Preparation of Chiral Monoliths with New Modulation of the Monolith Surface Chemistry for the Enantioseparation of Chiral Drugs by Nano-Liquid Chromatography.

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 alpha-Boc-Lys-HPMA (3A) and N alpha-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 alpha-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 alpha- 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 beta-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 7C-7C interactions on the aromate-rich and aromate-poor chiral molecules while enantioseparation mechanism of chiral drugs included mostly 7C-7C interactions and hydrogen bonding. Monolith II showed better enantioselectivity than Monolith I and the resolution values up to 2.12 were successfully achieved.