Hamilton B. Napolitano

Synthesis, characterization, and third-order nonlinear optical properties of a new neolignane analogue

Recently, a wide number of pharmacological activities, such as anti-leishmanial, antioxidant and antitumor, have been discovered for neolignane analogues. To provide a view of the non-linear optical behavior of the third order of the crystal 2-(4-nitrophenoxy)-1-phenylethanone (NPH-PE) in the static and dynamic cases, we calculated its linear polarizability (α) and second hyperpolarizability (γ). We used a new supermolecule approach combined with an iterative electrostatic system whose atoms of the neighboring molecules are represented by point charges. A comprehensive investigation of NPH-PE is reported by single crystal X-ray diffraction and FT-Raman and NMR spectroscopy. In addition, a combination of density functional theory (DFT) with the CAM-B3LYP functional and the 6-311+G(d) basis set was used to calculate the molecular structure optimization, the vibrational frequencies, and the intensity of the vibrational bands. Concerning the values of the third-order optical nonlinearity, the second hyperpolarizability of the embedded molecule showed an increase of 125 058% in comparison with the corresponding result in the static case.

Biological and structure-activity evaluation of chalcone derivatives against bacteria and fungi

O presente trabalho descreve as atividades antibacterianas e antifungicas de diversas chalconas obtidas diretamente atraves da condensacao aldolica tipo Claisen-Schmidt das quais se determinou a concentracao inibitoria minima frente a diferentes microrganismos (bacterias Gram-positivas e Gram-negativas e fungos). Estruturas no estado solido cristalino de sete chalconas foram determinadas por analise de difracao de raios X (XRD). Estudos quimiometricos foram realizados com intuito de identificar uma potencial relacao entre estrutura e atividade.

How genomics is contributing to the fight against artemisinin-resistant malaria parasites

Plasmodium falciparum, the malignant malaria parasite, has developed resistance to artemisinin, the most important and widely used antimalarial drug at present. Currently confined to Southeast Asia, the spread of resistant parasites to Africa would constitute a public health catastrophe. In this review we highlight the recent contributions of genomics to our understanding how the parasite develops resistance to artemisinin and its derivatives, and how resistant parasites may be monitored and tracked in real-time, using molecular approaches.

Synthesis, characterization, and computational study of the supramolecular arrangement of a novel cinnamic acid derivative

In this work, we present the synthesis, characterization, and computational study of the supramolecular arrangement of a new cinnamic acid derivative: ethyl-(2E)-3-(4-hydroxy-3,5-dimethoxyphenyl)-prop-2-enoate (EHD). Single crystals of EHD were obtained using ethyl ether as solvent and a slow evaporation technique. Its crystallographic structure, derived from X-ray diffraction experiments, includes a disordered water molecule on the EHD supramolecular structure. This water molecule participates in four O–H···O hydrogen bonds, which are arranged as a centrosymmetric H-bond array with the water at the center. Electronic and structural properties of the isolated EHD molecule and of the EHD molecule in the presence of one water molecule were calculated at the B3LYP/6-311++G(2d,2p) level of theory. These calculations show that the HOMO–LUMO energy gap of EHD decreases upon the introduction of the water molecule, suggesting that EHD becomes a stronger electron acceptor. These results indicate that the water molecule helps to stabilize the crystal structure in this system containing unequal numbers of acceptor and donor atoms. The supramolecular synthon involving the disordered water molecule and the supramolecular features presented here provide new possibilities in the design of functional materials and should also help us to gain a deeper understanding of the processes by which molecules recognize biological targets.

A novel dihydrocoumarin under experimental and theoretical characterization

Coumarins are natural and synthetic active ingredients widely applied in diverse types of medicinal treatments, such as cancer, inflammation, infection, and enzyme inhibition (monoamine oxidase B). Dihydrocoumarin compounds are of great interest in organic chemistry due to their structural versatilities and, as part of our investigations concerning the structural characterization of small molecules, this work focuses on crystal structure and spectroscopic characterization of the synthesized and crystallized compound 4-(4-methoxyphenyl)-3,4-dihydro-chromen-2-one (C16H14O3). Additionally, a theoretical calculation was performed using density functional theory to analyze the sites where nucleophilic or electrophilic attack took place and to examine the molecular electrostatic potential surface. Throughout all of these calculations, both density functional theory and Car–Parrinello molecular dynamics were performed by fully optimized geometry. The spectroscopic analysis indicated the presence of aromatic carbons and hydrogen atoms, and also the carbonyl and methoxy groups that were confirmed by the crystallographic structure. The C16H14O3 compound has a non-classical intermolecular interaction of type C–H⋅⋅⋅O that drives the molecular arrangement and the crystal packing. Moreover, the main absorbent groups were characterized throughout calculated harmonic vibrational frequencies. Also, natural bond orbital analysis successfully locates the molecular orbital with π-bonding symmetry and the molecular orbital with π* antibonding symmetry. Finally, the gap between highest occupied and lowest unoccupied molecular orbitals implies in a high kinetic stability and low chemical reactivity of title molecule.

DFT investigation on hydrogen bonding in cyclohexane-1,2,3,4,5-pentol crystal structure

The cyclohexane-1,2,3,4,5-pentol,C6H12O5 is a natural product extracted from Adiscanthus fusciflorus (Rutaceae). It crystallizes in the non-centrosymmetric space group P21 with one molecule in the asymmetric unit and it has been postulated to have at least ten strong O-H…O intermolecular interactions, two per each OH group of one molecule, producing a three-dimensional network. The crystal packing is defined by O-H…O hydrogen bonds. Due to the crucial role of the hydrogen bonds in defining the crystal structure, theoretical investigations in the gas phase have been carried out in order to explore the hydrogenbonding mechanism through a quantitative Kohn-Sham molecular orbital and corresponding energy decomposition analyses. The existence of a covalent component in hydrogen bonds has been proved which originates from donor-acceptor orbital interactions in the σ-electron system. Our analyses show that the stability of the crystal structure is enhanced by the formation of two hydrogen bonds with two vicinal molecules for each OH group in C6H12O5 molecule with respect to the formation of one or two hydrogen bonds with only one vicinal molecule, thus confirming the proposed existence of ten strong O-H…O intermolecular interactions for each molecule in the asymmetric unit. The presence of a cooperativity effect is observed which originates from a charge separation induced by the two vicinal molecules hydrogenbonded to an OH group in C6H12O5 molecule.

Structural insights into a novel anticancer sulfonamide chalcone

Natural products have stood out due to their wide range of biological activities. Among the various naturally occurring classes, we can highlight chalcones, sulfonamides and hybrid compounds formed by both. Although many pharmacological activities of these classes of compounds are known, new ones have arisen lately and require detailed structural and biological analyses. Herein, we report the synthesis and structural elucidation of a novel sulfonamide chalcone 2,5-dichloro-N-{3-[(2E)-3-(4-nitrophenyl)prop-2-enoyl]phenyl}benzenesulfonamide (BSC) by Single Crystal X-ray Diffraction and spectroscopy analysis (Infrared, NMR and Mass Spectroscopy). Topology was determined through Hirshfeld surface analysis and the electrostatic potential map, while the energy of frontier molecular orbitals was used to evaluate the stability of BSC. Additionally, the cytotoxicity of the title compound was evaluated through the MTT colorimetric method. We show that the BSC compound has a planar conformation in its chalcone portion, which is further corroborated by the low angle between the aromatic rings (5.23°). In addition, intermolecular interactions of type C–H⋯O and N–H⋯O make up a dimeric supramolecular arrangement. An inverse virtual screening approach allowed identifying potential biological applications for BSC, which indicated that BSC might interact with the binding sites of RARα and RARβ. Consequently, BSC was experimentally evaluated against three cancer cell lines, and was shown to hold potent anticancer activity. In addition, a cytotoxic effect was observed for all strains, which was more pronounced for HCT-116, a colon cancer cell line.

Conformation analysis of a novel fluorinated chalcone

Chalcones are an important class of natural compounds that exhibit numerous biological activities. In this paper, we report the synthesis and characterization of new fluorinated chalcone (FCH). The molecular geometry was determined by means of single crystal X-ray diffraction, and density functional theory (DFT) at B3LYP, M06-2X functionals and MP2 method, with the 6-311++G(d,p) basis set, was applied to optimize the ground state geometry and to study the molecular conformational stability. The molecular electrostatic potential (MEP) was also investigated at the same level of theory in order to identify and quantify the possible reactive sites. The FCH crystallizes in the centrossymmetric space group P1¯

Redetermination and comparative structural study of isopimpinellin: a new inhibitor against the Leishmania APRT enzyme

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