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Ionizable Cyclofructan 6-Based Stationary Phases for Hydrophilic Interaction Liquid Chromatography Using Superficially Porous Particles

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Abstract

One of the challenges of hydrophilic interaction liquid chromatography (HILIC) is the development of hydrolytically stable stationary phases. In this work, reproducible synthesis, characterization, and application of two new stable cyclofructan-6 (CF6) based stationary phases for HILIC, and mixed-mode chromatography are described. Herein, CF6 was covalently bonded to benzoic acid (BCF-6) and propyl sulfonic acid (SCF-6) groups, respectively. In past reports, sulfonating cyclofructan and bonding it to silica was challenging in terms of reproducibility. The derivatized cyclofructan was then bonded to 2.7 µm superficially porous particles (SPPs), producing a hydrolytically stable phase. The selectivity of the new SPP silica stationary phases was compared to a commercial native cyclofructan-based HILIC column. All the columns in this study were tested for their efficiency, hydrophilicity, and electrostatic character to assess their unique selectivity among 33 commercial columns. All three cyclofructan-6 based stationary phases were subjected to stability tests under a constant flow rate of HILIC mobile phases using acidic, neutral, and basic probe molecules. No significant shift in retention time was observed over one week of continuous operation. The BCF-6 stationary phase showed a significant change in retention of acidic, neutral, and basic as a function of pH in the range 5.5 to 3.5 as compared to FructoShell-N and SCF-6. The two new columns were evaluated using 49 different analytes, including a wide range of structural moieties. Most of the test probes are of biological and pharmaceutical interest.

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Acknowledgements

AZYP, LLC supported all the studies in this project. The authors thank Dr. J.T. Lee and Dr. M. Farooq Wahab for their assistance in this work. The authors would like to thank Agilent Technologies for providing silica particles. The data for all the commercial columns in Figure 3 was provided by Dr. Kunt Irgum (Umea University, Sweden), Dr. Charles A. Lucy, and Dr. M.E.A. Ibrahim (University of Alberta, Canada).

Funding

This research project was supported by the Robert A. Welch Foundation (Y-0026).

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  1. Department of Chemistry and Biochemistry, University of Texas At Arlington, Arlington, TX, 76019, USA

    Jeongjae Yu, Michael Wey, Sepideh Khaki Firooz & Daniel W. Armstrong

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  1. Jeongjae Yu
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Correspondence to Daniel W. Armstrong.

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Yu, J., Wey, M., Firooz, S.K. et al. Ionizable Cyclofructan 6-Based Stationary Phases for Hydrophilic Interaction Liquid Chromatography Using Superficially Porous Particles. Chromatographia 84, 821–832 (2021). https://doi.org/10.1007/s10337-021-04063-6

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