Selectively pulsed spin order transfer increases parahydrogen-induced NMR amplification of insensitive nuclei and makes polarization transfer more robust

TL;DR

This paper introduces a selective pulsed spin order transfer method for parahydrogen-induced polarization that achieves near 100% polarization in molecules, improving robustness and applicability for insensitive nuclei in NMR.

Contribution

The authors develop a novel frequency-selective pulsed SOT technique that enhances polarization transfer efficiency and robustness across weakly coupled spin systems, including partially labeled molecules.

Findings

Achieved up to 20% 13C polarization experimentally.

Simulations show near 100% conversion of spin order in ideal conditions.

Method is effective for all weakly coupled spin systems.

Abstract

We describe a new method for pulsed spin order transfer (SOT) of parahydrogen induced polarization (PHIP) that enables close to 100 % polarization in incompletely 2H-labeled molecules by exciting only the desired protons in a frequency-selective manner. While a selective pulse (SP) on 1H at the beginning of pulsed SOT had been considered before, using SPs during the SOT suppresses undesired indirect spin-spin interactions. As a result, we achieved a more robust SOT for the SP variants of the phINEPT+ sequence that we refer to as phSPINEPT+. Thereby, for the first time, we report a sequence that is effective for all weakly coupled spin systems. Our simulations show that the method converts close to 100 % of the parahydrogen-derived spin order into 13C hyperpolarization in weakly coupled three-spin systems and partially or fully 2H-labeled molecules if relaxation is neglected. Experimentally we demonstrate high hyperpolarization of 13C with 15.8 % for 1-13C-hydroxyethyl propionate-d3 and 12.6 % for 1-13C-ethyl acetate-d6, which corresponds to ~47 % and ~38 % if the enrichment of parahydrogen had been 100 %. Even in non-2H-labeled molecules, a remarkable 13C polarization is achieved, e.g. up to 20 % were simulated for 100 % pH2, and 1.25 % were obtained experimentally for 1-13C-ethyl pyruvate and 50 % pH2, which can be further improved by faster hydrogenation. As a result, full deuterium labeling may no longer be required e.g., when new PHIP agents are investigated, the synthesis of fully deuterated molecules is too complex, or when a kinetic isotope effect regarding the metabolic conversion rate of an agent is to be avoided. Using SPs during SOT seems very promising and may be extended to other sequences in the context of PHIP and be-yond to make them less prone to experimental imperfections or real molecular environments.