Synthesis and post-functionalization of alternate-linked-meta-para-[2 n .1 n ]thiacyclophanes.

In recent decades, considerable research attention has been devoted to new synthetic procedures for thiacyclophanes. Thiacyclophanes are widely used as host molecules for the molecular recognition of organic compounds as well as metals. Herein, we report the selective and high-yielding synthesis of novel alternate-linked-meta-para-thiacyclophanes. These novel thiacyclophanes are selectively synthesized in high-yielding procedures. Furthermore, post-functionalization of the phenolic moieties was successfully performed. The 3D structure of the alternate-linked-meta-para-[22.12]thiacyclophane was further elucidated via X-ray crystallographic analysis.

Acid-Sensitive BODIPY Dyes: Synthesis through Pd-Catalyzed Direct C(sp3 )-H Arylation and Photophysics.

A novel palladium-catalyzed direct C(sp3 )-H arylation of the methyl group at the 8-position of BODIPY by bromoarenes was established. A deprotonative cross-coupling process was supposed to be involved in the reaction. This approach allowed us to attach electron-donating/withdrawing, halogen substituted aryls and a heteroaryl with a yield running from 55 to 99 %. Novel pH sensors, which in the absence of acid showed the occurrence of photoinduced electron transfer, were synthesized by attaching dimethylaniline to the methyl at the C8-position of BODIPY. The reference compounds with dimethylaniline directly attached to the C8-position were also synthesized and besides photoinduced electron transfer also showed a charge-transfer emission. Their photophysical properties were investigated by steady-state fluorescence, time-correlated single-photon counting and femtosecond fluorescence up-conversion. Time-dependent density functional (TD-DFT) electronic-structure calculations on the properties of the excited states corresponding to local excitation of the BODIPY core and to charge transfer were conducted. Upon addition of trifluoroacetic acid in toluene and ethanol, the partial fluorescence intensity recovery was at least an order of magnitude more efficient with the newly synthesized sensors compared to the traditional reference sensors. The improved sensitivity of these novel BODIPY-based pH sensors was attributed to less efficient proton-coupled electron transfer of the protonated species.

Simultaneous analysis of bisphenol A based compounds and other monomers leaching from resin-based dental materials by UHPLC-MS/MS.

Resin-based dental materials have raised debates concerning their safety and biocompatibility, resulting in a growing necessity of profound knowledge on the quantity of released compounds into the oral cavity. In this context, the aim of this study was to develop a comprehensive and reliable procedure based on liquid chromatography with mass spectrometry for the simultaneous analysis of various leached compounds (including bisphenol A based compounds) in samples from in vitro experiments. Different experiments were performed to determine the optimal analytical parameters, comprising mass spectrometry parameters, chromatographic separation conditions, and sample preparation. Four internal standards were used as follows: deuterated diethyl phthalate and bisphenol A (commercially available), and deuterated analogues of triethylene glycol dimethacrylate and urethane dimethacrylate (custom-made). The optimized method was validated for linearity of the calibration curves and the associated correlation coefficient, lower limit of quantification, higher limit of quantification, and intra- and interassay accuracy and precision. Additionally, the developed liquid chromatography with tandem mass spectrometry method was applied to the analysis of leaching compounds from four resin-based dental materials. The results indicated that this method is suitable for the analysis of different target compounds leaching from dental materials. This method might serve as a valuable basis for quick and accurate quantification of leached compounds from resin-based dental materials in biological samples.

Homodiselenacalix[4]arenes: Molecules with Unique Channelled Crystal Structures.

A synthetic route towards homodiselenacalix[4]arene macrocycles is presented, based on the dynamic covalent chemistry of diselenides. The calixarene inner rim is decorated with either alkoxy or tert-butyl ester groups. Single-crystal X-ray analysis of two THF solvates with methoxy and ethoxy substituents reveals the high similarity of their molecular structures and alterations on the supramolecular level. In both crystal structures, solvent channels are present and differ in both shape and capacity. Furthermore, the methoxy-substituted macrocycle undergoes a single-crystal-to-single-crystal transformation during which the molecular structure changes its conformation from 1,3-alternate (loaded with THF/water) to 1,2-alternate (apohost form). Molecular modelling techniques were applied to explore the conformational and energetic behaviour of the macrocycles.

Poly(alanine): Structure and Stability of the D and L-Enantiomers.

High-performance, biobased materials can potentially be manufactured from polymerized α-amino acids (α-polypeptides). This paper reports on the synthesis, structure, and properties of both polyalanine enantiomers (PLAla and PDAla). The molecular structure of the polypeptide chains, their molecular weight, and polydispersity were investigated by (1)H NMR, MALDI-TOF, and size-exclusion chromatography. The secondary structure and crystalline order were probed via Fourier transform infrared spectroscopy, circular dichroism, and (synchrotron) wide-angle X-ray diffraction. The phase behavior and thermal stability were assessed by differential scanning calorimetry and thermogravimetric analysis. The kinetically trapped PAla chain conformation in the solid state, after synthesis or solvent treatments, is the α-helical shape. Upon heating, crystals from the α-helices convert into more stable crystals from ß-sheets at a temperature higher than 210 °C. This temperature is close to where polymer degradation sets in. The ß-sheet crystals combine melting with thermal degradation at temperatures above 330 °C. In the presence of superheated water, the conversion from α-helices to ß-sheets happens at lower temperatures, allowing for a conversion without degradation.

Nonviral Plasmid DNA Carriers Based on N,N'-Dimethylaminoethyl Methacrylate and Di(ethylene glycol) Methyl Ether Methacrylate Star Copolymers.

Star polymers with random and block copolymer arms made of cationic N,N'-dimethylaminoethyl methacrylate (DMAEMA) and nonionic di(ethylene glycol) methyl ether methacrylate (DEGMA) were synthesized via atom transfer radical polymerization (ATRP) and used for the delivery of plasmid DNA in gene therapy. All stars were able to form polyplexes with plasmid DNA. The structure and size of the polyplexes were precisely determined using light scattering and cryo-TEM microscopy. The hydrodynamic radius of a complex of DNA with star was dependent on the architecture of the star arms, the DEGMA content and the number of amino groups in the star compared to the number of phosphate groups of the nucleic acid (N/P ratio). The smallest polyplexes (Rh90°âˆ¼50 nm) with positive zeta potentials (∼15 mV) were formed of stars with N/P=6. The introduction of DEGMA into the star structure caused a decrease of polyplex cytotoxicity in comparison to DMAEMA homopolymer stars. The overall transfection efficiency using HT-1080 cells showed that the studied systems are prospective gene delivery agents. The most promising results were obtained for stars with random copolymer arms of high DEGMA content.

Highly efficient hyperbranched CNT surfactants: influence of molar mass and functionalization.

End-group-functionalized hyperbranched polymers were synthesized to act as a carbon nanotube (CNT) surfactant in aqueous solutions. Variation of the percentage of triphenylmethyl (trityl) functionalization and of the molar mass of the hyperbranched polyglycerol (PG) core resulted in the highest measured surfactant efficiency for a 5000 g/mol PG with 5.6% of the available hydroxyl end-groups replaced by trityl functions, as shown by UV-vis measurements. Semiempirical model calculations suggest an even higher efficiency for PG5000 with 2.5% functionalization and maximal molecule specific efficiency in general at low degrees of functionalization. Addition of trityl groups increases the surfactant-nanotube interactions in comparison to unfunctionalized PG because of π-π stacking interactions. However, at higher functionalization degrees mutual interactions between trityl groups come into play, decreasing the surfactant efficiency, while lack of water solubility becomes an issue at very high functionalization degrees. Low molar mass surfactants are less efficient compared to higher molar mass species most likely because the higher bulkiness of the latter allows for a better CNT separation and stabilization. The most efficient surfactant studied allowed dispersing 2.85 mg of CNT in 20 mL with as little as 1 mg of surfactant. These dispersions, remaining stable for at least 2 months, were mainly composed of individual CNTs as revealed by electron microscopy.

A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties.

The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions. Co-polymers with variable thiol or acrylate groups to thermo-responsive co-monomer ratios, ranging from 1% to 10%, were synthesized. Precise control of the crosslink density allowed customization of the hydrogel's mechanical properties to match different tissue stiffness levels. Increasing the temperature of the hydrogel above its transition temperature of 31 °C induced the formation of additional physical interactions. These additional interactions both further increased the stiffness of the material and impacted its relaxation behavior. The developed optimized hydrogels reach stiffnesses more than ten times higher compared to the state of the art using similar polymers. Furthermore, when adding cells to the precursor polymer solutions, homogeneous thermo-responsive hydrogels with good cell viability were created upon mixing. In future work, the influence of the mechanical micro-environment on the cell's behavior can be studied in vitro in a continuous manner by changing the incubation temperature.

Carbon nanotubes as a nitric oxide nano-reservoir improved the controlled release profile in 3D printed biodegradable vascular grafts.

Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S-nitroso-N-acetyl-D-penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5-4 × 10-10 mol cm-2 min-1 similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo, even as an approach towards personalized medicine.

Bolaamphiphiles bearing bipyridine as mesogenic core: rational exploitation of molecular architectures for controlled self-assembly.

A bolaamphiphile (5,5-B2NBr8) bearing a functional bipyridine moiety as the mesogenic core is reported for the first time. 5,5-B2NBr8 was found to self-assemble into uniform fibrous structure in aqueous solution, when the concentration was higher than cmc. Analogues of 5,5-B2NBr8 with structural differences in chain length, headgroup, mesogenic core, and substituted position were synthesized, elucidating that small variances of the molecular structure could lead to dramatic changes of the resulting assemblies. For example, compound 4,4-B2NBr8 showed only spherical colloidal aggregates rather than fibers as 5,5-B2NBr8 did, while the only difference between them was the position at which the alkyl chains were attached onto bipyridine. A probable model for the fibrous structure of 5,5-B2NBr8 was proposed. Moreover, exploiting the coordination capacity of bipyridine, assembly and disassembly of 5,5-B2NBr8 could be reversibly controlled through the addition of EDTA and Cu(II), respectively.

Homoselenacalix[4]arenes: synthetic exploration and metallosupramolecular chemistry.

Homoselenacalix[4]arenes were synthesized by a [2 + 2] reductive coupling protocol favouring the cyclotetramers. The inner and outer-rim decoration was varied and a bicyclic derivative was prepared by a similar one-pot procedure. Conformational analysis in solution and the solid state showed noticeable differences between the homoselenacalix[4]arenes and the analogous homothiacalix[4]arenes and provided insight into the metal binding potential of the Se-bridged macrocycles. The homoselenacalix[4]arenes were found to bind Ag(I). Complexation was visualized in the solid state and different packing networks were formed depending on the counter ions applied.

Selenium/Tellurium-Containing Hyperbranched Polymers: Effect of Molecular Weight and Degree of Branching on Glutathione Peroxidase-Like Activity.

A series of novel hyperbranched polyselenides and polytellurides with multiple catalytic sites at the branching units has been synthesized via the polycondensation of A2 + B3 monomers. The GPx-like activities of these polymer mimics were assessed and it was found that the polytellurides showed higher GPx-like activities than the corresponding polyselenides. Interestingly, the polymers with higher molecular weights and degree of branching (DB) showed higher GPx-like activities than the analogous lower molecular weight polymer. The enhancement in the catalytical activity of the hyperbranched polymers with increasing molecular weight affirmed the importance of the incorporation of multiple catalytic groups in the macromolecule which increases the local concentration of catalytic sites.

Fully-branched hyperbranched polymers with a diselenide core as glutathione peroxidase mimics.

A novel glutathione peroxidase (GPx) mimic has been prepared by incorporation of a selenium-based catalytic unit into the focal point of a fully-branched hyperbranched polymer. First, an AB(2) monomer consisting of isatin and an electron rich aromatic moiety was polycondensed in the presence of 5-nitroisatin as a core reagent, resulting in a polymer with 100% degree of branching. The latter was coupled to the catalytically active moiety, Br(CH(2))(5) SeSe(CH(2))(5) Br, by nucleophilic substitution of the bromides by the residual amide groups of the incorporated nitroisatin core. The obtained polymer has demonstrated prominent GPx activity as desired, which could be attributed to the hydrophobic, densely branched and core-shell structure of the polymer surrounding the catalytic center.

Homothiacalix[4]arenes: synthetic exploration and solid-state structures.

Homothiacalix[n]arenes have been largely underexposed compared with related (homo)heteracalixarenes, although their inherent structural features are particularly attractive for supramolecular host-guest chemistry. In this contribution, the synthetic macrocyclization protocols that afford homothiacalix[n]arenes have been reinvestigated and optimized, providing straightforward access to the parent homothiacalix[4]arene skeleton. Moreover, inner-rim (bis and tetrakis) ester functionalization and dimethylenethia bridge oxidation were successfully performed as well. Solution-phase (variable-temperature) NMR spectroscopy studies and solid-state X-ray structures provided complementary information on the conformational features of the novel macrocycles.

UV-responsive polymeric superamphiphile based on a complex of malachite green derivative and a double hydrophilic block copolymer.

We have prepared a UV-responsive polymeric superamphiphile, formed by a malachite green derivative and the double hydrophilic block copolymer methoxy-poly(ethylene glycol)(114)-block-poly(l-lysine hydrochloride)(200) (PEG-b-PLKC) on the basis of electrostatic interactions. The malachite green derivative undergoes photo-ionization upon UV irradiation, which makes it more hydrophilic, resulting in changes in the self-assembly behavior of the polymeric superamphiphile. For this reason, the polymeric superamphiphile originally self-assembles to form sheetlike aggregates, which disassemble after UV irradiation because of the increased solubility of the malachite green derivative. By use of Nile red as a probe, the polarity of the polymeric superamphiphile solution is confirmed to be increased after UV irradiation by fluorescence spectra, which also explains the disassembly of the polymeric superamphiphile.

Stimuli-responsive wettability of nonplanar substrates: pH-controlled floatation and supporting force.

We have prepared pH-responsive planar and nonplanar substrates by chemical modification of a rough gold surface with pH-responsive 2-(11-mercaptoundecanamido)benzoic acid (MUABA). The rough surface exhibits a pH-responsive behavior with an exceptionally large change in contact angle (CA) as a function of the pH, from nearly superhydrophobic (CA of about 144 degrees ) to superhydrophilic (CA of near 0 degrees ). The relationship between pH and the supporting force of gold threads coated by MUABA has been investigated. The pH-responsive coating on the gold thread can provide bigger supporting forces at low pH than at high pH due to the hydrophobicity in the former case. In addition, the change of surface wettability can influence its floatation as well, therefore providing a new approach for controlling the motion of gold threads on water.

Reversible dispersion of single-walled carbon nanotubes based on a CO2-responsive dispersant.

A CO(2)-responsive dispersant, N,N-dimethyl-N'-(pyren-1-ylmethyl) acetimidamidinium (PyAH(+)), which bears both a pyrene moiety and an amidinium cation, has been successfully synthesized. Through strong π-π interaction between the pyrene moiety and single-walled carbon nanotubes (SWNTs), we have demonstrated that PyAH(+) can be modified onto SWNT surfaces to promote the dispersion of SWNTs in water. Furthermore, taking advantage of gas triggered interconversions between the amidinium cation and amidine, reversible control on the solubility of SWNTs has been achieved simply through alternated bubbling of CO(2) and Ar. This work has demonstrated a new method for controlled dispersion and aggregation of SWNTs, and it may contribute to the development of gas responsive carbon materials.

Gastro-resistant encapsulation of amorphous solid dispersions containing darunavir by coaxial electrospraying.

The relatively simple technique of coaxial electrospraying allows to produce core-shell microparticles with potentially high encapsulation efficiencies. In this study, amorphous solid dispersions of a hydroxypropyl methylcellulose or polyvinlypyrrolidone based polymer matrix containing the active pharmaceutical ingredient darunavir were coated with a gastro-resistant shell polymer that does not dissolve at lower pH present in the stomach, but only later at a higher pH in the small intestine. A multitude of shell polymers were tested with the aim to identify a material that limits the drug release to less than 10% after two hours at a pH of 1 to comply with the European Pharmacopoeia regarding gastro-resistant formulations. In parallel, the core-shell structure of the particles was determined with confocal imaging and their surface morphology with SEM imaging. While the structural analysis revealed significant differences between the different formulations, all investigated shell polymers exhibited a burst drug release followed by a slow release for the remainder of a two hour period. Ultimately, the shell copolymer poly(methacrylic acid-co-methyl methacrylate), in particular for a monomer ratio 1/2, resulted consistently in darunavir release below the 10% upper limit compared to the other tested polymers, where such low releases were inaccessible. Further investigation of this shell polymer revealed that both the monomer ratio of methacrylic acid to methyl methacrylate in the copolymer and the utilized solvent are determining factors in the release performance of the final particles.

Metal-ligand coordination-induced self-assembly of bolaamphiphiles bearing bipyrimidine.

A new type of bolaamphiphile bearing bipyrimidine (bpym-8) has been designed and synthesized. The bipyrimidine moiety allows for metal-ligand coordination, thereby influencing the self-assembly of the bolaamphiphile. Before coordination, bpym-8 self-assembles in water to form spherical aggregates. An interesting finding is that the coordination of the Cu(II) ion with bipyrimidine can induce the assembly of bpym-8 to change from spheres to clustered aggregates. It should be noted that the assembly of bpym-8 can be reversibly converted back by removing the Cu(II) ion from the coordination. This study presents a new type of bolaamphiphile that is able to coordinate with metal ions, which may provide a new clue in fabricating reversibly tunable supramolecular nanomaterials.