Publications

Abstract Despite decades of research, it is still not clear what is the mechanism behind the efficient chemiexcitation of dioxetanones in chemiluminescent and bioluminescent reactions. In fact, long-standing theories (charge transfer-initiated luminescence and chemically induced electron-exchange luminescence) have been demonstrated to not be able to explain this phenomenon. Herein, a theoretical approach using reliable and up-to-date methodology was used to address this problem, by focusing on model dioxetanones. Time-dependent (TD)-Density functional theory (DFT) and multireference complete-active-space second-order perturbation theory (CASPT2) calculations provided evidence that points to efficient intramolecular chemiexcitation being the result of the reacting molecules having access to a long zone of the Potential energy surface (PES), within the biradicalar region, where S-0 and S-1 are degenerate. Molecules with inefficient chemiexcitation are unable to reach this zone of degeneracy. Our main finding is that access to the region of degeneracy appears to be given due to increased interaction between the keto and CO2 moieties, as supported by the use of the activation strain model and Born-Oppenheimer molecular dynamics, which extends the biradical region by delaying the rupture of the peroxide ring. Increased interaction derives from attractive electrostatic interactions between the moieties of dioxetanone. Thus, we hypothesize that efficient chemiexcitation results not only from electron/charge transfer and subsequent charge annihilation but is instead based on the degree of interaction between the keto and CO2 moieties, which controls the access to a region of degeneracy between the ground and excited states.

Abstract Herein we present a new synthesis methodology for the transprotection of the 1-phenylethyl protected tertiary amines to tert-butyloxycarbonyl (Boc) derivatives under exocyclic N-C hydrogenolysis catalyzed by Pd/C. We provide mechanistic insights into the N-dealkylation of hindered tertiary amines under the unrecognized role of tert-butyloxycarbonyl anhydride (Boc(2)O) as an additive to effectively promote the exocyclic N-C hydrogenolysis of tertiary amines by disclosing the role of Boc(2)O, which was not fully understood and studied until now. NMR and in silico experiments suggest the formation of a transient charged carbamate as the plausible intermediate. This selective transprotection enabled the development of a robust stereoselective methodology for the preparation of both enantiomers of 2-azanorbornane-3-exo-carboxylates by highly asymmetric aza-Diels-Alder reactions using (-)-8-phenylmenthol (8PM) and (+)-8-phenylneomenthol (8PnM) as chiral auxiliaries.

Abstract Novel C-60 and C70N-methyl-fulleropyrrolidine derivatives, containing both electron withdrawing and electron donating substituent groups, were synthesized by the well-known Prato reaction. The corresponding highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energy levels were determined by cyclic voltammetry, from the onset oxidation and reduction potentials, respectively. Some of the novel fullerenes have higher LUMO levels than the standards PC61BM and PC71BM. When tested in PffBT4T-2OD based polymer solar cells, with the standard architecture ITO/PEDOT:PSS/Active-Layer/Ca/Al, these fullerenes do not bring about any efficiency improvements compared to the standard PC71BM system, however they show how the electronic nature of the different substituents strongly affects the efficiency of the corresponding organic photovoltaic (OPV) devices. The functionalization of C-70 yields a mixture of regioisomers and density functional theory (DFT) calculations show that these have systematically different electronic properties. This electronic inhomogeneity is likely responsible for the lower performance observed in devices containing C-70 derivatives. These results help to understand how new fullerene acceptors can affect the performance of OPV devices.

Abstract This paper is concerned with experimental and computational thermochemical studies of epsilon-caprolactam and epsilon-caprothiolactam, molecules whose flexible ring structure provides several conformational forms. The gas-phase standard enthalpy of formation at the reference temperature of 298.15 K of the two title compounds have been determined from the enthalpy of formation in the crystalline phase, derived from bomb combustion calorimetry, and from the enthalpy of sublimation, derived from Calvet microcalorimetry and Knudsen effusion techniques. The equilibrium geometries and the thermodynamic properties of three minimum energy conformers obtained with the composite G3(MP2)//B3LYP approach were used to determine the conformational composition of the two lactam derivatives, by means of Boltzmann's distribution. The computed gas-phase standard molar enthalpies of formation of epsilon-caprolactam and epsilon-caprothiolactam have been determined using hypothetical gas-phase reactions, taking into account the conformational compositions of each one of the species. This parameter together with the corresponding experimental one are compared. (C) 2019 Elsevier Ltd.

Abstract <jats:title>Abstract</jats:title><jats:p>Consensus scoring has become a commonly used strategy within structure-based virtual screening (VS) workflows with improved performance compared to those based in a single scoring function. However, no research has been devoted to analyze the worth of docking scoring functions components in consensus scoring. We implemented and tested a method that incorporates docking scoring functions components into the setting of high performance VS workflows. This method uses genetic algorithms for finding the combination of scoring components that maximizes the VS enrichment for any target. Our methodology was validated using a dataset that contains ligands and decoys for 102 targets that has been widely used in VS validation studies. Results show that our approach outperforms other methods for all targets. It also boosts the initial enrichment performance of the traditional use of whole scoring functions in consensus scoring by an average of 45%. CompScore is freely available at: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://bioquimio.udla.edu.ec/compscore/">http://bioquimio.udla.edu.ec/compscore/</jats:ext-link></jats:p>

Abstract Molecular dynamics simulations of the electrical double layer at electrode-ionic liquid interfaces allow for molecular level interpretation of the interfacial phenomena and properties, such as differential capacitance (C). In this work, we have simulated an ionic liquid - 1-butyl-3-methylimidazolium hexafluorophosphate - at three gold surfaces, namely: Au(100), Au(110), and Au(111) surfaces. Atomic corrugation of the gold surface leads to higher C values due to the rapprochement of the surface and electrolyte charge planes. Likewise, by accounting for the shift of surface charge plane position towards the electrolyte also results in higher C values. The presented insight shows that a simple correction to the simulation data improves the agreement with the experimental data.

Abstract Background: Malaria or Paludism is a tropical disease caused by parasites of the Plasmodium genre and transmitted to humans through the bite of infected mosquitos of the Anopheles genre. This pathology is considered one of the first causes of death in tropical countries and, despite several existing therapies, they have a high toxicity. Computational methods based on Quantitative Structure-Activity Relationship studies have been widely used in drug design work flows. Objective: The main goal of the current research is to develop computational models for the identification of antimalarial hit compounds. Materials and Methods: For this, a data set suitable for the modeling of the antimalarial activity of chemical compounds was compiled from the literature and subjected to a thorough curation process. In addition, the performance of a diverse set of ensemble-based classification methodologies was evaluated and one of these ensembles was selected as the most suitable for the identification of antimalarial hits based on its virtual screening performance. Data curation was conducted to minimize noise. Among the explored ensemble-based methods, the one combining Genetic Algorithms for the selection of the base classifiers and Majority Vote for their aggregation showed the best performance. Results: Our results also show that ensemble modeling is an effective strategy for the QSAR modeling of highly heterogeneous datasets in the discovery of potential antimalarial compounds. Conclusion: It was determined that the best performing ensembles were those that use Genetic Algorithms as a method of selection of base models and Majority Vote as the aggregation method

Abstract This work was designed to assess the potential role of silicon dioxide nanomaterial (nano-SiO2) in enhancing barley's tolerance to nickel oxide nanomaterial (nano-NiO). For this purpose, plants were grown for 14 days under nano-NiO (120 mg kg(-1)) single and co-exposure with nano-SiO2 (3 mg kg(-1)). The exposure of barley to nano-NiO caused a significant decrease in growth-related parameters and induced a negative response on the photosynthetic apparatus. However, upon nano-SiO2 co-exposure, the inhibitory effects of nano-NiO were partially reduced, with lower reductions in fresh and dry biomass, and with the recovery of the photosynthesis-related parameters. Plants growing under nano-NiO stress showed an overproduction of superoxide anion (O-2(-)), which favored the occurrence of oxidative stress and the enhancement of lipid peroxidation (LP), but the co-treatment with nano-SiO2 reverted this tendency, generally lowering or maintaining the levels of LP and stimulating the redox pathway of thiols. The evaluation of the antioxidant (AOX) system revealed that nano-NiO induced the accumulation of proline, along with a decrease in ascorbate in leaves. Furthermore, superoxide dismutase (SOD) activity was significantly enhanced and catalase (CAT) and ascorbate peroxidase (APX) seemed to have a pivotal role in H2O2 detoxification in leaves and roots, respectively. The response of the AOX system was even more prominent upon nano-SiO2 co-exposure, reinforcing the ameliorating functions of this nanomaterial. Overall, the present study highlighted the protective role of nano-SiO2 in barley plants under nano-NiO stress, possibly due to the Si-mediated protection against oxidative stress, by a more proactive performance of the plant AOX system.

Abstract The wide ranges of uses for acetophenone make it more available and expected to accumulate in the biosphere, where consequently it can threat ecosystems. To remediate this problem, the use of Solanum nigrum L. plants for the clean-up of acetophenone-contaminated sites was explored. Also, plant root and shoot biometry and metabolism where assayed to better understand the effects of this organic compound and to pinpoint possible metabolic pathways to be targeted for future manipulations for increasing this plant species' remediation efficiency. Although undergoing through some stress, detected by increases in ROS and lipid peroxidation in both organs, plants were able to rapidly eliminate all acetophenone from the nutrient solution after 7 days of exposure, being this compound mainly detoxified at the root level. Additionally, acetophenone lead to a differential metabolic response in roots and shoots, where antioxidant mechanisms where differentially activated, while nitrogen assimilation was repressed in shoots and activated in roots. These results confirm that S. nigrum is a good phytoremediation tool for acetophenone and suggest that enhancing shoot GS activity may provide more nitrogen precursors for the synthesis of thiolated proteins and glutathione to increase tolerance to acetophenone in roots and shoots, respectively.