N-Sulfonyl-1,2,3,4-tetrahydroisoquinoline Derivatives: Synthesis, Antimicrobial Evaluations, and Theoretical Insights.

Microbial contamination remains a significant economic challenge in the food industry, emphasizing the need for innovative antimicrobial solutions. In this study, we synthesized N-sulfonyl-1,2,3,4-tetrahydroisoquinolines (NSTHIQ) derivatives using an environmentally friendly Preyssler heteropolyacid catalyst, obtaining moderate to high yields (35-91 %) under mild conditions. Two derivatives (5 and 6) exhibited significant antifungal properties against various fungal species, including Aspergillus spp, Penicillium spp, and Botrytis cinerea. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis revealed the absence of hepatic toxicity in all compounds, making derivatives 2, 3, 4, and 5 potential candidates for further development. However, derivatives 6 and 7 exhibited immunotoxicity. In support of our experimental findings, reactivity indices were computed using Density Functional Theory principles, deriving valuable insights into the chemical properties of these derivatives. This study underscores the potential of NSTHIQ compounds as potent antifungal agents, coupled with the importance of employing environmentally friendly catalysts in drug discovery.

Biochar-MgO from Soursop Seeds in the Production of Biofuel Additive Intermediates.

The conversion of residual biomass from fruit seeds into biochar can be achieved using MgCl2 as an activating agent and calcining at 700 °C. The resulting MgO-biochars were employed in the aldol condensation reaction between furfural and acetone. This reaction is essential as the first step in the obtention of biofuels derived from biomass. The biochars were characterized through various physicochemical techniques, revealing that the presence of MgO nanoparticles deposited on the carbon surface modifies the structural and acidic-basic properties of the carbonaceous materials with a graphitic structure. The biochar with a surface content of MgO of 0.34 % w/w enables the achievement of 100 % of selectivity towards 4-(2-furanyl)-3-buten-2-one (I) with quantitative conversions under optimized conditions. This property highlights the potential of using this type of biochar, commonly used for CO2 capture, as a versatile acidic-basic catalyst, thereby introducing a novel approach to sustainable chemistry.

Transfer Hydrogenation of Furfural to Furfuryl Alcohol Under Microwave Irradiation Using Mixed Oxides.

The reaction to obtain furan alcohols is one of the most important in the upgrading of furan derivates. An attractive route is the transfer hydrogenation of furfural using acidic-basic catalysts. In this work, mixed oxides derived from ternary hydrotalcites were employed to obtain furfuryl alcohol from furfural assisted by microwave irradiation. These materials were characterized via X-ray diffraction (XRD), N2 adsorption-desorption isotherms, Fourier-transform infrared (FTIR) and the CO2 temperature-programmed desorption (CO2 -TPD) analyses. The lamellar structure of hydrotalcite-type materials collapses during the calcination process, resulting in the loss of carbonate anions and hydroxyl groups, present in the interlayer space. This leads to the formation of mixed oxides that exhibit larger surface areas. Furthermore, these changes alter the basic nature of these materials, giving rise to the formation of strong basic sites. The reaction was studied using containing Co2+ and Ni2+ in their structure and was then optimized using distinct primary and secondary alcohols as hydrogen donor sources, as well as distinct temperatures and initial concentrations of furfural. The yields to furfuryl alcohol are strongly dependent on the type of Me2+ in layered oxides mainly due to higher basicity and to the donor employed in the reaction. The mixed oxide containing Co2+ showed complete conversion of furfural and higher yields to furfuryl alcohol (>95 %) at short times of reaction (<1 h).

Whey as an Alternative Nutrient Medium for Growth of Sporosarcina pasteurii and Its Effect on CaCO3 Polymorphism and Fly Ash Bioconsolidation.

Whey in large quantities can cause environmental problems when discarded, because it reduces dissolved oxygen and aquatic life. Nonetheless, it could be used as an easily available and economical alternative to reduce culture medium costs in microbially induced calcium carbonate precipitation (MICP). In this work, a native Sporosarcina pasteurii was isolated and then cultured by using different proportions of whey (W) in nutrient broth (NB). The solids were characterized by XRD, FT-IR, TGA, and SEM. The potential applications in bioconsolidation were also studied. Whey concentration was directly related to CaCO3 production. Higher whey concentrations reduced calcium carbonate purity to nearly 80%. All experiments showed calcite and vaterite fractions, where a whey increment in the media increased calcite content and decreased vaterite content, causing a decrease in crystal size. MICP improved compressive strength (CS) in sand and fly ash. The best CS results were obtained by fly ash treated with 25 W-75 NB (37.2 kPa) and sand with 75 W-25 NB (32.1 kPa). Whey changed crystal polymorphism in biogenic CaCO3 production. Material bioconsolidation depends on the CaCO3 polymorph, thus fly ash was effectively bioconsolidated by crystallization of vaterite and sand by crystallization of calcite.

Green Production of Cladribine by Using Immobilized 2'-Deoxyribosyltransferase from Lactobacillus delbrueckii Stabilized through a Double Covalent/Entrapment Technology.

Nowadays, enzyme-mediated processes offer an eco-friendly and efficient alternative to the traditional multistep and environmentally harmful chemical processes. Herein we report the enzymatic synthesis of cladribine by a novel 2'-deoxyribosyltransferase (NDT)-based combined biocatalyst. To this end, Lactobacillus delbrueckii NDT (LdNDT) was successfully immobilized through a two-step immobilization methodology, including a covalent immobilization onto glutaraldehyde-activated biomimetic silica nanoparticles followed by biocatalyst entrapment in calcium alginate. The resulting immobilized derivative, SiGPEI 25000-LdNDT-Alg, displayed 98% retained activity and was shown to be active and stable in a broad range of pH (5-9) and temperature (30-60 °C), but also displayed an extremely high reusability (up to 2100 reuses without negligible loss of activity) in the enzymatic production of cladribine. Finally, as a proof of concept, SiGPEI 25000-LdNDT-Alg was successfully employed in the green production of cladribine at mg scale.

Nanoestructuras de sílice, con diámetro y distribución de mesoporos variable, modificadas con ácido tungstofosfórico como catalizadores en la síntesis de quinoxalinas / Silica nanostructures, with variable diameter and mesopore size distribution, modified with tungstophosphoric acid as catalyst in the synthesis of quinoxalines / Nanoestruturas de sílica, com distribuição variável de diâmetro e tamanho de mesoporos, modificadas com ácido tungstofosfórico como catalisador na síntese de a síntese da quinoxalina

Resumen Se sintetizaron catalizadores (SNX#WPA) basados en ácido tungstofosfórico, en soportes de nanoestructuras de sílice (SNX), con distribución de diámetros y tamaños de mesoporos variables. Las SNX se prepararon en medio de octano/agua, usando poliestireno y bromuro de cetiltrimetilamonio como plantillas. Los materiales se caracterizaron por DRX, TEM y adsorción/desorción de nitrógeno. La relación octano/agua influyó tanto en la morfología y el tamaño de las SNX como en la distribución del tamaño de poro. Las SNX obtenidas utilizando relaciones OCT/H2O en el rango de 0,07-0,35, presentan mesoporos pequeños (5-6 nm) y grandes (28-34 nm), generados principalmente por poliestireno. Los mesoporos grandes y su contribución de volumen fueron claramente más altos que en las muestras SN1, SN2 y SN3. La estructura y la morfología de SNX#WPA fueron similares a las de las SNX usadas como soporte. Además, la caracterización de todos los materiales SNX#WPA por FT-IR y 31P NMR indicó la presencia de especies [PW12O40]3- y [H3-XPW12O40](3-X)- sin degradar. Según los resultados de la valoración potenciométrica, los sólidos presentaron sitios ácidos muy fuertes. Se evaluó la actividad de SNX#WPA como catalizadores en la síntesis de quinoxalinas, a partir de lo cual se obtuvieron altos rendimientos, sin formación de subproductos. De ello resultó que los materiales preparados son catalizadores altamente selectivos y reutilizables.

Abstract Tungstophosphoric acid supported on silica nanostructures (SNX#WPA) with variable diameter and mesopore size distribution were synthetized. Silica nanostructures (SNX) were prepared in octane/aqueous media using polystyrene and CTAB as organic templates. The materials were characterized by XRD, SEM, TEM and dinitrogen adsorption/ desorption isotherm analysis. The octane/ water ratio influenced the morphology and size of SNX prepared, as well as its pore size distribution. The SNX samples obtained using OCT/H2O ratios in the range 0.07-0.35 (SN4, SN5, and SN6 samples). present small (5-6 nm) and large (28-34 nm) mesopores (mainly generated by polystyrene). Large mesopores and their volume contribution were clearly higher than in the SN1, SN2, and SN3 samples. The structure and morphology of SNX#WPA samples were similar to those of the SNX. Furthermore, the characterization of all the SNX#WPA materials by FT-IR and 31P NMR indicated the presence of undegraded [PW12O40]3- and [H3-XPW12O40](3-X)-species. According to the potentiometric titration results, the solids presented very strong acid sites. The performance of SNX#WPA materials as catalysts in the synthesis of quinoxalines was evaluated. The yields achieved were high, without formation of by-products resulting from competitive reactions or decomposition products, so the prepared materials are highly selective and reusable catalysts.

Resumo Catalisadores (SNX#WPA) baseados em ácido tungsofosfórico suportado em nanoestruturas de sílica (SNX) foram sintetizados com distribuição de tamanhos e diâmetros variados de mesoporos. Os SNX foram preparados em meio octano/aquoso usando poliestireno e brometo de cetiltrimetilamônio como modelos orgânicos. Os materiais foram caracterizados por DRX, TEM e adsorção/ dessorção de nitrogénio. A razão octano/ agua influenciou a morfologia e o tamanho do SNX, bem como a distribuição do tamanho dos poros. O SNX obtido usando razões OCT/ H2O na faixa de 0,07-0,35, possui mesoporos pequenos (5-6 nm) e grandes (28-34 nm) (gerados principalmente por poliestireno). Mesoporos grandes e sua contribuição em volume foram claramente maiores do que nas amostras SN1, SN2 e SN3. A estrutura e a morfologia do SNX#WPA foram semelhantes às do SNX usado como suporte. Além disso, a caracterização de todos os materiais SNX#WPA por FT-IR e 31P NMR indicou a presença das espécies [PW12O40]3- e [H3-XPW12O40](3-X)- sem degradar. De acordo com os resultados da titulação potenciométrica, os sólidos apresentaram locais ácidos muito fortes. A atividade do SNX#WPA como catalisadores na síntese de quinoxalinas foi avaliada, produzindo altos rendimentos, sem formação de subprodutos, resultando em materiais catalisadores altamente seletivos e reutilizáveis.

A non-conformational QSAR study for plant-derived larvicides against Zika Aedes aegypti L. vector.

A set of 263 plant-derived compounds with larvicidal activity against Aedes aegypti L. (Diptera: Culicidae) vector is collected from the literature, and is studied by means of a non-conformational quantitative structure-activity relationships (QSAR) approach. The balanced subsets method (BSM) is employed to split the complete dataset into training, validation and test sets. From 26,775 freely available molecular descriptors, the most relevant structural features of compounds affecting the bioactivity are taken. The molecular descriptors are calculated through four different freewares, such as PaDEL, Mold2, EPI Suite and QuBiLs-MAS. The replacement method (RM) variable subset selection technique leads to the best linear regression models. A successful QSAR equation involves 7-conformation-independent molecular descriptors, fulfiling the evaluated internal (loo, l30%o, VIF and Y-randomization) and external (test set with Ntest = 65 compounds) validation criteria. The practical application of this QSAR model reveals promising predicted values for some natural compounds with unknown experimental larvicidal activity. Therefore, the present model constitutes the first one based on a large molecular set, being a useful computational tool for identifying and guiding the synthesis of new active molecules inspired by natural products.

Valorization of Oleuropein via Tunable Acid-Promoted Methanolysis.

The acid-promoted methanolysis of oleuropein was studied using a variety of homogeneous and heterogeneous acid catalysts. Exclusive cleavage of the acetal bond between the glucoside and the monoterpene subunits or further hydrolysis of the hydroxytyrosol ester and subsequent intramolecular rearrangement were observed upon identification of the most efficient catalyst and experimental conditions. Furthermore, selected conditions were tested using oleuropein under continuous flow and using a crude mixture extracted from olive leaves under batch. Formation of (-)-methyl elenolate was also observed in this study, which is a reported precursor for the synthesis of the antihypertensive drug (-)-ajmalicine.

Quantitative structure-activity relationship (QSAR) analysis of plant-derived compounds with larvicidal activity against Zika Aedes aegypti (Diptera: Culicidae) vector using freely available descriptors.

BACKGROUND: We have developed a quantitative structure-activity relationship (QSAR) model for predicting the larvicidal activity of 60 plant-derived molecules against Aedes aegypti L. (Diptera: Culicidae), a vector of several diseases such as dengue, yellow fever, chikungunya and Zika. The balanced subsets method (BSM) based on k-means cluster analysis (k-MCA) was employed to split the data set. The replacement method (RM) variable subset selection technique coupled with multivariable linear regression (MLR) proved to be successful for exploring 18 326 molecular descriptors and fingerprints calculated with PaDEL, Mold2 and EPI Suite open-source softwares. RESULTS: A robust QSAR model (Rtrain2=0.84, Strain = 0.20 and Rtest2=0.92, Stest = 0.23) involving five non-conformational descriptors was established. The model was validated and tested through the use of an external test set of compounds, the leave-one-out (LOO) and leave-more-out (LMO) cross-validation methods, Y-randomization and applicability domain (AD) analysis. CONCLUSION: The QSAR model surpasses previously published models based on geometrical descriptors, thereby representing a suitable tool for predicting larvicidal activity against the vector A. aegypti using a conformation-independent approach. © 2018 Society of Chemical Industry.

The quantitative structure-insecticidal activity relationships from plant derived compounds against chikungunya and zika Aedes aegypti (Diptera:Culicidae) vector.

The insecticidal activity of a series of 62 plant derived molecules against the chikungunya, dengue and zika vector, the Aedes aegypti (Diptera:Culicidae) mosquito, is subjected to a Quantitative Structure-Activity Relationships (QSAR) analysis. The Replacement Method (RM) variable subset selection technique based on Multivariable Linear Regression (MLR) proves to be successful for exploring 4885 molecular descriptors calculated with Dragon 6. The predictive capability of the obtained models is confirmed through an external test set of compounds, Leave-One-Out (LOO) cross-validation and Y-Randomization. The present study constitutes a first necessary computational step for designing less toxic insecticides.

Quinolines: Microwave-assisted synthesis and their antifungal, anticancer and radical scavenger properties.

An efficient method for the synthesis of quinolines using microwave irradiation was developed providing 28 quinolines with good yields. The reaction procedures are environmentally friendly, convenient, mild and of easy work-up. Quinolines were evaluated for their antifungal, anticancer and antioxidant properties and exhibited high activities in all tests performed.

Antifouling activity of green-synthesized 7-hydroxy-4-methylcoumarin.

In the search for new environmental-friendly antifoulants for replace metallic biocides, 7-hydroxy-4-methylcoumarin was synthesized according to green chemistry procedures. This compound was characterized by current organic analysis and its antifouling properties were firstly evaluated on the bivalve Mytilus edulis platensis in the laboratory. In the second stage, a soluble matrix antifouling coating formulated with this compound was assayed in marine environment. Laboratory experiments showed that 7-hydroxy-4-methylcoumarin was effective in inhibiting both the settlement as well as the byssogenesis of mussels. In addition, after exposure time in the sea, painted panels containing this compound showed strong antifouling effect on conspicuous species of the fouling community of Mar el Plata harbor. In conclusion, green-synthesized coumarin could be a suitable antifoulant candidate for marine protective coatings.

Quantitative Structure-Antifungal Activity Relationships for cinnamate derivatives.

Quantitative Structure-Activity Relationships (QSAR) are established with the aim of analyzing the fungicidal activities of a set of 27 active cinnamate derivatives. The exploration of more than a thousand of constitutional, topological, geometrical and electronic molecular descriptors, which are calculated with Dragon software, leads to predictions of the growth inhibition on Pythium sp and Corticium rolfsii fungi species, in close agreement to the experimental values extracted from the literature. A set containing 21 new structurally related cinnamate compounds is prepared. The developed QSAR models are applied to predict the unknown fungicidal activity of this set, showing that cinnamates like 38, 28 and 42 are expected to be highly active for Pythium sp, while this is also predicted for 28 and 34 in C. rolfsii.

QSAR analysis on tacrine-related acetylcholinesterase inhibitors.

BACKGROUND: The evaluation of the clinical effects of Tacrine has shown efficacy in delaying the deterioration of the symptoms of Alzheimer's disease, while confirming the adverse events consisting mainly in the elevated liver transaminase levels. The study of tacrine analogs presents a continuous interest, and for this reason we establish Quantitative Structure-Activity Relationships on their Acetylcholinesterase inhibitory activity. RESULTS: Ten groups of new developed Tacrine-related inhibitors are explored, which have been experimentally measured in different biochemical conditions and AChE sources. The number of included descriptors in the structure-activity relationship is characterized by 'Rule of Thumb'. The 1502 applied molecular descriptors could provide the best linear models for the selected Alzheimer's data base and the best QSAR model is reported for the considered data sets. CONCLUSION: The QSAR models developed in this work have a satisfactory predictive ability, and are obtained by selecting the most representative molecular descriptors of the chemical structure, represented through more than a thousand of constitutional, topological, geometrical, quantum-mechanical and electronic descriptor types.

An efficient protocol for the synthesis of quinoxaline derivatives at room temperature using recyclable alumina-supported heteropolyoxometalates.

We report a suitable quinoxaline synthesis using molybdophosphovanadates supported on commercial alumina cylinders as catalysts. These catalysts were prepared by incipient wetness impregnation. The catalytic test was performed under different reaction conditions in order to know the performance of the synthesized catalysts. The method shows high yields of quinoxaline derivatives under heterogeneous conditions. Quinoxaline formation was obtained using benzyl, o-phenylenediamine, and toluene as reaction solvent at room temperature. The CuH(2)PMo(11)VO(40) supported on alumina showed higher activity in the tested reaction. Finally, various quinoxalines were prepared under mild conditions and with excellent yields.

Quantitative structure-activity relationships of mosquito larvicidal chalcone derivatives.

The mosquito larvicidal activities of a series of chalcones and some derivatives were subjected to a quantitative structure-activity relationship (QSAR) study, using more than a thousand constitutional, topological, geometrical, and electronic molecular descriptors calculated with Dragon software. The larvicidal activity values for 28 active compounds of the series were predicted, showing in general a good approximation to the experimental values found in the literature. Chalcones having one or both electron-rich rings showed high toxicity. However, the activity of chalcones was reduced by electron-withdrawing groups, and this was roughly diminished by derivatization of the carbonyl group. A set of six chalcones being structurally similar to some of the active ones, with a still unknown larvicidal activity, were prepared. Their activity values were predicted by applying the developed QSAR models, showing that two chalcones of such set, both 32 and 34, were expected to be highly active.

Sustainable synthesis of flavonoid derivatives, QSAR study and insecticidal activity against the fall armyworm, Spodoptera frugiperda (Lep.: Noctuidae).

A simple, clean, solvent-free preparation of flavones by the use of a silica-supported Preyssler heteropolyacid as reusable catalyst is described. High selectivity and very good yields (87-94%) were obtained in short reaction times (7-13 min). Bioassays for insecticidal activity against Spodoptera frugiperda were carried out with a set of flavones. Bioassays showed that some of the flavones had moderate insecticidal activity. Quantitative structure-activity relationships were established on the available data with the purpose of predicting the insecticidal activity of a number of structurally related flavones. A relationship between the molecular structure and biological activity is proposed.

A suitable preparation of N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and their ring homologs with a reusable Preyssler heteropolyacid as catalyst.

The preparation of N-sulfonyl-1,2,3,4-tetrahydroisoquinolines, N-sulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepines and N-sulfonyl-1,2,3,4,5,6-hexahydrobenzazocine was catalyzed by a Preyssler heteropolyacid, H(14)[NaP(5)W(30)O(110)], (PA), supported on silica (PASiO(2)40) with excellent yields by means of the Pictet-Spengler reaction of N-aralkylsulfonamides with s-trioxane. The reactions proceed with 0.5 mol% of silica-supported catalyst in toluene at 70°C. The catalyst can be recycled without appreciable loss of the catalytic activity.

QSAR analysis on Spodoptera litura antifeedant activities for flavone derivatives.

We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED(50) feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure-Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds. After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure-activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-(alpha-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED(50)=1.162.

Spectroscopic and theoretical study of 2-acetylphenyl-2-naphthoate.

Mid-, far-infrared and Raman vibrational spectra of 2-acetylphenyl-2-naphthoate have been measured at room and low temperatures. The molecule was also analyzed by means of ab initio calculations. The conformational space has been scanned using molecular dynamics and complemented with functional density calculations that optimize the geometry of the lowest energy conformers 2-acetylphenyl-2-naphthoate as obtained in the simulations. The vibrational frequencies and the (1)H and (13)C NMR chemical shifts were assigned using functional density calculations. The theoretical chemical shift values were compared with the experimental ones. The molecular electrostatic potential maps were obtained and analyzed.