In this work, a simple method for alcohol synthesis with high enantiomeric purity was proposed. For this, colloidal gold and silver surface modifications with 3-mercaptopropanoic acid and cysteamine were used to generate carboxyl and amine functionalized gold and silver nanoparticles of 15 and 45 nm, respectively. Alcohol dehydrogenase from Thermoanaerobium brockii (TbADH) and its cofactor (NADPH) were physical and covalent (through direct adsorption and using cross-linker) immobilized on nanoparticles' surface. In contrast to the physical and covalent immobilizations that led to a loss of 90% of the initial enzyme activity and 98% immobilization, the use of a cross-linker in immobilization process promoted a loss to 30% of the initial enzyme activity and >92% immobilization. The yield of NADPH immobilization was about 80%. The best results in terms of activity were obtained with Ag-citr nanoparticle functionalized with carboxyl groups (Ag-COOH), Au-COOH(CTAB), and Au-citr functionalized with amine groups and stabilized with CTAB (Au-NH2(CTAB)) nanoparticles treated with 0.7% and 1.0% glutaraldehyde. Enzyme conformation upon immobilization was studied using fluorescence and circular dichroism spectroscopies. Shift in ellipticity at 222 nm with about 4 to 7 nm and significant decreasing in fluorescence emission for all bioconjugates were observed by binding of TbADH to silver/gold nanoparticles. Emission redshifting of 5 nm only for Ag-COOH-TbADH bioconjugate demonstrated change in the microenvironment of TbADH. Enzyme immobilization on glutaraldehyde-treated Au-NH2(CTAB) nanoparticles promotes an additional stabilization preserving about 50% of enzyme activity after 15 days storage. Nanoparticles attached-TbADH-NADPH systems were used for enantioselective (ee > 99%) synthesis of (S)-7-hydroxy-2-tetralol.

A search for new solid forms of an active pharmaceutical ingredient (API) is an integral part of the drug product development process. The studied compound, Ibrutinib, is a recently approved anticancer drug. The main aim of this study was to search for new solvates of Ibrutinib and to perform their structural characterization. To do so, we performed a tailor-made systematic solvate screening and tested several solution and slurry based methods in the solvate screening for their suitability and success rate. The phase composition of the screening samples was analyzed by Raman spectroscopy and powder X-ray diffraction. From the 11 tested solvents, eight solvates were prepared (with 4-hydroxy-4-methylpentan-2-on, dioxolane, α,α,α-trifluorotoluene, ortho-xylene, meta-xylene, para-xylene, anisole, and chlorobenzene). The crystal structures of all eight solvates were successfully solved from single-crystal X-ray diffraction data, and, to our best knowledge, this work is the first ever crystal structure study of Ibrutinib. The desolvation behavior of the prepared Ibrutinib solvates was studied by thermal methods (differential scanning calorimetry, thermogravimetric analysis, and hot-stage microscopy), and stability tests were performed to determine the strength of the API–solvent interaction. Dissolution experiments showed that the solvate formation can improve the dissolution rate by as much as 8.5 times, compared to the most stable nonsolvated form.

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In this study, bare gold nanoparticles (GNPs) immobilized in the sol-gel-pretreated fused-silica (FS) capillary as a stationary phase for open-tubular capillary electrochromatography (OT-CEC) are for the first time shown to be able to separate both hydrophobic polyaromatic hydrocarbons (PAHs) as well as hydrophilic cationic antimicrobial peptides. Model mixture of four PAHs, naphthalene, fluorene, phenanthrene, and anthracene, was resolved by OT-CEC in the GNP-modified FS capillaries using the hydro-organic background electrolyte (BGE) composed of 20 mmol/L sodium phosphate buffer, pH 7, modified with ACN at 8:2 v/v ratio. On the other hand, three synthetic analogues of an antimicrobial peptide mastoparan PDD-B, basic tetradecapeptides INWKKLGKKILGAL-NH(2), INSLKLGKKILGAL-NH(2) and NWLRLGRRILGAL-NH(2), were separated in aqueous acidic BGEs, pH 2.1-3.1, composed of weak acids (formic and acetic) or amphoteric amino or imino acids (aspartic or iminodiacetic), utilizing the advantage of a slow reversed (anodic) EOF and slightly positive charge of the GNP-modified FS capillary suppressing the adsorption of cationic peptides on the inner capillary wall and improving their resolution.

In this paper, we present a comprehensive crystallographic study of Ibrutinib polymorphs and their behavior. Three neat polymorphs (A, B, and C) and a methanol solvate (F) were obtained and characterized. The structures of forms A, C, and F were solved from single-crystal diffraction data. Form B has only ever been prepared as a powder, and its structure solution has, so far, not been successful. Polymorph C is a desolvate of the methanol solvate F, and its structure was solved via the single-crystal to singlecrystal transformation. The analysis of the solved structures revealed significant differences in the crystal packing of form A in comparison with the previously described Ibrutinib structures, enabling it to crystallize in a higher symmetry space group (monoclinic vs triclinic). The structures also revealed a high similarity between forms C and F, explaining their mutual transformability. To further analyze the solids, we performed DSC, long-term slurry transformations, intrinsic dissolution experiments, and DVS. FT-Raman spectroscopy was used for the preliminary characterization and fast distinction between the forms. We have also performed basic energy calculations to estimate the strength of the various present H-bonds. All methods confirmed the polymorph A to be the thermodynamically most stable form.