Study of microheterogeneity of silatrane-based silica surface bonding chemistry and its optimization for the synthesis of chiral stationary phases for enantioselective liquid chromatography

Abstract

The present work systematically investigates the chemical microheterogeneity as part of the optimization of a single-step surface bonding chemistry of 3-mercaptopropylsilatrane (MPS) on mesoporous silica gel in comparison to the state-of-the-art silane chemistry with 3-mercaptopropyltrimethoxysilane (MPTMS). MPS functionalization turns out to be a favourable chemistry for the further use in thiol-ene click reactions such as the immobilization of chiral selectors, herein tert-butylcarbamoylquinine (tBuCQN), for the synthesis of chiral stationary phases (CSPs). MPS has higher reactivity than MPTMS and prefers the formation of trifunctional siloxane bondings unlike MPTMS which favours difunctional siloxane bonds to silica, as investigated by solid-state cross-polarization/magic angle spinning (CP/MAS) NMR (²⁹Si and ¹³C nuclei). Reaction conditions (ternary mixtures of methanol, water and toluene; with and without acid; prewetting of silica; HCl pretreatment of silica) were evaluated with the aim to find conditions which promote the formation of a horizontal siloxane polymer layer on top of the silica surface. Silanization reaction times could be reduced to 2 h. The ²⁹Si NMR signal corresponding to trifunctional siloxane bonding could be increased to 60% with no T1 signal that refers to monofunctional siloxane bonding in spite of water in the ternary reaction mixture. Furthermore, no significant disulfide bridges were formed in this approach, leading to high selector loadings. The thiol and selector coverage reached up to 4.6 and 1.4 µmol/m², respectively. With the preferred CSP, the enantioselectivity could be increased for a chiral probe (FMOC-Phe) and the mass transfer resistance (C-term) bisected compared to the corresponding CSP prepared from benchmark MPTMS-modified silica (2.54 vs 5.72 ms). It is demonstrated that the fine-tuning of the microstructure on the silica surface can have a significant influence on enantioselectivity and mass transfer kinetics of the resultant CSPs.

Keywords: Chiral stationary phase; Self-assembled monolayer; Silica gel functionalization; Solid-state NMR; Thiol-ene click reaction.