Browsing by Author "Tapia, Ricardo A."

Now showing 1 - 13 of 13
  • Thumbnail Image
    Item
    A ternary eutectic solvent for cellulose nanocrystal production: exploring the recyclability and pre-pilot scale-up
    (2023) Mariño, Mayra A. ; Paredes Gutierrez, Maria Gabriela; Martinez Ahumada, Natalia del Pilar; Millan, Daniela ; Tapia, Ricardo A. ; Ruiz, Domingo ; Isaacs Casanova, Mauricio Alejandro; Pavez Guerrero, Paulina Isabel
    Deep eutectic solvents (DES) formed using choline chloride (ChCl), p-toluenesulfonic acid (pTSA) of stoichiometry ChCl: pTSA (1:1) and (1:2), and its ternary eutectic mixtures with phosphoric acid (PA) 85% as an additive (ChCl: pTSA: PA) were evaluated for cellulose nanocrystal (CNC) isolation. Initially, the hydrolytic efficiency to produce CNC of each DES was compared before and after adding phosphoric acid by Hammett acidity parameters and the Gutmann acceptor number. Moreover, different DES molar ratios and reaction time were studied at 80°C for CNC optimization. The nanomaterial characteristics were analyzed by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The ternary eutectic mixture ChCl: pTSA: PA molar ratio (1:1:1.35) was chosen as a suitable recyclable ternary system at the laboratory scale. A CNC yield of about 80% was obtained from the hydrolysis of commercial cellulose in five cycles of recovery, but it dropped to 35% in pre-pilot scaling. However, no variation in the average size of the resulting CNC was observed (132 ± 50 nm x 23 ± 4 nm), which presented high thermal stability (Tmax 362°C) and high crystallinity of about 80% after 3 h of reaction time.
  • No Thumbnail Available
    Item
    Experimental Analyses Emphasize the Stability of the Meisenheimer Complex in a SNAr Reaction Toward Trends in Reaction Pathways
    (2020) Campodonico, Paola R.; Olivares, Belen; Tapia, Ricardo A.
    The mechanism of SNAr reactions between 2-chloro-5-nitropyrimidine with primary and secondary alicyclic amines, respectively, have been studied by kinetic measurements. The kinetic data obtained in aqueous media opens a controversial discussion based on Bronsted-type plots analysis. The first approach based on the kinetic data reveals a non-catalyzed pathway. Then, the subtlety of the mathematical treatment of the kinetic data is discussed over a concerted or stepwise mechanism, respectively.
  • No Thumbnail Available
    Item
    How the Nature of an Alpha-Nucleophile Determines a Bronsted Type-Plot and Its Reaction Pathways. An Experimental Study
    (2022) Campodonico, Paola R.; Tapia, Ricardo A.; Suarez-Rozas, Cristian
    The reactions between 2-chloro-5-nitro pyrimidine with a serie of alpha-nucleophile derivatives were kinetically evaluated. The kinetic study was carried out in aqueous media and the data shown an unusual split on the Bronsted type-plot, opening a controversial discussion based on reactivities and possible reaction pathways. These split Bronsted type-plots are discussed over the hypothetical transition state (TS) structures associated to concerted or stepwise mechanisms with emphasis on hydrogen bond interactions between electrophile/nucleophile pair able to determine the reactivities and the plausible reaction routes.
  • No Thumbnail Available
    Item
    Influence of Organic Nitrogen Derived from Recycled Wine Lees and Inorganic Nitrogen on the Chemical Composition of Cabernet Sauvignon Wines Fermented in the Presence of Non-Saccharomyces Yeasts Candida boidinii, C. oleophila, and C. zemplinina
    (Multidisciplinary Digital Publishing Institute (MDPI), 2024) López Lira, Claudia; Valencia, Pedro; Urtubia, Alejandra; Landaeta Campos, Esteban Alonso; Tapia, Ricardo A.; Franco Melazzini, Wendy Verónica
    In this study, the influences of inorganic nitrogen source (INS) and organic nitrogen source (ONS) supplementation during the wine fermentation process using three non-Saccharomyces yeasts (Candida zemplinina, Candida oleophila, and Candida boidinii) were analyzed. Diamine phosphate (DAP) was used as an INS, and lees enzymatic hydrolysate was used as an ONS. Complete alcoholic fermentation and a higher concentration of volatile compounds were obtained in fermentations with ONS, mainly esters from 81 to 4564 µg/L, alcohols from 231 to 7294 µg/L, and isoamyl acetate ester compounds from 12.3–22.8 ppb, with a very marked odorant activity value (OAV). In addition, malic acid was detected due to its influence on yeast metabolism and, consequently, on aroma production. Using a Y15 enzymatic autoanalyzer, residues of 1.30 g/L in ONS and 1.35 g/L in INS were obtained on the last day of alcoholic fermentation. In summary, we obtained promising results concerning the production of wine with enhanced functionalities due to higher concentrations of some volatile and polyphenolic compounds.
  • Thumbnail Image
    Item
    Microwave-Assisted Reaction of 2,3-Dichloronaphthoquinone with Aminopyridines
    (SOC BRASILEIRA QUIMICA, 2009) Tapia, Ricardo A.; Cantuarias, Lorena; Cuellar, Mauricio; Villena, Joan
    The synthesis of pyridylaminonaphthoquinones by microwave-assisted reaction of 2,3-dichloro1,4-naphthoquinone with aminopyridines is described. The use of microwave irradiation diminished the reaction times and improved the yields substantially in all these reactions. The compounds were tested for their cytotoxic activities against MCF-7 breast cancer cell line.
  • No Thumbnail Available
    Item
    Mode of action of p-quinone derivatives with trypanocidal activity studied by experimental and in silico models
    (2023) Ballesteros-Casallas, Andres; Quiroga, Cristina; Ortiz, Cecilia; Benitez, Diego; Denis, Pablo A.; Figueroa, David; Salas, Cristian O.; Bertrand, Jeanluc; Tapia, Ricardo A.; Sanchez, Patricio; Miscione, Gian Pietro; Comini, Marcelo A.; Paulino, Margot
    Quinones are attractive pharmacological scaffolds for developing new agents for the treatment of different transmissible and non-transmissible human diseases due to their capacity to alter the cell redox homeostasis.The bioactivity and potential mode of action of 19 p-quinone derivatives fused to different aromatic rings (carbo or heterocycles) and harboring distinct substituents were investigated in infective Trypanosoma brucei brucei. All the compounds, except for a furanequinone (EC50=38 mu M), proved to be similarly or even more potent (EC50 = 0.5-5.5 mu M) than the clinical drug nifurtimox (EC50 = 5.3 mu M). Three furanequinones and one thia-zolequinone displayed a higher selectivity than nifurtimox. Two of these selective hits resulted potent inhibitors of T. cruzi proliferation (EC50=0.8-1.1 mu M) but proved inactive against Leishmania infantum amastigotes.Most of the p-quinones induced a rapid and marked intracellular oxidation in T. b. brucei. DFT calculations on the oxidized quinone (Q), semiquinone (Q center dot-) and hydroquinone (QH2) suggest that all quinones have negative Delta G for the formation of Q center dot-. Qualitative and quantitative structure-activity relationship analyses in two or three dimensions of different electronic and biophysical descriptors of quinones and their corresponding bioactivities (killing potency and oxidative capacity) were performed.Charge distribution over the quinone ring carbons of Q and Q.-and the frontier orbitals energies of SUMO (Q.-) and LUMO (Q) correlate with their oxidative and trypanocidal activity. QSAR analysis also highlighted that both bromine substitution in the p-quinone ring and a bulky phenyl group attached to the furane and thiazole rings (which generates a negative charge due to the 7C electron system polarized by the nearby heteroatoms) are favorable for activity.By combining experimental and in silico procedures, this study disclosed important information about p-qui-nones that may help to rationally tune their electronic properties and biological activities.
  • Thumbnail Image
    Item
    New Approaches to 6-Oxoisoaporphine and Tetrahydroisoquinoline Derivatives
    (WILEY-BLACKWELL, 2010) Sobarzo Sanchez, Eduardo; Uriarte, Eugenio; Santana, Lourdes; Tapia, Ricardo A.; Perez Lourido, Paulo
    2,3-Dihydro-6-hydroxy-5-methoxy-7H-dibenzo[de,h]quinolin-7-one, 6-hydroxy-5-methoxy-7H-dibenzo[de,h]quinolin-7-one, and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-l-yl)benzyl benzoate, easily available by a Bischler-Napieralski cyclization, were used as starting materials to afford 6-oxoisoaporphine and 2,3-dimethoxy-5,6,8,12b-tetrahydroisoindolo[1,2-a]isoquinoline as the main products. However, the catalytic hydrogenation of the benzyl benzoate derivative afforded, under mild conditions, 1,2,3,4-tetrahydro-6.7-dimethoxy-1 -(2-methylphenyl)isoquinoline.
  • No Thumbnail Available
    Item
    New benzimidazolequinones as trypanosomicidal agents
    (2021) Lopez-Lira, Claudia; Tapia, Ricardo A.; Herrera, Alejandra; Lapier, Michel; Maya, Juan D.; Soto-Delgado, Jorge; Oliver, Allen G.; Lappin, A. Graham; Uriarte, Eugenio
    Herein, the design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives as potential anti-Trypanosoma cruzi agents are described. The compounds were evaluated in vitro against the epimastigotes and trypomastigote forms of Trypanosoma cruzi. The replacing of a benzene moiety in the naphthoquinone system by an imidazole enhanced the trypanosomicidal activity against Trypanosoma cruzi. Three of the tested compounds (11a-c) showed potent trypanosomicidal activity and compound 11a, with IC50 of 0.65 mu M on the trypomastigote form of T. cruzi, proved to be 15 times more active than nifurtimox. Additionally, molecular docking studies indicate that the quinone derivatives 11a-c could have a multitarget profile interacting preferentially with trypanothione reductase and Old Yellow Enzyme.
  • Thumbnail Image
    Item
    NL MIND-BEST: A web server for ligands and proteins discovery-Theoretic-experimental study of proteins of Giardia lamblia and new compounds active against Plasmodium falciparum
    (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2011) Gonzalez Diaz, Humberto; Prado Prado, Francisco; Sobarzo Sanchez, Eduardo; Haddad, Mohamed; Chevalley, Severine Maurel; Valentin, Alexis; Quetin Leclercq, Joelle; Dea Ayuela, Maria A.; Teresa Gomez Munos, Maria; Munteanu, Cristian R.; Jose Torres Labandeira, Juan; Garcia Mera, Xerardo; Tapia, Ricardo A.; Ubeira, Florencio M.
    There are many protein ligands and/or drugs described with very different affinity to a large number of target proteins or receptors. In this work, we selected Ligands or Drug-target pairs (DTPs/nDTPs) of drugs with high affinity/non-affinity for different targets. Quantitative Structure-Activity Relationships (QSAR) models become a very useful tool in this context to substantially reduce time and resources consuming experiments. Unfortunately most QSAR models predict activity against only one protein target and/or have not been implemented in the form of public web server freely accessible online to the scientific community. To solve this problem, we developed here a multi-target QSAR (mt-QSAR) classifier using the MARCH-INSIDE technique to calculate structural parameters of drug and target plus one Artificial Neuronal Network (ANN) to seek the model. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 20:20-15-1:1. This MLP classifies correctly 611 out of 678 DTPs (sensitivity=90.12%) and 3083 out of 3408 nDTPs (specificity=90.46%), corresponding to training accuracy=90.41%. The validation of the model was carried out by means of external predicting series. The model classifies correctly 310 out of 338 DTPs (sensitivity=91.72%) and 1527 out of 1674 nDTP (specificity = 91.22%) in validation series, corresponding to total accuracy = 91.30% for validation series (predictability). This model favorably compares with other ANN models developed in this work and Machine Learning classifiers published before to address the same problem in different aspects. We implemented the present model at web portal Bio-AIMS in the form of an online server called: Non-Linear MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (NL MIND-BEST), which is located at URL: http://miaja.tic.udc.es/Bio-AIMS/NL-MIND-BEST.php. This online tool is based on PHP/HTML/Python and MARCH-INSIDE routines. Finally we illustrated two practical uses of this server with two different experiments. In experiment 1, we report by first time Quantum QSAR study, synthesis, characterization, and experimental assay of antiplasmodial and cytotoxic activities of oxoisoaporphine alkaloids derivatives as well as NL MIND-BEST prediction of potential target proteins. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF, and -TOF/TOF MS, MASCOT search, MM/MD 3D structure modeling, and NL MIND-BEST prediction for different peptides a new protein of the found in the proteome of the human parasite Giardia lamblia, which is promising for anti-parasite drug-targets discovery. (c) 2011 Elsevier Ltd. All rights reserved.
  • Thumbnail Image
    Item
    Phenoxy- and Phenylamino-Heterocyclic Quinones: Synthesis and Preliminary Anti-Pancreatic Cancer Activity
    (WILEY-V C H VERLAG GMBH, 2022) Sanchez, Patricio; Salas, Cristian O.; Gallardo-Fuentes, Sebastian; Villegas, Alondra; Veloso, Nicolas; Honores, Jessica; Inman, Martyn; Isaacs, Mauricio; Contreras, Renato; Moody, Christopher J.; Cisterna, Jonathan; Brito, Ivan; Tapia, Ricardo A.
    The successful application of fragment-based drug discovery strategy for the efficient synthesis of phenoxy- or phenylamino-2-phenyl-benzofuran, -benzoxazole and -benzothiazole quinones is described. Interestingly, in the final step of the synthesis of the target compounds, unusual results were observed on the regiochemistry of the reaction of bromoquinones with phenol and aniline. A theoretical study was carried out for better understanding the factors that control the regiochemistry of these reactions. The substituted heterocyclic quinones were evaluated in vitro to determine their cytotoxicity by the MTT method in three pancreatic cancer cell lines (MIA-PaCa-2, BxPC-3, and AsPC-1). Phenoxy benzothiazole quinone 26a showed potent cytotoxic activity against BxPC-3 cell lines, while phenylamino benzoxazole quinone 20 was the most potent on MIA-PaCa-2 cells. Finally, electrochemical properties of these quinones were determined to correlate with a potential mechanism of action. All these results, indicate that the phenoxy quinone fragment led to compounds with increased activity against pancreatic cancer cells.
  • No Thumbnail Available
    Item
    Recycled ionic liquid vs . deep eutectic solvent in cellulose nanocrystals production: Characterization, techno-economic analysis, and life cycle assessment
    (2024) Marino, Mayra A.; Rueda-Ordonez, Diego; Paredes, Maria G.; Tapia, Ricardo A.; Pita, Ramon; Pavez, Paulina
    Three scenarios involving aqueous mixtures of neoteric solvents have been evaluated as solvents and catalysts for the cellulose hydrolysis reaction to obtain CNC in high yields (>70%). The scenarios considered were: scenario 1 (S1) involves a recyclable ionic liquid dilution of [Hmim][(HSO4)(H2SO4)]/H2O (64 wt% IL); scenario 2 (S2) another recyclable dilution of [Hmim][(HSO4)(H2SO4)]//H2O (80 wt% IL) and scenario 3 (S3) S3 ) a non-recyclable ternary deep eutectic solvent (60 wt% DES: choline chloride: oxalic acid/30 wt% PA/10 wt% water). Experimental analysis, techno-economic, and life cycle analysis (LCA) indicate that S1 emerges as a suitable scenario among the three analyzed. S1 demonstrated the highest competitiveness, with a lower raw material cost per gram of CNC produced (US$0.81/g) and lower environmental contributions concerning climate change and fossil fuel depletion, accounting mainly for its recyclability. Therefore, the recyclable dilution of 64 wt% IL used in S1 appears to be the most viable option for sustainable and environmentally conscious CNC production. Besides, the physicochemical properties of the CNC were revealed: aspect ratio range 7-8, high dispersion stability related to zeta potential >-40 mV, good crystallinity range 50-80%, and thermal stability with Tonset> 300 degrees C. These results guided towards a scenario with crucial advantages: a diluted IL that retains its acidity after reuse cycles by a facile recovery process, maintaining high CNC production performance and providing low environmental impacts.
  • No Thumbnail Available
    Item
    Thermal storage density of ionic liquid mixtures: A preliminary study as thermal fluid
    (2019) Mora, Sebastian; Neculqueo, Gloria; Tapia, Ricardo A.; Urzua, Julio, I
    For the purpose of calculate and compare the variation in thermal storage density, data for the thermal stability, heat capacity, and density properties of equimolar binary mixtures of 1-octyl-3-methylimidazolium and 1-octyl-2,3-dimethylimidazolium based ionic liquids have been measured. Preliminary analysis of fifteen mixtures obtained from six ionic liquid provide evidence that certain mixtures increase its heat capacity and hence its thermal storage density, offering a viable alternative to materials currently used in solar energy storage. (C) 2019 Elsevier B.V. All rights reserved.
  • Thumbnail Image
    Item
    Trypanosoma cruzi: Activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms
    (PERGAMON-ELSEVIER SCIENCE LTD, 2008) Salas, Cristian; Tapia, Ricardo A.; Ciudad, Karina; Armstrong, Veronica; Orellana, Myriam; Kemmerling, Ulrike; Ferreira, Jorge; Maya, Juan Diego; Morello, Antonio
    Derivatives of natural quinones with biological activities, such as lapachol, alpha- and beta-lapachones, have been synthesized and their trypanocidal activity evaluated in vitro in Trypanosoma cruzi cells. All tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity as compared with current trypanocidal drugs, nifurtimox and benznidazole. The results presented here show that the anti-T Cruzi activity of the alpha-lapachone derivatives can be increased by the replacement of the benzene ring by a pyridine moiety. Free radical production and consequently oxidative stress through redox cycling or production of electrophilic metabolites are the potential biological mechanism of action for these synthetic quinones. (c) 2007 Elsevier Ltd. All rights reserved.