Boosting Dissolution-Dynamic Nuclear Polarization by Multiple-Step Dipolar Order Mediated 1H->13C Cross-Polarization

Dissolution-dynamic nuclear polarization can be boosted by employing multiplecontact cross-polarization techniques to transfer polarization from 1H to 13C spins. The method is efficient and significantly reduces polarization build-up times, however, it involves high-power radiofrequency pulses in a superfluid helium environment which limit its implementation and applicability and prevent a significant scaling-up of the sample size. We propose to overcome this limitation by a stepwise transfer of polarization using a lowenergy and low-peak power radiofrequency pulse sequence where the 1H®13C polarization transfer is mediated by a dipolar spin order reservoir. An experimental demonstration is presented for [1-13C]sodium acetate. A solid-state 13C polarization of ~43.5% was achieved using this method with a build-up time constant of ~5.1 minutes, leading to a ~28.5% 13C polarization in the liquidstate after sample dissolution. The low-power multiple-step polarization transfer efficiency with respect to the most advanced and highest-power multiple-contact cross-polarization approach was found to be ~0.69.</p

Fragment Screening and Fast Micromolar Detection on a Benchtop NMR Spectrometer Boosted by Photoinduced Hyperpolarization

Fragment-based drug design is a well-established strategy for rational drug design, with nuclear magnetic resonance (NMR) on high-field spectrometers as the method of reference for screening and hit validation. However, high-field NMR spectrometers are not only expensive, but require specialized maintenance, dedicated space, and depend on liquid helium cooling which became critical over the recurring global helium shortages. We propose an alternative to high-field NMR screening by applying the recently developed approach of fragment screening by photoinduced hyperpolarized NMR on a cryogen-free 80 MHz benchtop NMR spectrometer yielding signal enhancements of up to three orders in magnitude. It is demonstrated that it is possible to discover new hits and kick-off drug design using a benchtop NMR spectrometer at low micromolar concentrations of both protein and ligand. The approach presented performs at higher speed than state-of-the-art high-field NMR approaches while exhibiting a limit of detection in the nanomolar range. Photoinduced hyperpolarization is known to be inexpensive and simple to be implemented, which aligns greatly with the philosophy of benchtop NMR spectrometers. These findings open the way for the use of benchtop NMR in near-physiological conditions for drug design and further life science applications.ISSN:1433-7851ISSN:1521-3773ISSN:0570-083