A combined experimental and theoretical study of the supramolecular self-assembly of the natural benzopyran 2,2-dimethyl-3-hydroxy-6-acetyl-chromane and its isomeric benzofuran 10,11-dihydro-10-hydroxytremetone

Epoxidation of 4HMBA, the main metabolite of the medicinal plant Sencecionutans, produces an unstable epoxide eventually giving rise to a mixture of four derivatives, three of them previously reported as natural products. The epoxide product easily undergoes an intra-molecular attack of the phenolic hydroxyl against the epoxide group carbons to produce either a benzofuran or a chromane derivative. When dissolved in methanol-water mixture at room temperature the epoxide is completely solvolyzed to give the corresponding diol (hydrolysis) or vicinal hydroxyl-methoxy (methanolysis) derivative. All the compounds involved in the above reactions were characterized by IR, Raman, H NMR and UV–vis spectroscopies, and by mass spectrometry. Density functional theory (DFT) computations were used to optimize the structure conformations. The optimized structures were further subjected to a Natural Bond Orbital (NBO) and electrostatic potentials analysis. The crystal structures of the title compounds (for short, 3 and 4 respectively) were determined by X-ray diffraction methods. Compound 3 crystallizes in the triclinic P-1 space group with a = 6.4289 (6) Å, b = 8.7120 (6) Å, c = 10.952 (1) Å, α = 92.280 (7)°, β = 95.738 (7)°, γ = 103.973 (7)°, and Z = 2 molecules per unit cell and 4 in the monoclinic P21/c space group with a = 11.2891 (6) Å, b = 9.1902 (4) Å, c = 12.4272 (7) Å. Β = 113.689 (7)°, and Z = 4. In 3 neighboring molecules are linked to each other by OH⋯O (keto) bonds giving rise to a polymeric structure. In 4 the OH group is a bifurcate H-bond donor. It forms a weak intra-molecular OH⋯O (furan) bond and also a much stronger inter-molecular OH⋯O (keto) bond giving rise to a zig-zag polymeric structure. A detailed analysis of the solid state molecular interactions of compounds 3 and 4 has been performed using Hirshfeld surface analysis and their associated 2D fingerprint plots.Instituto de Física La Plat

A combined experimental and theoretical study of the supramolecular self-assembly of the natural benzopyran 2,2-dimethyl-3-hydroxy-6-acetyl-chromane and its isomeric benzofuran 10,11-dihydro-10-hydroxytremetone

Epoxidation of 4HMBA, the main metabolite of the medicinal plant Sencecionutans, produces an unstable epoxide eventually giving rise to a mixture of four derivatives, three of them previously reported as natural products. The epoxide product easily undergoes an intra-molecular attack of the phenolic hydroxyl against the epoxide group carbons to produce either a benzofuran or a chromane derivative. When dissolved in methanol-water mixture at room temperature the epoxide is completely solvolyzed to give the corresponding diol (hydrolysis) or vicinal hydroxyl-methoxy (methanolysis) derivative. All the compounds involved in the above reactions were characterized by IR, Raman, H NMR and UV–vis spectroscopies, and by mass spectrometry. Density functional theory (DFT) computations were used to optimize the structure conformations. The optimized structures were further subjected to a Natural Bond Orbital (NBO) and electrostatic potentials analysis. The crystal structures of the title compounds (for short, 3 and 4 respectively) were determined by X-ray diffraction methods. Compound 3 crystallizes in the triclinic P-1 space group with a = 6.4289 (6) Å, b = 8.7120 (6) Å, c = 10.952 (1) Å, α = 92.280 (7)°, β = 95.738 (7)°, γ = 103.973 (7)°, and Z = 2 molecules per unit cell and 4 in the monoclinic P21/c space group with a = 11.2891 (6) Å, b = 9.1902 (4) Å, c = 12.4272 (7) Å. Β = 113.689 (7)°, and Z = 4. In 3 neighboring molecules are linked to each other by OH⋯O (keto) bonds giving rise to a polymeric structure. In 4 the OH group is a bifurcate H-bond donor. It forms a weak intra-molecular OH⋯O (furan) bond and also a much stronger inter-molecular OH⋯O (keto) bond giving rise to a zig-zag polymeric structure. A detailed analysis of the solid state molecular interactions of compounds 3 and 4 has been performed using Hirshfeld surface analysis and their associated 2D fingerprint plots.Instituto de Física La Plat

Crystal structure, physicochemical properties, Hirshfeld surface analysis and antibacterial activity assays of transition metal complexes of 6-methoxyquinoline

Five monomeric complexes of Co(ii), Cu(ii), Ni(ii), Zn(ii) and Ag(i) with 6-methoxyquinoline (6-MeOQ) as ligand have been prepared, and their crystal structures have been determined by single X-ray diffractions. The Cu(ii), Ni(ii) and Zn(ii) complexes are formulated as M(6-MeOQ) 2 Cl 2 , completing MN 2 Cl 2 coordination spheres. On the other hand, Co(ii) and Ag(i) compounds are ionic with formulae [Ag(6-MeOQ) 2 ] + NO 3 - and H(6-MeOQ) + [Co(6-MeOQ)Cl 3 ] - (where H(6-MeOQ) + is the protonated ligand). Hirshfeld surface analysis was employed to study the intermolecular interactions in the crystal lattices and from these studies it was found that π-stacking contacts play an important role. Besides, the complexes have been characterized by FTIR, UV-visible and emission spectroscopies. The singlet oxygen production and fluorescence quantum yields were measured for all the complexes employing steady-state methodologies. Finally, the antibacterial activity of the complexes was screened against both Gram-positive and Gram-negative bacteria.Fil: Villa Perez, Cristian. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; ArgentinaFil: Ortega, I.C.. Universidad Nacional de Colombia; ColombiaFil: Vélez Macías, Andrea. Universidad Nacional de Colombia; ColombiaFil: Payán, A. M.. Universidad Nacional de Colombia; ColombiaFil: Echeverría, Gustavo Alberto. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; ArgentinaFil: Soria, Delia Beatriz. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; ArgentinaFil: Valencia Uribe, Gloria Cristina. Universidad Nacional de Colombia; Colombi

Crystal structure, physicochemical properties, Hirshfeld surface analysis and antibacterial activity assays of transition metal complexes of 6-methoxyquinoline

Five monomeric complexes of Co(ii), Cu(ii), Ni(ii), Zn(ii) and Ag(i) with 6-methoxyquinoline (6-MeOQ) as ligand have been prepared, and their crystal structures have been determined by single X-ray diffractions. The Cu(ii), Ni(ii) and Zn(ii) complexes are formulated as M(6-MeOQ) 2 Cl 2 , completing MN 2 Cl 2 coordination spheres. On the other hand, Co(ii) and Ag(i) compounds are ionic with formulae [Ag(6-MeOQ) 2 ] + NO 3 - and H(6-MeOQ) + [Co(6-MeOQ)Cl 3 ] - (where H(6-MeOQ) + is the protonated ligand). Hirshfeld surface analysis was employed to study the intermolecular interactions in the crystal lattices and from these studies it was found that π-stacking contacts play an important role. Besides, the complexes have been characterized by FTIR, UV-visible and emission spectroscopies. The singlet oxygen production and fluorescence quantum yields were measured for all the complexes employing steady-state methodologies. Finally, the antibacterial activity of the complexes was screened against both Gram-positive and Gram-negative bacteria.Centro de Química InorgánicaInstituto de Física La Plat

Diethylaminophenyl-based Schiff base Cu( ii ) and V( iv ) complexes: experimental and theoretical studies and cytotoxicity assays

An N,N,O,O donor Schiff base blocking ligand [H2L = 6,6′-((1E,1′E)-(ethane-1,2-diylbis(azaneylylidene))bis(methaneylylidene))bis(3-(diethylamino)phenol), 1] has been used to synthesize mononuclear [CuL]·H2O (2) and [VO(L)] (3) complexes. The ligand and complexes have been characterized by elemental, spectral (FTIR and UV-vis) and thermogravimetric analysis. The molecular structures of 1 and 2 have been confirmed by single crystal X-ray diffraction studies. The crystal structure of the ligand (1) indicates that the molecule is sited on a crystallographic inversion centre and the planar conformation of the salicylideneimine moiety is favored by two intramolecular O?H⋯N1 hydrogen bonds forming S(6) ring motifs. The copper(II) center in complex 2 is coordinated in a square planar fashion. The presence of an extended π-system in the complex (two chelate rings and two phenyl rings) facilitates the formation of chelate ring (CR)⋯π non-covalent interactions. DFT calculations have been performed to explore the energetic features of unconventional CR⋯π and hydrogen bonding interactions that are observed and described in the solid state of 2. Moreover, we have studied how the energy of the CR⋯π interaction is influenced by the substituent of the phenyl ring. In addition, the cytotoxic effect of the compounds has been tested against MG-63 (human osteosarcoma), HT-29 (human colorectal) and MCF7 (breast) cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Fil: Rocha, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Ruiz, María C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Echeverría, Gustavo A.. Universidad Nacional de la Plata. Facultad de Cs.exactas. Instituto de Física de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Piro, Oscar Enrique. Universidad Nacional de la Plata. Facultad de Cs.exactas. Instituto de Física de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Di Virgilio, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Frontera, Antonio. Universitat de Les Illes Balears; EspañaFil: Gil, Diego Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentin

A substituted sulfonamide and its Co (II), Cu (II), and Zn (II) complexes as potential antifungal agents

A sulfonamide 1-tosyl-1-H-benzo(d)imidazol-2-amine (TBZA) and three new complexes of Co(II), Cu(II), and Zn(II) have been synthesized. The compounds have been characterized by elemental analyses, FTIR, 1H, and 13C-NMR spectroscopy. The structure of the TBZA, and its Co(II) and Cu(II) complexes, was determined by X-ray diffraction methods. TBZA and its Co(II) complex crystallize in the triclinic P-1 space group, while the Cu(II) complex crystallizes in the monoclinic P21/c space group. Antifungal activity was screened against eight pathogenic yeasts: Candida albicans (DMic 972576), Candida krusei (DMic 951705), Candida glabrata (DMic 982882), Candida tropicalis (DMic 982884), Candida dubliniensis (DMic 93695), Candida guilliermondii (DMic 021150), Cryptococcus neoformans (ATCC 24067), and Cryptococcus gattii (ATCC MYA-4561). Results on the inhibition of various human (h) CAs, hCA I, II, IV, VII, IX, and XII, and pathogenic beta and gamma CAs are also reported.Facultad de Ciencias ExactasInstituto de Física La PlataCentro de Química Inorgánic

Synthesis, crystal structure and cytotoxicity assays of a copper(II) nitrate complex with a tridentate ONO acylhydrazone ligand. Spectroscopic and theoretical studies of the complex and its ligand

The new copper complex, [Cu(HL)(OH2)2](NO3), including the tridentate N-acyhydrazone derived from 4-hydroxy-benzohydrazide and 2-hydroxy-3-methoxybenzaldehyde, (H2L), has been synthesized and characterized in the solid state and in solution by spectroscopic (FTIR, Ra, UV–vis, EPR) methods. The results were compared with those obtained for the hydrazone ligand and complemented with computational methods based on DFT. The crystal structure of the complex has been determined by X-ray diffraction. It crystallizes in the triclinic space group with Z = 2. The Cu(II) ion is in a distorted square pyramidal environment, coordinated to a planar HL- anion acting as a tridentate ligand. The 5-fold coordination is completed with two water molecules. It is arranged in the lattice as H-bonded ribbon-like polymers that extends along the [1 2 1] crystal direction. The cytotoxicity of the complex together with that of the H2L ligand and the copper ion were evaluated in vitro against five different human cancer cell lines namely A549 (lung), MG-63 (bone), MCF-7 and MDA-MB-231 (breast) and Jurkat (leukemia). The copper complex inhibits the cell viability in a dose dependent manner with a greater potency than the H2L ligand and the free copper ion displaying even higher antitumor activity than the well-known anticancer metallodrug cisplatin.CONICET (PIP 11220130100651CO and PIP 0034), UNLP (111/X673) and ANPCyT (PICT 2014-2223) of Argentina. Consejería de Educación CyL and FFEDER BU076U16, BU022G18 and Ministerio de Economía y Competitividad CTQ2016-75023-C2-1-P and CTQ2015-70371-REDTMetDrugs Network (Spain

Cu(ii) and Zn(ii) complexes with a poly-functional ligand derived from o-vanillin and thiophene. Crystal structure, physicochemical properties, theoretical studies and cytotoxicity assays against human breast cancer cells

The interaction of a poly-functional ligand derived from o-vanillin and 2-thiophenemethylamine (oVATPNH2) with transition metal ions Cu(II) and Zn(II) leads to the formation of stable coordination compounds, namely [Cu(oVATPNH2)2] and [Zn(oVATPNH2)2]. Their crystal structures have been determined by X-ray diffraction methods. Two molecules of the deprotonated ligand acting in a bidentate fashion build a nearly square planar environment around Cu(II) and a distorted tetrahedral coordination arrangement for Zn(II). The complexes were characterized by spectroscopic techniques, including solid state FTIR, Raman, EPR and diffuse reflectance and solution UV-vis and EPR. Their thermal behavior has been analyzed by means of TGA and DTA. DFT theoretical studies, using computational methods based on DFT, were employed to assist the interpretation and assignment of spectroscopic data. Cytotoxicity assays against two human breast cancer cell lines, namely MCF-7 and MDA-MB-231, revealed an enhancement of the effectiveness of the complexes as compared with both the ligand and the free metal ions. The results for the copper compound are promising, as its cytotoxic effect was stronger than the reference metallodrug cisplatin in both cancer cell lines tested.CONICET-CCT-La Plata (PIP 0651 and 0034), ANPCyT (PICT 2016-1574) and UNLP (11/X-473) (Argentina) and also by Consejerı´a de Educacio´n CyL and FFEDER BU076U16, BU022G18 and Ministerio de Economı´a y Competitividad CTQ2016-75023-C2-1-P and CTQ2015-70371- REDT MetDrugs Network (Spai

Supramolecular self-assembly of a new multi-conformational Schiff base through hydrogen bonds: Crystal structure, spectroscopic and theoretical investigation

The compound 4-(4-dimethylaminobenzylidene)aminoacetophenone was synthesized by condensation of 4-aminoacetophenone and 4-(dimethylamino) benzaldehyde in ethanol. This compound was characterized by CG-MS, infrared, Raman, UVeVis, 1H and 13C NMR spectroscopy. The crystal structure was solved by single-crystal X-ray diffraction methods. The crystallographic data reveals that there are four independent molecules per asymmetric unit, that mainly differ from one another in rotations around the σ-bond of the azomethine N-atom with the phenyl ring. A detailed analysis of the intermolecular interactions in the four conformers of the compound has been performed using Hirshfeld surfaces and their associated two-dimensional fingerprint plots. The optimized geometrical parameters and calculated spectroscopic features obtained by quantum chemical calculations at B3LYP method show a very good agreement with the experimental data. Moreover, Natural Bond Orbital (NBO) analysis confirms the strong hyper-conjugative LP N(n1) → σ* C(n9)–H interaction between the lone pair located in the N-atom of the azomethine group and the C–H bond. Liquid crystalline properties of the Schiff base were studied by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and Powder X-ray diffraction techniques. Mesomorphic behaviour was observed in this unsymmetrical azomethine. Based on POM and DSC measurements, the hexatic Smetic B phase was detected.Facultad de Ciencias ExactasCentro de Química InorgánicaInstituto de Física La Plat

Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion

Introduction: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver ischemia or cirrhosis. Our objectives were to establish whether endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock. Methods: After anesthesia, 12 sheep were subjected to hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to lipopolysaccharide (LPS) (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a three-hour study period. After 60 minutes of shock, animals were fluid resuscitated to normalize mean arterial pressure. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. Both groups included an intravenous bolus followed by serial blood sampling to draw a curve using the least squares method. Results: Significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 (3.1 to 6.7) versus 1.8 (1.5 to 3.7) mmol/L), increasing to 10.2 (7.8 to 12.3) mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. No within-group difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (point D: 915 (773 to 1,046) versus 655 (593 to 1,175) ml/min), mitochondrial respiration, liver enzymes or sorbitol clearance was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 (30 to 180) versus 1,212 (743 to 2,116) ml/min, P <0.01; point D: 113 (65 to 322) versus 944 (363 to 1,235) ml/min, P <0.01). Conclusions: Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion