Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, No.24 Tongjiaxiang, Nanjing, Jiangsu, 210009, People's Republic of China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
Mikrochim Acta. 2021 May 12;188(6):186. doi: 10.1007/s00604-021-04840-y.
Metal-organic framework (UiO-66-NH)-incorporated organic polymer monolith was prepared by thermal polymerization. By virtue of the superior physical and chemical properties, the UiO-66-NH-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-NH-ethylene glycol dimethacrylate) (cellulase@poly(GMA-UiO-66-NH-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-NH, the cellulase@poly(GMA-UiO-66-NH-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-NH 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-NH-modified organic polymer monolith for enantioseparating five racemic β-blockers. UiO-66-NH 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.
介孔金属有机骨架（UiO-66-NH）复合有机聚合物整体柱通过热聚合制备。凭借其优越的物理和化学性质，UiO-66-NH 改性的有机整体柱然后通过手性选择剂纤维素酶通过伯氨基和醛基之间的缩合反应进行功能化。合成材料通过傅里叶变换红外光谱、高分辨率透射电子显微镜、扫描电子显微镜、X 射线光电子能谱、热重分析和氮吸附等温线进行了表征。纤维素酶@聚（甲基丙烯酸缩水甘油酯-UiO-66-NH-乙二醇二甲基丙烯酸酯）（纤维素酶@聚（GMA-UiO-66-NH-EDMA））整体柱用于对盐酸美托洛尔、阿替洛尔、艾司洛尔、比索洛尔和普萘洛尔这 5 种碱性外消旋形式进行对映体分离。与没有 UiO-66-NH 的纤维素酶@聚（GMA-co-EDMA）整体柱相比，纤维素酶@聚（GMA-UiO-66-NH-EDMA）整体柱对盐酸美托洛尔（Rs：0→1.67）、阿替洛尔（Rs：0→1.50）、艾司洛尔（Rs：0→1.52）、比索洛尔（Rs：0→0.36）和普萘洛尔（Rs：0→0.44）表现出显著提高的对映体选择性。详细评估了纤维素酶的固定化 pH 值、缓冲液 pH 值、UiO-66-NH 浓度以及有机改性剂的比例，用手性分子对其进行对映体分离。讨论了日内、日间、柱间和批间精度，结果令人满意，分离参数的相对标准偏差（RSD）<4.3%。用于对外消旋β-受体阻滞剂进行对映体分离的 UiO-66-NH 修饰有机聚合物整体柱的制备示意图。UiO-66-NH 被合成并转化为整体柱作为固定相。然后，含有纤维素酶作为手性选择剂的改性整体柱应用于毛细管电色谱系统中，用于对手性药物进行对映体分离。
