Novel Supports Based on Polysaccharides for Sustained‐Release of Isosorbide Dinitrate

Novel supports based on carboxymethylcellulose (CMC), crosslinked with epichlorohydrin (EPC), and microparticles based on acetylphthalylcellulose (APC), for sustained‐release of isosorbide dinitrate (Isoket, Ik), were obtained. The drug has been included into CMC hydrogels through diffusion from ethanol‐water solution. Studies about the ethanol–water ratio influence on including the drug have shown an increased amount of included drug at higher content of water in the alcohol‐water mixture. Isoket–ACP microparticles have been obtained by drug and polymer co‐precipitation from emulsified aqueous solution.

The kinetics for “in vitro” release of Ik from polymeric materials, in simulated conditions for intestinal tract medium, where the drug is preferentially absorbed, has been analyzed. The experimental data have shown a “zero” order kinetic for drug release, which is characteristic for systems controlled by diffusion.     

Crosslinked Networks Based on Polysaccharides and Collagen for Pilocarpine Sustained Release

The paper presents the experimental studies regarding synthesis and characterization of hydrogels based on gellan (Gel)/chitosan (CS) and collagen (Col), obtained by crosslinking with glutaraldehyde (GLA). The influence of the polysaccharide content and GLA ratio on the final composition and swelling characteristics was evaluated. Hydrogels swelling analysis, in distilled water and phosphate buffer (PBS, pH 7.2) has shown higher swelling degrees at increased concentration of polysaccharide into hydrogels. In vitro release of pilocarpine has demonstrated the possibility to use gellan-collagen and chitosan-collagen hydrogels as ophthalmic drug delivery matrix.     

Bioactive Polymers. XXVI. Immobilization of Pepsin on Biozan R

Pepsin was immobilized on BIOZAN R (Hercules) with dicyclohexylcarbodiimide as activator. The reaction product obtained has a protein content of 35–110 mg/g of polymer and a proteolytic activity between 20.85–28.75 μmol tyrosine/L·min·g of polymer). The coupling reaction rate is maximum under the following conditions: pepsin/BIOZAN R ratio = 0.52 g/g, DCCI/BIOZAN R ratio = 0.2 g/g, pH = 3.4, reaction time = 4 h.     

Simultaneous serum desalting and total protein determination by macroporous reversed-phase chromatography

Macroporous reversed-phase (mRP) chromatography was successfully used to develop an accurate and precise method for total protein in serum. The limits of detection (0.83 μg, LOD) and quantification (2.51 μg, LOQ) for the mRP method are comparable with those of the widely used micro BCA protein assay. The mRP method can be used to determine the total protein concentration across a wide dynamic range by detecting chromatographic peaks at 215 nm and 280 nm. The method has the added advantage of desalting and denaturing proteins, leading to more complete digestion by trypsin and to better LC–MS–MS identification in shotgun proteomics experiments.

Multivariate linear regression with missing values

This contribution presents and discusses an efficient algorithm for multivariate linear regression analysis of data sets with missing values. The algorithm is based on the insight that multivariate linear regression can be formulated as a set of individual univariate linear regressions. All available information is used and the calculations are explicit. The only restriction is that the independent variable matrix has to be non-singular. There is no need for imputation of interpolated or otherwise guessed values which require subsequent iterative refinement.     

The unambiguous synthesis and NMR assignment of 4-alkoxy and 3-alkylquinazolines

Contrary to a number of reports, alkylations of the privileged 3,4-dihydroquinazoline scaffold provide N3-alkylated products, and not 4-alkoxyquinazolines. To correctly assign the structure, ¹³C NMR shifts of the –Z–CH_n– (Z=O, N) fragment are necessary; resonances in the 45–55 ppm range are indicative of N3-alkylation. Treatment of 3,4-dihydroquinazoline-4-one with p-TsCl afforded the N3-tosylated compound, whose reaction with an amine yielded the corresponding N3-alkyl derivative. A mechanism corroborated by ¹⁵N-labeling involving pyrimidine ring opening and recyclisation is proposed. Finally, the unambiguous preparation of 4-alkoxyquinazolines is described via treatment of 3,4-dihydroquinazoline-4-ones with PCl₅ followed by an alkoxide.     

Amide,urea and thiourea‐containing triphenylene derivatives: influence of H‐bonding on mesomorphic properties

The synthesis and thermotropic properties are reported for a series of hexaalkoxytriphenylenes that contain an amide, urea or thiourea group in one of their alkoxy tails. The intermolecular hydrogen bonding abilities of these molecules have a disturbing influence on the formation and stability of the columnar liquid crystalline phases. The stronger the hydrogen bonding the more the liquid crystallinity is suppressed, probably due to disturbance of the π–π stacking of the triphenylene discs. As a direct result, urea‐ and amide‐containing triphenylene derivatives are not liquid crystalline, but several thiourea derivatives show hexagonal columnar mesophases.     

Non‐symmetric bent‐core mesogens with one terminal vinyl group

Two series of non‐symmetric banana‐shaped compounds, both with one alkyl and one alkenyl terminal tail, have been synthesized and studied. Both series were compared with the corresponding series with two saturated terminal alkyl tails. All the compounds have a bent central 1,3‐phenylene bis(4‐benzoyloxy)benzoate core; their mesophases were characterized by polarizing optical microscopy, differential scanning calorimetry, X‐ray diffraction and switching current response experiments. In all four series one of the terminal tails is varied from OC₈H₁₇ to OC₁₆H₃₃. The other terminal tails are OC₁₁H₂₃, O(CH₂)₉CH?=?CH₂, OC₁₀H₂₁ and O(CH₂)₈CH?=?CH₂. The short‐tailed compounds show monotropic or enantiotropic B₁ phases and the long‐tailed compounds the B₂ phase. The introduction of one terminal vinyl group slightly lowers the transition temperatures. The introduction of a second terminal vinyl group further suppresses the liquid crystalline properties. All compounds with B₂ phases have layer spacings that suggest a tilt of ～45° of the bent molecules in the layers, and their switching behaviour is antiferroelectric.     

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Two new prodrugs, bearing two and three 5‐fluorouracil (5‐FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5‐FU, they were intended to form complexes through H‐bonds to an organo‐bridged silane prior to hydrolysis‐condensation through sol–gel processes to construct acid‐responsive bridged silsesquioxanes (BS). Whereas 5‐FU itself and the prodrug bearing two 5‐FU units completely leached out from the corresponding materials, the prodrug bearing three 5‐FU units was successfully maintained in the resulting BS. Solid‐state NMR (²⁹Si and ¹³C) spectroscopy show that the organic fragments of the organo‐bridged silane are retained in the hybrid through covalent bonding and the ¹H NMR spectroscopic analysis provides evidence for the hydrogen‐bonding interactions between the prodrug bearing three 5‐FU units and the triazine‐based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and ¹³C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5‐FU thanks to a controlled and targeted drug delivery.     

Self‐Assembled Tetragonal Prismatic Molecular Cage Highly Selective for Anionic π Guests

The metal‐directed supramolecular synthetic approach has paved the way for the development of functional nanosized molecules. In this work, we report the preparation of the new nanocapsule 3? (CF₃SO₃)₈ with a A₄B₂ tetragonal prismatic geometry, where A corresponds to the dipalladium hexaazamacrocyclic complex Pd‐1 , and B corresponds to the tetraanionic form of palladium 5,10,15,20‐tetrakis(4‐carboxyphenyl)porphyrin ( 2 ). The large void space of the inner cavity and the supramolecular affinity for guest molecules towards porphyrin‐based hosts converts this nanoscale molecular 3D structure into a good candidate for host–guest chemistry. The interaction between this nanocage and different guest molecules has been studied by means of NMR, UV/Vis, ESI‐MS, and DOSY experiments, from which highly selective molecular recognition has been found for anionic, planar‐shaped π guests with association constants (K_a) higher than 10⁹ M ^?1, in front of non‐interacting aromatic neutral or cationic substrates. DFT theoretical calculations provided insights to further understand this strong interaction. Nanocage 3? (CF₃SO₃)₈ can not only strongly host one single molecule of M(dithiolene)₂ complexes (M=Au, Pt, Pd, and Ni), but also can finely tune their optical and redox properties. The very simple synthesis of both the supramolecular cage and the building blocks represents a step forward for the development of polyfunctional supramolecular nanovessels, which offer multiple applications as sensors or nanoreactors.