Mixed-mode chromatography with zwitterionic phosphopeptidomimetic selectors from Ugi multicomponent reaction

Area of Science:

• Analytical Chemistry
• Organic Synthesis
• Chromatography

Background:

• Mixed-mode chromatography combines different separation mechanisms for enhanced selectivity.
• Developing novel stationary phases with tunable properties is crucial for complex separations.
• Existing mixed-mode, HILIC, and RP columns have limitations in certain applications.

Purpose of the Study:

• To synthesize novel zwitterionic chromatographic selectors using a Ugi multicomponent reaction (MCR).
• To immobilize these selectors onto silica beads via thiol-ene click chemistry to create new stationary phases.
• To evaluate the chromatographic performance and retention characteristics of the novel stationary phases in mixed-mode chromatography.

Main Methods:

• Synthesis of aminophosphonate zwitterionic ligands via a one-pot microwave-assisted Ugi-MCR.
• Immobilization of ligands onto silica beads using thiol-ene click chemistry.
• Chromatographic evaluation of stationary phases with diverse analytes and analysis using Principal Component Analysis (PCA).

Main Results:

• Successful synthesis and immobilization of zwitterionic ligands, creating novel reversed-phase/zwitterionic ion-exchanger (RP/ZWIX) stationary phases.
• Demonstration of multimodal retention capabilities, including ion-exchange, hydrophobic, and hydrophilic interactions.
• PCA analysis confirmed that RP/ZWIX phases are complementary to existing RP, HILIC, and mixed-mode columns.

Conclusions:

• The novel Ugi-MCR approach enables the facile generation of diverse zwitterionic selectors for mixed-mode chromatography.
• The developed RP/ZWIX stationary phases offer complementary selectivity and are promising for impurity profiling and 2D-HPLC.
• This synthetic strategy provides a versatile platform for designing advanced chromatographic selectors for various applications, including affinity and chiral chromatography.