Department of Chemistry, Bingöl University, Bingöl, Türkiye.
Department of Chemistry, Bingöl University, Bingöl, Türkiye; Food Analysis and Research Laboratory, Bingöl University, Bingöl, Türkiye; Department of Food Engineering, Bingöl University, Bingöl, Türkiye.
J Chromatogr A. 2024 Jan 4;1713:464573. doi: 10.1016/j.chroma.2023.464573. Epub 2023 Dec 9.
Here, we report the preparation and application of two new chiral monoliths for the enantioseparation of chiral drugs in nano-LC. Using 3‑chloro-2-hydroxypropylmethacrylate (HPMA-Cl, 2) as a precursor monomer, two different chiral monomers namely, N-Boc-Lys-HPMA (3A) and N-Fmoc-Lys-HPMA (3B) were synthesized and used for the preparation of chiral polymer monoliths. The first monolithic column (referred to as monolith I) was prepared by an in-situ polymerization of N-Boc-Lys-HPMA as the chiral monomer and ethylene dimethacrylate while the second monolithic column (referred to as monolith II) was prepared by an in-situ polymerization of N-Fmoc-Lys-HPMA as the chiral monomer and ethylene dimethacrylate as the crosslinker. Methanol and 1-propanol were used as the porogenic solvents. The prepared chiral monoliths were investigated for the enantioseparation of chiral drugs, including β-blockers (e.g., atenolol, propranolol, metoprolol) and anti-inflammatory drugs (e.g., ketoprofen, ibuprofen, flurbiprofen, naproxen, etodolac). The enantioseparation could be achieved via the formation of π-π interactions on the aromate-rich and aromate-poor chiral molecules while enantioseparation mechanism of chiral drugs included mostly π-π interactions and hydrogen bonding. Monolith II showed better enantioselectivity than Monolith I and the resolution values up to 2.12 were successfully achieved.
在这里，我们报告了两种新型手性整体柱的制备及其在手性药物的纳升液相色谱中的应用。以 3-氯-2-羟丙基甲基丙烯酸酯（HPMA-Cl，2）为前驱体单体，合成了两种不同的手性单体，即 N-Boc-Lys-HPMA（3A）和 N-Fmoc-Lys-HPMA（3B），并用于制备手性聚合物整体柱。第一个整体柱（简称整体柱 I）通过 N-Boc-Lys-HPMA 作为手性单体和二乙二醇二甲基丙烯酸酯的原位聚合制备，而第二个整体柱（简称整体柱 II）通过 N-Fmoc-Lys-HPMA 作为手性单体和二乙二醇二甲基丙烯酸酯的原位聚合制备。甲醇和 1-丙醇被用作致孔剂。研究了制备的手性整体柱对手性药物的拆分，包括β-受体阻滞剂（如阿替洛尔、普萘洛尔、美托洛尔）和抗炎药（如酮洛芬、布洛芬、氟比洛芬、萘普生、依托度酸）。通过芳香族丰富和芳香族贫手性分子之间的π-π相互作用实现了对映体分离，而手性药物的对映体分离机制主要包括π-π相互作用和氢键。整体柱 II 显示出比整体柱 I 更好的对映选择性，成功达到了 2.12 的分辨率值。
