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

Abstract

ABSTRACT 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 SSFP for fragment‐based screening, achieving broadband excitation ( 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 SSFP as a robust approach for rapid fragment screening in drug discovery.