In this work, the molecular properties of the (E)-3-(4-nitrobenzylidene)-2-(4-methoxyphenyl)-2,3-dihydro-1-(phenylsulfonyl)-quinolin-4(1H)-one were studied, both in a solid and isolated state. The effect of changing the substituent groups –OCH3 and –Cl in the phenyl portion was verified, where the structural and electronic properties were compared. The density functional theory was employed using the hybrid exchange-correlation functional with long-range correction M06-2X, combined with the polarized and diffuse basis set 6-311++G(d,p), in the gas phase. The electronic structure was also analyzed by frontier molecular orbitals and molecular electrostatic potential maps, where information about its chemical reactivity was obtained. Also, the supramolecular arrangement was analyzed by Hirshfeld surface (HS), 2D fingerprint plots, and quantum theory of atoms in molecules (QTAIM). The natural bond orbitals (NBO) calculations were carried out to analyze the stability and hyperconjugation energy. Finally, molecular docking was carried out to investigate the affinities of the quinoline-chalcone with a bacterial protein (Agrobacterium pathogens) and an ecdysone receptor-potential pesticidal activity. The results encourage further in vitro and in vivo analyses of the two kinds of organisms investigated. work E34nitrobenzylidene24methoxyphenyl2,3dihydro1phenylsulfonylquinolin41Hone E34nitrobenzylidene24methoxyphenyl23dihydro1phenylsulfonylquinolin41Hone EnitrobenzylidenemethoxyphenyldihydrophenylsulfonylquinolinHone E 3 4 nitrobenzylidene 2 methoxyphenyl 2,3 dihydro 1 phenylsulfonyl quinolin 1H one H studied state OCH3 OCH –OCH Cl verified compared exchangecorrelation exchange correlation longrange long range M062X, M062X MX M06 2X, 2X M X M06-2X 6311++Gd,p, 6311Gdp Gdp 6 311++G d,p , 311 G d p 6-311++G(d,p) phase maps obtained Also HS, HS (HS) D plots QTAIM. QTAIM . (QTAIM) NBO (NBO energy Finally quinolinechalcone quinoline chalcone Agrobacterium pathogens receptorpotential receptor activity investigated E34nitrobenzylidene24methoxyphenyl2 3dihydro1phenylsulfonylquinolin41Hone phenylsulfonylquinolin Hone 23 2, M0 6311 Gd 6311++Gd,p 311G dp 31 6-311++G(d,p (HS (QTAIM Enitrobenzylidenemethoxyphenyl E34nitrobenzylidene24methoxyphenyl dihydrophenylsulfonylquinolinHone 631 63

The Brazilian Cerrado biome is considered one of the 25 hotspots worldwide that contain bioactive compounds due to its great biodiversity; however, the reduction of its native area over time due to the expansion of urbanization and agribusiness may have compromised knowledge of its biological variety. In this context, knowledge about Cerrado species can contribute to its biodiversity preservation. This study aims to describe the isolation, molecular architecture and theoretical calculations of the compound (3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R)-5 ethyl -6-methylheptan-2 yl]-10,13 dimethyl 2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H cyclopenta[a]phenanthren-3 ol, extracted from the Brazilian Cerrado Miconia burchellii plant. The supramolecular arrangement was described by Hirshfeld surface analysis, demonstrating the intermolecular interactions in the crystalline packing. The structure-property relationship shows the electrostatic potential map analysis, which reveals that the oxygen region is susceptible to electrophilic attack, and the frontier molecular orbital confirmed the kinetic stability of this compound. This study represents another step forward in the knowledge of compounds with pharmacological and medicinal properties extracted from the Cerrado. 2 however variety context preservation isolation 3S,8S,9S,10R,13R,14S,17R172R,5R5 3S8S9S10R13R14S17R172R5R5 SSSRRSRRR 3S,8S,9S,10R,13R,14S,17R 17 2R,5R 5 3S 8S 9S 10R 13R 14S 17R 2R 5R S R (3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R)- 6methylheptan2 methylheptan 6 -6-methylheptan- yl10,13 yl1013 yl 10,13 10 13 yl]-10,1 2,3,4,7,8,9,11,12,14,15,16,17dodecahydro1H 234789111214151617dodecahydro1H dodecahydroH 2,3,4,7,8,9,11,12,14,15,16,17 dodecahydro 1H 3 4 7 8 9 11 12 14 15 16 H cyclopentaaphenanthren3 cyclopentaaphenanthren cyclopenta a phenanthren cyclopenta[a]phenanthren- ol plant analysis packing structureproperty structure property attack 17R172R 5R5 3S,8S,9S,10R,13R,14S,17R172R,5R 3S8S9S10R13R14S17R172R5R 3S8S9S10R13R14S17R SSSRRSR 1 2R5R RR (3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R) 6methylheptan -6-methylheptan yl10 yl10,1 yl101 1013 10,1 yl]-10, 17dodecahydro1H 234789111214151617 2,3,4,7,8,9,11,12,14,15,16,1 cyclopenta[a]phenanthren (3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R yl1 yl10, 101 10, yl]-10 23478911121415161 2,3,4,7,8,9,11,12,14,15,16, yl]-1 2347891112141516 2,3,4,7,8,9,11,12,14,15,16 yl]- 234789111214151 2,3,4,7,8,9,11,12,14,15,1 yl] 23478911121415 2,3,4,7,8,9,11,12,14,15, 2347891112141 2,3,4,7,8,9,11,12,14,15 234789111214 2,3,4,7,8,9,11,12,14,1 23478911121 2,3,4,7,8,9,11,12,14, 2347891112 2,3,4,7,8,9,11,12,14 234789111 2,3,4,7,8,9,11,12,1 23478911 2,3,4,7,8,9,11,12, 2347891 2,3,4,7,8,9,11,12 234789 2,3,4,7,8,9,11,1 23478 2,3,4,7,8,9,11, 2347 2,3,4,7,8,9,11 234 2,3,4,7,8,9,1 23 2,3,4,7,8,9, 2,3,4,7,8,9 2,3,4,7,8, 2,3,4,7,8 2,3,4,7, 2,3,4,7 2,3,4, 2,3,4 2,3, 2,3 2,

Resumen El Cerrado en el centro de Brasil está compuesto por tipos de vegetación únicos con una gran fuente de compuestos bioactivos. Las décadas de 1970 y 1980 estuvieron marcadas por la intensa incorporación de estas áreas nativas a pastos y cultivos, lo que incrementó el consumo de plaguicidas como el glifosato y la atrazina. Hoy en día, continúa habiendo una pérdida constante de vegetación natural en este bioma, y la presión del uso de la tierra está causando pérdidas significativas de vegetación nativa, impulsadas principalmente por la expansión agrícola. Este artículo proporciona un mapeo del consumo promedio estimado de pesticidas por cultivo, así como una comprensión de los riesgos asociados con la contaminación por glifosato y atrazina en el estado de Goiás. Ambas áreas sirven como base para comprender los desafíos y oportunidades de sostenibilidad asociados con agricultura en el estado de Goiás Cerrado brasileño. bioactivos 197 198 cultivos día bioma nativa agrícola cultivo brasileño 19 1

Abstract The Cerrado in Central Brazil is composed of unique vegetation types with a large source of bioactive compounds. The 1970s and 1980s were marked by the intensive incorporation of these forested areas into pastures and cropland, which increased the consumption of pesticides like glyphosate and atrazine. Today there continues to be a constant loss of native vegetation in this biome, and the pressure from land use is causing significant losses of native vegetation, driven mainly by agricultural expansion. This article offers a mapping of the estimated average consumption of pesticide per crop as well as an understanding of the risks associated with glyphosate and atrazine contamination in the state of Goiás. Both of these areas serve as a basis for understanding the challenges and opportunities for sustainability associated with agriculture in the Brazilian Cerrado. compounds s cropland biome expansion Goiás

Resumo O Cerrado no Brasil Central é composto por tipos de vegetação únicos com uma grande fonte de compostos bioativos. As décadas de 1970 e 1980 foram marcadas pela intensa incorporação dessas áreas com vegetação nativa a pastagens e lavouras, o que aumentou o consumo de agrotóxicos como glifosato e atrazina. Hoje continua a haver uma perda constante de vegetação natural neste bioma, e a pressão do uso da terra está causando perdas significativas de vegetação nativa, impulsionadas principalmente pela expansão agrícola. Este artigo oferece um mapeamento do consumo médio estimado de agrotóxicos por safra, bem como uma compreensão dos riscos associados à contaminação por glifosato e atrazina no estado de Goiás. Ambas as áreas servem de base para entender os desafios e oportunidades de sustentabilidade associados à agricultura no Cerrado brasileiro. bioativos 197 198 lavouras bioma agrícola safra Goiás brasileiro 19 1

This work describes the synthesis, molecular structure, and packaging of the compounds 6-bromo-2,3-dimethoxybenzaldehyde (6-BRB) and 5-bromo-2,3-dimethoxybenzaldehyde (5 BRB). Characterization in the solid-state was carried out by X-ray diffraction, and the analysis of the interactions was described by the Hirshfeld surface, which helps in understanding the effect of replacing the bromine position in the aromatic ring. Both compounds (6-BRB and 5-BRB) crystallized in the space group P21/c and are stabilized with C-HO interactions, but only the 6-BRB has a halogen-type interaction. Theoretical calculations, carried out by the density functional theory at the CAM-B3LYP/6-311++G(d,p) level of theory in gas phase, provided information on their electronic properties. The geometric properties were compared to experimental data, and the analyses of the frontier molecular orbitals and the molecular electrostatic potential (MEP) maps were obtained to predict the physical-chemical properties. The supramolecular arrangements were analyzed throughout complexation interactions and corrected by counterpoise method. Hyperconjugation energies were employed to examine the stability of the intermolecular interactions of the compounds. The interaction intensities were determined through the topological parameters obtained through the quantum theory of atoms in molecules model.

Benzimidazole and its derivatives are molecules that have diverse biological properties, therefore we synthesized and studied a new benzimidazole to understand their physical/chemical properties. The compound was obtained through a new synthetic route, using graphite oxide, in the absence of solvent, with crystalline packaging supported by C-H…N and C-H…π interactions. According to the frontier molecular orbitals, the compound is kinetically stable while the molecular electrostatic potential map confirms the site of molecular interactions involving nitrogen atoms and the π-system. This comprehensive study on synthesis, structural description and theoretical calculations can support ongoing studies in pharmaceutical science.

Resumen El uso de materiales orgánicos como materiales ópticos no lineales se ha explorado intensamente en los últimos años, debido a la facilidad de manipulación de estas estructuras moleculares y la flexibilidad de síntesis en relación con el cambio de grupos sustituyentes. En el presente trabajo, las propiedades lineales y no lineales de dos derivados de chalcona (E)-1-(4-metilfenil)-3-fenilprop-2-en-1-ona (4MP3P) y (E)-1-(4-nitrofenil)-3-fenilprop-2-en-1-ona (4NP3P), los cuales difieren en la posición del sustituyente en el anillo de fenilo, se estudiaron en presencia de disolventes próticos y apróticos simulados por el Modelo Continuo Polarizable a nivel DFT/B3LYP/6-311+G(d). Además, se estudiaron parámetros moleculares estáticos y dinámicos (1064 nm) como el momento dipolar, la polarización lineal y la primera y la segunda hiperpolarización en función del valor constante dieléctrico del disolvente. El comportamiento geométrico se estudió como ángulos de enlace químico, ángulos de torsión y distribución de carga parcial de compuestos, incluidos los cálculos de energía de huecos en varios solventes. Los resultados mostraron que el cambio del sustituyente CH3 (4MP3P) a NO2 (4NP3P) beneficia las propiedades ópticas no lineales de los compuestos en presencia del medio solvente, los valores absolutos de la primera hiperpolarizabilidad paralela fueron los que presentaron la mayor variación.

Abstract The use of organic as nonlinear optical materials has been intensively explored in the recent years due to the ease of manipulation of the molecular structure and the synthetic flexibility regarding the change of substituent groups. In the present work, the linear and nonlinear properties of two chalcones derivatives (E)-1-(4-methylphenyl)-3-phenylprop-2-en-1-one (4MP3P) and (E)-1-(4-Nitrophenyl)-3-phenylprop-2-en-1-one (4NP3P), that differ by the substituent position at the phenyl ring, were studied in the presence of protic and aprotic solvents simulated by the Polarizable Continuum Model (PCM) at DFT/B3LYP/6-311+G(d) level. The static and dynamic (1064 nm) molecular parameters as the dipole moment, linear polarizability, first and second hyperpolarizabilities were studied as function of the solvent dielectric constant value. The geometrical behavior as the chemical bond angles, torsion angles, and partial charges distribution of the compounds were studied, including calculations of gap energies in various solvents. The obtained results revealed that the substituent change of CH3 (4MP3P) to NO2 (4NP3P) benefits the nonlinear optical properties of the compounds in the presence of the solvent media, the absolute values of the parallel first hyperpolarizability were the ones that present the greater variation.

Resumo O uso de materiais orgânicos como materiais ópticos não lineares tem sido intensamente explorado nos últimos anos, devido à facilidade de manipulação dessas estruturas moleculares e à flexibilidade de síntese em relação à mudança de grupos substituintes. No presente trabalho, as propriedades lineares e não lineares de dois derivados de chalconas (E)-1-(4-metilfenil)-3-fenilprop-2-en-1-ona (4MP3P) e (E)-1-(4-nitrofenil)-3-fenilprop-2-en-1-ona (4NP3P), que diferem pela posição do substituinte no anel fenil, foram estudados na presença de solventes próticos e apróticos simulados pelo Modelo Continuo Polarizável (PCM) no nível DFT/B3LYP/6-311+G(d). Os parâmetros moleculares estáticos e dinâmicos (1064 nm) como momento dipolar, polarizabilidade linear, primeira e segunda hiperpolarizabilidades foram estudados em função do valor da constante dielétrica do solvente. Estudou-se o comportamento geométrico como ângulos de ligação química, ângulos de torção e distribuição parcial de cargas dos compostos, incluindo cálculos de energias de gap em vários solventes. Os resultados obtidos revelaram que a mudança do substituinte de CH3 (4MP3P) para NO2 (4NP3P) beneficia as propriedades ópticas não lineares dos compostos na presença do meio solvente, os valores absolutos da primeira hiperpolarizabilidade paralela foram os que apresentaram a maior variação.

Quinolinones are a class of organic compounds known as alkaloids found in several plants and also can be synthesized. Their large use in therapies regards their wide biological potential like antitumor, psychiatric and neurological agents. Two substances were structurally characterized: (E)-3-(2-nitrobenzylidene)-2-(4-methoxyphenyl)-1-(phenylsulfonyl)-2,3-dihydroquinolin-4(1H)‑one (NMQ), and (E)-3-(2-chlorobenzylidene)-2-(2-methoxyphenyl)-1-(phenylsulfonyl)-2,3‑dihydroquinolin-4(1H)-one (CMQ). These compounds were synthesized, crystallized, characterized by single crystal X-ray diffraction and theoretical calculations. The NMQ and CMQ crystals are formed by a pair of enantiomers and crystallized in the centrosymmetric group P21/c with similar volume and density. Differences noted on crystal packing and supramolecular arrangement are associated to substituent group chlorine in CMQ and nitro in NMQ. The calculated infrared (IR) spectra show a good agreement with experimental values. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies show CMQ more kinetically stable with a higher resistance to transfer charge than NMQ.

Chalcones are compounds with wide interesting biological activities including Alzheimer’s disease. A comparative study was performed between the chalcones (E)-1-(2-aminophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one and 1-(6-amino-1,3-benzodioxol-5-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one regarding the influence of benzodioxol group on their molecular conformations. The first chalcone was neutralized with dilute hydrochloric acid, while solid of the second was filtered and recrystallized from ethanol, both on centrosymmetric space group P21/c. Their molecular packing were evaluated by Hirshfeld surfaces, and both frontier molecular orbitals and molecular electrostatic potential (MEP) map were carried out by density functional theory (DFT) calculations. The compounds are stabilized by C–H…O and C–H…p interactions, as observed on MEP map, while the HOMO-LUMO gap indicated the conformational stability. The pharmacophore mapping approach was carried out for the identification of potential target candidates and then, further molecular docking analysis targeting the beta-secretase 1 (BACE-1) protein as a tactic to develop potential AD inhibitors, was performed. The AutoDock Vina score in redocking result for 2OHQ is –7.4 and –7.6 kcal moL-1. Additionally, the docking results for compounds inside the active site of the 2OHQ structure showed that both compounds bound to the BACE-1 active site with AutoDock Vina score of –6.0 kcal moL-1.

Heterocyclic chalcones have been prominent in the scientific community due to various biological activities reported for these compounds. The structural knowledge of heterocyclic chalcones can help in the understanding of their mechanism of action. The Hirshfeld surfaces were used to study the supramolecular arrangement of two conformers present into asymmetric unit of the heterocyclic chalcone (2E)-3-(4-methylphenyl)-1-(pyridin-3-yl)-prop-2-en-1-one on crystalline state. In addition, the linear polarizability (α), the first hyperpolarizability (β||z), and the second hyperpolarizability (γ) of the conformers were calculated to get a better insight on the linear and nonlinear optical behaviors of these structures in presence of solvent medium, as well as their band-gap energies. The Hirshfeld surfaces confirmed the presence of C−H···N, C−H···O and C−H···C interactions in packaging stabilization. Finally, the 2D fingeprint plot was used to the quantification of contacts and indicated that there are both π···π and C−H···π interactions present in the compound.

The structures of two methoxylated chalcones, namely (E)-1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one and (E)-3-(4-ethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one, reveal the effect of the inclusion of the methoxyl and ethoxyl substituents of the conformation on methoxy-chalcone. Structural comparative study between two chalcones was done in this work and some effects on geometric parameters, such as planarity and dihedral angles, were described. In addition, intermolecular interactions responsible for crystalline packaging were investigated by Hirshfeld surfaces and the values of those interactions were analysed by comparing experimental and theoretical models. The molecular stability was expressed in terms of softness and hardness, both obtained from frontier molecular orbitals. Finally, there is a good agreement between calculated and experimental infrared spectrum, which allowed the assignment of the normal vibrational modes.

O presente trabalho descreve as atividades antibacterianas e antifúngicas de diversas chalconas obtidas diretamente através da condensação aldólica tipo Claisen-Schmidt das quais se determinou a concentração inibitória mínima frente a diferentes microrganismos (bactérias Gram-positivas e Gram-negativas e fungos). Estruturas no estado sólido cristalino de sete chalconas foram determinadas por análise de difração de raios X (XRD). Estudos quimiométricos foram realizados com intuito de identificar uma potencial relação entre estrutura e atividade.

The present work describes the antibacterial and antifungal activities of several chalcones obtained by a straight Claisen-Schmidt aldol condensation determined by the minimal inhibitory concentration against different microorganisms (Gram-positive and Gram-negative bacteria and fungi). Solid state crystal structures of seven chalcones were determined by X-ray diffraction (XRD) analysis. Chemometric studies were carried out in order to identify a potential structure-activity relationship.

Com o objetivo de relacionar os descritores geométricos e eletrônicos dos derivados análogos da rutaercarpina com a atividade biológica contra o câncer do sistema nervoso central (CNS), cálculos de química quântica molecular em nível B3LYP/6-31(d) e análise estatística foram realizados para os 21 derivados análogos da rutaecarpina. Dos 86 descritores moleculares calculados, 5 foram selecionados na construção do modelo de análises de componentes principais (PCA). A componente PC1, a qual responde por 46,11% da variância total dos dados, foi capaz sozinha de discriminar completamente os compostos em duas classes: ativos e inativos. Todos os descritores moleculares selecionados pelo modelo PCA são parâmetros eletrônicos. A análise de agrupamento hierárquico (HCA) foi também aplicada aos descritores selecionados pelo modelo PCA. Baseado nos 5 descritores selecionados é possível sugerir novos derivados ativos da rutaercarpina para serem sintetizados. Além disso, um modelo de mínimos quadrados parciais para análise discriminante (PLS-DA) supervisionado foi construído e aplicado com sucesso na discriminação dos análogos à rutaercarpina, o qual foi validado usando um conjunto independente de compostos.

In order to relate the geometric and electronic descriptors of the rutaecarpine analogous to their biological activity against cancer of the central nervous system (CNS), molecular quantum chemical calculations at B3LYP/6-31(d) level and statistical analysis were carried out for 21 rutaecarpine analogous. Out of the 86 molecular descriptors calculated, 5 were selected to build the principal component analysis (PCA) model. The PC1 component that accounts for 46.11% of the total variance of the data was alone able to discriminate completely the compounds into two classes: active and inactive. All molecular descriptors selected by PCA model are electronic parameters. The hierarchical cluster analysis (HCA) was also applied on the selected descriptors. Based on the 5 electronic descriptors selected, it is possible to suggest new compounds to be synthesized with activity against CNS cancer. In addition to that, a supervised partial least squares discriminant analysis (PLS-DA) model was built and successfully applied to discriminate rutaecarpine analogues, being validated through an independent test set and considered robust to overfitting.

A reação de enaminonas com o derivado metoximetilênico do ácido de Meldrum forneceu N-adutos e/ou C-adutos das enaminonas, em rendimentos moderados a bons. A regioquímica da reação se revelou dependente do substituinte do nitrogênio da enaminona, e o C-aduto formado é precursor para 2-piridonas. A análise da difração de raios X de dois N-adutos revelou que estes adutos possuem a configuração Z-s-Z.

The reaction of acyclic enaminones with methoxymethylene Meldrum's acid afforded N-adduct and/or C-adduct of enaminones in moderate to good yields. The regiochemistry of this reaction depends on the N-amino substituent of the enaminone. The C-adduct is a precursor to 2-pyridones. X-ray analysis of two N-adducts were investigated and the Z-s-Z configuration assigned.