The selective removal of structural elements plays a decisive role in three-dimensional (3D) printing applications enabling complex geometries. To date, the fabrication of complex structures on the microscale is severely limited by multi-step processes. Herein, we report a subtractive photoresist platform technology that is transferable from microscopic 3D printing via Direct Laser Writing (DLW) to macroscopic structures via Stereolithography (SLA). All resist components are readily accessible and exchangeable, offering fast adaptation of the resist's property profile. The micro-and macroprinted structures can be removed in a facile fashion, without affecting objects based on standard photoresists. The cleavage is analyzed by time-lapse images as well as via in-depth spectroscopic assessment. The mechanical properties of the printed materials are investigated by nanoindentation. Critically, we demonstrate the power of our subtractive resist platform by constructing complex 3D objects with flying features on the microscale.

At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high-throughput, cost-effective, and early evaluation of passive intestinal absorption of active principles in medicinal plants. In phytochemical studies, obtaining effective passive permeability values of pharmacologically active natural products is important to predict if natural products showing interesting activities in vitro may have a chance to reach their target in vivo.

An 80-membered library of gels composed of monofunctional 2-ethyl-2-oxazoline and 2-nonyl-2-oxazoline and one of four selected difunctional 2-oxazolines (containing either ether or ester bonds) were synthesized by microwave-assisted ring-opening polymerizations. The difunctional 2-oxazolines were prepared from the thiol-ene reaction of glycol dimercaptoacetate or 2,2′-(ethylenedioxy)diethanethiol and 2-but-3′-enyl-2-oxazoline or 2-dec-9′-enyl-2-oxazoline. 53 of the gels exhibited glass-transition temperatures, which ranged from −5.9 to 45.3 °C. 13 Derivatives exhibited glass-transition temperatures in the range from 20 to 30 °C, which renders them stiff at room temperature and flexible at body temperature. The gels that did not contain any 2-ethyl-2-oxazoline acted as lipogels, whereas the gels that did not contain any 2-nonyl-2-oxazoline acted as hydrogels; all other gels may be classified as amphigels. The swelling degrees were measured by gravimetry and maximum swelling degrees of 6 (in water) were observed for the gels with the lowest degrees of crosslinking. In a second approach, the synthesis of crosslinked networks had been achieved by performing the polymeranalogous thiol-ene reaction of copoly(2-oxazoline)s containing olefinic side-chains and glycol dimercaptoacetate. This soft strategy enabled the straightforward loading of such gels with active pharmaceutical ingredients without altering them. This method delivered gels with selected composition exhibiting a targeted disc-shape and loaded with active pharmaceutical ingredients from one-step syntheses. The maximum swelling degrees of these specimens were found to be in accordance with the ones from the first route investigated. Preliminary degradation studies were performed at 25 °C; these types of gels were found to be degraded in alkaline media as well as by esterases.

The human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off-target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low μM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays, and its low cytotoxicity in vitro, suggested its potential for drug development.

Waste production associated with the use of non-degradable materials in packaging is a growing cause of environmental concern, with the polyurethane (PU) class being notorious for their lack of degradability....

technique. Details about growth procedure and crystal morphology are given elsewhere [8]. Plates, oriented along the fiber axis (3±4 mm length), were cut from the fiber and polished using a fine diamond paste. These plates showed a parallel pattern of uniform size lamellae as observed under the optical microscope.Film Preparation and Characterization: About 400 nm thick YBCO films were deposited on these substrates using the metal-organic chemical vapor deposition technique, under the standard conditions described elsewhere [21]. By using electron probe microanalysis, the average cation composition of the film was found to be 1.2:2.0:2.8 (Y:Ba:Cu). The oxygen content, measured by micro-Raman spectroscopy, was found to be 6.8±6.9, which is near the optimum value for a high-T c YBCO phase. The film surface morphology was imaged by scanning electron microscopy (SEM). Film texture, as well as substrate orientation was analyzed using X-ray diffraction (XRD) in a Philips MRD system equipped with a four-circle goniometer. Resistivity measurements were carried out using the direct current four-contact method and a current of 20 mA. Electrical contacts to the samples were made by using graphite paste either in longitudinal (L) or transverse (T) configurations with respect to the strips, the typical distance between two of them being 200±300 mm. Transition width, DT c , was defined as 10±90 % of the full resistive transition.

The copoly(2-oxazoline) pNonOx80-stat-pDc=Ox20 can be synthesized from the cationic ring-opening copolymerization of 2-nonyl-2-oxazoline NonOx and 2-dec-9′-enyl-2-oxazoline Dc=Ox in the ionic liquid n-hexyl methylimidazolium tetrafluoroborate under microwave irradiation in 250 g/batch quantities. The polymer precipitates upon cooling, enabling easy recovery of the polymer and the ionic liquid. Both monomers can be obtained from fatty acids from renewable resources. pNonOx80-stat-pDc=Ox20 can be used as polymer in a photoresist (resolution of 1 μm) based on UV-induced thiol–ene reactions.

Herein, we demonstrate that the photochemical cleavage of linear polymers containing a midchain photocleavable moiety strongly depends on the chain length. Based on an ortho-nitrobenzyl (oNB) difunctional reversible addition–fragmentation chain-transfer agent, well-defined poly­(methyl acrylate)­s (M n = 1.59–67.6 kg mol–1, Đ = 1.3–1.4) were synthesized following a core-first approach. Photolysis at λmax = 350 nm of the ortho-nitrobenzyl moiety led to the generation of equally sized polymer segments. The rate of oNB-driven polymer fragmentation, which can be well described by first-order kinetics, strongly increases with increasing molecular weight in a nonlinear fashion, potentially caused by entropic considerations and is compared to the ideal chain model. The current study thus demonstrates that polymer photolysis is dependent on the polymer chain length, with critical implications for photocleavable network design.