permeability of AT increased using beta CD. In contrast, the ternary system did not have the capacity to diffuse through the membrane. Nevertheless, the antibacterial assays have demonstrated that AT is transferred from beta CD-AT-AuNPs, being available to exert its antibacterial activity. In conclusion, this novel beta CD-AT-AuNPs ternary system is a promising alternative to improve the delivery of AT drugs in therapy. |
2016 |
Miranda-Rojas, S; Salazar-Molina, R; Kastner, J; Arratia-Perez, R; Mendizabal, F Theoretical Exploration of Seleno and Tellurophenols as Promising Alternatives to Sulfur Ligands for Anchoring to Gold (111) Materials Artículo de revista Rsc Advances, 6 (6), pp. 4458-4468, 2016, ISSN: 2046-2069. Resumen | Enlaces | BibTeX | Etiquetas: basis-sets, chain-length, charge-transfer, chemistry, complexes, interface, monolayers, nanoparticles, pseudopotentials, self-assembled tellurium titanium @article{RN306, title = {Theoretical Exploration of Seleno and Tellurophenols as Promising Alternatives to Sulfur Ligands for Anchoring to Gold (111) Materials}, author = { S. Miranda-Rojas and R. Salazar-Molina and J. Kastner and R. Arratia-Perez and F. Mendizabal}, url = {/brokenurl#<Go to ISI>://WOS:000369510500023}, doi = {10.1039/c5ra21964g}, issn = {2046-2069}, year = {2016}, date = {2016-01-01}, journal = {Rsc Advances}, volume = {6}, number = {6}, pages = {4458-4468}, abstract = {It is widely known that sulfur ligands, such as alkanethiols or phenothiols and their derivatives, are useful anchor systems for gold materials due to the high affinity of sulfur to gold surfaces. In this study we use DFT calculations and a 42-atom gold cluster model to study the interaction between selenophenol and tellurophenol-derivatives with the Au(111) surface to gain information towards potential new gold-based materials. We modulated the interaction strength by controlling the charge transfer process of a particular interaction by chemically modifying the ligands. To obtain a complete analysis, we studied the ligands in their protonated, anionic and radical states aiming to cover the three possibilities in which these may interact with the gold cluster. In order to get a deeper insight into the nature of the interaction we used several analysis techniques such as energy decomposition analysis (EDA), non-covalent interactions (NCI) and natural population analysis (NPA). Our results reveal that tellurium in the anionic state provides complexes of better thermodynamic stability by similar to 12.0 kcal mol, when compared with the strongest sulfur-gold complex, also in the anionic state. Furthermore, this indicates that the anionic ligand is probably the dominant state for both selenium and tellurium as observed previously for sulfur. The extent to which the interaction strength could be controlled directly depends on the state of the anchor atom. In our case the anionic state is the most suitable for tuning the interaction. Finally, our main findings suggest that exchanging sulfur with selenium or tellurium involves an important increase of the interaction strength, thus, making these selenophenol and tellurophenol derivatives attractive for the development of new functional materials.}, keywords = {basis-sets, chain-length, charge-transfer, chemistry, complexes, interface, monolayers, nanoparticles, pseudopotentials, self-assembled tellurium titanium}, pubstate = {published}, tppubtype = {article} } It is widely known that sulfur ligands, such as alkanethiols or phenothiols and their derivatives, are useful anchor systems for gold materials due to the high affinity of sulfur to gold surfaces. In this study we use DFT calculations and a 42-atom gold cluster model to study the interaction between selenophenol and tellurophenol-derivatives with the Au(111) surface to gain information towards potential new gold-based materials. We modulated the interaction strength by controlling the charge transfer process of a particular interaction by chemically modifying the ligands. To obtain a complete analysis, we studied the ligands in their protonated, anionic and radical states aiming to cover the three possibilities in which these may interact with the gold cluster. In order to get a deeper insight into the nature of the interaction we used several analysis techniques such as energy decomposition analysis (EDA), non-covalent interactions (NCI) and natural population analysis (NPA). Our results reveal that tellurium in the anionic state provides complexes of better thermodynamic stability by similar to 12.0 kcal mol, when compared with the strongest sulfur-gold complex, also in the anionic state. Furthermore, this indicates that the anionic ligand is probably the dominant state for both selenium and tellurium as observed previously for sulfur. The extent to which the interaction strength could be controlled directly depends on the state of the anchor atom. In our case the anionic state is the most suitable for tuning the interaction. Finally, our main findings suggest that exchanging sulfur with selenium or tellurium involves an important increase of the interaction strength, thus, making these selenophenol and tellurophenol derivatives attractive for the development of new functional materials. |
Gallardo-Fuentes, S; Contreras, R; Isaacs, M; Honores, J; Quezada, D; Landaeta, E; Ormazabal-Toledo, R On the Mechanism of Co2 Electro-Cycloaddition to Propylene Oxides Artículo de revista Journal of Co2 Utilization, 16 , pp. 114-120, 2016, ISSN: 2212-9820. Resumen | Enlaces | BibTeX | Etiquetas: atmospheric calculations, capture carbonate catalyst co2 co2, complexes, conversion, cyclic density dioxide, efficient electro-cycloaddition, electrochemical functional high-capacity, ionic liquids, mechanism, reaction recovery, reduction, salen synthesis, system @article{RN327, title = {On the Mechanism of Co2 Electro-Cycloaddition to Propylene Oxides}, author = { S. Gallardo-Fuentes and R. Contreras and M. Isaacs and J. Honores and D. Quezada and E. Landaeta and R. Ormazabal-Toledo}, url = {/brokenurl#<Go to ISI>://WOS:000389089200013}, doi = {10.1016/j.jcou.2016.06.007}, issn = {2212-9820}, year = {2016}, date = {2016-01-01}, journal = {Journal of Co2 Utilization}, volume = {16}, pages = {114-120}, publisher = {2016 Elsevier Ltd.}, abstract = {We herein present a systematic study on the mechanism of CO2 electro-cycloaddition to propylene oxide, using both experimental and theoretical procedures. The study considers the analysis of mild and sustainable conditions to obtain cyclic carbonates from CO2 recycling. Within the electrochemical approach, the application of an overpotential in the reaction enhances the reaction yield significantly with respect to the thermal pathway. The quantum-mechanical approach provides relevant information about the reaction mechanism. Specifically, the use of the Lewis acid catalyst Mg2+ in the presence of the [C(4)C(1)Im][Br] ionic liquid provides the best condition for the electro-synthesis. The theoretical predictions were confirmed by a new set of experiments.}, keywords = {atmospheric calculations, capture carbonate catalyst co2 co2, complexes, conversion, cyclic density dioxide, efficient electro-cycloaddition, electrochemical functional high-capacity, ionic liquids, mechanism, reaction recovery, reduction, salen synthesis, system}, pubstate = {published}, tppubtype = {article} } We herein present a systematic study on the mechanism of CO2 electro-cycloaddition to propylene oxide, using both experimental and theoretical procedures. The study considers the analysis of mild and sustainable conditions to obtain cyclic carbonates from CO2 recycling. Within the electrochemical approach, the application of an overpotential in the reaction enhances the reaction yield significantly with respect to the thermal pathway. The quantum-mechanical approach provides relevant information about the reaction mechanism. Specifically, the use of the Lewis acid catalyst Mg2+ in the presence of the [C(4)C(1)Im][Br] ionic liquid provides the best condition for the electro-synthesis. The theoretical predictions were confirmed by a new set of experiments. |
Miranda-Rojas, S; Sierra-Rosales, P; Munoz-Castro, A; Arratia-Perez, R; Zagal, J H; Mendizabal, F Catalytic Aspects of Metallophthalocyanines Adsorbed on Gold-Electrode. Theoretical Exploration of the Binding Nature Role Artículo de revista Physical Chemistry Chemical Physics, 18 (42), pp. 29516-29525, 2016, ISSN: 1463-9076. Resumen | Enlaces | BibTeX | Etiquetas: complexes, fe iron-phthalocyanine, metal monolayers, oxidation phthalocyanines, pseudopotentials, scanning-tunneling-microscopy, self-assembled supramolecular surfaces @article{RN308, title = {Catalytic Aspects of Metallophthalocyanines Adsorbed on Gold-Electrode. Theoretical Exploration of the Binding Nature Role}, author = { S. Miranda-Rojas and P. Sierra-Rosales and A. Munoz-Castro and R. Arratia-Perez and J.H. Zagal and F. Mendizabal}, url = {/brokenurl#<Go to ISI>://WOS:000387024300053}, doi = {10.1039/c6cp06156g}, issn = {1463-9076}, year = {2016}, date = {2016-01-01}, journal = {Physical Chemistry Chemical Physics}, volume = {18}, number = {42}, pages = {29516-29525}, abstract = {The need of deeper insights regarding the inner working of catalysts represents a current challenge in the search of new ways to tune their activities towards new chemical transformations. Within this field, metallophthalocyanines-based (MPc) electrocatalysis has gained tremendous attention due to their versatility, low cost, great stability and excellent turn-over properties. In this concern, here we present a quantum chemical study of the formation of supramolecular complexes based on the adsorption of MPcs on gold substrates, and the effect of the substrate on their electrocatalytic properties. For this purpose, we used iron-(FePc), cobalt( CoPc) and copper-phthalocyanines (CuPc). To model the gold surface we used two gold clusters of different sizes, given by Au-26 and Au-58 accounting for gold electrode Au(111) surface. Thus, both electronic and binding strength features of the adsorption process between the complexes were analyzed in detail in order to gain a deeper description of the nature of the MPc-Au(111) formation, by using Density Functional Theory (DFT) calculations, at the PBE and TPSS levels including the dispersive contribution according to the Grimme approach (D3). Our results show that dispersion forces rule the MPc-gold interaction, with binding strengths ranging between 61 and 153 kcal mol(-1), in agreement to the reported experimental data. To provide a detailed picture of our findings we used the non-covalent interactions index (NCIs) analysis, which offers additional chemical insights regarding the forces that control their interaction strength. Finally, our calculations revealed that among the three MPcs, CuPc required less energy for its oxidation. However, the removal of the electron involves a tremendous decrease of the MPc-gold surface interaction strength thus suggesting its desorption, which would prevent the required reversibility of the redox reaction, explaining its low performance observed experimentally.}, keywords = {complexes, fe iron-phthalocyanine, metal monolayers, oxidation phthalocyanines, pseudopotentials, scanning-tunneling-microscopy, self-assembled supramolecular surfaces}, pubstate = {published}, tppubtype = {article} } The need of deeper insights regarding the inner working of catalysts represents a current challenge in the search of new ways to tune their activities towards new chemical transformations. Within this field, metallophthalocyanines-based (MPc) electrocatalysis has gained tremendous attention due to their versatility, low cost, great stability and excellent turn-over properties. In this concern, here we present a quantum chemical study of the formation of supramolecular complexes based on the adsorption of MPcs on gold substrates, and the effect of the substrate on their electrocatalytic properties. For this purpose, we used iron-(FePc), cobalt( CoPc) and copper-phthalocyanines (CuPc). To model the gold surface we used two gold clusters of different sizes, given by Au-26 and Au-58 accounting for gold electrode Au(111) surface. Thus, both electronic and binding strength features of the adsorption process between the complexes were analyzed in detail in order to gain a deeper description of the nature of the MPc-Au(111) formation, by using Density Functional Theory (DFT) calculations, at the PBE and TPSS levels including the dispersive contribution according to the Grimme approach (D3). Our results show that dispersion forces rule the MPc-gold interaction, with binding strengths ranging between 61 and 153 kcal mol(-1), in agreement to the reported experimental data. To provide a detailed picture of our findings we used the non-covalent interactions index (NCIs) analysis, which offers additional chemical insights regarding the forces that control their interaction strength. Finally, our calculations revealed that among the three MPcs, CuPc required less energy for its oxidation. However, the removal of the electron involves a tremendous decrease of the MPc-gold surface interaction strength thus suggesting its desorption, which would prevent the required reversibility of the redox reaction, explaining its low performance observed experimentally. |
Urra, F A; Weiss-Lopez, B; Araya-Maturana, R Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells Artículo de revista Current Pharmaceutical Design, 22 (39), pp. 5998-6008, 2016, ISSN: 1381-6128. Resumen | Enlaces | BibTeX | Etiquetas: alpha-ketoglutarate, anti-cancer cancer carboxylation, cells, complex-i, complexes, glutamine glutamine-metabolism, impairment, metabolic metabolism, mitochondrial nadh-ubiquinone ovarian-cancer, oxidative oxidative-phosphorylation, oxidoreductase, pancreatic-cancer, phosphorylation, reductive remodeling, respiratory respiratory-chain, slow-cycling solid tumor-cells, tumors @article{RN326, title = {Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells}, author = { F.A. Urra and B. Weiss-Lopez and R. Araya-Maturana}, url = {/brokenurl#<Go to ISI>://WOS:000390650400011}, doi = {10.2174/1381612822666160719122626}, issn = {1381-6128}, year = {2016}, date = {2016-01-01}, journal = {Current Pharmaceutical Design}, volume = {22}, number = {39}, pages = {5998-6008}, abstract = {Recent evidence highlights that energy requirements of cancer cells vary greatly from normal cells and they exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation (OXPHOS). Interestingly, mitochondrial electron transport chain (ETC) has been identified as an essential component in bioenergetics, biosynthesis and redox control during proliferation and metastasis of cancer cells. This dependence converts ETC of cancer cells in a promising target to design small molecules with anti-cancer actions. Several small molecules have been described as ETC inhibitors with different consequences on mitochondrial bioenergetics, viability and proliferation of cancer cells, when the substrate availability is controlled to favor either the glycolytic or OXPHOS pathway. These ETC inhibitors can be grouped as 1) inhibitors of a respiratory complex (e.g. rotenoids, vanilloids, alkaloids, biguanides and polyphenols), 2) inhibitors of several respiratory complexes (e.g. capsaicin, ME-344 and epigallocatechin-3 gallate) and 3) inhibitors of ETC activity (e.g. elesclomol and VLX600). Although pharmacological ETC inhibition may produce cell death and a decrease of proliferation of cancer cells, factors such as degree of inhibition of ETC activity by small molecules, bioenergetic profile and metabolic flexibility of different cancer types or subpopulations of cells in a particular cancer type, can affect the impact of the anti-cancer actions. Particularly interesting are the adaptive mechanisms induced by ETC inhibition, such as induction of glutamine-dependent reductive carboxylation, which may offer a strategy to sensitize cancer cells to inhibitors of glutamine metabolism.}, keywords = {alpha-ketoglutarate, anti-cancer cancer carboxylation, cells, complex-i, complexes, glutamine glutamine-metabolism, impairment, metabolic metabolism, mitochondrial nadh-ubiquinone ovarian-cancer, oxidative oxidative-phosphorylation, oxidoreductase, pancreatic-cancer, phosphorylation, reductive remodeling, respiratory respiratory-chain, slow-cycling solid tumor-cells, tumors}, pubstate = {published}, tppubtype = {article} } Recent evidence highlights that energy requirements of cancer cells vary greatly from normal cells and they exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation (OXPHOS). Interestingly, mitochondrial electron transport chain (ETC) has been identified as an essential component in bioenergetics, biosynthesis and redox control during proliferation and metastasis of cancer cells. This dependence converts ETC of cancer cells in a promising target to design small molecules with anti-cancer actions. Several small molecules have been described as ETC inhibitors with different consequences on mitochondrial bioenergetics, viability and proliferation of cancer cells, when the substrate availability is controlled to favor either the glycolytic or OXPHOS pathway. These ETC inhibitors can be grouped as 1) inhibitors of a respiratory complex (e.g. rotenoids, vanilloids, alkaloids, biguanides and polyphenols), 2) inhibitors of several respiratory complexes (e.g. capsaicin, ME-344 and epigallocatechin-3 gallate) and 3) inhibitors of ETC activity (e.g. elesclomol and VLX600). Although pharmacological ETC inhibition may produce cell death and a decrease of proliferation of cancer cells, factors such as degree of inhibition of ETC activity by small molecules, bioenergetic profile and metabolic flexibility of different cancer types or subpopulations of cells in a particular cancer type, can affect the impact of the anti-cancer actions. Particularly interesting are the adaptive mechanisms induced by ETC inhibition, such as induction of glutamine-dependent reductive carboxylation, which may offer a strategy to sensitize cancer cells to inhibitors of glutamine metabolism. |
2015 |
Mendizabal, F; Miranda-Rojas, S; Barrientos-Poblete, L A Comparative Study between Post-Hartree-Fock Methods and Density Functional Theory in Closed-Shell Aurophilic Attraction Artículo de revista Computational and Theoretical Chemistry, 1057 , pp. 74-79, 2015, ISSN: 2210-271x. Resumen | Enlaces | BibTeX | Etiquetas: attraction, au, aurophilic chemistry, clusters, complexes, correction, crystal-structures, cu dft, dimers, dispersion gold interaction, kinetics, metallophilic theoretical thermochemical @article{RN254, title = {A Comparative Study between Post-Hartree-Fock Methods and Density Functional Theory in Closed-Shell Aurophilic Attraction}, author = { F. Mendizabal and S. Miranda-Rojas and L. Barrientos-Poblete}, url = {/brokenurl#<Go to ISI>://WOS:000352042300010}, doi = {10.1016/j.comptc.2015.01.021}, issn = {2210-271x}, year = {2015}, date = {2015-01-01}, journal = {Computational and Theoretical Chemistry}, volume = {1057}, pages = {74-79}, publisher = {2015 Elsevier B.V.}, abstract = {The inter- and intramolecular aurophilic [ClAuPH3](2), [S(AuPH3)(2)] and [AuPH3](4)(2+) interactions were studied using ab initio post-Hartree-Fock and DFT methodologies. The post-Hartree-Fock methods provide results closer to the experimental data than DFT-based methods. It is possible to highlight the results obtained by the SCS-MP2 and CCSD(T) methods. In the classic [ClAuPH3](2) dimer, the aurophilic interaction is driven by the induction and dispersion terms. When DFT is used, the best results of geometry and interaction energy are obtained with the PW91 level. We find -D3 Grimme correction, M06HF, M06L, M06 M062X, M052X, CAM-B3LYP and LC-omega PBE provided results of similar accuracy as MP2.}, keywords = {attraction, au, aurophilic chemistry, clusters, complexes, correction, crystal-structures, cu dft, dimers, dispersion gold interaction, kinetics, metallophilic theoretical thermochemical}, pubstate = {published}, tppubtype = {article} } The inter- and intramolecular aurophilic [ClAuPH3](2), [S(AuPH3)(2)] and [AuPH3](4)(2+) interactions were studied using ab initio post-Hartree-Fock and DFT methodologies. The post-Hartree-Fock methods provide results closer to the experimental data than DFT-based methods. It is possible to highlight the results obtained by the SCS-MP2 and CCSD(T) methods. In the classic [ClAuPH3](2) dimer, the aurophilic interaction is driven by the induction and dispersion terms. When DFT is used, the best results of geometry and interaction energy are obtained with the PW91 level. We find -D3 Grimme correction, M06HF, M06L, M06 M062X, M052X, CAM-B3LYP and LC-omega PBE provided results of similar accuracy as MP2. |
Delgado, R A; Galdámez, A; Villena, J; Reveco, P G; Thomet, F A Synthesis, Characterization and in Vitro Biological Evaluation of [Ru(Eta(6)-Arene)(N,N)Cl] Pf6 Compounds Using the Natural Products Arenes Methylisoeugenol and Anethole Artículo de revista Journal of Organometallic Chemistry, 782 , pp. 131-137, 2015, ISSN: 0022-328x. Resumen | Enlaces | BibTeX | Etiquetas: bond cancer, complexes, cytotoxicity, diastereomers, drugs, isomerization, natural ovarian oxaliplatin, products, single-crystal, tumor-models @article{RN259, title = {Synthesis, Characterization and in Vitro Biological Evaluation of [Ru(Eta(6)-Arene)(N,N)Cl] Pf6 Compounds Using the Natural Products Arenes Methylisoeugenol and Anethole}, author = { R.A. Delgado and A. Gald\'{a}mez and J. Villena and P.G. Reveco and F.A. Thomet}, url = {/brokenurl#<Go to ISI>://WOS:000351637900020}, doi = {10.1016/j.jorganchem.2014.09.005}, issn = {0022-328x}, year = {2015}, date = {2015-01-01}, journal = {Journal of Organometallic Chemistry}, volume = {782}, pages = {131-137}, publisher = {2014 Elsevier B.V.}, abstract = {Five new organometallic Ru(II) compounds (VI-X) with the general formula [Ru(eta(6)-arene)(N,N)CI]PF6, where arene-N,N correspond to methylisoeugenol-bipyridine (VI); anethole-bipyridine (VII); methylisoeugenol-ethylenediamine (VIII); anethole-ethylenediamine (IX) and methylisoeugenol-1,2-diaminobenzene (X), have been synthesized, fully characterized and biologically evaluated in vitro. The reaction conditions based on the reduction of [Ru(1,5-COD)Cl-2](n) in situ with methyleugenol and estragole, which are natural ligands, induced an alkene isomerization on the allylic substituent of coordinated arenes. The Ru(II)-arene bond formation and isomerization of the C=C bond on the allyl substituent was confirmed using 1H NMR spectroscopy; this result was validated for compound VIII by X-ray diffraction. An XRD analysis revealed the presence of both enantiomers of the complex in the single-crystal. Compounds IX and X exhibited a better cytotoxic activity in vitro than carboplatin, which is a commercial drug, against three human tumor cell lines (MCF-7, PC-3 and HT-29).}, keywords = {bond cancer, complexes, cytotoxicity, diastereomers, drugs, isomerization, natural ovarian oxaliplatin, products, single-crystal, tumor-models}, pubstate = {published}, tppubtype = {article} } Five new organometallic Ru(II) compounds (VI-X) with the general formula [Ru(eta(6)-arene)(N,N)CI]PF6, where arene-N,N correspond to methylisoeugenol-bipyridine (VI); anethole-bipyridine (VII); methylisoeugenol-ethylenediamine (VIII); anethole-ethylenediamine (IX) and methylisoeugenol-1,2-diaminobenzene (X), have been synthesized, fully characterized and biologically evaluated in vitro. The reaction conditions based on the reduction of [Ru(1,5-COD)Cl-2](n) in situ with methyleugenol and estragole, which are natural ligands, induced an alkene isomerization on the allylic substituent of coordinated arenes. The Ru(II)-arene bond formation and isomerization of the C=C bond on the allyl substituent was confirmed using 1H NMR spectroscopy; this result was validated for compound VIII by X-ray diffraction. An XRD analysis revealed the presence of both enantiomers of the complex in the single-crystal. Compounds IX and X exhibited a better cytotoxic activity in vitro than carboplatin, which is a commercial drug, against three human tumor cell lines (MCF-7, PC-3 and HT-29). |
2013 |
Barrientos-Poblete, L; Lang, E; Zapata-Torres, G; Celis-Barros, C; Orellana, C; Jara, P; Yutronic, N Structural Elucidation of Supramolecular Alpha-Cyclodextrin Dimer/Aliphatic Monofunctional Molecules Complexes Artículo de revista Journal of Molecular Modeling, 19 (5), pp. 2119-2126, 2013, ISSN: 1610-2940. Resumen | Enlaces | BibTeX | Etiquetas: complexes, constants elucidation, host-guest inclusion-compounds, interaction, structural supramolecular @article{RN80, title = {Structural Elucidation of Supramolecular Alpha-Cyclodextrin Dimer/Aliphatic Monofunctional Molecules Complexes}, author = { L. Barrientos-Poblete and E. Lang and G. Zapata-Torres and C. Celis-Barros and C. Orellana and P. Jara and N. Yutronic}, url = {/brokenurl#<Go to ISI>://WOS:000318274700022}, doi = {10.1007/s00894-012-1675-x}, issn = {1610-2940}, year = {2013}, date = {2013-01-01}, journal = {Journal of Molecular Modeling}, volume = {19}, number = {5}, pages = {2119-2126}, abstract = {The structural elucidation of 2 alpha-cyclodextrin/1-octanethiol, 2 alpha-cyclodextrin/1-octylamine and 2 alpha-cyclodextrin/1-nonanoic acid inclusion complexes by nuclear magnetic resonance (NMR) spectroscopy and molecular modeling has been achieved. The detailed spatial configurations are proposed for the three inclusion complexes based on 2D NMR method. ROESY experiments confirm the inclusion of guest molecules inside the alpha-cyclodextrin (alpha-CD) cavity. On the other hand, the host-guest ratio observed was 2:1 for three complexes. The detailed spatial configuration proposed based on 2D NMR methods were further interpreted using molecular modeling studies. The theoretical calculations are in good agreement with the experimental data.}, keywords = {complexes, constants elucidation, host-guest inclusion-compounds, interaction, structural supramolecular}, pubstate = {published}, tppubtype = {article} } The structural elucidation of 2 alpha-cyclodextrin/1-octanethiol, 2 alpha-cyclodextrin/1-octylamine and 2 alpha-cyclodextrin/1-nonanoic acid inclusion complexes by nuclear magnetic resonance (NMR) spectroscopy and molecular modeling has been achieved. The detailed spatial configurations are proposed for the three inclusion complexes based on 2D NMR method. ROESY experiments confirm the inclusion of guest molecules inside the alpha-cyclodextrin (alpha-CD) cavity. On the other hand, the host-guest ratio observed was 2:1 for three complexes. The detailed spatial configuration proposed based on 2D NMR methods were further interpreted using molecular modeling studies. The theoretical calculations are in good agreement with the experimental data. |
Mendizabal, F; Donoso, D; Salazar, R Theoretical Study of Complexes of the Type [Pt-3(M-L)(3)(L ')(3)]-X (L=Co,So2,Cnh; L '=Ph3,Cnh; X=Tl+, Hg-0, Mph3+ (M = Cu, Au, Ag)) Artículo de revista Journal of the Chilean Chemical Society, 58 (1), pp. 1562-1570, 2013, ISSN: 0717-9707. Resumen | Enlaces | BibTeX | Etiquetas: approximation, chemical-reactivity, chemistry cluster clusters, complexes, crystal-structure, electronegativity, electrophilicity index, interactions, metallic platinum pseudopotentials, reactivity, units @article{RN142, title = {Theoretical Study of Complexes of the Type [Pt-3(M-L)(3)(L ')(3)]-X (L=Co,So2,Cnh; L '=Ph3,Cnh; X=Tl+, Hg-0, Mph3+ (M = Cu, Au, Ag))}, author = { F. Mendizabal and D. Donoso and R. Salazar}, url = {/brokenurl#<Go to ISI>://WOS:000331236900014}, issn = {0717-9707}, year = {2013}, date = {2013-01-01}, journal = {Journal of the Chilean Chemical Society}, volume = {58}, number = {1}, pages = {1562-1570}, abstract = {The interaction between the [Pt-3(mu-L)(3)(L')(3)] cluster (L = CO, SO2, CNH; L' = PH3, CNH) and a series of fragments X (Tl+, Hg(0), AuPH3+, CuPH3+ and AgPH3+) was studied using ab initio methodology. The calculations suggest that the complexes formed are stable. We have studied these complexes at the HF, MP2, B3LYP and PBE levels of theory. The magnitude of the interaction energies and Pt-3-MPH3+ distances indicate a substantial covalent character of the bond. On the other hand, in [Pt-3(mu-L)(3)(L')(3)]-X (Tl+ and Hg) the energy magnitudes are in the order of metallophilic interaction, which indicates that the dispersion and ionic terms are found as the main contribution to stability. These results have been confirmed by orbital diagrams. In addition, the Fukui index of electrophilic attack and electrophilicity index on the [Pt-3(mu-L)(3)(L')(3)] clusters were used to explore possible sites that may play a role in chemical reactivity.}, keywords = {approximation, chemical-reactivity, chemistry cluster clusters, complexes, crystal-structure, electronegativity, electrophilicity index, interactions, metallic platinum pseudopotentials, reactivity, units}, pubstate = {published}, tppubtype = {article} } The interaction between the [Pt-3(mu-L)(3)(L')(3)] cluster (L = CO, SO2, CNH; L' = PH3, CNH) and a series of fragments X (Tl+, Hg(0), AuPH3+, CuPH3+ and AgPH3+) was studied using ab initio methodology. The calculations suggest that the complexes formed are stable. We have studied these complexes at the HF, MP2, B3LYP and PBE levels of theory. The magnitude of the interaction energies and Pt-3-MPH3+ distances indicate a substantial covalent character of the bond. On the other hand, in [Pt-3(mu-L)(3)(L')(3)]-X (Tl+ and Hg) the energy magnitudes are in the order of metallophilic interaction, which indicates that the dispersion and ionic terms are found as the main contribution to stability. These results have been confirmed by orbital diagrams. In addition, the Fukui index of electrophilic attack and electrophilicity index on the [Pt-3(mu-L)(3)(L')(3)] clusters were used to explore possible sites that may play a role in chemical reactivity. |
2012 |
Lara, N; Aranda, P; Ruiz, A I; Manriquez, V; Ruiz-Hitzky, E Intercalation and Electrical Behavior of Taxmo1-Xs2 (X > 0.5) Layered Mixed Disulfides Artículo de revista Journal of the Brazilian Chemical Society, 23 (3), pp. 415-+, 2012, ISSN: 0103-5053. Resumen | Enlaces | BibTeX | Etiquetas: chalcogenides, complexes, conducting conductivity, dichalcogenides, encapsulation, intercalation, lithium molybdenum-disulfide, mos2, nanocomposites, peo, polymers, pyridine, solids sulfides, transition-metal @article{RN90, title = {Intercalation and Electrical Behavior of Taxmo1-Xs2 (X > 0.5) Layered Mixed Disulfides}, author = { N. Lara and P. Aranda and A.I. Ruiz and V. Manriquez and E. Ruiz-Hitzky}, url = {/brokenurl#<Go to ISI>://WOS:000302461200007}, doi = {10.1590/S0103-50532012000300007}, issn = {0103-5053}, year = {2012}, date = {2012-01-01}, journal = {Journal of the Brazilian Chemical Society}, volume = {23}, number = {3}, pages = {415-+}, abstract = {This work reports a systematic study of the structural and electrical behavior of three ternary phases of the TaxMo1-xS2 system (x = 0.55, 0.75 and 0.90) and their intercalation compounds resulting from both chemical and electrochemical lithium insertions, as well as from pyridine and poly(ethylene oxide) intercalations. The three ternary phases were prepared by direct reaction of their constituting elements, without any other additive, at 900 degrees C in inert atmosphere. The resulting compounds were characterized by means of X-ray powder diffractometry (XRD), thermogravimetric and differential thermal (TGA/DTA) analyses, energy dispersive X-ray fluorescence (EDX) and field emission-scanning electron microscopy (FE-SEM). The electrical conductivity of the different products was measured in the 1.5-300 K temperature range using the conventional four probe van der Pauw method in the presence of a 9 T magnetic field in order to verify the occurrence of magnetoresistivity phenomena.}, keywords = {chalcogenides, complexes, conducting conductivity, dichalcogenides, encapsulation, intercalation, lithium molybdenum-disulfide, mos2, nanocomposites, peo, polymers, pyridine, solids sulfides, transition-metal}, pubstate = {published}, tppubtype = {article} } This work reports a systematic study of the structural and electrical behavior of three ternary phases of the TaxMo1-xS2 system (x = 0.55, 0.75 and 0.90) and their intercalation compounds resulting from both chemical and electrochemical lithium insertions, as well as from pyridine and poly(ethylene oxide) intercalations. The three ternary phases were prepared by direct reaction of their constituting elements, without any other additive, at 900 degrees C in inert atmosphere. The resulting compounds were characterized by means of X-ray powder diffractometry (XRD), thermogravimetric and differential thermal (TGA/DTA) analyses, energy dispersive X-ray fluorescence (EDX) and field emission-scanning electron microscopy (FE-SEM). The electrical conductivity of the different products was measured in the 1.5-300 K temperature range using the conventional four probe van der Pauw method in the presence of a 9 T magnetic field in order to verify the occurrence of magnetoresistivity phenomena. |
2011 |
Aguilera-Venegas, B; Olea-Azar, C; Norambuena, E; Aran, V J; Mendizabal, F; Lapier, M; Maya, J D; Kemmerling, U; Lopez-Munoz, R Esr, Electrochemical, Molecular Modeling and Biological Evaluation of 4-Substituted and 1,4-Disubstituted 7-Nitroquinoxalin-2-Ones as Potential Anti-Trypanosoma Cruzi Agents Artículo de revista Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy, 78 (3), pp. 1004-1012, 2011, ISSN: 1386-1425. Resumen | Enlaces | BibTeX | Etiquetas: anion, behavior binding-site, chagas chagas-disease, complexes, crystal-structure, disease, epimastigote, esr, glutathione-reductase, modeling, molecular nifurtimox, nitro nitroquinoxaline, radical-anion, reductase, superoxide trypanothione trypomastigote @article{RN19h, title = {Esr, Electrochemical, Molecular Modeling and Biological Evaluation of 4-Substituted and 1,4-Disubstituted 7-Nitroquinoxalin-2-Ones as Potential Anti-Trypanosoma Cruzi Agents}, author = { B. Aguilera-Venegas and C. Olea-Azar and E. Norambuena and V.J. Aran and F. Mendizabal and M. Lapier and J.D. Maya and U. Kemmerling and R. Lopez-Munoz}, url = {/brokenurl#<Go to ISI>://WOS:000288046600012}, doi = {10.1016/j.saa.2010.12.017}, issn = {1386-1425}, year = {2011}, date = {2011-01-01}, journal = {Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy}, volume = {78}, number = {3}, pages = {1004-1012}, publisher = {2010 Elsevier B.V.}, abstract = {Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action.}, keywords = {anion, behavior binding-site, chagas chagas-disease, complexes, crystal-structure, disease, epimastigote, esr, glutathione-reductase, modeling, molecular nifurtimox, nitro nitroquinoxaline, radical-anion, reductase, superoxide trypanothione trypomastigote}, pubstate = {published}, tppubtype = {article} } Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action. |
Publicaciones 2011-2020
