Combining fast magic angle spinning dynamic nuclear polarization with indirect detection to further enhance the sensitivity of solid-state NMR spectroscopy

Highlights

• Dynamic nuclear polarization (DNP) and fast magic angle spinning are jointly used to boost sensitivity of solid-state NMR.

• Proton-detected 2D heteronuclear correlation (idHETCOR) DNP experiments on ¹³C, ¹¹³Cd, ¹⁵N, and ⁸⁹Y nuclei are reported.

• For ¹⁵N and ⁸⁹Y these experiments provide better absolute sensitivities than the DNP-enhanced 2D HETCOR experiments.

Abstract

Dynamic nuclear polarization (DNP) and indirect detection are two commonly applied approaches for enhancing the sensitivity of solid-state NMR spectroscopy. However, their use in tandem has not yet been investigated. With the advent of low-temperature fast magic angle spinning (MAS) probes with 1.3-mm diameter rotors capable of MAS at 40 ​kHz it becomes feasible to combine these two techniques. In this study, we performed DNP-enhanced 2D indirectly detected heteronuclear correlation (idHETCOR) experiments on ¹³C, ¹⁵N, ¹¹³Cd and ⁸⁹Y nuclei in functionalized mesoporous silica, CdS nanoparticles, and Y₂O₃ nanoparticles. The sensitivity of the 2D idHETCOR experiments was compared with those of DNP-enhanced directly-detected 1D cross polarization (CP) and 2D HETCOR experiments performed with a standard 3.2-mm rotor. Due to low CP polarization transfer efficiencies and large proton linewidth, the sensitivity gains achieved by indirect detection alone were lower than in conventional (non-DNP) experiments. Nevertheless, despite the smaller sample volume the 2D idHETCOR experiments showed better absolute sensitivities than 2D HETCOR experiments for nuclei with the lowest gyromagnetic ratios. For ⁸⁹Y, 2D idHETCOR provided 8.2 times better sensitivity than the 1 D⁸⁹Y-detected CP experiment performed with a 3.2-mm rotor.

Introduction

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful technique for the atomic level characterization of organic, inorganic, biological, and hybrid materials. SSNMR, however, suffers from an intrinsically low sensitivity which derives from the small gyromagnetic ratios of nuclei, low natural isotopic abundance, large anisotropic interactions and unfavorable relaxation times. This drawback is further exacerbated in samples with dilute sites, such as functionalized mesoporous silica nanoparticles (MSNs), metal-organic frameworks (MOFs), semiconductor nanoparticles, and biological macromolecules. Researchers have devoted a tremendous effort to overcome this issue. Over the past two decades, two techniques have emerged to improve the sensitivity of SSNMR spectroscopy: the indirect detection, commonly through protons, performed with fast magic angle spinning (MAS) [[1], [2], [3], [4], [5], [6], [7], [8]] and high-field MAS dynamic nuclear polarization (DNP) [[9], [10], [11], [12], [13], [14], [15], [16], [17]].

The two-dimensional (2D) heteronuclear correlation experiments with indirect detection (idHETCOR) in SSNMR were inspired by heteronuclear single quantum correlation (HSQC) [1,2,4,18] and heteronuclear multiple quantum correlation (HMQC) experiments [19,20] in solution NMR. In idHETCOR, polarization transfers can be achieved either through-space, usually with cross-polarization (CP) [1,2,4,21], or through-bond, via INEPT [5,18]. CP-based idHETCOR experiments are more routine and generally provide better sensitivity. In 2000, Ishii and Tycko first demonstrated that under fast MAS condition the CP idHETCOR experiment provided better sensitivity than the established HETCOR experiment with direct detection of ¹³C and ¹⁵N [1]. In 2003, Paulson et al. illustrated a modified version of this experiment in which the constant time concept was introduced to better suppress water peaks and reduce the t₁-noise [21]. In subsequent work, HORROR saturation pulses were combined with a z-filter to eliminate the uncorrelated ¹H magnetization remaining after the evolution period and further diminish the t₁-noise [2,4]. In 2009, Mao and Pruski replaced the second CP transfer with refocused INEPT, which resulted in through-bond correlation spectra [18]. In 2014, with the advent of ultrafast MAS probeheads, Nishiyama et al. extended the dimensionality of indirect detection experiment to three [22]. In 2018, Venkatesh et al. demonstrated that idHETCOR experiments could be applied to nuclei with very low gyromagnetic ratio, like ⁸⁹Y, ¹⁰³Rh, ¹⁰⁹Ag and ¹⁸³W [8].

DNP enhances the sensitivity by transferring the much larger spin polarization of unpaired electron spins to nearby nuclei under microwave (MW) irradiation [11]. In high field DNP experiments under MAS, the unpaired electron spins are most commonly supplied by wetting the sample or dissolving it within a glass-forming solution of nitroxide biradicals [23,24]. To improve the sensitivity gains from DNP, researchers have devoted great efforts to design and synthesize new radicals [[25], [26], [27]], optimize the sample preparation procedures [[28], [29], [30], [31], [32]], construct cryogenic hardware [[33], [34], [35], [36]], and develop dedicated pulse sequences [[37], [38], [39], [40], [41], [42]]. This progress led to many spectacular applications of DNP to the studies of various classes of organic and inorganic solids in chemistry, materials science, and biochemistry [28,[43], [44], [45]]. Until recently, DNP SSNMR experiments were performed with low MAS frequencies of 20 ​kHz or less. However, the development of a commercial 1.3-mm probe capable of 40 ​kHz MAS at ~100 ​K has opened new opportunities for DNP SSNMR [16,46,47]. Chaudhari et al. observed the enhancement factor in such a probe to be roughly constant in the MAS frequency range of 10–40 ​kHz, for a 60:30:10 glycerol-d8/D₂O/H₂O sample, but that an increase in MAS frequency led to a reduced contribution factor (θ) and longer DNP build-up times [16]. Similarly, Perras and Pruski observed a monotonic decrease of sensitivity in the same range of MAS frequencies for protonated, and partially-deuterated, 1,1,2,2-tetrachoroethane (TCE) solutions as well as for crystalline sucrose [48], which is in agreement with theoretical models of CE DNP with nitroxide biradicals [[49], [50], [51]]. Importantly, the advent of fast MAS DNP probes offers the possibility for combining indirect detection with DNP; however, the feasibility and potential benefits of DNP idHETCOR have not been broadly assessed.

To determine the utility of combining ¹H-detection with DNP, HETCOR and idHETCOR experiments were performed on nuclei with a wide range of gyromagnetic ratios (¹³C, ¹⁵N, ¹¹³Cd, ⁸⁹Y). The materials involved are functionalized MSNs, cadmium sulfide nanoparticles (CdS NPs), and yttrium oxide NPs. Note that the terms ¹H-detection and indirect detection are used interchangeably throughout the manuscript. The sensitivities of indirectly detected experiments with a 1.3-mm probe were systematically compared to their directly detected counterpart acquired using a 3.2-mm probe under DNP conditions to account for the reduced sample size in the 1.3-mm rotor.