Reduction-triggered Disassembly of Organic Cationic Nanorods Produces a Cysteine Protease Mimic (Miravet et†al.).

The emergence of catalytic activity associated with a disassembly process is reported, reminiscent of complex biological systems. A cystine derivative with pendant imidazole groups self-assembles into cationic nanorods in the presence of the cationic surfactants cetylpyridinium chloride (CPC) or cetyltrimethylammonium bromide (CTAB). Disulfide reduction triggers nanorod disassembly and the generation of a simple cysteine protease mimic, which shows a dramatically improved catalytic efficiency in the hydrolysis of p-nitrophenyl acetate (PNPA).

Photodynamic inactivation of Staphylococcus aureus in the presence of aggregation-prone photosensitizers based on BODIPY used at submicromolar concentrations.

Two new brominated BODIPYs (1 and 2) bearing amino acid-based chains (l-valine for 1, and dimethyl-l-lysine for 2) were synthesized and characterized. In organic solvents, 1 and 2 were fully soluble and showed the photophysical properties expected for brominated BODIPY dyes, including efficient generation of singlet oxygen (1O2), upon irradiation. In contrast, in aqueous media, both compounds were prone to aggregation and the photo-induced generation of 1O2 was halted. Despite the lack of generation of this reactive species in aqueous media (in cuvette), both 1 and 2 have positive antimicrobial Photodynamic Inactivation (aPDI) effect. The activity against gram-positive Staphylococcus aureus and gram-negative Escherichia coli was determined through the inactivation curves, with a total energy dose of 5.3 J/cm2 (white light LED used as an energy source). Compound 2 was highly active against both gram-positive and gram-negative bacteria (3 log CFU/mL reduction was obtained at 0.16 µM for S. aureus and 2.5-5.0 µM for E. coli), whereas 1 was less effective to kill S. aureus (3 log CFU/mL at 0.32 µM) and ineffective for E. coli. The higher efficiency of 2, as compared to 1, to reduce the population of bacteria, can reside in the presence of a protonatable residue in 2, allowing a more effective interaction of this molecule with the cell walls of the microorganisms. In order to explain the lack of reactivity in pure aqueous media (in cuvette) and the contrasting good activity in the presence of bacterial cells it can be hypothesized that upon interaction with the walls of the microorganisms, the aggregated photosensitizers suffer a disaggregation process restoring the ability to generate 1O2, and hence leading to efficient photodynamic activity against these pathogenic microorganisms, in agreement with the similar effect observed recently for porphyrinoid photosensitizers.

Glutathione-responsive molecular nanoparticles from a dianionic bolaamphiphile and their use as carriers for targeted delivery.

The formation in aqueous media of molecular nanoparticles from a bolaamphiphile (SucIleCsa) incorporating a disulfide moiety is described. The particles can be loaded efficiently with the lipophilic mitochondrial marker DiOC6(3), quenching its fluorescence, which is recovered upon reductive particle disassembly. DiOC6(3) transport into human colorectal adenocarcinoma cells (HT-29) is demonstrated using flow cytometry and confocal scanning fluorescence microscopy. A significant increase in intracellular fluorescence is observed when the cells are stimulated to produce glutathione (GSH). These new molecular nanoparticles can be considered a theranostic tool that simultaneously achieves targeted delivery of lipophilic substances and signals high levels of GSH.

Photoreversible formation of nanotubes in water from an amphiphilic azobenzene derivative.

An anionic azobenzene-appended derivative of L-ValylGlycine self-assembles into nanotubes in water. Irradiation with 365 nm light provokes trans-cis isomerization of the azobenzene unit and subsequent tube disassembly. Thermal or photoinduced (457 nm light) recovery of the trans isomer restores the nanotubes.

Deamidation of pseudopeptidic molecular hydrogelators and its application to controlled release.

HYPOTHESIS: The incorporation of a succinic acid-derived moiety in amino acid derivatives would favor an intramolecular catalysis of a deamidation reaction. Such reaction would permit controlled disassembly of molecular hydrogelators and the use of the hydrogels for controlled release of actives. EXPERIMENTAL: Low molecular weight hydrogelators containing a succinic acid-derived moiety were prepared by conventional organic synthesis procedures. Hydrogels were examined by electron microscopy and 1HNMR studies were carried out to evaluate the solubility in water of the hydrogelators and the deamidation reaction. Liberation of Rose Bengal entrapped in the hydrogels was monitored by UV-Vis spectroscopy. FINDINGS: Molecular hydrogels formed by pseudopeptidic derivatives of l-valine suffer a thermal deamidation reaction, leading to partial disassembly. The succinic acid-derived moiety present in the gelators is responsible of intramolecular catalysis of a deamidation reaction. Such neighboring group effect is reminiscent of biochemical processes such as protein deamidation and self-excision of inteins. It has been found that the thermodynamic equilibrium of the deamidation reaction is regulated by the efficiency of hydrogelation. As a proof of concept, the thermally promoted deamidation is applied to controlled release of Rose Bengal.