DSpace Angular :: Browsing by Author "Perez, Edwin G."

Browsing by Author "Perez, Edwin G."

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A new strategy to build electrochemical enzymatic biosensors using a nanohybrid material based on carbon nanotubes and a rationally designed schiff base containing boronic acid
(2024) Tamborelli, Alejandro; Mujica, Michael Lopez; Sanchez-Velasco, Oriel A.; Hormazabal-Campos, Cristobal; Perez, Edwin G.; Gutierrez-Cutino, Marlen; Venegas-Yazigi, Diego; Dalmasso, Pablo; Rivas, Gustavo; Hermosilla-Ibanez, Patricio
We report a nanohybrid material obtained by non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) with the new ligand (((1E,1 ' E)-(naphthalene-2,3-diylbis(azaneylylidene))bis(methaneylylidenedene)) bis (4-hyoxy-3,1-phenylene))doronic acid (SB-dBA), rationally designed to mimic some recognition properties of biomolecules like concanavalin A, for the development of electrochemical biosensors based on the use of glycobiomolecules as biorecognition element. We present, as a proof-of-concept, a hydrogen peroxide biosensor obtained by anchoring horseradish peroxidase (HRP) at a glassy carbon electrode (GCE) modified with the nanohybrid prepared by sonication of 2.0 mg mL- 1 MWCNTs and 0.50 mg mL- 1 SB-dBA in N,N-dimethyl formamide (DMF) for 30 min. The hydrogen peroxide biosensing was performed at -0.050 V in the presence of 5.0 x 10-4 M hydroquinone. The analytical characteristics of the resulting biosensor are the following: linear range between 0.175 mu M and 6.12 mu M, detection limit of 58 nM, and reproducibility of 2.0 % using the same nanohybrid (6 biosensors), and 9.0 % using three different nanohybrids. The sensor was successfully used to quantify hydrogen peroxide in enriched milk and human blood serum samples and in a commercial disinfector.
Assessment of the Activity of Nitroisoxazole Derivatives against Trypanosoma cruzi
(2024) Moncada-Basualto, Mauricio; Saavedra-Olavarria, Jorge; Rivero-Jerez, Paula S.; Rojas, Cristian; Maya, Juan D.; Liempi, Ana; Zuniga-Bustos, Matias; Olea-Azar, Claudio; Lapier, Michel; Perez, Edwin G.; Pozo-Martinez, Josue
The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 +/- 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 +/- 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.
Characterization of a Novel Drosophila SERT Mutant: Insights on the Contribution of the Serotonin Neural System to Behaviors
(2017) Hidalgo, Sergio; Molina-Mateo, Daniela; Escobedo, Pia; Zarate, Rafaella V.; Fritz, Elsa; Fierro, Angelica; Perez, Edwin G.; Iturriaga-Vasquez, Patricio; Reyes-Parada, Miguel; Varas, Rodrigo; Fuenzalida-Uribe, Nicolas; Campusano, Jorge M.
A better comprehension on how different molecular components of the serotonergic system contribute to the adequate regulation of behaviors in animals is essential in the interpretation on how they are involved in neuropsychiatric and pathological disorders. It is possible to study these components in "simpler" animal models including the fly Drosophila melanogaster, given that most of the components of the serotonergic system are conserved between vertebrates and invertebrates. Here we decided to advance our understanding on how the serotonin plasma membrane transporter (SERT) contributes to serotonergic neurotransmission and behaviors in Drosophila. In doing this, we characterized for the first time a mutant for Drosophila SERT (dSERT) and additionally used a highly selective serotonin-releasing drug, 4-methylthioamphetamine (4-MTA), whose mechanism of action involves the SERT protein. Our results show that dSERT mutant animals exhibit an increased survival rate in stress conditions, increased basal motor behavior, and decreased levels in an anxiety-related parameter, centrophobism. We also show that 4-MTA increases the negative chemotaxis toward a strong aversive odorant, benzaldehyde. Our neurochemical data suggest that this effect is mediated by dSERT and depends on the 4-MTA-increased release of serotonin in the fly brain. Our in silico data support the idea that these effects are explained by specific interactions between 4-MTA and dSERT. In sum, our neurochemical, in silico, and behavioral analyses demonstrate the critical importance of the serotonergic system and particularly dSERT functioning in modulating several behaviors in Drosophila.
Different Classes of Antidepressants Inhibit the Rat α7 Nicotinic Acetylcholine Receptor by Interacting within the Ion Channel: A Functional and Structural Study
(2021) Duarte, Yorley; Rojas, Maximiliano; Canan, Jonathan; Perez, Edwin G.; Gonzalez-Nilo, Fernando; Garcia-Colunga, Jesus
Several antidepressants inhibit nicotinic acetylcholine receptors (nAChRs) in a non-competitive and voltage-dependent fashion. Here, we asked whether antidepressants with a different structure and pharmacological profile modulate the rat alpha 7 nAChR through a similar mechanism by interacting within the ion-channel. We applied electrophysiological (recording of the ion current elicited by choline, I-Ch, which activates alpha 7 nAChRs from rat CA1 hippocampal interneurons) and in silico approaches (homology modeling of the rat alpha 7 nAChR, molecular docking, molecular dynamics simulations, and binding free energy calculations). The antidepressants inhibited I-Ch with the order: norfluoxetine similar to mirtazapine similar to imipramine < bupropion similar to fluoxetine similar to venlafaxine similar to escitalopram. The constructed homology model of the rat alpha 7 nAChR resulted in the extracellular vestibule and the channel pore is highly negatively charged, which facilitates the permeation of cations and the entrance of the protonated form of antidepressants. Molecular docking and molecular dynamics simulations were carried out within the ion-channel of the alpha 7 nAChR, revealing that the antidepressants adopt poses along the receptor channel, with slightly different binding-free energy values. Furthermore, the inhibition of I-Ch and free energy values for each antidepressant-receptor complex were highly correlated. Thus, the alpha 7 nAChR is negatively modulated by a variety of antidepressants interacting in the ion-channel.
Effect of the introduction of ethylenedioxythiophene and styrilnitroisooxazol groups on the properties and photovoltaic performances of tryphenylamine based π -conjugated push-pull molecules
(2024) Arteaga, Gean C.; Louarn, Guy; Ramos-Hernandez, Andrea; Romero, Mario; Arzel, Ludovic; Bernede, Jean Christian; Saavedra-Olavarria, Jorge; Perez, Edwin G.; Maza, Julio R.; Romero, Jonathan; Cattin, Linda
Properties of pi-conjugated push-pull molecules based on triphenylamine have been modified through the introduction of ethylenedioxythiophene and a styrilnitroisooxazol group. It is shown that the obtained new molecule called GC8 exhibits light absorption in the visible, between 400 nm and 700 nm and a high hole mobility of 210-5 cm2V- 1s- 1, which places this organic donor among those with good mobility in this family of compounds. It behaves as electron donor in organic photovoltaic cells, with a HOMO of 5.35 eV, a LUMO of 2.94 eV which gives a band gap of 2.41 eV, these values being obtained from theoretical estimation using TD-DFT theory. The measured experimental optical band gap is 1.9 eV, this difference in value between theory and experiment is reasonable for small molecules. GC8 has been introduced as electron donor in planar heterojunctions organic photovoltaic cells (PHJ-OPVs), fullerenes (C60 or C70) being used as electron acceptor. It is shown that the optimum GC8 layer thickness is 20 nm, while a 5 min annealing at 100 degrees C improves the power conversion efficiency (PCE) by 10%. The high light absorption of C70 allows improving cells performances compared to that using C60, the champion cell having a 6.15% efficiency. The PCE improvement after the annealing is due to an increase of the hole mobility and optical absorption.
Fast and efficient synthesis of 2-(benzyloxy)-N,N-disubtituted-2-phenylethan-1-amines
(2023) Rivero-Jerez, Paula S.; Saavedra-Olavarria, Jorge; Perez, Edwin G.
A concise, metal catalyst free synthesis of 6-benzyloxyphenethylamines using the regioisomeric mixture obtained in the dialkylamine styrene oxide-ring opening products which reacted with MsCl to produce an aziridinium intermediate. This intermediate reacts, separately, with different benzyl alcohols to produce the desired products but using modern techniques such as fast heating in both steps.& COPY; 2023 Elsevier Ltd. All rights reserved.
Fast Heating-Assisted One-Pot Copper-Catalyzed Sulfonylation and Sulfochlorination of Styrenes
(2022) Saavedra-Olavarria, Jorge; Hermosilla-Ibanez, Patricio; Almodovar, Iriux; Perez, Edwin G.
Here, a strategy for the synthesis under fast-heating conditions of vinyl sulfones and beta-chlorosulfones from styrene derivatives, tosyl chloride (TsCl) as sulfonyl and chlorine source, and CuBr-neocuproine as the catalytic system is reported. The reaction occurs through an atom transfer radical addition (ATRA) mechanism to generate the sulfochlorinated adducts followed by E2 elimination to generate the vinyl sulfones. This methodology allows a wide range of vinyl sulfones and beta-chlorosulfones to be obtained using inexpensive reagents in one and five minutes respectively. These reactions appear as an interesting fast and easy-to-handle alternative to obtain these compounds.
Functionalization using biocompatible carboxylated cyclodextrins of iron-based nanoMIL-100
(2021) Carmona, Thais; Marco, Jose F.; Gimenez-Marques, Monica; Canon-Mancisidor, Walter; Gutierrez-Cutino, Marlen; Hermosilla-Ibanez, Patricio; Perez, Edwin G.; Minguez Espallargas, Guillermo; Venegas-Yazigi, Diego
Here we report the first example of nanoMIL-100 particles modified with monomeric cyclodextrin derivatives of different length by exploiting strong interactions between non-saturated iron trimers at the external surface and carboxylate functionalities located at the end of biocompatible and flexible linkers of cyclodextrins. The main results revealed that, after the functionalization, the cyclodextrins are selectively located at the external surfaces covering the nanoparticles. Z potential measurements show that this functionalization induced changes respect to the bare nanoMIL-100 particles, however, the presence of the cyclodextrins does not modify the size neither porosity of the nanoparticles. The amount of cyclodextrins attached, investigated by thermogravimetry, increases with the length of the linker between CD cavity and nanoparticle surface, reaching up a 9 % wt. Auger spectroscopy suggested a clear predominant sp(3) character after the functionalizations (vs. sp(2) predominance in the unmodified nanoMIL-100). This study supposes the creation of an alternative family of hybrids based on carboxylated monomeric cyclodextrins.
Hydrofluoroether Synthesis through One-Pot Anodic Iodoalkoxylation of Alkenes
(2024) Becerra-Ruiz, Martin; Winterson, Bethan; Perez, Edwin G.; Wirth, Thomas
The incorporation of carbon-fluorine bonds can profoundly influence the chemical and physical properties of drugs, agrochemicals, and materials. Different methods allow the installation of CF3, CF2H units and C-F bonds including trifluoro- and difluoromethoxylations, reflecting the limited diversity of reactions available to synthetic chemists. We introduce the 2,2,2-trifluoroethoxy group through an electro-oxidative iodination of alkenes as a versatile substituent for fluorine chemists. An iodoarene serves as an unusual iodine source facilitating the 1,2-iodoalkoxylation of a broad range of industrially relevant aliphatic alkenes in high yields (31-98%) showing high Markovnikov regioselectivity.
N-Arylation of 3-Formylquinolin-2(1H)-ones Using Copper(II)-Catalyzed Chan-Lam Coupling
(2022) Valencia, Jhesua; Sanchez-Velasco, Oriel A.; Saavedra-Olavarria, Jorge; Hermosilla-Ibanez, Patricio; Perez, Edwin G.; Insuasty, Daniel
3-formyl-2-quinolones have attracted the scientific community's attention because they are used as versatile building blocks in the synthesis of more complex compounds showing different and attractive biological activities. Using copper-catalyzed Chan-Lam coupling, we synthesized 32 new N-aryl-3-formyl-2-quinolone derivatives at 80 degrees C, in air and using inexpensive phenylboronic acids as arylating agents. 3-formyl-2-quinolones and substituted 3-formyl-2-quinolones can act as substrates, and among the products, the p-methyl derivative 9a was used as a substrate to obtain different derivatives such as alcohol, amine, nitrile, and chalcone.
PALLADIUM COMPLEX BEARING 3,5-BIS(BENZOTRIAZOL-1-YLMETHYL) TOLUENE LIGAND CATALYZES OXIDATIVE AMINATION OF ALLYL BUTYL ETHER
(2013) Hurtado, John; Rojas, Rene S.; Perez, Edwin G.; Valderrama, Mauricio
The reaction of 3,5-bis(bromomethyl)toluene with benzotriazole yields the bidentate ligand 3,5-bis(benzotriazol-1-ylmethyl)toluene (1). This ligand reacts with [PdCl2(cod)] (cod = 1,5-cyclooctadiene) to give the complex [PdCl2{3,5-bis(benzotriazol-1-ylmethyl)tolyl}] (2). These compounds were characterized by elemental analyses, mass spectra, and FTIR and NMR (H-1, C-13) spectroscopies. The palladium(II) complex 2 shows high activity as catalyst for oxidative amination, involving allyl butyl ether and phthalimide as substrates and PhICl2 as a stoichiometric oxidant.
Quinolin-2(1H-)-one-isoxazole dye as an acceptor for mild addition of bisulfite in cationic or zwitterionic aqueous micellar solutions
(2024) Quintero, Guillermo E.; Espinoza, Catalina; Valencia, Jhesua; Insuasty, Daniel; Tiznado, William; Leiva-Parra, Luis; Santos, Jose G.; Perez, Edwin G.; Aliaga, Margarita E.
(E)-6-Methoxy-1-methyl-3-(2-(3-methyl-4-nitroisoxazol-5-yl)vinyl)quinolin-2(1H)-one dye (MQI) has been synthesized, and its structural and electronic properties have been characterized by employing UV-vis spectroscopy in combination with computational methods. The MQI dye has been assessed as an activated Michael acceptor-type probe toward bisulfite ions. This reaction was kinetically tested in different mild, cationic (cetyltrimethylammonium bromide, cetyltrimethylammonium chloride, and cetylpyridinium bromide), and zwitterionic (N-decyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, and N-hexacyl-N,N-dimethyl-3-ammonio-1-propanesulfonate) micellar solutions at pH similar to 5.5. Both micellar media remarkably allow the addition reactions, increasing the reactivity of MQI towards bisulfite ions, the biggest effects were found in the presence of cationic micelles. The binding constants of MQI with the micelles and the rate constants were determined from kinetic data, which were interpreted on the basis of the pseudophase kinetic model. The kinetic study and the product analysis allow us to highlight the relevant role of the association between MQI dye and the micellized surfactant, allowing efficient nucleophilic addition of bisulfite ions. The findings of this work will be valuable for the use of micellar solutions as an alternative medium to replace the use of toxic solvents to carry out organic reactions to perform nucleophilic addition reactions of bisulfite.
Side Groups Convert the α7 Nicotinic Receptor Agonist Ether Quinuclidine into a Type I Positive Allosteric Modulator
(2023) Viscarra, Franco; Chrestia, Juan Facundo; Sanchez, Yaima; Perez, Edwin G.; Biggin, Philip C.; Bouzat, Cecilia; Bermudez, Isabel; Lopez, Jhon J.
The quinuclidine scaffold has been extensively used forthe developmentof nicotinic acetylcholine receptor (nAChR) agonists, with hydrophobicsubstituents at position 3 of the quinuclidine framework providingselectivity for & alpha;7 nAChRs. In this study, six new ligands (4-9) containing a 3-(pyridin-3-yloxy)quinuclidinemoiety (ether quinuclidine) were synthesized to gain a better understandingof the structural-functional properties of ether quinuclidines.To evaluate the pharmacological activity of these ligands, two-electrodevoltage-clamp and single-channel recordings were performed. Only ligand 4 activated & alpha;7 nAChR. Ligands 5 and 7 had no effects on & alpha;7 nAChR, but ligands 6, 8, and 9 potentiated the currents evokedby ACh. Ligand 6 was the most potent and efficaciousof the potentiating ligands, with an estimated EC50 forpotentiation of 12.6 & PLUSMN; 3.32 & mu;M and a maximal potentiationof EC20 ACh responses of 850 & PLUSMN; 120%. Ligand 6 increased the maximal ACh responses without changing thekinetics of the current responses. At the single-channel level, thepotentiation exerted by ligand 6 was evidenced in thelow micromolar concentration range by the appearance of prolongedbursts of channel openings. Furthermore, computational studies revealedthe preference of ligand 6 for an intersubunit site inthe transmembrane domain and highlighted some putative key interactionsthat explain the different profiles of the synthesized ligands. Notably,Met276 in the 15 & PRIME; position of the transmembrane domain 2 almostabolished the effects of ligand 6 when mutated to Leu.We conclude that ligand 6 is a novel type I positiveallosteric modulator (PAM-I) of & alpha;7 nAChR.
Supramolecular Control of Reactivity toward Hydrolysis of 7-Diethylaminocoumarin Schiff Bases by Cucurbit[7]uril Encapsulation
(2021) Alcazar, Jackson J.; Geue, Niklas; Valladares, Veronica; Canete, Alvaro; Perez, Edwin G.; Garcia-Rio, Luis; Santos, Jose G.; Aliaga, Margarita E.
A series of aromatic Schiff bases, featuring 7-diethylamino-coumarin and with five different substituents at an adjacent phenyl ring, were synthesized and characterized. With the aim of assessing the stability of these dyes in acidic medium, their hydrolysis reactions were kinetically studied in the absence and presence of the macrocycle cucurbit[7]uril (CB[7]). Our results are consistent with a model containing three different forms of substrates (un-, mono-, and diprotonated) and three parallel reaction pathways. The pK(a) values and the rate constants were estimated and discussed in terms of the presence of a hydroxyl group at the ortho position and electron-releasing groups on the phenyl ring of the dyes. The kinetic study in the presence of CB[7] led to two different behaviors. Promotion of the reaction by CB[7] was observed for the hydrolysis of the Schiff bases containing only one coordination site toward the macrocycle. Conversely, an inhibitor effect was observed for the hydrolysis of a Schiff base with two coordination sites toward CB[7]. The latter effect could be explained with a model as a function of a prototropic tautomeric equilibrium and the formation of a 2:1 host/guest complex, which prevents the attack of water. Therefore, the kinetic results demonstrated a supramolecular control of the macrocycle toward the reactivity and stability of 7-diethylaminocoumarin Schiff bases in acidic medium.
Synthesis of N-Arylcytisine Derivatives Using the Copper-Catalyzed Chan-Lam Coupling
(2021) Sanchez-Velasco, Oriel A.; Saavedra-Olavarria, Jorge; Araya-Santelices, Daniel A. A.; Hermosilla-Ibanez, Patricio; Cassels, Bruce K.; Perez, Edwin G.
N-Arylcytisine derivatives are quite rare. We report here a practical methodology to obtain these compounds. Using the copper-catalyzed Chan-Lam coupling, we synthesized new N-arylcytisine derivatives at room temperature, in air and using inexpensive phenylboronic acids. Cytisine and 3,5-dihalocytisines can act as substrates, and among the products, the p-Br-derivative 2r was used as a substrate to obtain biaryl derivatives under Pd-coupling conditions; ester 2j was converted into its acid and amide derivatives using classical carbodiimide conditions. This shows that the Chan-Lam cross-coupling reaction can be included as a versatile synthetic tool in the derivatization of natural products.
Synthesis of N-arylsulfonamides via Chan-Lam Coupling Between Aryl Boronic Acids and N-[(sulfonyl)imino]phenyliodinanes
(2021) Merchan-Arenas, Diego R.; Rivero-Jerez, Paula S.; Perez, Edwin G.
We synthesized a library of 32 sulfonamides via CuBr2 catalyzed Chan-Lam C-N coupling, reaching excellent yields (until 81 %) under ligand-base-free, mild conditions, and short reaction times. A new non-toxic, versatile and easy to prepare starting materials, N-[(Sulfonyl)imino]phenyliodinanes were first time proposed as the nitrogen source in this synthetic tool. Finally, the sulfonamides were used as valuable building blocks in the synthesis of mono-alkyl anilines through their alkylation and Fukuyama deprotection steps.
Synthesis, Photophysical Properties, Theoretical Studies, and Living Cancer Cell Imaging Applications of New 7-(Diethylamino)quinolone Chalcones
(2024) Insuasty, Daniel; Mutis, Mario; Trilleras, Jorge; Illicachi, Luis A.; Rodriguez, Juan D.; Ramos-Hernandez, Andrea; San-Juan-Vergara, Homero G.; Cadena-Cruz, Christian; Mora, Jose R.; Paz, Jose L.; Mendez-Lopez, Maximiliano; Perez, Edwin G.; Aliaga, Margarita E.; Valencia, Jhesua; Marquez, Edgar
In this article, three unsymmetrical 7-(diethylamino)quinolone chalcones with D-pi-A-D and D-pi-A-pi-D type push-pull molecular arrangements were synthesized via a Claisen-Schmidt reaction. Using 7-(diethylamino)quinolone and vanillin as electron donor (D) moieties, these were linked together through the alpha,beta-unsaturated carbonyl system acting as a linker and an electron acceptor (A). The photophysical properties were studied, revealing significant Stokes shifts and strong solvatofluorochromism caused by the ICT and TICT behavior produced by the push-pull effect. Moreover, quenching caused by the population of the TICT state in THF-H2O mixtures was observed, and the emission in the solid state evidenced a red shift compared to the emission in solution. These findings were corroborated by density functional theory (DFT) calculations employing the wb97xd/6-311G(d,p) method. The cytotoxic activity of the synthesized compounds was assessed on BHK-21, PC3, and LNCaP cell lines, revealing moderate activity across all compounds. Notably, compound 5b exhibited the highest activity against LNCaP cells, with an LC50 value of 10.89 mu M. Furthermore, the compounds were evaluated for their potential as imaging agents in living prostate cells. The results demonstrated their favorable cell permeability and strong emission at 488 nm, positioning them as promising candidates for cancer cell imaging applications.

Browsing by Author "Perez, Edwin G."

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