基于L-谷氨酸的手性硅胶球的制备及其应用

无机介孔硅球因其具有足够的机械强度、热稳定性,以及适应多种流动相的优点,成为高效液相色谱(HPLC)柱填料中使用最广泛和最重要的材料。但在此研究领域中,并未见球形的全无机手性硅胶用作HPLC手性固定相。该文以无机球形介孔硅胶作为研究对象,通过堆砌硅珠法,以硅溶胶为原料,L-谷氨酸(L-Glu)为手性源,在手性环境中制造出脲醛树脂与胶体二氧化硅混合的小球,在550 ℃高温下煅烧除去树脂部分,制备基于L-Glu的无机介孔硅胶球。通过元素分析、红外光谱、扫描电镜、透射电镜和氮气吸附等表征证明这是一种具有规则球形的手性硅胶球,其手性来源于硅胶球自身的骨架和孔结构。将L-Glu手性硅胶球作为固定相制备了HPLC色谱柱,以正己烷-异丙醇(9∶1, v/v)作为流动相,流速为0.1 mL/min,考察了该手性柱对一系列外消旋化合物的拆分性能。实验表明,该手性柱拆分了15种外消旋化合物,其中特罗格尔碱、吡喹酮、3-苄氧基-1,2-丙二醇、1,2-环氧己烷、3-羟基-2-丁酮、2-甲基四氢呋喃-3-酮、异丙基缩水甘油醚达到基线分离;还分离了10种苯系位置异构体,o,m,p-氨基苯酚、o,p-氯苯酚、o,m,p-碘苯胺、o,m,p-甲苯胺、o,m,p-二硝基苯、o,m,p-氯苯胺、o,m,p-硝基苯酚、o,m,p-溴苯胺达到基线分离。实验表明,L-Glu手性硅胶球在手性分离方面具有良好的可行性,与普通硅胶相比不需要进一步修饰就可以有较好的手性分离效果,是一种低成本、制备便捷的手性无机硅胶固定相。

Preparation and application of chiral silica gel spheres based on L-glutamic

Inorganic mesoporous silica gel spheres, which possess sufficient mechanical strength, thermal stability, and mobile phase endurance, are the most important and widely used materials for column packing in high performance liquid chromatography (HPLC). However, amorphous silica gel is generally reported as an inorganic chiral silica gel, and spherical all-inorganic chiral silica gel has not been reportedly used as the chiral stationary phase for HPLC. In this paper, inorganic spherical mesoporous silica gel was used in the method of polymerization-induced colloid aggregation (PICA), with silica sol as the raw material and L-glutamic acid (L-Glu) as the chiral monomer, to obtain mixed spheres of urea-formaldehyde resin and colloidal silica in a chiral environment. After high-temperature calcination (at 550 ℃) to remove the resin, inorganic mesoporous silica gel spheres based on L-Glu were prepared. Elemental analysis revealed that the prepared L-Glu chiral silica gel spheres were calcined completely, indicating that there were no organic constituents. Scanning electron microscopy (SEM) images of the silica gel spheres showed that the surface of the silica gel spheres was not smooth, with a uniform particle size of 3.0-4.5 μm. Transmission electron microscopy (TEM) images showed that the pore size distribution of the synthetic silica gel spheres was uniform due to the accumulation of pores. Nitrogen adsorption tests revealed that the specific surface area of L-Glu chiral silica gel spheres was 117.844 m²/g, the pore volume was 0.411 cm³/g, and the average pore size was 12.312 nm. All the characterizations indicated that the inorganic chiral mesoporous silicon had a regular spherical shape. The silica gel spheres possess frameworks and pore structures, providing a chiral microenvironment that is suitable as a chiral stationary phase for separating racemic compounds by HPLC. Because of the chiral pore structure and frameworks, the enantiomers were retained to different degrees and separation was achieved. The porous structure also increased the contact surface between the racemates and the active sites of the inner wall and improved the separation efficiency. Hydrogen bonding between the chiral stationary phase and the racemates, dipole interactions, and van der Waals forces were also involved in enantiomer resolution. An HPLC column was prepared with L-Glu chiral silica gel as the stationary phase and n-hexane-isopropanol (9∶1, v/v) as the mobile phase. Fifteen racemic compounds were successfully separated on the chiral HPLC column, including seven racemic compounds for baseline separation, at a flow rate of 0.1 mL/min using 254 nm as the detection wavelength at 25 ℃. The separation of 10 benzene position isomers was successfully achieved, and eight of the benzene position isomers reached baseline separation. Experimental results showed that the chiral silica gel spheres possess sufficient mechanical strength and thermal stability, along with good chiral recognition ability and the ability to separate positional isomers. Compared with ordinary silica gel, these chiral silica gel spheres afforded better chiral separation and better separation of benzene position isomers, without further modification. The preparation of this chiral stationary phase also has the advantages of being cheap, convenient, and feasible.