Diamino acid derivatives of PpIX as potential photosensitizers for photodynamic therapy of squamous cell carcinoma and prostate cancer: In vitro studies

Photodynamic therapy (PDT) is an alternative treatment modality involving light activated drugs, called photosensitizers (PSs), to treat cancer and non-cancerous conditions. The search for new compounds which might become effective PSs is the major direction for PDT development. In the present work we have studied the dark toxicity, intracellular localization and photodynamic properties of four potential, water soluble, second generation PSs – PP(Arg)₂, PP(Ser)₂Arg₂, PP(Ala)₂Arg₂, PP(Phe)₂Arg₂, all diamino acid derivatives of protoporphyrin IX. Human prostate cancer (DU-145) and squamous carcinoma (A431) cells were used as experimental model.Among investigated compounds PP(Ser)₂Arg₂ exhibited the lowest dark toxicity and the highest PDT effectiveness towards both cell lines. Fluorescence microscopy revealed the time-dependent changes in intracellular localization of the PS which were related to the phototoxicity. The results show that PP(Ser)₂Arg₂ may be a potential PS for PDT.     

Voltammetric study of gold-supported lipid membranes in the presence of perfluorooctanesulphonic acid

The effect of perfluorooctanesulphonic acid (PFOS) on lipid membranes was studied using supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer as the model membrane. Phospholipid bilayer was deposited on gold electrode using a combination of the Langmuir–Blodgett and Langmuir–Schaefer (LB/LS) techniques. Electrodes were modified with two different types of membranes: DMPC bilayers initially containing PFOS and pure DMPC bilayers later exposed to the PFOS solutions. Such approach allowed studying both the changes in membrane characteristic imposed by the perfluorinated compound present in the model membrane and the process of its incorporation into the membrane. Studies with anticancer drug doxorubicin revealed that PFOS inhibits drug transport through the phospholipid bilayer and its effect can be compared to that of cholesterol. Moreover, the different trends observed in the changes in electron transfer rate constant (k_s) calculated for ferricyanides and in peak current of hexaamineruthenium chloride showed that electrostatic interactions between electroactive probes and PFOS molecules incorporating into phospholipid bilayers play an important role and should be taken into account while explaining the interactions of perfluorooctanesulphonic acid with model biological membranes.     

Deformation of gradient shape as a result of preferential adsorption of solvents in mixed mobile phases

Gradient elution has been studied in typical normal and reversed-phase systems. Deformations of gradient profiles have been evidenced as a result of preferential adsorption of modifiers of the mobile phase. This phenomenon was pronounced in the normal-phase system, for which gradient profiles deviated significantly from those programmed. This influenced the retention and shapes of band profiles of the eluting solute. Hence, in order to predict gradient propagation correctly the adsorption equilibrium of modifiers has been quantified. Moreover, at low modifier content, deformations of band profiles of the solute has been registered as a result of the competitive adsorption in the system solute-modifier. This effect has been predicted by a competitive adsorption model. For the reversed-phase systems the influence of the modifier adsorption on gradient propagation was insignificant for typical mobile phases investigated. Therefore, the work has been focused on gradient predictions in the normal-phase system.     

N,N'-carbonyldiimidazole-mediated cyclization of amino alcohols to substituted azetidines and other N-heterocycles

Amino alcohols are important synthons for N-heterocycles. We have developed an efficient method to activate hydroxyl groups, which avoids the use of toxic reagents and tolerates a wide variety of functional groups. Our strategy has been applied to the synthesis of functionalized p-methoxyphenyl-protected azetidines, pyrrolidines, and piperidines. The required amino alcohols were synthesized according to an optimized proline-catalyzed Mannich protocol. An azetidine analogue of ezetimibe was synthesized to demonstrate the potential for the synthesis of drug-like molecules.     

Modulation of humoral immune response to oral BCG vaccination by Mycobacterium bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults

We hypothesize that the energy strategy of a cell is a key factor for determining how, or if, the immune system interacts with that cell. Cells have a limited number of metabolic states, in part, depending on the type of fuels the cell consumes. Cellular fuels include glucose (carbohydrates), lipids (fats), and proteins. We propose that the cell's ability to switch to, and efficiently use, fat for fuel confers immune privilege. Additionally, because uncoupling proteins are involved in the fat burning process and reportedly in protection from free radicals, we hypothesize that uncoupling proteins play an important role in immune privilege. Thus, changes in metabolism (caused by oxidative stresses, fuel availability, age, hormones, radiation, or drugs) will dictate and initiate changes in immune recognition and in the nature of the immune response. This has profound implications for controlling the symptoms of autoimmune diseases, for preventing graft rejection, and for targeting tumor cells for destruction.     

HERFD XAS/ATR-FTIR batch reactor cell

An autoclave reactor was modified to perform simultaneously high energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD XAS) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy measurements without altering the reactor design. This operando cell allows one to follow changes in the electronic and geometric structure of the catalyst with HERFD XAS and relate them to the simultaneously detected activity and reaction species with ATR-FTIR formed during the reaction in the liquid phase. The capability of the cell is demonstrated by two studies. The first shows the reduction of Au/CeO(2) precursors in different solvents. The second shows that mainly Au(0) is present in the hydrogenation of nitrobenzene over Au/CeO(2).     

Biocompatible titania hydrogels with chemically triggered release of a photosensitive dye

5,10,15,20-Tetrakis(4-sulfonatophenyl)porphyrin was entrapped into biocompatible hydrogels formed by self-assembling micelles of the titanium dioxide prepared by hydrolysis of titanium ethoxide modified with triethanolamine (TEA). The materials were characterized by their optical and photosensitive properties. The immobilization led to changes of the absorption spectra of the dye and decreased its molar absorption coefficient. The TiO₂ matrix did not degrade the entrapped porphyrin upon u.v. irradiation. The formation of TEA–titanium(IV) chelates facilitated a controlled and triggered release of the immobilized dye from the hydrogels in lactate and citrate buffers. The released dye prolonged the sterility of citrate–phosphate buffer and its illumination with visible light inhibited growth of Aspergillus niger.     

Copper-catalyzed sulfenylation of pyrroles with disulfides or thiols: directly synthesis of sulfenyl pyrroles

We present here the synthesis of sulfenyl pyrroles by copper-catalyzed sulfenylation of pyrroles with organic disulfides or thiols. The direct sulfenylation of pyrroles with organic disulfides has been accomplished in the presence of 3 mol % of CuI in DMSO at 110 °C under air atmosphere. In the other hand, sulfenylation of pyrroles with thiols were performed in the same solvent and temperature, however it is necessary 5 mol % of CuI and nitrogen atmosphere. Using these protocols we were able to produce 2-sulfenyl pyrroles in good to excellent yields and with high selectivity without use of any ligand or additive.     

Development of a stereoselective Ugi reaction starting from an oxanorbornene β-amino acid derivative

We have synthesised a novel oxanorbornene β-aminoacid derivative and employed it in a stereoselective Ugi reaction. Hypothesis regarding the mechanism taking place during the reaction have been made and validated through the determination of the relative and absolute configuration of the Ugi adducts. Use of the correct choice of solvents can increase stereoselection. The resulting bicyclic peptidomimetics can be used as a novel class of pluripotent substrates to be elaborated according to the synthetic strategies previously elaborated in our laboratories.     

Solid-state syntheses of coordination polymers by thermal conversion of molecular building blocks and polymeric precursors

The syntheses and crystal structures of a mononuclear cadmium complex and five novel coordination polymers based on 1,2,4-triazolyl benzoates are presented. The compounds (∞)(3)[Cd(H-Me-trz-pba)(2)] (2), (∞)(3)[Cd(Me-3py-trz-pba)(2)] (4), and (∞)(3)[Zn(H-Me-trz-pba)(2)] (6) can be obtained by solvothermal synthesis or simple heating of the starting materials in appropriate solvents, and are also accessible by thermal conversion of the complex [Cd(H-Me-trz-pba)(2)(H(2)O)(4)] (1), the one-dimensional (1D) coordination polymer (∞)(1)[Cd(Me-3py-trz-pba)(2)(H(2)O)(2)]·H(2)O (3), and the porous three-dimensional (3D) framework (∞)(3)[Zn(H-Me-trz-pba)2]·4H(2)O (5), respectively. The driving force for these conversions is the formation of thermally stable, nonporous, crystalline 3D coordination polymers. The structural transformations are accompanied by the loss of water and reveal significant changes of the coordination spheres of the metal ions caused by a rearrangement of the triazolyl benzoate ligands. Compounds 2, 4, 5, and 6 exhibit 4- and 5-fold interpenetration of diamondoid networks (dia) and are thermally stable up to 380 °C.