Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal structure, and molecular modeling studies.

Cancer is one of the leading causes of death worldwide and requires intense and growing research investments from the public and private sectors. This is expected to lead to the development of new medicines. A determining factor in this process is the structural understanding of molecules with potential anticancer properties. Since the major compounds used in cancer therapies fail to encompass every spectrum of this disease, there is a clear need to research new molecules for this purpose. As it follows, we have studied the class of quinolinones that seem effective for such therapy. This paper describes the structural elucidation of a novel dihydroquinoline by single-crystal X-ray diffraction and spectroscopy characterization. Topology studies were carried through Hirshfeld surfaces analysis and molecular electrostatic potential map; electronic stability was evaluated from the calculated energy of frontier molecular orbitals. Additionally, in silico studies by molecular docking indicated that this dihydroquinoline could act as an anticancer agent due to their higher binding affinity with human aldehyde dehydrogenase 1A1 (ALDH 1A1). Tests in vitro were performed for VERO (normal human skin keratinocytes), B16F10 (mouse melanoma), and MDA-MB-231 (metastatic breast adenocarcinoma), and the results certified that compound as a potential anticancer agent. A Dihydroquinoline derivative was tested against three cancer cell lines and the results attest that compound as potential anticancer agent.

Synthesis and structural studies on (E)-3-(2,6-difluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one: a promising nonlinear optical material.

A new fluorinated chalcone (E)-3-(2,6-difluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one was synthesized in 90% yield and crystallized by a slow evaporation technique. Its full structural characterization and purity were determined by scanning electron microscopy, infrared spectroscopy, gas chromatography-mass spectrometry, 1H, 13C and 19F nuclear magnetic resonance, thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman microspectroscopy, UV-Vis absorption spectroscopy, single crystal X-ray diffraction (XRD) and Hirshfeld surface (HS) analysis. The fluorinated chalcone crystallized in centrosymmetric space group P21/c stabilized by the C-H⋯O and C-H⋯F interactions and the π⋯π contact. The crystalline environment was simulated through the supermolecule approach where a bulk with 378 000 atoms was built. The electric parameters were calculated at the DFT/CAM-B3LYP/6-311++G(d,p) level as function of the electric field frequency. The macroscopic parameters such as linear refractive index and third-order nonlinear susceptibility (χ (3)) were calculated, and the results were compared with experimental data obtained from the literature. The χ (3)-value for the chalcone crystal is 369.294 × 10-22 m2 V-2, higher than those obtained from a few similar types of molecule, showing that the chalcone crystal can be considered as a nonlinear optical material. Also, molecular theoretical calculations such as infrared spectrum assignments, frontier molecular orbital analysis and MEP were implemented, revealing that the most positive region is around the hydrogen atoms of the aromatic rings, and electrophilic attack occurs on the carbonyl group.

A comprehensive study on crystal structure of a novel sulfonamide-dihydroquinolinone through experimental and theoretical approaches.

Quinolinones and sulfonamides are moieties with biological potential that can be linked to form new hybrid compounds with improved potential. However, there are few hybrids of these molecules reported. In this sense, this work presents a structural description of a new sulfonamide-dihydroquinolinone (E)-2-(2-methoxyphenyl)-3-(3-nitrobenzylidene)-1-(phenylsulfonyl)-2,3 dihydroquinolin-4(1H)-one (DHQ). The molecular structure of DHQ was elucidated by X-ray diffraction, nuclear magnetic resonance and infrared spectroscopy, and both molecular packing and intermolecular interactions were analyzed by Hirshfeld surfaces and fingerprint maps. In addition, theoretical calculations on frontier orbitals, molecular electrostatic potential maps, and assignments were performed. The crystal packing of DHQ was found to be stabilized by a dimer through a weak C-H⋯O interaction along the c axis. Moreover, the structure is stabilized mainly by C-H⋯O and C-H⋯π interactions, since the interaction C25-H25⋯π contributes to a chain formation. The Hirshfeld normalized surface shows that the closest interactions are around the atoms linked to the dimer formation. The calculations indicate that DHQ possesses electrophilic sites near O atoms and depleted electrons around the H atoms. There is a band GAP of 3.29 eV between its frontier orbitals, which indicates that DHQ is more reactive than other analogues published.

Biodegradability of Chlorophenols in Surface Waters from the Urban Area of Buenos Aires.

Biodegradability of 2-Chlorophenol (2-CP), 3-Chlorophenol (3-CP), 4-Chlorophenol (4-CP), 2,4-Dichlorophenol (2,4-DCP) and 2,4,6 Trichlorophenol (2,4,6-TCP) has been tested in surface waters in the urban area of Buenos Aires. Samples were taken from the La Plata River and from the Reconquista and Matanza-Riachuelo basins, with a total amount of 18 sampling points. Water quality was established measuring chemical oxygen demand (COD), biochemical oxygen demand (BOD5), and both Escherichia coli and Enterococcus counts. Biodegradability was carried out by a respirometric method, using a concentration of 20 mg L-1 of chlorophenol, and the surface water as inoculum. Chlorophenols concentration in the same water samples were simultaneously measured by a solid phase microextraction (SPME) procedure followed by gas chromatography-mass spectrometry (GC-MS). 2,4-DCP was the most degradable compound followed by 2,4,6-TCP, 4-CP, 3-CP and 2-CP. Biodegradability showed no correlation with compound concentration. At most sampling points the concentration was below the detection limit for all congeners. Biodegradability does not correlate even with COD, BOD5, or fecal contamination. Biodegradability assays highlighted information about bacterial exposure to contaminants that parameters routinely used for watercourse characterization do not reveal. For this reason, they might be a helpful tool to complete the characterization of a site.

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.

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.

(E)-1-(4-Meth-oxy-phen-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one.

The title compound, C(19)H(20)O(5), was synthesized by reaction of 4-meth-oxy-acetophenone and 3,4,5-trimeth-oxy-benzaldehyde. The aromatic rings form a dihedral angle of 36.39 (7)°. Two intramolecular C-H⋯O hydrogen bonds occur. The crystal packing features weak C-H⋯O inter-actions.

Theoretical investigation of the interaction of glycerol with aluminum and magnesium phthalocyanines.

Glycerol is a byproduct produced in great quantity by biodiesel industries in transesterification reactions. Finding new applications for glycerol is a current concern of many research groups around the world. This work focuses on a theoretical investigation, at the B3LYP/6-31G* level of theory, into the possibility of using aluminum phthalocyanine (AlPc) and magnesium phthalocyanine (MgPc) in the modelling of catalysts to convert glycerol into alcohol, which has wider industrial applicability. According to our calculations there are strong interactions between the O-terminus of glycerol and the central metal atom of AlPc and MgPc. By applying the Fukui function, HSAB theory and analysis of the frontier molecular orbital, it was possible to explain the way in which glycerol interacts with AlPc and MgPc. As a result of these interactions, there is a considerable change in both electronic and geometric parameters of glycerol, which can be used in designing new strategies to convert glycerol into alcohol.

Preliminary crystallographic analysis of sugar cane phosphoribosylpyrophosphate synthase.

Phosphoribosylpyrophosphate synthases (PRS; EC 2.7.6.1) are enzymes that are of central importance in several metabolic pathways in all cells. The sugar cane PRS enzyme contains 328 amino acids with a molecular weight of 36.6 kDa and represents the first plant PRS to be crystallized, as well as the first phosphate-independent PRS to be studied in molecular detail. Sugar cane PRS was overexpressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. Using X-ray diffraction experiments it was determined that the crystals belong to the orthorhombic system, with space group P2(1)2(1)2 and unit-cell parameters a = 213.2, b = 152.6, c = 149.3 A. The crystals diffract to a maximum resolution of 3.3 A and a complete data set to 3.5 A resolution was collected and analysed.

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes

Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compund was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 æM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes.

Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 microM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.