High-Throughput Small-Scale Platform for Synthesis, Characterization, and Modeling of Per- and Polyfluoroalkyl...

Area of Science:

• Environmental Chemistry
• Analytical Chemistry
• Organic Synthesis

Background:

• Per- and polyfluoroalkyl substances (PFAS) pose global environmental and health risks due to their persistence, bioaccumulation, and toxicity.
• The expanding number of emerging PFAS challenges effective monitoring and remediation strategies.
• Current methods for PFAS transformation and analysis are often slow and limited.

Purpose of the Study:

• To develop a rapid, high-throughput method for the chemical transformation of perfluorocarboxylic acids (PFCAs).
• To generate novel PFCA analogs for potential use as safer alternatives and to expand monitoring libraries.
• To establish a data-driven workflow integrating synthesis, structural confirmation, and multidimensional profiling.

Main Methods:

• Implementation of a high-throughput (1 Hz) desorption electrospray ionization mass spectrometry (HT-DESI-MS) platform.
• Utilizing tandem mass spectrometry (MS/MS) for online structural confirmation and diagnostic fragment identification.
• Integrating ion mobility spectrometry (IMS) for multidimensional profiling and quantum mechanical calculations for reactivity prediction.

Main Results:

• Successfully synthesized 915 new PFCA analogs with an 89% success rate.
• Identified key reactivity trends in PFCA transformations.
• Demonstrated standard-free LC-MS/MS analysis and enhanced feature annotation in untargeted PFAS analysis using IMS data.

Conclusions:

• The developed HT-DESI-MS workflow enables rapid synthesis and characterization of novel PFAS analogs.
• This approach has significant potential for discovering safer PFAS alternatives and advancing environmental monitoring techniques.
• Combining synthesis, structural annotation, and multidimensional profiling offers a powerful strategy for addressing the PFAS challenge.