Immobilization of cellulase on monolith supported with Zr(IV)-based metal-organic framework as chiral stationary phase for enantioseparation of five basic drugs in capillary electrochromatography.

Metal-organic framework (UiO-66-NH2)-incorporated organic polymer monolith was prepared by thermal polymerization. By virtue of the superior physical and chemical properties, the UiO-66-NH2-modified organic monolith was then functionalized by chiral selector cellulase via the condensation reaction between the primary amino groups and aldehyde groups. The synthesized materials were characterized by Fourier transform infrared spectroscopy, high-resolution transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectrometry, thermogravimetric analysis, and nitrogen sorption isotherm. The cellulase@poly(glycidyl methacrylate-UiO-66-NH2-ethylene glycol dimethacrylate) (cellulase@poly(GMA-UiO-66-NH2-EDMA)) monolith was applied to enantiomerically separate the basic racemic forms of metoprolol, atenolol, esmolol, bisoprolol, and propranolol. In contrast to the cellulase@poly(GMA-co-EDMA) monolith without UiO-66-NH2, the cellulase@poly(GMA-UiO-66-NH2-EDMA) monolith reveals significantly improved enantiodiscrimination performance for metoprolol (Rs: 0 → 1.67), atenolol (Rs: 0 → 1.50), esmolol (Rs: 0 → 1.52), bisoprolol (Rs: 0 → 0.36), and propranolol (Rs: 0 → 0.44). The immobilization pH of cellulase, buffer pH, UiO-66-NH2 concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The intra-day, inter-day, column-to-column, and inter-batch precision have been discussed, the result was preferable, and the relative standard deviation (RSD) of separation parameters was <4.3%. Schematic representation of the preparation of a UiO-66-NH2-modified organic polymer monolith for enantioseparating five racemic ß-blockers. UiO-66-NH2 was synthesized and converted into a monolith as the stationary phase. Then, the modified monolith containing cellulase as the chiral selector was applied in a capillary electrochromatography system for enantioseparating chiral drugs.

Application of response surface modeling and chemometrics methods for the determination of Atenolol, Metoprolol and Propranolol in blood sample using dispersive liquid-liquid microextraction combined with HPLC-DAD.

A novel dispersive liquid-liquid microextraction (DLLME) method using ionic liquids (ILs) followed by high-performance liquid chromatography-diode array detector (HPLC-DAD) has been devised to specify Atenolol, Atenolol, Metoprolol and Propranolol in blood real samples. Fourteen effective parameters in DLLME process, including pH of aqueous sample, volume of the dispersion and extraction solvents and ionic strength of donor phase, etc.; were screened using fractional factorial screening methodology (FFSM) based on Placket-Burman design (PBD) and subsequently were optimized by response surface methodology using central composite design (CCD). A mixture of IL (1-butyl-3-methyl imidazolium hexa fluoro phosphate) and disperser solvent (methanol) was quickly injected into the sample solution leading to the formation of the semi cloudy solution. Afterwards, HPLC-DAD was applied to examine the sedimented IL drop. The detection limits (LOD) for all analytes ranges were 0.00268-0.00300 µg L-1. The relative standard deviations (RSDs) for seven experiments were between 3.832% and 4.432% for three target analytes. The proposed method illustrated wide dynamic linear range (DLR, 0.009-1 µg L-1), desirable linearity (R2 ≈ 0.997), high enrichment factors (EF, 313-330) and good relative recoveries (RR, 96-104%). Clear separation and desirable chromatogram was quickly reached without the intervention of the matrix. Besides, a comparison of this method with previous methods indicated that the suggested method is a reproducible, quick and dependable sample pretreatment technique for extraction and determination of pharmaceuticals in blood sample.

A novel antimicrobial epoxide isolated from larval Galleria mellonella infected by the nematode symbiont, Photorhabdus luminescens (Enterobacteriaceae).

A novel antimicrobial epoxide, 2-isopropyl-5-(3-phenyl-oxiranyl)-benzene-1,3-diol (1), was identified from larval Galleria mellonella infected by a symbiotically associated bacterium-nematode complex (Photorhabdus luminescens C9-Heterorhabditis megidis 90). Its structure was determined with spectroscopic analysis and confirmed by chemical synthesis starting from a known antibiotic, 2-isopropyl-5-(2-phenylethenyl)-benzene-1,3-diol (2). Epoxide 1 was active against Bacillus subtilis, Escherichia coli, Streptococcus pyogenes, and a drug-resistant, clinical strain of Staphylococcus aureus (RN4220) with minimum inhibitory concentrations in the range of 6.25-12.5 microg/ml. Epoxide 1 was cytotoxic against human cancer cell lines, MCF-7 wt, H460, and Jurkat, with GI(50) of 2.14, 0.63, and 0.42 microM, respectively, but was less toxic on normal, mouse splenic lymphocytes with a GI(50) of 45.00 microM.