Barbellatanic acid, a new antitrypanosomal pseudo-disesquiterpenoid isolated from Nectandra barbellata, displayed interaction with protozoan cell membrane.

As part of our ongoing studies involving the discovery of new natural prototypes with antiprotozoal activity against Trypanosoma cruzi from Brazilian plant species, the chromatographic fractionation of hexane extract from leaves of Nectandra barbellata afforded one new pseudo-disesquiterpenoid, barbellatanic acid. The structure of this compound was elucidated by NMR and HR-ESIMS data analysis. Barbellatanic acid displayed a trypanocidal effect with IC50 of 13.2 µM to trypomastigotes and no toxicity against NCTC cells (CC50 > 200 µM), resulting in an SI value higher than 15.1. The investigation of the lethal mechanism of barbellatanic acid in trypomastigotes, using both fluorescence microscopy and spectrofluorimetric analysis, revealed a time-dependent permeation of the plasma membrane. Based on these results, this compound was incorporated in cellular membrane models built with lipid Langmuir monolayers. The interaction of barbellatanic acid with the models was inferred by tensiometric, rheological, spectroscopical, and morphological techniques, which showed that this compound altered the thermodynamic, viscoelastic, structural, and morphological properties of the film. Taking together, these results could be employed when this prodrug interacts with lipidic interfaces, such as protozoa membranes or liposomes for drug delivery systems.

Interaction of isolinderanolide E obtained from Nectandra oppositifolia with biomembrane models.

A long-tail lactone, named isolinderanolide E, was obtained from Nectandra oppositifolia and incorporated in Langmuir monolayers of dipalmitoyl-phosphoethanolamine (DPPE) as a model of microbial membranes. The compound was dissolved in chloroform and mixed with DPPE to provide mixed solutions spread on the air-water interface. After solvent evaporation, mixed monolayers were formed, and surface pressure-area isotherms, dilatational rheology, Brewster angle microscopy (BAM), and infrared spectroscopy were employed to characterize the prodrug-membrane interactions. Isolinderanolide E expanded DPPE monolayers, denoting repulsive interactions. At 30 mN/m, the monolayer presented higher viscoelastic and in-plane elasticity parameters and an increased ratio of all-trans/gauche conformers of the alkyl chains, confirming molecular order. Morphology of the monolayer was analyzed by BAM, which revealed a more homogeneous distribution of Isolinderanolide E along the DPPE monolayer than the prodrug directly spread at the interface, which tends to aggregate. A molecular model proposing the molecular orientation of the amphiphilic drug is presented and explained by the distortion of the alkyl chains as well as by viscoelastic changes. In conclusion, the prodrug changes the thermodynamic, rheological, morphological, and structural properties of the DPPE monolayer, which may be essential to understand, at the molecular level, the action of bioactives in selected membrane models.

A bactericide peptide changing the static and dilatational surface elasticity properties of zwitterionic lipids at the air-water interface: Relationship with the thermodynamic, structural and morphological properties.

In this paper, we studied how different hydrophilicity degrees of the polar groups of the lipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoyl phosphatidylethanolamine (DPPE) influence the interaction of the antibiotic peptide vancomycin (VC), affecting the physicochemical properties of the monolayers, including thermodynamic, rheological, structural and morphological ones. Lipid Langmuir monolayers were prepared at air-water interfaces with VC aqueous solution as subphase and characterized with tensiometry, Brewster angle microscopy, infrared spectroscopy, dilatational, and interfacial shear rheology. The presence of PC or PE groups as polar head groups of the phospholipid monolayers modulated the interaction of VC adsorbing from the aqueous subphase since for DPPC, vancomycin condenses the monolayer, making it less stable, fluid, and more disordered. In contrast, for DPPE, vancomycin expands the monolayer, making it more stable, keeping the compressibility, and leading to the formation of interfacial aggregates, which are not observed for DPPC. We concluded thatelectrostatic interactions induced the insertion of the peptide into the polar heads of the monolayers (DPPE), while hydrophobic interactions, in addition to ion-dipole interactions, induced the adsorption of the peptide onto the polar head of the monolayers (DPPC).

Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface.

In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 ± 1.7 µM), similar to the positive control benznidazole (IC50 of 18.7 ± 4.1 µM), reduced mammalian cytotoxicity (CC50 > 200 µM), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, submitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level.

Interfacial vibrational spectroscopy and Brewster angle microscopy distinguishing the interaction of terpineol in cell membrane models at the air-water interface.

In this paper, γ-terpineol, a known monoterpene with biological activity, including in lipidic interfaces, was incorporated in Langmuir monolayers of selected phospholipids as a model for cellular membranes. Surface pressure-area isotherms showed that selected amounts of γ-terpineol expand DPPC and DPPE monolayers and decreased the monolayer elasticity, confirming the lipid/compound interaction. Characterization with vibrational spectroscopy and Brewster angle microscopy pointed that γ-terpineol adsorbs on the polar heads of the phospholipids, affecting the gauche conformations of the aliphatic chains, and different patterns were observed for DPPC and DPPE monolayers, indicating a characteristic molecular accommodation of γ-terpineol along the polar head of the phospholipids. Therefore, distinctive interactions with DPPC and DPPE could be observed regarding the incorporation of γ-terpineol with each lipid, leading to particular molecular arrangements at the air-water interface and pointing the modulation of the interaction according to the chemical composition of the monolayer.

Crystal structure at 100†K of bis-[1,2-bis-(di-phenyl-phosphan-yl)ethane]-nickel(II) bis-(tri-fluoro-methane-sulfonate): a possible negative thermal expansion mol-ecular material.

In the title salt, [Ni(C26H24P2)2](CF3SO3)2 or [Ni(dppe)2]2+·(OTf-)2 [dppe = 1,2-bis-(di-phenyl-phosphan-yl)ethane and OTf- = tri-fluoro-methane-sulfonate], the Ni atom (site symmetry ) has a square-planar geometry with the bidentate ligands chelating the metal. As a result of the steric hindrance of the phenyl rings, the counter-ions are blocked from the metal coordination sphere. The dynamic disorder of the anion existing at 296 K is reduced at 100 K and based on these two temperatures, negative thermal expansion behaviour is observed.

Lipids mediating the interaction of metronidazole with cell membrane models at the air-water interface.

In this paper, metronidazole, a known compound with microbicide effect, was incorporated in Langmuir monolayers of selected phospholipids in order to investigate the interactions of this compound with cell membrane models by using tensiometric, spectroscopic and morphological techniques. Surface pressure-area isotherms showed that selected amounts of metronidazole condense DPPC monolayers, but expand DPPE monolayers. Vibrational spectroscopy pointed that metronidazole adsorbs on the polar heads of the phospholipids, affecting the gauche conformations of the aliphatic chains, and different patterns were observed for DPPC and DPPE monolayers containing metronidazole in terms of Brewster angle microscopy images. As a result, distinctive interactions with DPPC and DPPE could be pointed regarding the incorporation of metronidazole with each lipid, leading to particular molecular arrangements at the air-water interface.

Autoensamblaje de un cuadrado supramolecular a partir del complejo [Ni(dppe)(TOF)2] con 4,4'-bipiridina / Self-assembly of a supramolecular square between [Ni(dppe)(TOF)2] and 4,4'-bipyridine / Automontagem de um quadrado supra-molecular a partir do complexo [Ni(dppe)(TOF)2] com 4,4'-bipiridina

El interés principal de esta investigación, es contribuir al desarrollo y comprensión de la química supramolecular y de las arquitecturas moleculares, construidas mediante el autoensamblaje de entidades complementarias. Por lo cual se realizó, la síntesis y caracterización (UV, FT-IR, Raman, análisis elemental, RMN ¹H, 31P, 19F, COSY ¹H-¹H) de un cuadrado supramolecular de níquel (II) [7]. Este proceso se realizó, a partir de la síntesis del complejo inicial: [Ni(dppe)Cl2] [3], el cual fue sintetizado entre el cloruro de níquel [1] y difenilfosfino etano (dppe) [2]. Luego se realizó la síntesis del complejo de interés: [Ni(dppe)(TOF)2 ] [5], entre el complejo [3] y el trifluorometanosulfonato de plata (Ag-TOF) [4]. Finalmente el proceso de autoensamblaje se realizó entre el complejo [5] y el ligando orgánico 4,4'-bipiridina [6], los cuales actúan como vértice y arista respectivamente, en la estructura del cuadrado. De acuerdo a los diferentes análisis realizados, se encontró que el autoensamblaje generó una única especie supramolecular, siendo la especie cuadrada, la estructura termodinámica más probable.

The main interest of this research is to contribute to the development and understanding of supramolecular chemistry and molecular architectures, which are constructed by the self-assembly of supramolecular entities. Therefore, the synthesis and characterization (IR, UV, ¹H NMR, 31P, 19F, ¹H-¹H COSY) of a nickel (II) supramolecular square [7] was performed through the synthesis between nickel chloride [1]and diphenylphosphinoethane (dppe) [2] to form the precursor complex [Ni(dppe)Cl2] [3]. This was followed by the synthesis of the complex of interest, [Ni(dppe)(TOF)2] [5], using the precursor and silver trifluoromethanesulfonate (Ag-TOF). Finally, the self-assembly was performed between the complex [1,2-bis (diphenylphosphinoethane) bistriflatonickel(II)] [Ni(dppe)(OSO2CF3)2] [5] and the organic ligand 4,4'-bipyridine [6], which act as vertex and edge, respectively. According to various analyses, it was found that the self-assembly generated only one supramolecular species; a square is the most probable thermodynamic structure.

O interesse principal de esta investigação foi contribuir ao desenvolvimento e entendimento da química supra-molecular e as arquiteturas moleculares, construídas mediante a automontagem de entidades complementarias. Assim, se realizou, a sínteses e caracterização (UV, FT-IR, Raman, análises elementar, RMN ¹H, 31P, 19F, COSY ¹H-¹H) de um quadrado supra-molecular de níquel (II) [7]. Este processo se realizou, a partir da sínteses do complexo inicial: [Ni(dppe)Cl2] [3], o cual foi sintetizado entre o cloreto de níquel [1] e difenilfosfino etano (dppe) [2]. De seguida, foi realizada a sínteses do complexo de interesse: [Ni(dppe)(TOF)2] [5], entre o complexo [3]e o trifluorometanosulfonato de prata (Ag-TOF) [4]. Finalmente, o processo de automontagem, foi realizado entre o complexo [5] e o ligando orgânico 4,4'-bipiridina [6], os quais atuam como vértice y arista na estrutura do quadrado, respectivamente. De acordo aos diferentes análises realizados, se encontrou que a automontagem originou uma única espécie supra-molecular, sendo a espécie quadrada, a estrutura termodinâmica mais provável.