Near infrared dye-labelled polymeric micro- and nanomaterials: in vivo imaging and evaluation of their local persistence.

The use of micro- and nanomaterials as carriers of therapeutic molecules can enhance the efficiency of treatments while avoiding side effects thanks to the development of controlled drug delivery systems. The binding of a dye to a drug or to a drug carrier has opened up a wide range of possibilities for an effective in vivo optical tracing of drug biodistribution by using non-invasive real-time technologies prior to their potential use as therapeutic vectors. Here, we describe the fluorescent tagging of polymeric micro- and nanomaterials based on poly(lactic-co-glycolic) acid and on the thermoresponsive poly(N-isopropylacrylamide) with the fluorescent probe IR-820 which was chemically modified for its covalent coupling to the materials. The chemical modification of the dye and the polymers yielded micro- and nanoparticulated labelled materials to be potentially used as drug depots of different therapeutic molecules. In vitro biological studies revealed their reduced cytotoxicity. A spatiotemporal in vivo micro- and nanoparticle tracking allowed the evaluation of the biodistribution of materials showing their local persistence and high biocompatibility after pathological studies. These results underline the suitability of these materials for the local, sustained, not harmful and/or on-demand drug delivery and the remarkable importance of evaluating the biodistribution of materials and tissue persistence for their use as local drug depots.

Release of proteins and enzymes from vesicular compartments by alternating magnetic fields.

The magnetic release of catalytically active enzymes from vesicular compartments within aggregated nanomaterials has been demonstrated. These nanomaterials, magnetic nanoparticle-vesicle aggregates (MNPVs), were formed by the self-assembly of biotinylated silica-coated Fe3O4 nanoparticles, biotinylated vesicles and tetrameric avidin. The unique features of nanoscale magnetite allow adhesion between membranes to be combined with magnetically triggered transit of reagents across membranes. Adding short spacers between the adhesive biotin groups and the nanoparticle or vesicle surfaces was found to strengthen binding to avidin, with binding of avidin to biotinylated bilayers and biotinylated nanoparticles monitored by quartz crystal microgravimetry with dissipation (QCM-D). Three different reagents were released from the vesicle compartments of MNPVs by a pulse of alternating magnetic field, with the release of a dye modelling the release of small molecule substrates, and the release of cytochrome c modelling the release of biological polymers, such as enzymes. To confirm that enzymes could be released and maintain activity, trypsin was encapsulated and shown to digest casein after magnetically triggered release.

Fructose controlled ionophoric activity of a cholate-boronic acid.

Wulff-type boronic acids have been shown to act as ionophores at pH 8.2 by transporting Na(+) through phospholipid bilayers. A cholate-boronic acid conjugate was synthesised and shown to be an ionophore, although the hydroxyl-lined face of the cholate moiety did not enhance ion transport. Mechanistic studies suggested a carrier mechanism for Na(+) transport. The addition of fructose (>5 mM) strongly inhibited ionophoric activity of the cholate-boronic acid conjugate, mirrored by a strong decrease in the ability of this compound to partition into an organic phase. Modelling of the partitioning and ion transport data, using a fructose/boronic acid binding constant measured at pH 8.2, showed a good correlation with the extent of fructose/boronic acid complexation and suggested high polarity fructose/boronic acid complexes are poor ionophores. The sensitivity of ion transport to fructose implies that boronic acid-based antibiotic ionophores with activity modulated by polysaccharides in the surrounding environment may be accessible.

Self-Sorting of cyclic peptide homodimers into a heterodimeric assembly featuring an efficient photoinduced intramolecular electron-transfer process.

We describe the thermodynamic characterisation of the self-sorting process experienced by two homodimers assembled by hydrogen-bonding interactions through their cyclopeptide scaffolds and decorated with Zn-porphyrin and fullerene units into a heterodimeric assembly that contains one electron-donor (Zn­porphyrin) and one electron-acceptor group (fullerene). The fluorescence of the Zn-porphyrin unit is strongly quenched upon heterodimer formation. This phenomenon is demonstrated to be the result of an efficient photoinduced electron-transfer (PET) process occurring between the Zn-porphyrin and the fullerene units of the heterodimeric system. The recombination lifetime of the charge-separated state of the heterodimer complex is in the order of 180 ns. In solution, both homo- and heterodimers are present as a mixture of three regioisomers: two staggered and one eclipsed. At the concentration used for this study, the high stability constant determined for the heterodimer suggests that the eclipsed conformer is the main component in solution. The application of the bound-state scenario allowed us to calculate that the heterodimer exists mainly as the eclipsed regioisomer (75-90 %). The attractive interaction that exists between the donor and acceptor chromophores in the heterodimeric assembly favours their arrangement in close contact. This is confirmed by the presence of charge-transfer bands centred at 720 nm in the absorption spectrum of the heterodimer. PET occurs in approximately 75% of the chromophores after excitation of both Zn-porphyrin and fullerene chromophores. Conversely, analogous systems, reported previously, decorated with extended tetrathiafulvalene and fullerene units showed a PET process in a significantly reduced extent (33%). We conclude that the strength (stability constant (K) x effective molarity (EM)) of the intramolecular interaction established between the two chromophores in the Zn-porphyrin/fullerene cyclopeptide-based heterodimers controls the regioisomeric distribution and regulates the high extent to which the PET process takes place in this system.

Influence of the solvent and metal center on supramolecular chirality induction with bisporphyrin tweezer receptors. Strong metal modulation of effective molarity values.

We describe the synthesis of a bisporphyrin tweezer receptor 1·H(4) and its metalation with Zn(II) and Rh(III) cations. We report the thermodynamic characterization of the supramolecular chirality induction process that takes place when the metalated bisporphyrin receptors coordinate to enantiopure 1,2-diaminocyclohexane in two different solvents, toluene and dichloromethane. We also performed a thorough study of several simpler systems that were used as models for the thermodynamic characterization of the more complex bisporphyrin systems. The initial complexation of the chiral diamine with the bisporphyrins produces a 1:1 sandwich complex that opens up to yield a simple 1:2 complex in the presence of excess diamine. The CD spectra associated with the 1:1 and 1:2 complexes of both metalloporphyrins, 1·Zn(2) and 1·Rh(2), display bisignate Cotton effects when the chirogenesis process is studied in toluene solutions. On the contrary, in dichloromethane solutions, only 1·Zn(2) yields CD-active 1:1 and 1:2 complexes, while the 1:2 complex of 1·Rh(2) is CD-silent. In both solvents, porphyrin 1·Zn(2) features a stoichiometrically controlled chirality inversion process, which is the sign of the Cotton effect of the 1:1 complex is opposite to that of the 1:2 complex. In contrast, porphyrin 1·Rh(2) affords 1:1 and 1:2 complexes in toluene solutions with the same sign for their CD couplets. Interestingly, in both solvents, the signs of the CD couplets associated with the 1:1 sandwich complexes of 1·Zn(2) and 1·Rh(2) are opposite. The amplitudes of the CD couplets are higher for 1·Zn(2) than for 1·Rh(2). This observation is in agreement with 1·Rh(2) having a smaller extinction coefficient than 1·Zn(2). We performed DFT-based calculations and assigned molecular structures to the 1:1 and 1:2 complexes that explain the observed signs for their CD couplets. Unexpectedly, the quantification of the thermodynamic stability of the two metallobisporphyrin/diamine 1:1 sandwich complexes revealed the existence of interplay between effective molarity values (EM) and the strength of the intermolecular interaction (K(m); N···Zn or N···Rh) used in their assembly. The EM for the N···Rh(III) intramolecular interaction is 3 orders of magnitude smaller than that for the N···Zn(II) interaction, both of which are embedded in the same scaffold of the 1·M(2) bisporphyrin receptor.

Supramolecular inclusion complexes of two cyclic zinc bisporphyrins with C60 and C70: structural, thermodynamic, and photophysical characterization.

The formation of thermodynamically stable inclusion complexes between two cyclic zinc bisporphyrins, differing in the saturation degree of the hydrocarbon linkers that connect their porphyrin units, and the fullerenes C(60) and C(70) is described. Binding and photophysical studies were performed in two solvents of very different polarity: toluene and dichloromethane. UV/Vis and fluorescence titration experiments showed π-π interactions between the cyclic zinc bisporphyrins and the fullerenes. Solid-state structures were determined by X-ray diffraction analysis and gave valuable insight into the different complexation behaviors of the two macrocyclic systems towards the fullerenes. NMR titrations were also helpful in understanding the geometry of the complexes in solution. Upon fullerene complexation, the two macrocyclic bisporphyrins adopt very distinct conformations. Charge-transfer absorption bands point to ground-state interactions, and quenching of the porphyrin component luminescence indicates fast reactivity in the excited states. Energy transfer plus HOMO-HOMO and LUMO-LUMO electron-transfer processes occur within the complexes. Charge-separated states characterized by a reduced fullerene and an oxidized porphyrin radical, with lifetimes in the order of several hundred picoseconds, are detected.

Experimental test of curvature-driven dynamics in the phase ordering of a two dimensional liquid crystal.

We study electric field driven deracemization in an achiral liquid crystal through the formation and coarsening of chiral domains. It is proposed that deracemization in this system is a curvature-driven process. We test this prediction using the recently obtained exact result for the distribution of hull-enclosed areas in two-dimensional coarsening with nonconserved scalar order parameter dynamics [J. J. Arenzon et al., Phys. Rev. Lett. 98, 145701 (2007)]. The experimental data are in very good agreement with the theory. We thus demonstrate that deracemization in such bent-core liquid crystals belongs to the Allen-Cahn universality class, and that the exact formula, which gives us the statistics of domain sizes during coarsening, can also be used as a strict test for this dynamic universality class.

TTF-based bent-core liquid crystals.

The synthesis and characterization of bent-core liquid crystals which incorporate TTF groups is reported; different bent-core mesophases are induced depending on the molecular structure and properties derived from their compact packing have been studied.

Self-assembled bent-core side-chain liquid crystalline polymers.

The synthesis of H-bonded bent-core side-chain liquid crystal polymers carried out by two alternative synthetic routes and their properties are reported.