Pseudomorphic synthesis of pore size-tunable mesoporous silica spherical particles and their application for the fraction of low-molecular-weight heparin.

In this study, spherical silica with pore size varied from 30 to 200 Å was synthesized by pseudomorphic transformation at atmospheric pressure. 40-80 Å silica particles with a narrow pore distribution were obtained by using quaternary amine cationic surfactants and different kinds of swelling agents, including polypropylene glycol, 1,3,5-trimethylbenzene, alkanes, and alkanols. Alkyl imidazolium ionic liquid surfactants were used to synthesize large pore size distribution silica spheres with pore sizes in the range of 110-200 Å. All these silica particles can be synthesized under mild conditions within 12 h, which provides a facile synthesis method for the preparation of a chromatographic matrix with tunable pore size. The method is reproducible and the relative standard deviation of silica sphere pore structure parameters in scaled-up preparations is less than 6%. The pore size on the fraction of low-molecular-weight heparin (LMWH) was investigated in size exclusion chromatography. Matrixes with different pore size distributions have various size exclusion regions. By using UPS-60-Diol columns in a twin-column recirculation separation process, LMWH with >85% heparin with molecular weight within the range of 3000-8000 Da were separated in five-column volumes.