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This chapter covers a sesquiterpene quinone, commonly named perezone. This molecule is documented as the first secondary metabolite isolated in crystalline form in the New World in 1852. An introduction, with its structure, the IUPAC nomenclature, and the most recent physical and spectroscopic characterizations are firstly described initially. Alongside this, a timeline and scheme with summarized information of the history of this molecule is given including the "Códice Badiano de la Cruz, 1552, highlighting the year of its isolation culminating with information up to 2005. Subsequently, in a chronological order the most recent advances of the target molecule are included and organized in subsections covering the last 15-year period 2006-2020. Finally, recently submitted contributions from the laboratory of the authors are described. It is important to note that the details provided highlight the importance and relevance of perezone.

The Baeyer–Villiger (BV) reaction of acetophenones R-COCH3 (R = phenyl, 4-methylphenyl, 3,4-dimethoxyphenyl) with performic acid (PFA) in formic acid (FA) as the catalyst and solvent was reinvestig...

Se seleccionó la licencia Creative Commons para este envío. El documento trae lo siguiente: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). (En caso de duda consultar a Meilyn Garro). There is ongoing interest in the alcohol industry to significantly reduce and/or add value to the liquid residue, vinasse, produced after the distillation and rectification of ethanol from sugar cane. Vinasse contains potassium, glycerol, and a protein component that can cause environmental issues if improperly disposed of. Currently, some industries have optimized their processes to reduce waste, and a significant proportion of vinasse is being considered for use as an additive in other industrial processes. In the manufacture of cement and asphalt, vinasse has been used in the mixtures at low concentrations, albeit with some physical and mechanical problems. This work is the first molecular approximation of the components of the sugar cane vinasse in an industrial context, and it provides atomic details of complex molecular events. In the current study, the major components of sugar cane vinasse, alone or complexed on the surface of calcium carbonate, were modeled and simulated using molecular dynamics. The results showed that the protein component, represented by the mannoprotein Mp1p, has a high affinity for forming hydrogen bonds with potassium and glycerol in the vinasse. Additionally, it provides atomic stability to the calcium carbonate surface, preserving the calcite crystalline structure in the same way potassium ions interact with the carbonate group through ion–dipole interactions to improve the cohesion of the modeled surface. On the contrary, when the glycerol molecule interacts with calcium carbonate using more than two hydrogen bonds, it triggers the breakdown of the crystalline structure of calcite expanding the ionic pair. Existe un interés constante en la industria del alcohol por reducir significativamente y / o agregar valor al residuo líquido, la vinaza, que se produce después de la destilación y rectificación del etanol de la caña de azúcar. La vinaza contiene potasio, glicerol y un componente proteico que puede causar problemas ambientales si se desecha de manera inadecuada. Actualmente, algunas industrias han optimizado sus procesos para reducir los residuos y se está considerando una proporción significativa de vinaza para su uso como aditivo en otros procesos industriales. En la fabricación de cemento y asfalto, la vinaza se ha utilizado en las mezclas en bajas concentraciones, aunque con algunos problemas físicos y mecánicos. Este trabajo es la primera aproximación molecular de los componentes de la vinaza de caña de azúcar en un contexto industrial y proporciona detalles atómicos de eventos moleculares complejos. En el estudio actual, los componentes principales de la vinaza de caña de azúcar, solos o acomplejados en la superficie del carbonato de calcio, se modelaron y simularon utilizando dinámica molecular. Los resultados mostraron que el componente proteico, representado por la manoproteína Mp1p, tiene una alta afinidad por formar enlaces de hidrógeno con el potasio y el glicerol en la vinaza. Además, proporciona estabilidad atómica a la superficie del carbonato de calcio, preservando la estructura cristalina de la calcita de la misma manera que los iones de potasio interactúan con el grupo carbonato a través de interacciones ion-dipolo para mejorar la cohesión de la superficie modelada. Por el contrario, cuando la molécula de glicerol interactúa con el carbonato de calcio usando más de dos enlaces de hidrógeno, desencadena la ruptura de la estructura cristalina de la calcita expandiendo el par iónico. Universidad Nacional, Costa Rica Universidad Santiago de Cali, Colombia. Instituto Tecnológico de Costa Rica Universidad Estatal a Distancia, Costa Rica. Universidad Nacional Autónoma de México Universidad Icesi, Colombia. Departamento de Física

Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) functional and basis set, the interaction of the aflatoxin B1 (AFB1) molecule and the functional groups present in the Pyracantha koidzumii biosorbent was investigated. Dissociation free energy and acidity equilibrium constant values were obtained theoretically both in solution (water) and gas phases. Additionally, the molecular electrostatic potential for the protonated molecules was calculated to verify the reactivity. Thus, methanol (hydroxyl group), methylammonium ion (amino group), acetate ion (carboxyl group), and acetone (carbonyl group), were used as representatives of the substrates present in the biomass, these references were considered using the corresponding protonated or unprotonated forms at a pH value of 5. The experimental infrared spectrophotometric data suggested the participation of these functional groups in the AFB1 biosorption process, indicating that the mechanism was dominated by electrostatic interactions between the charged functional groups and the positively charged AFB1 molecule. The theoretical determination indicated that the carboxylate ion provided the highest interaction energy with the AFB1 molecule. Consequently, an enriched biosorbent with compounds containing carboxyl groups could improve the yield of the AFB1 adsorption when using in vitro and in vivo trials.

Lactose is an important additive because of its food, pharmaceutical, and cosmetic applications. Among lactose polymorphs, anhydrous β-lactose stands out due to its thermodynamic stability. Thus, a simple method to produce the inter-conversion from monohydrate α-lactose to anhydrous β-lactose was investigated employing a methanolic solution and different reaction variables (catalyst type, temperature, and stirring). Pure β-lactose powders were synthesized in short reaction time (2–16 h), with a moderate temperature (reflux: 65 °C), and low concentration (0.014 M) of catalysts (NaOH and KOH). The SEM analysis revealed a change in the morphology from fine needles to tomahawk shape, which is dependent on the content of β-lactose. The products were appropriately characterized using common analytic procedures (XRD, FTIR, and MDSC). In addition, an exhaustive discussion of the obtained results is provided. Finally, it seems to be the first work, where the inter-conversion to pure β-lactose is reported successfully.

Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) functional and basis set, the interaction of the aflatoxin B1 (AFB1) molecule and the functional groups present in the Pyracantha koidzumii biosorbent was investigated. Dissociation free energy and acidity equilibrium constant values were obtained theoretically both in solution (water) and gas phases. Additionally, the molecular electrostatic potential for the protonated molecules was calculated to verify the reactivity. Thus, methanol (hydroxyl group), methylammonium ion (amino group), acetate ion (carboxyl group), and acetone (carbonyl group), were used as representatives of the substrates present in the biomass; these references were considered using the corresponding protonated or unprotonated forms at a pH value of 5. The experimental infrared spectrophotometric data suggested the participation of these functional groups in the AFB1 biosorption process, indicating that the mechanism was dominated by electrostatic interactions between the charged functional groups and the positively charged AFB1 molecule. The theoretical determination indicated that the carboxylate ion provided the highest interaction energy with the AFB1 molecule. Consequently, an enriched biosorbent with compounds containing carboxyl groups could improve the yield of the AFB1 adsorption when using in vitro and in vivo trials.

The structure of four type bis-1,4-dihydropyridine molecules was completely optimized employing semiempirical (PM3), ab initio (HF/3-21G(d), B3LYP/6-31G(d) and B3LYP/6-311++G(d,p) methods. The B3LYP/6-311++G(d,p) theory level provided a flat boat conformation. The observed ring distortions were not found to be influenced to a great extent by the position of the substituent present in the 4-phenyl ring, the second dihydropyridine ring. The HOMO, LUMO, chemical hardness, global softness, chemical electrophilicity and molecular electrostatic potential values were also appropriately calculated. The electronic parameters allowed to establish the reactivity of the four bis-1,4-dihydropyridine molecules. Moreover, the interactions between these compounds with two models of the voltage-gated calcium channel receptor were evaluated in connection to the reported vasodilator activity of these compounds.

Fenofibrate, an oral fibrate lipid lowering agent, and simvastatin, which reduces plasma levels of low-density lipoprotein cholesterol, are active pharmaceutical ingredients (APIs), currently in the market. We characterized these APIs by thermal analysis and conducted X-ray powder diffraction techniques. Studies should be carried out in the formulation stage before the final composition of a polypill may be established. Thus, it was found in thermochemical studies that both compounds present no chemical interactions in an equimolar mixture of solid samples at room temperature. Theoretical studies were employed to determine possible interactions between fenofibrate and simvastatin. A very weak intramolecular hydrogen bond is formed between the hydroxyl group (O 5 H 5 ) of the simvastatin with chlorine and carbonyl group (C 11 O 4 , C 1 O 2 ) of the fenofibrate molecule. These weak energy hydrogen bonds have no effect on the chemical stability of the compounds studied. The results were obtained using Density Functional Theory methods; particularly the BPE1BPE and B3LYP functional and 6-31++G** basis set. The values of energy show good approximation when are compared with similar calculations previously reported. Infrared spectra of monomers and dimers were obtained via theoretical calculations.

Alzheimer’s disease (AD) represents the principal cause of dementia among the elderly. Great efforts have been established to understand the physiopathology of AD. Changes in neurotransmitter systems in patients with AD, including cholinergic, GABAergic, serotoninergic, noradrenergic, and histaminergic changes have been reported. Interestingly, changes in the histaminergic system have been related to cognitive impairment in AD patients. The principal pathological changes in the brains of AD patients, related to the histaminergic system, are neurofibrillary degeneration of the tuberomammillary nucleus, the main source of histamine in the brain, low histamine levels, and altered signaling of its receptors. The increase of histamine levels can be achieved by inhibiting its degrading enzyme, histamine N-methyltransferase (HNMT), a cytoplasmatic enzyme located in astrocytes. Thus, increasing histamine levels could be employed in AD patients as co-therapy due to their effects on cognitive functions, neuroplasticity, neuronal survival, neurogenesis, and the degradation of amyloid beta (Aβ) peptides. In this sense, the evaluation of the impact of HNMT inhibitors on animal models of AD would be interesting, consequently highlighting its relevance.

Citrulline Malate (CM) is a pre-workout energy supplement, frequently used to reduce fatigue in sports that require high levels of energy. Typically, oral intake should occur at least 2 h before undertaking sport, in order for effects to take place. In this study, we have developed a method for immediate dermal release, which would considerably increase the amount of supplement delivered, in a continuous manner. The method was based on polyvinyl alcohol (PVA)-CM integrated fibers, which were fabricated using an electrospinning technique and which ranged between 168 and 396 nm in diameter. The PVA fibers hosted and released the energetic supplement of up to 5 g of CM, equivalent to 5 doses of 1 gr/day. FTIR and Raman measurements indicated a physical rather than a chemical interaction. PVA-CM systems were of relatively low crystallinity and patched fibers became more flexible when CM was increased. Total experimental time of up to 20 h was proportional to the amount of CM released and followed transport mechanism type II, where the first order Korsmeyer-Peppas model correlated the release results. Hydrolytic degradation took place over 4 steps and was proportional to hydrolytic degradation of polymeric fibers. Theoretical calculations at the level of density functional theory (DFT), using the functional B3LYP with the set of bases 6–311 ++ G (d, p), made it possible to determine the nature of the intermolecular interactions between PVA and CM. Electronic and spectroscopic properties were also determined in order to contribute to and complement molecular characterization.

Cancer is one of the leading causes of morbidity and mortality worldwide. This disease is characterized by uncontrolled growth and proliferation of abnormal cells with a high probability to develop metastasis. Recently, it was demonstrated that perezone, a sesquiterpene quinone, is capable to induce cell death in leukemia (K562), prostate (PC-3), colorectal (HCT-15) and lung (SKLU-1) cancer cell lines; however, its mechanism of action is unknown. Therefore, in this study, in vitro and computational studies were performed to determine the mechanism of action of perezone. Firstly, changes in K562 cell viability, as well as changes in the redox status of the cell in response to treatment with several concentrations of perezone were analyzed. The type of cell death induced, and the modification of the cell cycle were determined. In addition, MD simulations and docking studies were performed to investigate the interaction of perezone with seven regulators of the apoptotic process. Finally, the ability of perezone to inhibit PARP-1 was evaluated by in vitro studies. K562 cells treated with perezone exhibited decreased viability and more oxidized status, being this effect concentration-dependent. In addition, the increase of G0/G1 phase of cell cycle and apoptosis were observed. According to the performed computational studies conducted, perezone showed the highest affinity to PARP-1 enzyme being this complex the most stable due to the presence of a small and deep cavity in the active site, which allows perezone to fit deeply by forming hydrogen bonds and hydrophobic interactions, which drive this interaction. The activity of perezone as PARP-1 inhibitor was corroborated with an IC50 = 181.5 μM. The pro-apoptotic action of perezone may be related to PARP-1 inhibition and changes in the redox state of the cell. The obtained results allowed to understand the biological effect of perezone and, consequently, these could be employed to develop novel PARP-1 inhibitors.

A green approach to produce the indolyl derivatives from four natural quinones (perezone, isoperezone, menadione, and plumbagin) was performed; in this regard, a comparative study was accomplished among the typical mantle heating and three nonconventional activating modes of reaction (microwave, near-infrared, and high speed ball milling or tribochemical), under solventless conditions and using bentonitic clay as a catalyst. In addition, the tribochemical production of isoperezone from perezone is also commented on. It is also worth noting that the cytotoxicity of the synthesized indolylquinones in human breast cancer cell was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, with the 3-indolylisoperezone being the most active. The structural attribution of the target molecules was performed by typical spectroscopic procedures; moreover, the experimental and computed1H and13C NMR chemical shifts data, with previous acquisition of the corresponding minimum energetic structures, were in good agreement.

The structure of the ortho-, meta- and para- hybrid diindolylmethane-phenylboronic acids and their interactions were optimized with by a quantum chemical method, using density functional theory at the (DFT) level. Thus, infrared bands were assigned based on the scaled theoretical wavenumbers by correlating the respective experimental data of the molecules. In addition, the corresponding 1H-/13C-/11B-NMR experimental and theoretical chemical shifts were correlated. The target molecules showed a poor treatment of the OH shifts in the GIAO method due to the absence of explicit solvent effects in these calculations; therefore, they were explicitly considered with acetone molecules. Moreover, the electron density at the hydrogen bond critical point increased, generating stabilization energy, from weak to moderate or weak to strong, serving as an indicator of the strength of the hydrogen bond between the different intermolecular interactions. Finally, some properties related to the reactive behavior of the target molecules associated with their cytotoxic effects and metabolic pathways were also calculated.

Chemical degradation of orlistat, (ORT) after melting and reaction of decomposition byproducts with sibutramine, SIB was studied. Interactions between the active pharmaceutical ingredients by using thermal analysis, TA, methods and other experimental techniques such as PXRD, IR and UV–vis spectroscopies were carried out to investigate chemical reactions between components. It was found that orlistat melts with decomposition and byproducts quickly affect sibutramine molecule and then reacting also with carnitine, CRN when the three active pharmaceutical ingredients (API’s) are mixed. However ORT byproducts do not react when ORT is mixed only with carnitine. It was found that compounds containing chlorine atoms react easily with orlistat when the temperature increases up to its melting point. Some reaction mechanisms of orlistat decomposition are proposed, the fragments in the mechanisms were found in the corresponding mass spectra. Results obtained indicate that special studies should be carried out in the formulation stage before the final composition of a poly-pill could be established. Similar results are commonly found for compounds very prone to react in presence of water, light and/or temperature. In order to explain the reactivity of orlistat with sibutramine and carnitine, theoretical calculations were carried out and the results are in agreement with the experimental results.

The interactions of L-aminoglucosidic stereoisomers such as rhodostreptomycins A (Rho A) and B (Rho B) with cations (Mg2+, Ca2+, and H+) were studied by a quantum mechanical method that utilized DFT with B3LYP/6-311G**. Docking studies were also carried out in order to explore the surface recognition properties of L-aminoglucoside with respect to Mg2+ and Ca2+ ions under solvated and nonsolvated conditions. Although both of the stereoisomers possess similar physicochemical/antibiotic properties against Helicobacter pylori, the thermochemical values for these complexes showed that its high affinity for Mg2+ cations caused the hydration of Rho B. According to the results of the calculations, for Rho A–Ca2+(H2O)6, ΔH = −72.21 kcal mol−1; for Rho B–Ca2+(H2O)6, ΔH = −72.53 kcal mol−1; for Rho A–Mg2+(H2O)6, ΔH = −72.99 kcal mol−1 and for Rho B–Mg2+(H2O)6, ΔH = −95.00 kcal mol−1, confirming that Rho B binds most strongly with hydrated Mg2+, considering the energy associated with this binding process. This result suggests that Rho B forms a more stable complex than its isomer does with magnesium ion. Docking results show that both of these rhodostreptomycin molecules bind to solvated Ca2+ or Mg2+ through hydrogen bonding. Finally, Rho B is more stable than Rho A when protonation occurs.

Solubility data from sibutramine (SBA) in a family of alcohols were obtained at different temperatures. Sibutramine was characterized by using thermal analysis and X-ray diffraction technique. Solubility data were obtained by the saturation method. The van’t Hoff equation was used to obtain the theoretical solubility values and the ideal solvent activity coefficient. No polymorphic phenomena were found from the X-ray diffraction analysis, even though this compound is a racemic mixture of (+) and (−) enantiomers. Theoretical calculations showed that the polarisable continuum model was able to reproduce the solubility and stability of sibutramine molecule in gas phase, water and a family of alcohols at B3LYP/6-311++G (d,p) level of theory. Dielectric constant, dipolar moment and solubility in water values as physical parameters were used in those theoretical calculations for explaining that behavior. Experimental and theoretical results were compared and good agreement was obtained. Sibutramine solubility increased from methanol to 1-octanol in theoretical and experimental results.

The transesterification reaction, and in particular the methanolysis of ethyl acetate with sulfuric acid as catalyst, is used as a model reaction to study the acid-catalyzed nucleophilic addition to a carbonyl group. Continuum solvation methods (SMD and IEF-PCM) and the MPWB1K functional are used. The reaction mechanism is studied in methanol and in acetonitrile as solvents. Our results indicate that the acid-catalyzed addition mechanism is stepwise, and the transition state (TS) is a contact ion-pair. The counteranion of the acid catalyst remains in the reaction site playing an important role in the TS of this reaction. Changes in the reaction kinetics and the ionic/nonionic nature of the TS with the ionizing ability of the solvent and the strength of the acid catalyst are explored. Additional calculations at the CBS-Q3 level of theory reinforce the conclusions of this paper. The results obtained allow the generalization of important ideas regarding the mechanism of the nucleophilic addition to carbonyl groups.

CH [Formula: see text] X (X = N, O, or Cl) hydrogen bonds formed intramolecularly in 2-methyl-4-(2-chloro-4,5-dimethoxyphenyl)thiazole (Ia), 2-amino-4-(2-chloro-4,5-dimethoxy phenyl)thiazole (Ib), 2-amino-4-(2,4,5-trimethoxyphenyl)thiazole (Ic), and 2-methyl-4-(2,4,5-trimethoxyphenyl)thiazole (Id) were studied by means of all-electron calculations performed with the B3LYP/6-311++G(d,p) method. Computed ground states, in the gas phase, show the presence of a single H-bond, CH [Formula: see text] Cl, in each Ia and Ib moiety, and two H-bonds, CH [Formula: see text] N and CH [Formula: see text] O, for each Ic and Id molecule. H [Formula: see text] Cl, H [Formula: see text] N, and H [Formula: see text] O distances are shorter than the sum of the X and H van der Waals radii. H-bond energies of ≅2.0 kcal/mol were estimated for Ia and Ib and ≅4.0 kcal/mol for Ic and Id. These results agree with those of the theory of atoms in molecules, since bond critical points were found for these H [Formula: see text] X bonds. Finally, the chemical shifts in the (1)H NMR were calculated by the GIAO method; in Ia and Ib they are merely due to the different topological positions of the H atoms. But in Ic and Id the shifts of H [Formula: see text] N and H [Formula: see text] O have signatures of H-bond formations.

Solubility experimental data from Simvastatin in a family of alcohols were obtained at different temperatures. Simvastatin was characterized by using thermal analysis and X-ray diffraction. From the experimental solubility data an anomalous behavior was observed, since an increase the number of alcohol carbon atoms shows an increase in solubility only for the three first alcohols, ethanol, 1-propanol and 1-butanol. A decrease in solubility was obtained for 1-pentanol, 1-hexanol and 1-octanol. Van’t·Hoff equation was used to obtain the theoretical solubility value and the ideal activity coefficient. Experimental error was very low and does not affect the plots and equations used. No polymorphic phenomenon was found from the Simvastatin characterization. Theoretical calculations were carried out in order to corroborate the experimental solubility data. Trends and results are similar in both cases. The geometry optimizations of Simvastatin was carried out using density functional theory with Becke’s three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with 6-311++G∗∗ basis set. The solvent effect was treated using a continuum model as modeled in water, methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol and 1-octanol. Moreover, dielectric constant, dipolar moment and solubility in the solvents were obtained for explaining the former behavior.

CHX (X = N, O, or Cl) hydrogen bonds formed intramolecularly in 2-methyl-4-(2-chloro-4,5-dimethoxyphenyl)thiazole (Ia), 2-amino-4-(2-chloro-4,5-dimethoxy phenyl)thiazole (Ib), 2-amino-4-(2,4,5-trimethoxyphenyl)thiazole (Ic), and 2-methyl-4-(2,4,5-trimethoxyphenyl)thiazole (Id) were studied by means of all-electron calculations performed with the B3LYP/6-311++G(d,p) method. Computed ground states, in the gas phase, show the presence of a single H-bond, CHCl, in each Ia and Ib moiety, and two H-bonds, CHN and CHO, for each Ic and Id molecule. HCl, HN, and HO distances are shorter than the sum of the X and H van der Waals radii. H-bond energies of ≅2.0 kcal/mol were estimated for Ia and Ib and ≅4.0 kcal/mol for Ic and Id. These results agree with those of the theory of atoms in molecules, since bond critical points were found for these HX bonds. Finally, the chemical shifts in the 1H NMR were calculated by the GIAO method; in Ia and Ib they are merely due to the different topological positions of the H atoms...

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC50 value ranking, i.e: indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed.

A set of 84 known N-aryl-monosubstituted derivatives (42 amides: series 1 and 2, and 42 imides: series 3 an 4, from maleic and succinic anhydrides, respectively) that display inhibitory activity toward both acetylcholinesterase and butyrylcholinesterase (ChEs) was considered for Quantitative structure–activity relationship (QSAR) studies. These QSAR studies employed docking data from both ChEs that were previously submitted to molecular dynamics (MD) simulations. Donepezil and galanthamine stereoisomers were included to analyze their quantum mechanics properties and for validating the docking procedure. Quantum parameters such as frontier orbital energies, dipole moment, molecular volume, atomic charges, bond length and reactivity parameters were measured, as well as partition coefficients, molar refractivity and polarizability were also analyzed. In order to evaluate the obtained equations, four compounds: 1a (4-oxo-4-(phenylamino)butanoic acid), 2a ((2Z)-4-oxo-4-(phenylamino)but-2-enoic acid), 3a (2-phenylcyclopentane-1,3-dione) and 4a (2-phenylcyclopent-4-ene-1,3-dione) were employed as independent data set, using only equations with r m ( test ) 2 >0.5. It was observed that residual values gave low value in almost all series, excepting in series 1 for compounds 3a and 4a, and in series 4 for compounds 1a, 2a and 3a, giving a low value for 4a. Consequently, equations seems to be specific according to the structure of the evaluated compound, that means, series 1 fits better for compound 1a, series 3 or 4 fits better for compounds 3a or 4a. Same behavior was observed in the butyrylcholinesterase (BChE). Therefore, obtained equations in this QSAR study could be employed to calculate the inhibition constant (Ki) value for compounds having a similar structure as N-aryl derivatives described here. The QSAR study showed that bond lengths, molecular electrostatic potential and frontier orbital energies are important in both ChE targets. Docking studies revealed that despite the multiple conformations obtained through MD simulations on both ChEs, the ligand recognition properties were conserved. In fact, the complex formed between ChEs and the best N-aryl compound reproduced the binding mode experimentally reported, where the ligand was coupled into the choline-binding site and stabilized through π–π interactions with Trp82 or Trp86 for BChE and AChE, respectively, suggesting that this compound could be an efficient inhibitor and supporting our model.

The current role of the “Green Chemistry Protocol” in multicomponent reactions is first highlighted. Then, the green approach to the production of three novel hybrid diindolylmethanes-phenylboronic acids via a 3MCR is discussed, which features the following: solventless conditions, the use of microwave irradiation to activate the reactions, the absence of catalyst, and an efficient atom economy. The products were achieved with moderate yields (41–61%) within a short time frame (5 min) and appropriately characterized by elemental analysis and spectroscopic methods (NMR:1H,13C,11B; MS: EI, CI, FAB+, HRMS). During the FAB+MS determinations, various artifacts that are associated with the boron atom via an interaction with thioglycerol from the matrix were noted in the corresponding FAB+mass spectra; in addition, the accurate mass determination of these adducts unequivocally confirmed the presence of the target molecules. Moreover, the activity of these target molecules was evaluated in the presence of six cancer cell lines (U251 = glia of the central nerve system, PC-3 = prostate, K562 = leukemia, HCT-15 = colon, MCF-7 = breast, and SKLU-1 = lung), which resulted in themeta-regioisomer being the most active. Finally, the products were also analyzed using computational chemistry in order to determine their most stable geometries and reactivities by computing the respective molecular electrostatic potentials.

Theoretical studies of 8-chloro-9-hydroxy-aflatoxin B1 (2) were carried out by Density Functional Theory (DFT). This molecule is the reaction product of the treatment of aflatoxin B1 (1) with hypochlorous acid, from neutral electrolyzed water. Determination of the structural, electronic and spectroscopic properties of the reaction product allowed its theoretical characterization. In order to elucidate the formation process of 2, two reaction pathways were evaluated—the first one considering only ionic species (Cl+ and OH−) and the second one taking into account the entire hypochlorous acid molecule (HOCl). Both pathways were studied theoretically in gas and solution phases. In the first suggested pathway, the reaction involves the addition of chlorenium ion to 1 forming a non-classic carbocation assisted by anchimeric effect of the nearest aromatic system, and then a nucleophilic attack to the intermediate by the hydroxide ion. In the second studied pathway, as a first step, the attack of the double bond from the furanic moiety of 1 to the hypochlorous acid is considered, accomplishing the same non-classical carbocation, and again in the second step, a nucleophilic attack by the hydroxide ion. In order to validate both reaction pathways, the atomic charges, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were obtained for both substrate and product. The corresponding data imply that the C9 atom is the more suitable site of the substrate to interact with the hydroxide ion. It was demonstrated by theoretical calculations that a vicinal and anti chlorohydrin is produced in the terminal furan ring. Data of the studied compound indicate an important reduction in the cytotoxic and genotoxic potential of the target molecule, as demonstrated previously by our research group using different in vitro assays.

Tonsil Actisil FF, a commercial bentonitic clay, promotes the formation of a series of electrophilic-aromatic-substitution products from para-methoxybenzyl acetate in carbon disulfide. The molecules obtained correspond to linear isomeric dimers, trimers, tetramers and a pentamer, according to their spectroscopic data. A clear indication of the title mechanistic pathway for the oligomerization growth was obtained from the analysis of a set of computational-chemistry calculations using the density-functional-theory level B3LYP/6-311++G(d,p). The corresponding conclusions were based on the computed dipole moments, the HOMO/LUMO distributions, and a natural-populations analysis of the studied molecules.

This study involved quantum mechanical calculations to explain the chemical behavior of the lactone ring of aflatoxin B1, which is a carcinogenic hazardous compound. The aflatoxin B1 compound, produced by the fungi Aspergillum flavus, was studied with the B3LYP/6-311+G(d,p) method; its reactivity properties were accounted for by means of the calculated geometrical and electronic parameters. The results obtained indicate that the fused A, B, C, and D rings of aflatoxin adopt a continuous planar conformation. The carbon atom of the lactone group presents a highly electrophilic character, since the population analysis yields a high positive charge for this atom, whereas high negative charges were recorded for both oxygen sites of that group. Thus, in an acidic aqueous medium, the oxygen atoms could be protonated and the carbon site may suffer a nucleophilic attack by water. Accordingly, the OC-O bond length has been lengthened substantially. So it was demonstrated that the lactonic ring of aflatoxin B1 is hydrolyzed under acidic conditions by an acid-acyl bimolecular mechanisms, A(AC)2, suggesting the deletion of its carcinogenic properties.

Among the multiple factors that induce Alzheimer's disease, aggregation of the amyloid β peptide (Aβ) is considered the most important due to the ability of the 42-amino acid Aβ peptides (Aβ1-42) to form oligomers and fibrils, which constitute Aβ pathological aggregates. For this reason, the development of inhibitors of Aβ1-42 pathological aggregation represents a field of research interest. Several Aβ1-42 fibrillization inhibitors possess tertiary amine and aromatic moieties. In the present study, we selected 26 compounds containing tertiary amine and aromatic moieties with or without substituents and performed theoretical studies that allowed us to select four compounds according to their free energy values for Aβ1-42 in α-helix (Aβ-α), random coil (Aβ-RC) and β-sheet (Aβ-β) conformations. Docking studies revealed that compound 5 had a higher affinity for Aβ-α and Aβ-RC than the other compounds. In vitro, this compound was able to abolish Thioflavin T fluorescence and favored an RC conformation of Aβ1-42 in circular dichroism studies, resulting in the formation of amorphous aggregates as shown by atomic force microscopy. The results obtained from quantum studies allowed us to identify a possible pharmacophore that can be used to design Aβ1-42 aggregation inhibitors. In conclusion, compounds with higher affinity for Aβ-α and Aβ-RC prevented the formation of oligomeric species.