Mechanistic Insight into the Cu-Catalyzed C-S Cross-Coupling of Thioacetate with Aryl Halides: A Joint Experimental-Computational Study.

The mechanism of the Ullmann-type reaction between potassium thioacetate (KSAc) and iodobenzene (PhI) catalyzed by CuI associated with 1,10-phenanthroline (phen) as a ligand was explored experimentally and computationally. The study on C-S bond formation was investigated by UV-visible spectrophotometry, cyclic voltammetry, mass spectrometry, and products assessment from radical probes. The results indicate that under experimental conditions the catalytically active species is [Cu(phen)(SAc)] regardless of the copper source. An examination of the aryl halide activation mechanism using radical probes was undertaken. No evidence of the presence of radical species was found during the reaction process, which is consistent with an oxidative addition cross-coupling pathway. The different reaction pathways leading to the experimentally observed reaction products were studied by DFT calculation. The oxidative addition-reductive elimination mechanism via an unstable CuIII intermediate is energetically more feasible than other possible mechanisms such as single electron transfer, halogen atom transfer, and σ-bond methatesis.

Stereoselective one-pot synthesis of ß-alkylsulfide enol esters. Base-triggered rearrangement under mild conditions.

A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a base-triggered rearrangement. This transition metal-free multicomponent approach can be performed under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and generally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration.

Riboflavin and Eosin Y Supported on Chromatographic Silica Gel as Heterogeneous Photocatalysts.

The application of photocatalysis for organic synthesis, both in the laboratory and on an industrial scale, will depend on the achieving of good yields and the ease with which it can be applied. Selective irradiation of the photocatalyst with LED light has made it possible to activate the reactions easily, without the need for UV or heat filters. However, a common problem is the need to separate the photocatalyst from the reaction products through extraction and chromatography isolation processes. These procedures make it difficult to recover and reuse the catalyst, which is not compatible with scale-up applications. Photocatalysts attached to heterogeneous supports resulted in an alternative, which facilitates their removal and reuse. In this study, we use chromatographic silica gel as a low-cost heterogeneous support to bind photosensitizers such as Riboflavin or Eosin Y. The modified silica gel was analyzed by FTIR-ATR and diffuse reflectance UV-visible spectroscopy, thermogravimetric analysis, and optical microscopy. These hybrid materials have a suitable size for easy separation by decantation and were found to be photoactive against two photooxidation reactions. These easy-to-handle materials open the door to effective applications for photoinduced organic synthesis methods at medium to large scale.

A simple experiment to show photodynamic inactivation of bacteria on surfaces.

New suitable approaches were investigated to visualize the photodynamic inactivation (PDI) of bacteria immobilized on agar surfaces. The PDI capacities of a cationic photosensitizer (5,10,15,20-tetra(4-N,N,N-trimethylammoniumphenyl)porphyrin) and an anionic photosensitizer (5,10,15,20-tetra(4-sulfonatophenyl)porphyrin) were analyzed on a typical Gram-negative bacterium Escherichia coli following two procedures. In Experiment I, the E. coli cells were grown as lawn on agar surface containing the sensitizers spread in a small area (10 nmol in ∼0.6 cm(2) ). After irradiation with visible light (10 min, 90 milliwatts/cm(2) ), no cells were grown in the area containing the cationic porphyrin. In Experiment II, small colonies (∼2-mm diameter) of E. coli on agar were treated with a solution of sensitizer (10 nmol) and irradiated with visible light for 3 h. Overnight incubation at 37 °C shows a growth delay of E. coli colonies treated with the cationic photosensitizer. In contrast, the anionic porphyrin did not produce appreciable photodamage. These experiments could be either used in an undergraduate project for natural science advance students or used for a postgraduate practical training course. This methodology illustrates the application of PDI to treat bacteria growing as localized foci of infection.

Mechanistic insight of the photodynamic inactivation of Escherichia coli by a tetracationic zinc(II) phthalocyanine derivative.

Photodynamic inactivation (PDI) of Escherichia coli has been studied in cultures treated with zinc(II) 2,9,16,23-tetrakis[4-(N-methylpyridyloxy)]phthalocyanine (ZnPPc(+4)) to obtain insight about the mechanism of damage. This phthalocyanine is rapidly bound to cells, reaching a value of approximately 0.8 nmol/10(6) cells when the cultures were incubated with 2 microM sensitizer. After 30 min of irradiation, a 4 log decrease of E. coli survival was observed. The photocytotoxic action was investigated in plasmid and genomic DNA by electrophoretic analysis. Absorption spectroscopic studies showed that this cationic phthalocyanine interacts strongly with DNA (K(DNA)=4.7 x 10(6)M(-1)). Photocleavage of calf thymus DNA sensitized by ZnPPc(+)4 was not found even after long irradiation periods. Similar results were also observed in genomic DNA extracted from E. coli cells after PDI treatment. Modifications of plasmid DNA isolated from bacteria were only observed after long irradiation periods. However, under these conditions transmission electron microscopy of the PDI bacteria revealed an aggregation of cytoplasmic macromolecules and irregularities in cell barriers. Also, scanning electron microscopy showed a shrunken appearance in cells after PDI. Even so, release of intracellular biopolymers was not detected by absorption. On the other hand, outer and inner membranes permeabilization assays showed an increase in the permeability. Consequently, alterations in the cell membrane functionality induced by ZnPPc(+4) appear to be the major cause of E. coli inactivation upon PDI.

Photodynamic properties and photoantimicrobial action of electrochemically generated porphyrin polymeric films.

Spectroscopic and photodynamic properties of polymeric films bearing porphyrin units have been studied in both solution containing photooxidizable substrates and in vitro on Escherichia coli and Candida albicans microorganisms. The films were formed by electrochemical polymerization of 5,10,15,20-tetra(4-N,N-diphenylaminophenyl)porphyrin (H2P-film) and its complex with Pd(II) (PdP-film) on optically transparent indium tin oxide (ITO) electrodes. Absorption spectroscopic studies show the characteristic Soret and Q bands of the porphyrin in the visible region and a band at approximately 350 nm corresponding to the tetraphenylbenzidine units. Upon excitation, the H2P-film exhibits two bands of fluorescence emission from porphyrin, while it is not detected using PdP-film. The singlet molecular oxygen, O2(1Deltag), productions of these surfaces were evaluated using 9,10-dimethylanthracene in N,N-dimethylformamide. Also, the photodynamic activity was compared in solutions of L-tryptophan. Under these conditions, oxidation of these substrates takes place indicating an efficient photodynamic action of both polymeric films. In vitro investigations show that these films produce photosensitized inactivation of microbial cells in aqueous suspensions. These films exhibit a photosensitizing activity causing a approximately 3 log decrease of E. coil and approximately 2.5 log of C. albicans cellular survival after 30 min of irradiation with visible light. The photodynamic effect of the surfaces was also tested by growth delay experiments. The results indicate that porphyrins immobilized on electropolymeric films are interesting and versatile photodynamic surfaces to inactivate microorganisms in liquid suspensions.

Mechanisms of Escherichia coli photodynamic inactivation by an amphiphilic tricationic porphyrin and 5,10,15,20-tetra(4-N,N,N-trimethylammoniumphenyl) porphyrin.

The mechanistic aspects of Escherichia coli photodynamic inactivation (PDI) have been investigated in bacteria treated with 5,10,15-tris[4-(3-N,N,N-trimethylammoniumpropoxy)phenyl]-20-(4-trifluoromethylphenyl)porphyrin iodide (A3B3+) and visible light. The photosensitization activity of A3B3+ porphyrin was compared with that of 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP4+), which is an active tetracationic sensitizer to eradicate bacteria. The PDI damages on plasmid and genomic DNA were analyzed by electrophoresis. DNA photocleavage was observed after a long period of irradiation, when the bacterial cells are largely photoinactivated. Transmission electron microscopy (TEM) revealed structural changes with appearance of low density areas into the cells and irregularities in cell barriers, which could affect the normal cell membrane functionality. Also, damages on the cell-wall were not detected by scanning electron microscopy (SEM) and release of intracellular biopolymers was not found after PDI. These results indicate that the photodynamic activity of these cationic porphyrins produces DNA photodamage after a long period of irradiation. Therefore, an interference with membrane functions could be the main cause of E. coli photoinactivation upon short PDI treatments.

Photodynamic inactivation of Escherichia coli immobilized on agar surfaces by a tricationic porphyrin.

The photodynamic activity of 5,10,15-tris[4-(3-N,N,N-trimethylammoniumpropoxy)phenyl]-20-(4-trifluoromethylphenyl)porphyrin iodide (A3B3+) has been studied in vitro on a typical Gram-negative bacterium Escherichia coli immobilized on agar surfaces. The results obtained for the tricationic A3B3+ porphyrin were compared with those of 5,10,15,20-tetra(4-N,N,N-trimethylammoniumphenyl)porphyrin p-tosylate (TTAP4+), which is a standard active sensitizer established to eradicate E. coli in cellular suspension. The photobleaching of these porphyrins in solution was evaluated by decay in absorbance and in fluorescence. In both cases, a higher photostability was found for A3B3+ than for TTAP4+. Photodynamic inactivation capacities of these sensitizers were analyzed in E. coli cells immobilized on agar surfaces. Small colonies were treated with different amount of sensitizer (0-14 nmol) and irradiated with visible light for 3h. The light source used was either a projector or midday sun. The A3B3+ porphyrin produced a growth delay of E. coli colonies on agar surfaces. Similar result was obtained irradiating only one isolated colony through an optical fiber. Under these conditions, A3B3+ porphyrin shows a high activity to inactivate localized bacterial cells. The higher photodynamic activity of A3B3+ was confirmed by mechanical spreading of the colonies before treatment. This procedure produces complete inactivation of E. coli cells on the agar surface. Therefore, tricationic A3B3+ porphyrin is an interesting sensitizer with potential applications in photodynamic inactivation of bacteria growing as localized foci of infection.

Photodynamic inactivation of Escherichia coli by novel meso-substituted porphyrins by 4-(3-N,N,N-trimethylammoniumpropoxy)phenyl and 4-(trifluoromethyl)phenyl groups.

The photodynamic effect of novel cationic porphyrins, with different pattern of meso-substitution by 4-(3-N,N,N-trimethylammoniumpropoxy)phenyl (A) and 4-(trifluoromethyl)phenyl (B) groups, have been studied in both solution bearing photooxidizable substrates and in vitro on a typical Gram-negative bacterium Escherichia coli. In these sensitizers, the cationic groups are separated from the macrocycle ring by a propoxy spacer. Thus, the charges have a high mobility and a minimal influence on photophysical properties of the porphyrin. These compounds produce singlet molecular oxygen, O2(1Delta(g)), with quantum yields of approximately 0.41-0.53 in N,N-dimethylformamide. In methanol, the l-tryptophan photodecomposition increases with the number of cationic charges in the sensitizer. In vitro investigations show that cationic porphyrins are rapidly bound to E. coli cells in approximately 5 min. A higher binding was found for A3B3+ porphyrin, which is tightly bound to cells still after three washing steps. Photosensitized inactivation of E. coli cellular suspensions follows the order: A3B3+ > A44+>> ABAB2+ > AB3+. Under these conditions, a negligible effect was found for 5,10,15,20-tetra(4-sulfonatophenyl)porphyrin (TPPS4(4-)) that characterizes an anionic sensitizer. Also, the results obtained for these new cationic porphyrins were compared with those of 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin (TTAP4+), which is a standard active sensitizer established to eradicate E. coli. The photodynamic activity of TTAP4+ is quite similar to that produced by A4(4+). Studies in an anoxic condition indicate that oxygen is necessary for the mechanism of action of photodynamic inactivation of bacteria. The higher photodynamic activity of A3B3+ was confirmed by growth delay experiments. Photodynamic inactivation capacities of these sensitizers were also evaluated in E. coli cells immobilized on agar surfaces. Under these conditions, A3B3+ porphyrin retains a high activity to inactivate localized bacterial cells. Therefore, tricationic porphyrin A3B3+ is an interesting sensitizer with potential applications in photodynamic inactivation of bacteria in liquid suspensions or on surfaces.