Elsevier

Chemical Physics Letters

Volume 661, 16 September 2016, Pages 77-82
Chemical Physics Letters

Research paper
Enhancing NMR of insensitive nuclei by transfer of SABRE spin hyperpolarization

https://doi.org/10.1016/j.cplett.2016.08.037Get rights and content

Highlights

  • Methods for enhancing NMR signals of “insensitive” nuclei are described.

  • Spin order transfer from parahydrogen by INEPT-type pulse sequences is exploited.

  • Free substrate and substrate bound to a complex with parahydrogen are polarized.

  • Sensitive detection of hetero-nuclear 2D NMR spectra is feasible.

Abstract

We describe the performance of methods for enhancing NMR (Nuclear Magnetic Resonance) signals of “insensitive”, but important NMR nuclei, which are based on the SABRE (Signal Amplification By Reversible Exchange) technique, i.e., on spin order transfer from parahydrogen (H2 molecule in its nuclear singlet spin state) to a substrate in a transient organometallic complex. Here such transfer is performed at high magnetic fields by INEPT-type NMR pulse sequences, modified for SABRE. Signal enhancements up to three orders of magnitude are obtained for 15N nuclei; the possibility of sensitive detection of 2D-NMR 1H-15N spectra of SABRE complexes and substrates is demonstrated.

Introduction

SABRE (Signal Amplification By Reversible Exchange) [1], [2] is a promising method for boosting weak NMR signals. SABRE exploits spin order transfer from parahydrogen (pH2, the H2 molecule in its singlet nuclear spin isomer) to a substrate, S, in a suitable transient Ir-based organometallic complex, see Scheme 1. As a result, the substrate acquires strong non-thermal spin polarization, also termed spin hyperpolarization, which can exceed the equilibrium (Boltzmann) polarization by several orders of magnitude. Accordingly, NMR signals of the substrate (both in its free form in solution and in the bound form at the SABRE complex) are strongly enhanced. The spin order transfer in the SABRE complex is efficient at low magnetic fields, notably, at spin Level Anti-Crossings (LACs) of the SABRE complex [3], [4], [5]; recently, it has been shown [6], [7], [8], [9] that high-field SABRE becomes feasible when RF-excitation is used (in order to mimic the low-field conditions, i.e., to create LACs in the RF-rotating frame) or appropriate pulse sequences are exploited.

Despite the fact that the SABRE method is relatively new, several promising applications of this technique in NMR spectroscopy and imaging have already been demonstrated. Notably, applicability of high-field SABRE for trace analysis in complex mixtures has been shown [9], [10], [11]. At the same time, for many NMR applications it is of importance to record spectra not only for protons, but also for hetero-nuclei; furthermore, multi-dimensional hetero-nuclear NMR techniques [12] enable precise characterization of molecules and complexes. In order to perform SABRE experiments on hetero-nuclei and to record multi-dimensional spectra, efficient spin order transfer from pH2 to spin-1/2 hetero-nuclei is a prerequisite. The feasibility of such a transfer directly at the high magnetic field of an NMR spectrometer has been demonstrated [7], [8], [13], but so far not the feasibility of running two-dimensional (2D) hetero-nuclear SABRE-enhanced NMR experiments.

In this work, we make use of pulse sequences based on the INEPT (Insensitive Nuclei Enhanced by Polarization Transfer) method [14] in order to perform spin order transfer from pH2 to hetero-nuclei (in this work, to 15N) and to record 2D NMR spectra. Previously, it was shown [13] that INEPT-based methods are compatible with the SABRE method (although the SABRE technique was named differently in that paper). We demonstrate that the new techniques enable fast and efficient polarization transfer; moreover, polarization of hetero-nuclei can be generated in a continuous way. We also perform a detailed study of the resulting polarization on inter-pulse delays of the pulse sequences, which allow us to optimize the resulting signal enhancement and to determine parameters of SABRE complexes and to measure complex dissociation rates. Experimental studies are performed for pyridine, which is presently the most widely used SABRE substrate, and for imidazole, which also can be polarized by SABRE and used as a pH-sensitive probe [15].

Section snippets

Materials and methods

The pulse sequences, used in our experiments, are presented in Scheme 2 in the order of increasing complexity: each pulse sequence contains the previous one as an initial building block. As we demonstrate below, the first three sequences (a, b and c) allow one to polarize hetero-nuclei; one can choose a specific pulse sequence in order to change the spectral pattern in a desired way or to polarize predominantly the free or bound substrate S. Here, we use two sequences, PH-INEPT and PH-INEPT+.

Results and discussion

First, we utilized the PH-INEPT sequence [23], [24], which is different from the classical INEPT sequence by the flip angle of the first pulse in the proton channel (with pH2, π/4 pulses should be used [23], [25] to generate transverse spin magnetization). In this case, the substrate (in this example, Py) can be strongly polarized, see Fig. 1a, predominantly, ePy. The 15N NMR enhancement achieved is about 3200 for ePy; enhanced 15N NMR lines are also observed for fPy. The enhancement, hereafter

Conclusions

Thus, we have performed a systematic study of polarization transfer from parahydrogen to 15N-nuclei in SABRE experiments. Such a polarization transfer allows one to hyperpolarize “insensitive” but important NMR nuclei in transient SABRE complexes. The methods used here exploit INEPT-type pulse sequences for spin order transfer, leading to NMR signal enhancement of 2–3 orders of magnitude for 15N nuclei. The PH-INEPT, PH-INEPT+ and SABRE-INEPT sequences allow one to polarize substrate molecules

Acknowledgements

We are thankful to Stephan Knecht (Freiburg) for stimulating discussions and Dr. Pavel A. Petrov (Novosibirsk) for providing the IMes pre-catalyst. This work was financially supported by the Russian Science Foundation (Grant 15-13-20035). KLI and AVY acknowledge FASO Russia for the NMR facility (project 0333-2014-0001).

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