Dual action: the Lewis acid CuF(2) ⋅2 H(2)O efficiently catalyzes the reaction between electrophilic fluoroalkylating agents and α,β-unsaturated carboxylic acids by dually activating both reactants, thus affording di- and trifluoromethyl alkenes in high yields with excellent E/Z selectivity.

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In this work, we developed a rapid and high-sensitivity method for simultaneous analyses of fatty alcohols, fatty aldehydes, and sterols by combining the optimized derivatization reaction with electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS). Pyridine and thionyl chloride were used as derivatization reagents as they were easily removed after the derivatization reaction and could generate permanently charged tags on different functional groups including hydroxyls and aldehydes. Through this one-step derivatization reaction, the sensitivity of detection for fatty alcohols, fatty aldehydes, and sterols was significantly increased. Moreover, the introduction of ion mobility spectrometry (IMS), offering an additional resolution power, ensured more sensitive and accurate detection of derivative products without increasing analytical time. Being connected with high-performance liquid chromatography, more than 15 kinds of compounds were analyzed within 4 min. Relative quantification using peak intensity ratios between d 0-/d 5-labeled ions were subsequently applied for analyzing these 15 kinds of compounds in human thyroid carcinoma and para-carcinoma tissues. The results showed significant differences in content of some analytes between these two kinds of tissues (p < 0.05). The correlations between most of the analytes in thyroid carcinoma tissues are better than the correlations in para-carcinoma tissues.

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Doppelfunktion: Die Lewis‐Säure CuF2⋅2 H2O katalysiert effizient die Umsetzung von α,β‐ungesättigten Carbonsäuren mit elektrophilen Fluoralkylierungsreagentien, die Di‐ und Trifluormethylalkene in hohen Ausbeuten und mit ausgezeichneter E/Z‐Selektivität liefert. Das Kupfersalz aktiviert dabei beide Reaktanten.

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In-depth characterization of charge heterogeneity is a pivotal step desired in the therapeutics antibody development.To this end, a novel on-line multidimensional liquid chromatography-mass spectrometry (MDLC-MS) method for charge variant characterization was developed to dig out potential risks on safety and efficacy. This method implemented 96-well plate fractionation and on-column preconcentration by multi-injection, thereby facilitating detection of charged species at low abundance. Eleven charge variants of mAb-A were preliminarily characterized by 2DLC(CEX × RP-C 4 )-MS. TRVHS and RVHS signal peptide variants of mAb-A were found in basic peaks of the CEX profile. The results supported process development in a timely manner, and the signal peptide-containing variants with potential immunogenicity were successfully removed by an optimized purification process. The retained seven charge variants of mAb-A were further characterized by 4DLC(CEX × RP-C 4 × Trypsin×RP-C 18 )-MS. Post-translational modifications including deamidation, cyclization of N-terminal glutamine, C-terminal lysine truncation as well as proline amidation, and methionine oxidation were identified, and their potential risks were evaluated. Biological activity of the seven charge variants was evaluated by 2DLC (CEX × FcγRIIIa). Increased FcγRIIIa receptor binding affinity was observed in the acidic variants. The MDLC-MS detection can be completed in 72 h with 1.25 mg of mAb, demonstrating to be sample-economic, timeeffective, and labor-saving. It provided a powerful and timely tool for charge variant characterization and met the aggressive timeline desired for antibody development.