Rapid Fragment Screening by 19F Steady-State Free Precession NMR

Steady-state free precession (SSFP) NMR is emerging as a powerful tool across multiple fields of magnetic resonance, driven by its high sensitivity and advances in acquisition and processing. By continuously detecting steady-state transverse magnetization, SSFP achieves superior signal-to-noise ratios per square-root unit time compared to conventional NMR methods that require magnetization recovery between scans. Here, we demonstrate the application of ¹⁹F SSFP for fragment-based screening, achieving broadband excitation (>120 kHz) and a 2.6–3.3-fold average sensitivity enhancement relative to broadband Carr–Purcell–Meiboom–Gill approaches. This gain translates into up to a tenfold reduction in experimental time, enabling reliable screening of up to 2000 compounds per day. Together, these features establish ¹⁹F SSFP as a robust approach for rapid fragment screening in drug discovery.