15N optimal control pulses: an efficient approach to enhance heteronuclear-detected NMR experiments at high magnetic fields

Carbon-13 detected Nuclear Magnetic Resonance (NMR) experiments have become a well-established and powerful tool for investigating a wide variety of biomolecular systems, offering unique insights into structure and dynamics. High field NMR spectrometers offer unprecedented resolution, particularly when working at 1.2 GHz, which is crucial in general and particularly important for samples with crowded NMR spectra. However, operating at such high fields introduces new challenges, including the need for efficient spin manipulations across broad frequency ranges while adhering to the power limitations of modern probes. Optimal control (OC) theory offers a powerful framework for designing Radio-Frequency (RF) pulses that achieve desired spin manipulations with high efficiency, even under strict experimental constraints. In this work, we focus on the implementation of OC-designed 15N pulses to enhance the performance of 13C-detected experiments at 1.2 GHz. Specifically, we demonstrate how these pulses improve both excitation bandwidth and signal sensitivity. The approach is validated using a small, well-folded protein and a more challenging intrinsically disordered protein (IDP) dissolved in a high-salt buffer as commonly required for IDPs' stability. Our results show that 15N OC pulses provide clear benefits across sample types and conditions, confirming their utility as a robust solution for bandwidth-limited NMR experiments at the highest available magnetic fields.