Polarizing agents for efficient high field DNP solid-state NMR spectroscopy under magic-angle spinning: from design principles to formulation strategies.

Dynamic Nuclear Polarization (DNP) has recently emerged as a cornerstone approach to enhance the sensitivity of solid-state NMR spectroscopy under Magic Angle Spinning (MAS), opening unprecedented analytical opportunities in chemistry and biology. DNP relies on a polarization transfer from unpaired electrons (present in endogenous or exogenous polarizing agents) to nearby nuclei. Developing and designing new polarizing sources for DNP solid-state NMR spectroscopy is currently an extremely active research field per se, that has recently led to significant breakthroughs and key achievements, in particular at high magnetic fields. This review describes recent developments in this area, highlighting key design principles that have been established over time and led to the introduction of increasingly more efficient polarizing sources. After a short introduction, Section 2 presents a brief history of solid-state DNP, highlighting the main polarization transfer schemes. The third section is devoted to the development of dinitroxide radicals, discussing the guidelines that were progressively established to design the fine-tuned molecular structures in use today. In Section 4, we describe recent efforts in developing hybrid radicals composed of a narrow EPR line radical covalently linked to a nitroxide, highlighting the parameters that modulate the DNP efficiency of these mixed structures. Section 5 reviews recent advances in the design of metal complexes suitable for DNP MAS NMR as exogenous electron sources. In parallel, current strategies that exploit metal ions as endogenous polarization sources are discussed. Section 6 briefly describes the recent introduction of mixed-valence radicals. In the last part, experimental aspects regarding sample formulation are reviewed to make best use of these polarizing agents in a broad panel of application fields.

Speciation and Structures in Pt Surface Sites Stabilized by N-Heterocyclic Carbene Ligands Revealed by Dynamic Nuclear Polarization Enhanced Indirectly Detected 195Pt NMR Spectroscopic Signatures and Fingerprint Analysis.

N-Heterocyclic carbenes (NHCs) are widely used ligands in transition metal catalysis. Notably, they are increasingly encountered in heterogeneous systems. While a detailed knowledge of the possibly multiple metal environments would be essential to understand the activity of metal-NHC-based heterogeneous catalysts, only a few techniques currently have the ability to describe with atomic-resolution structures dispersed on a solid support. Here, we introduce a new dynamic nuclear polarization (DNP) surface-enhanced solid-state nuclear magnetic resonance (NMR) approach that, in combination with advanced density functional theory (DFT) calculations, allows the structure characterization of isolated silica-supported Pt-NHC sites. Notably, we demonstrate that the signal amplification provided by DNP in combination with fast magic angle spinning enables the implementation of sensitive 13C-195Pt correlation experiments. By exploiting 1J(13C-195Pt) couplings, 2D NMR spectra were acquired, revealing two types of Pt sites. For each of them, 1J(13C-195Pt) value was determined as well as 195Pt chemical shift tensor parameters. To interpret the NMR data, DFT calculations were performed on an extensive library of molecular Pt-NHC complexes. While one surface site was identified as a bis-NHC compound, the second site most likely contains a bidentate 1,5-cyclooctadiene ligand, pointing to various parallel grafting mechanisms. The methodology described here represents a new step forward in the atomic-level description of catalytically relevant surface metal-NHC complexes. In particular, it opens up innovative avenues for exploiting the spectral signature of platinum, one of the most widely used transition metals in catalysis, but whose use for solid-state NMR remains difficult. Our results also highlight the sensitivity of 195Pt NMR parameters to slight structural changes.

Molecular and Electronic Structure of Isolated Platinum Sites Enabled by the Expedient Measurement of 195Pt Chemical Shift Anisotropy.

Techniques that can characterize the molecular structures of dilute surface species are required to facilitate the rational synthesis and improvement of Pt-based heterogeneous catalysts. 195Pt solid-state NMR spectroscopy could be an ideal tool for this task because 195Pt isotropic chemical shifts and chemical shift anisotropy (CSA) are highly sensitive probes of the local chemical environment and electronic structure. However, the characterization of Pt surface-sites is complicated by the typical low Pt loadings that are between 0.2 and 5 wt% and broadening of 195Pt solid-state NMR spectra by CSA. Here, we introduce a set of solid-state NMR methods that exploit fast MAS and indirect detection using a sensitive spy nucleus (1H or 31P) to enable the rapid acquisition of 195Pt MAS NMR spectra. We demonstrate that high-resolution wideline 195Pt MAS NMR spectra can be acquired in minutes to a few hours for a series of molecular and single-site Pt species grafted on silica with Pt loading of only 3-5 wt%. Low-power, long-duration, sideband-selective excitation, and saturation pulses are incorporated into t1-noise eliminated dipolar heteronuclear multiple quantum coherence, perfect echo resonance echo saturation pulse double resonance, or J-resolved pulse sequences. The complete 195Pt MAS NMR spectrum is then reconstructed by recording a series of 1D NMR spectra where the offset of the 195Pt pulses is varied in increments of the MAS frequency. Analysis of the 195Pt MAS NMR spectra yields the 195Pt chemical shift tensor parameters. Zeroth order approximation density functional theory calculations accurately predict 195Pt CS tensor parameters. Simple and predictive orbital models relate the CS tensor parameters to the Pt electronic structure and coordination environment. The methodology developed here paves the way for the detailed structural and electronic analysis of dilute platinum surface-sites.

Design Principles for the Development of Gd(III) Polarizing Agents for Magic Angle Spinning Dynamic Nuclear Polarization.

Nuclear magnetic resonance suffers from an intrinsically low sensitivity, which can be overcome by dynamic nuclear polarization (DNP). Gd(III) complexes are attractive exogenous polarizing agents for magic angle spinning (MAS) DNP due to their high chemical stability in contrast to nitroxide-based radicals. However, even the state-of-the-art Gd(III) complexes have so far provided relatively low DNP signal enhancements of ca. 36 in comparison to standard DNP biradicals, which show enhancements of over 200. Here, we report a series of new Gd(III) complexes for DNP and show that the observed DNP enhancements of the new and existing Gd(III) complexes are inversely proportional to the square of the zero-field splitting (ZFS) parameter D, which is in turn determined by the ligand-type and the local coordination environment. The experimental DNP enhancements at 9.4 T and the ZFS parameters measured with pulsed electron paramagnetic resonance (EPR) spectroscopy agree with the above model, paving the way for the development of more efficient Gd(III) polarizing agents.

Efficient Dynamic Nuclear Polarization up to 230 K with Hybrid BDPA-Nitroxide Radicals at a High Magnetic Field.

Pairing the spectral resolution provided by high magnetic fields at ambient temperature with the enhanced sensitivity offered by dynamic nuclear polarization (DNP) is a major goal of modern solid-state NMR spectroscopy, which will allow one to unlock ever-challenging applications. This study demonstrates that, by combining HyTEK2, a hybrid BDPA-nitroxide biradical polarizing agent, with ortho-terphenyl (OTP), a rigid DNP matrix, enhancement factors as high as 65 can be obtained at 230 K, 40 kHz magic angle spinning (MAS), and 18.8 T. The temperature dependence of the DNP enhancement and its behavior around the glass transition temperature (Tg) of the matrix is investigated by variable-temperature EPR measurements of the electron relaxation properties and numerical simulations. A correlation is suggested between the decrease in enhancement at the passage of the Tg and the concomitant drop of both transverse electron relaxation times in the biradical.

The Structure of Molecular and Surface Platinum Sites Determined by DNP-SENS and Fast MAS 195Pt Solid-State NMR Spectroscopy.

The molecular level characterization of heterogeneous catalysts is challenging due to the low concentration of surface sites and the lack of techniques that can selectively probe the surface of a heterogeneous material. Here, we report the joint application of room temperature proton-detected NMR spectroscopy under fast magic angle spinning (MAS) and dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP-SENS), to obtain the 195Pt solid-state NMR spectra of a prototypical example of highly dispersed Pt sites (single site or single atom), here prepared via surface organometallic chemistry, by grafting [(COD)Pt(OSi(OtBu)3)2] (1, COD = 1,5-cyclooctadiene) on partially dehydroxylated silica (1@SiO2). Compound 1@SiO2 has a Pt loading of 3.7 wt %, a surface area of 200 m2/g, and a surface Pt density of around 0.6 Pt site/nm2. Fast MAS 1H{195Pt} dipolar-HMQC and S-REDOR experiments were implemented on both the molecular precursor 1 and on the surface complex 1@SiO2, providing access to 195Pt isotropic shifts and Pt-H distances, respectively. For 1@SiO2, the measured isotropic shift and width of the shift distribution constrain fits of the static wide-line DNP-enhanced 195Pt spectrum, allowing the 195Pt chemical shift tensor parameters to be determined. Overall the NMR data provide evidence for a well-defined, single-site structure of the isolated Pt sites.

Open and Closed Radicals: Local Geometry around Unpaired Electrons Governs Magic-Angle Spinning Dynamic Nuclear Polarization Performance.

The development of magic-angle spinning dynamic nuclear polarization (MAS DNP) has allowed atomic-level characterization of materials for which conventional solid-state NMR is impractical due to the lack of sensitivity. The rapid progress of MAS DNP has been largely enabled through the understanding of rational design concepts for more efficient polarizing agents (PAs). Here, we identify a new design principle which has so far been overlooked. We find that the local geometry around the unpaired electron can change the DNP enhancement by an order of magnitude for two otherwise identical conformers. We present a set of 13 new stable mono- and dinitroxide PAs for MAS DNP NMR where this principle is demonstrated. The radicals are divided into two groups of isomers, named open (O-) and closed (C-), based on the ring conformations in the vicinity of the N-O bond. In all cases, the open conformers exhibit dramatically improved DNP performance as compared to the closed counterparts. In particular, a new urea-based biradical named HydrOPol and a mononitroxide O-MbPyTol yield enhancements of 330 ± 60 and 119 ± 25, respectively, at 9.4 T and 100 K, which are the highest enhancements reported so far in the aqueous solvents used here. We find that while the conformational changes do not significantly affect electron spin-spin distances, they do affect the distribution of the exchange couplings in these biradicals. Electron spin echo envelope modulation (ESEEM) experiments suggest that the improved performance of the open conformers is correlated with higher solvent accessibility.

TinyPols: a family of water-soluble binitroxides tailored for dynamic nuclear polarization enhanced NMR spectroscopy at 18.8 and 21.1 T.

Dynamic Nuclear Polarization (DNP) has recently emerged as a key method to increase the sensitivity of solid-state NMR spectroscopy under Magic Angle Spinning (MAS). While efficient binitroxide polarizing agents such as AMUPol have been developed for MAS DNP NMR at magnetic fields up to 9.4 T, their performance drops rapidly at higher fields due to the unfavorable field dependence of the cross-effect (CE) mechanism and AMUPol-like radicals were so far disregarded in the context of the development of polarizing agents for very high-field DNP. Here, we introduce a new family of water-soluble binitroxides, dubbed TinyPols, which have a three-bond non-conjugated flexible amine linker allowing sizable couplings between the two unpaired electrons. We show that this adjustment of the linker is crucial and leads to unexpectedly high DNP enhancement factors at 18.8 T and 21.1 T: an improvement of about a factor 2 compared to AMUPol is reported for spinning frequencies ranging from 5 to 40 kHz, with ε H of up to 90 at 18.8 T and 38 at 21.1 T for the best radical in this series, which are the highest MAS DNP enhancements measured so far in aqueous solutions at these magnetic fields. This work not only breathes a new momentum into the design of binitroxides tailored towards high magnetic fields, but also is expected to push the application frontiers of high-resolution DNP MAS NMR, as demonstrated here on a hybrid mesostructured silica material.

A Factor Two Improvement in High-Field Dynamic Nuclear Polarization from Gd(III) Complexes by Design.

Gadolinium(III) complexes have recently been demonstrated to have potential as polarizing agents for high-field dynamic nuclear polarization (DNP) NMR spectroscopy. By tailoring the ligand design to reduce the zero-field splitting (ZFS), we demonstrate a quadratic improvement in DNP through the investigation of a stable, water-soluble, narrow-line Gd(III) complex, [Gd(tpatcn)], doubling the magic-angle-spinning DNP enhancement of the previous state-of-the-art [Gd(dota)(H2O)]- at 9.4 T and 100 K.

BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T.

Dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance (NMR) has developed into an invaluable tool for the investigation of a wide range of materials. However, the sensitivity gain achieved with many polarizing agents suffers from an unfavorable field and magic angle spinning (MAS) frequency dependence. We present a series of new hybrid biradicals, soluble in organic solvents, that consist of an isotropic narrow electron paramagnetic resonance line radical, α,γ-bisdiphenylene-ß-phenylallyl (BDPA), tethered to a broad line nitroxide. By tuning the distance between the two electrons and the substituents at the nitroxide moiety, correlations between the electron-electron interactions and the electron spin relaxation times on one hand and the DNP enhancement factors on the other hand are established. The best radical in this series has a short methylene linker and bears bulky phenyl spirocyclohexyl ligands. In a 1.3 mm prototype DNP probe, it yields enhancements of up to 185 at 18.8 T (800 MHz 1H resonance frequency) and 40 kHz MAS. We show that this radical gives enhancement factors of over 60 in 3.2 mm sapphire rotors at both 18.8 and 21.1 T (900 MHz 1H resonance frequency), the highest magnetic field available today for DNP. The effect of the rotor size and of the microwave irradiation inside the MAS rotor is discussed. Finally, we demonstrate the potential of this new series of polarizing agents by recording high field 27Al and 29Si DNP surface enhanced NMR spectra of amorphous aluminosilicates and 17O NMR on silica nanoparticles.