pH-Induced conversion of bolaamphiphilic vesicles to reduction-responsive nanogels for enhanced Nile Red and Rose Bengal delivery.

This study details the preparation and investigation of molecular nanogels formed by the self-assembly of bolaamphiphilic dipeptide derivatives containing a reduction-sensitive disulfide unit. The described bolaamphiphiles, featuring amino acid terminal groups, generate cationic vesicles at pH 4, which evolve into gel-like nanoparticles at pH 7. The critical aggregation concentration has been determined, and the nanogels' size and morphology have been characterized through Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM).

Reduction-Responsive Cationic Vesicles from Bolaamphiphiles with Ionizable Amino Acid or Dipeptide Polar Heads.

This paper presents a study of the aggregation of cationic bolaamphiphilic molecules into vesicles. These molecules are based on a cystamine core with protonated terminal dipeptide groups. The study found that vesicles can be formed at pH 4 for all of the dipeptide-terminated bolaamphiphiles containing different combinations of l-valine, l-phenylalanine, and l-tryptophan.

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).

Alkaline cations dramatically control molecular hydrogelation by an amino acid-derived anionic amphiphile.

Understanding the factors that control the formation of (supra)molecular hydrogels permits a rational tuning of their properties and represents a primary challenge for developing smart biocompatible soft materials. Hydrogel formation by molecular amphiphilic anions at millimolar concentrations is counterintuitive, considering the solubility of these species in water. Here we report hydrogel formation by a simple anionic molecular amphiphile and a rationale for the fibrillisation process observed.

Non-Polymeric Nanogels as Versatile Nanocarriers: Intracellular Transport of the Photosensitizers Rose Bengal and Hypericin for Photodynamic Therapy.

The use of nanocarriers for intracellular transport of actives has been extensively studied in recent years and represents a central area of nanomedicine. The main novelty of this paper lies on the use of nanogels formed by a low-molecular-weight gelator (). Here, non-polymeric, molecular nanogels are successfully used for intracellular transport of two photodynamic therapy (PDT) agents, Rose Bengal (RB) and hypericin (HYP).

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 - isomerization of the azobenzene unit and subsequent tube disassembly. Thermal or photoinduced (457 nm light) recovery of the isomer restores the nanotubes.

Photobehavior of the antipsychotic drug cyamemazine in a supramolecular gel protective environment.

In this work, a molecular hydrogel made of gelator (S)-4-((3-methyl-1-(nonylamino)-1-oxobutan-2-yl)amino)-4-oxobutanoic acid (SVN) has been employed as soft container to modify the photochemical and photophysical behavior of the antipsychotic drug cyamemazine (CMZ). The interaction of CMZ with the gel network has been evidenced by fluorescence spectroscopy through a hypsochromic shift of the emission band (from λ = 521 nm in solution to λ = 511 nm in the gel) and an increase of the fluorescence lifetime (5.6 ns in PBS vs.

Liposome-Enveloped Molecular Nanogels.

Novel hydrogel@liposome particles were prepared by pH-triggered molecular gel formation inside of liposomes loaded with a low-molecular weight gelator derived from l-valine (). Liposome formation was carried out using l-α-phosphatidylcholine (PC) and cholesterol as components of the lipid bilayer. Molecular hydrogelator and pyranine, a ratiometric fluorescent pH probe, were entrapped in the liposomes at pH 9 and posterior acidification with d-glucono-1,5-lactone to pH 5-6 provoked intraliposomal gel formation.

Self-Assembly Controls Reactivity with Nitric Oxide: Implications for Fluorescence Sensing.

Three molecules containing the fluorophore 4-amino-1,8-naphthalimide (ANI) and showing different tendencies to self-assembly in aqueous environment have been prepared and fully characterized. The fluorescence emissions of two of these compounds in aqueous solutions are efficiently quenched in the presence of nitric oxide (NO) in aerated medium. Nuclear magnetic resonance and mass spectrometry techniques indicate that NO/O induces deamination of the ANI fluorophore, resulting in nonemissive 1,8-naphtalimide derivatives.

Photoactive Hexanuclear Molybdenum Nanoclusters Embedded in Molecular Organogels.

Hexanuclear molybdenum clusters are attractive species because of their outstanding photonic properties, and in the past they have been attached to a variety of supports such as organic polymers and inorganic nanoparticles, as described in the recent literature. Here, a cluster of the formula TBA[MoIAc] (TBA = tetrabutylammonium; Ac = acetate) has been supported on molecular organogels for the first time, resulting in a new soft material with remarkable photoactivity. Electron and confocal microscopic analyses showed the alignment of the nanoclusters to 1D self-assembled fibers formed by the organic gelator, and emission spectroscopy corroborated the interaction of the emissive clusters with such fibrillary structures.

In between molecules and self-assembled fibrillar networks: highly stable nanogel particles from a low molecular weight hydrogelator.

The preparation of molecular, non-polymeric nanogels from a low molecular weight hydrogelator is reported. The molecular nanogels are expected to overcome issues associated with the use of polymeric nanogels in biomedicine such as biodegradability, stimuli responsiveness, polydispersity, and batch-to-batch reproducibility. Nanogels formed by compound 1 were reproducibly prepared by sonication of a xerogel in PBS, with a total concentration of ca.

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.

Synthesis of a Double-Network Supramolecular Hydrogel by Having One Network Catalyse the Formation of the Second.

Self-assembly of biomolecules catalytically controls the formation of natural supramolecular structures, giving highly ordered complex materials. Such desirable hybrid systems are very difficult to design and construct synthetically. A hybrid double-network hydrogel with a maximum storage modulus (G' ) of up to 55 kPa can be synthesized by using a self-assembled hydrogel that catalyses the formation of another kinetically arrested hydrogel network.

Tandem reactions in self-sorted catalytic molecular hydrogels.

By equipping mutually incompatible carboxylic acid and proline catalytic groups with different self-assembling motives we have achieved self-sorting of the resulting catalytic gelators, namely and , into different supramolecular fibers, thus preventing the acidic and basic catalytic groups from interfering with each other. The resulting spatial separation of the incompatible catalytic functions is found to be essential to achieve one-pot deacetalization-aldol tandem reactions with up to 85% efficiency and 90% enantioselectivity. On the contrary, when was co-assembled with a structurally similar catalytically active hydrogelator (), self-sorting was precluded and no tandem catalysis was observed.

Sucrose-fueled, energy dissipative, transient formation of molecular hydrogels mediated by yeast activity.

A biologically mediated, energy dissipative, reversible formation of fibrillar networks is reported. The process of gelation is linked to sucrose-fueled production of CO2 by baker's yeast (Saccharomyces cerevisiae). Continuous fueling of the system is required to maintain the self-assembled fibrillar network.

Improved Efficiency of Molecular-Gel Formation by Adjusting Preorganization of Amino-Acid-Derived Flexible Molecules: A NMR and Thermodynamic study.

The efficiency of the formation of molecular gels of simple derivatives of l-valine and l-isoleucine is greatly improved in different organic solvents when a hexyl fragment is replaced by a bulkier cyclohexyl one. A study using NMR and IR spectroscopy provides information on the preferred conformations of the molecules, indicating that the cyclohexyl moiety precludes intramolecular H bonding and preorganises the system for intermolecular interactions, which are responsible for fiber formation. NMR data of the gels provides thermodynamic data on fibrillization, revealing that the origin of this effect is mainly entropic.

In situ synthesis-gelation at room temperature vs. heating-cooling procedure. Fine tuning of molecular gels derived from succinic acid and L-valine.

Hypothesis: The reaction between succinic anhydride and a diamine derived from L-valine should afford efficiently a molecular gelator. Based on this reaction, it should be feasible to prepare molecular gels at room temperature, avoiding the conventional thermal treatment required for the solubilization of the gelator, by in situ, simultaneous, synthesis and gelation. The gels prepared by in situ and conventional heating-cooling protocols could present important differences relevant for potential practical applications of these materials.

Synthesis and biological properties of the cytotoxic 14-membered macrolides aspergillide A and B.

Total, stereoselective syntheses of the naturally occurring, cytotoxic macrolides aspergillide A and B are described. Olefin metatheses and asymmetric allylations were key steps in the synthetic sequences. Cytotoxicity assays against several tumor cell lines have been performed for the two aspergillides and some of the intermediates or side products of the synthetic sequence.

Stereoselective synthesis and structural correction of the naturally occurring lactone stagonolide G.

A convergent synthesis of the structure proposed for the naturally occurring lactone stagonolide G is described. All three stereocenters were created with the aid of asymmetric Brown allylations. The lactone ring was built by means of a ring-closing metathesis (RCM).

Stereoselective synthesis of the cytotoxic 14-membered macrolide aspergillide A.

A stereoselective synthesis of the cytotoxic 14-membered macrolide aspergillide A has been performed. The preparation of a cis-2,6-disubstituted tetrahydropyran ring via stereoselective reduction of an intermediate cyclic hemiacetal was one key feature of the synthesis. The macrocyclic lactone ring was created by means of a ring-closing metathesis (RCM), whereby the new C=C bond displayed exclusively the undesired Z configuration.