Frédéric A. Perras

Natural abundance 17O DNP two-dimensional and surface-enhanced NMR spectroscopy

Due to its extremely low natural abundance and quadrupolar nature, the (17)O nuclide is very rarely used for spectroscopic investigation of solids by NMR without isotope enrichment. Additionally, the applicability of dynamic nuclear polarization (DNP), which leads to sensitivity enhancements of 2 orders of magnitude, to (17)O is wrought with challenges due to the lack of spin diffusion and low polarization transfer efficiency from (1)H. Here, we demonstrate new DNP-based measurements that extend (17)O solid-state NMR beyond its current capabilities. The use of the PRESTO technique instead of conventional (1)H-(17)O cross-polarization greatly improves the sensitivity and enables the facile measurement of undistorted line shapes and two-dimensional (1)H-(17)O HETCOR NMR spectra as well as accurate internuclear distance measurements at natural abundance. This was applied for distinguishing hydrogen-bonded and lone (17)O sites on the surface of silica gel; the one-dimensional spectrum of which could not be used to extract such detail. Lastly, this greatly enhanced sensitivity has enabled, for the first time, the detection of surface hydroxyl sites on mesoporous silica at natural abundance, thereby extending the concept of DNP surface-enhanced NMR spectroscopy to the (17)O nuclide.

Direct investigation of covalently bound chlorine in organic compounds by solid-state 35Cl NMR spectroscopy and exact spectral line-shape simulations.

35/37Cl NMR spectroscopy studies of organic systems are very rare, with only a few neat liquids having been studied.1 The lack of chlorine NMR spectroscopy data may be explained by the fact that 35Cl and 37Cl are quadrupolar (spin I=3/2) and low-frequency isotopes. The quadrupole moments of the chlorine nuclei couple with the electric field gradient (EFG) tensor at the nuclei; this phenomenon is known as the quadrupolar interaction (QI). The quadrupolar coupling constant, CQ, and the quadrupolar asymmetry parameter, ηQ, describe the magnitude and asymmetry of the QI. In solution, one of the consequences of the QI is fast relaxation, which means that the 35/37Cl NMR signals for covalently bound chlorines are very broad and are of low intensity.1 For these reasons, chemically distinct chlorine sites are very difficult to distinguish with solution NMR spectroscopy. However, in the solid state, nuclear spin relaxation is typically slower, thus enabling higher quality 35Cl NMR spectra to be collected, at least in principle. Unfortunately, the magnitude of the QI for covalently bound chlorines is very large because of the substantial, anisotropic EFG at the Cl atom, owing mainly to its electronic configuration when it forms a chlorine–carbon bond. Conventional wisdom is that such chlorine sites cannot be studied in powders by solid-state NMR spectroscopy as the central transition (CT; mI=1/2↔−1/2) can span tens of megahertz in typical commercially available magnetic fields. For this reason, only ionic chlorides2 and inorganic chlorides3 have been studied, as the EFG at these chlorides is often an order of magnitude smaller than at covalently bound chlorine atoms in organic molecules. The bonding environments for these types of chlorine atoms are substantially different from the environments in those chloride-containing molecules that have been studied previously.2, 3 A partial 35Cl NMR spectrum for hexachlorophene has been briefly mentioned in the literature.4 On the other hand, most of the interesting chlorine chemistry occurs when Cl is covalently bound to a carbon atom, where the chlorine atom often acts as a leaving group. Chlorine atoms are also important in many organic pharmaceuticals as well as in crystal design applications where they can form halogen bonds.5 Recent studies show that covalently bound chlorine is also important in biological chemistry where, for example, the tryptophan 7-halogenase was found to selectively chlorinate tryptophan moieties.6

QUEST—QUadrupolar Exact SofTware: A fast graphical program for the exact simulation of NMR and NQR spectra for quadrupolar nuclei

We present a new program for the exact simulation of solid-state NMR spectra of quadrupolar nuclei in stationary powdered samples which employs diagonalization of the combined Zeeman-quadrupolar Hamiltonian. The program, which we call QUEST (QUadrupolar Exact SofTware), can simulate NMR spectra over the full regime of Larmor and quadrupolar frequency ratios, which encompasses scenarios ranging from high-field NMR to nuclear quadrupole resonance (NQR, where the Larmor frequency is zero) and does not make use of approximations when treating the quadrupolar interaction. With the use of the fast powder averaging scheme of Alderman, Solum, and Grant, exact NMR spectral simulations are only marginally slower than the second-order perturbation theory counterpart. The program, which uses a graphical user interface, also incorporates chemical shift anisotropy and non-coincident chemical shift and quadrupolar tensor frames. The program is validated against newly-acquired experimental data through several examples including: the low-field (79/81)Br NMR spectra of CaBr(2), the (14)N overtone NMR spectrum of glycine, the (187)Re NQR spectra of Re(2)(CO)(10), and lastly the (127)I overtone NQR spectrum of SrI(2), which, to the best of our knowledge, represents the first direct acquisition of an overtone NQR spectrum for a powdered sample.

Signal enhancement in solid-state NMR of quadrupolar nuclei

Recent progress in the development and application of signal enhancement methods for NMR of quadrupolar nuclei in solids is presented. First, various pulse schemes for manipulating the populations of the satellite transitions in order to increase the signal of the central transition (CT) in stationary and rotating solids are evaluated (e.g., double-frequency sweeps, hyperbolic secant pulses). Second, the utility of the quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) and WURST-QCPMG pulse sequences for the rapid and efficient acquisition of particularly broad CT powder patterns is discussed. Third, less frequently used experiments involving polarization transfer from abundant nuclear spins (cross-polarization) or from unpaired electrons (dynamic nuclear polarization) are assessed in the context of recent examples. Advantages and disadvantages of particular enhancement schemes are highlighted and an outlook on possible future directions for the signal enhancement of quadrupolar nuclei in solids is offered.

Potent inhibition of ice recrystallization by low molecular weight carbohydrate-based surfactants and hydrogelators

Ice recrystallization inhibition (IRI) activity is a very desirable property for an effective cryoprotectant. This property was first observed in biological antifreezes (BAs), which cannot be utilized in cryopreservation due to their ability to bind to ice. To date, potent IRI active compounds have been limited to BAs or synthetic C-linked AFGP analogues (1 and 2), all of which are large peptide-based molecules. This paper describes the first example of low molecular weight carbohydrate-based derivatives that exhibit potent IRI activity. Non-ionic surfactant n-octyl-β-D-galactopyranoside (4) exhibited potent IRI activity at a concentration of 22 mM, whereas hydrogelator N-octyl-D-gluconamide (5) exhibited potent IRI activity at a low concentration of 0.5 mM. Thermal hysteresis measurements and solid-state NMR experiments indicated that these derivatives are not exhibiting IRI activity by binding to ice. For non-ionic surfactant derivatives (3 and 4), we demonstrated that carbohydrate hydration is important for IRI activity and that the formation of micelles in solution is not a prerequisite for IRI activity. Furthermore, using solid-state NMR and rheology we demonstrated that the ability of hydrogelators 5 and 6 to form a hydrogel is not relevant to IRI activity. Structure–function studies indicated that the amide bond in 5 is an essential structural feature required for potent IRI activity.

DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal–Organic Frameworks

Ultrawideline dynamic nuclear polarization (DNP)-enhanced (195)Pt solid-state NMR (SSNMR) spectroscopy and theoretical calculations are used to determine the coordination of atomic Pt species supported within the pores of metal-organic frameworks (MOFs). The (195)Pt SSNMR spectra, with breadths reaching 10 000 ppm, were obtained by combining DNP with broadbanded cross-polarization and CPMG acquisition. Although the DNP enhancements in static samples are lower than those typically observed under magic-angle spinning conditions, the presented measurements would be very challenging using the conventional SSNMR methods. The DNP-enhanced ultrawideline NMR spectra served to separate signals from cis- and trans-coordinated atomic Pt(2+) species supported on the UiO-66-NH2 MOF. Additionally, the data revealed a dominance of kinetic effects in the formation of Pt(2+) complexes and the thermodynamic effects in their reduction to nanoparticles. A single cis-coordinated Pt(2+) complex was confirmed in MOF-253.

Pharmaceutical TechnologySodium-23 Ssolid-Sstate Snuclear Smagnetic Sresonance of Scommercial Ssodium Snaproxen and its Ssolvates

We report on the investigation of sodium coordination environments with solid-state ²³Na nuclear magnetic resonance (NMR) spectroscopy of various hydrates and solvates of sodium naproxen (SN), a commercially available anti-inflammatory drug sold over the counter as Aleve®, among other names. The ²³Na quadrupolar coupling constant is found to change significantly depending on the hydration state, and subtle changes in oxygen coordination environment about the sodium cations were apparent in the NMR spectra. High-resolution double-rotation NMR experiments are also performed on powdered samples to obtain solution-like ²³Na NMR spectra. Our attempts at crystallizing various solvates of SN have led to the characterization of the first crystal structure for the heminonahydrated form. The composition of commercial SN is also investigated and it is shown that Aleve® is composed of approximately 80% monohydrate solvate. Density-functional theory calculations, using the gauge-including projector-augmented-wave formalism, allow for the assignment of ²³Na NMR peaks to specific sodium sites in the reported X-ray crystal structure.

Sodium-23 Solid-State Nuclear Magnetic Resonance of Commercial Sodium Naproxen and its Solvates

We report on the investigation of sodium coordination environments with solid-state ²³Na nuclear magnetic resonance (NMR) spectroscopy of various hydrates and solvates of sodium naproxen (SN), a commercially available anti-inflammatory drug sold over the counter as Aleve®, among other names. The ²³Na quadrupolar coupling constant is found to change significantly depending on the hydration state, and subtle changes in oxygen coordination environment about the sodium cations were apparent in the NMR spectra. High-resolution double-rotation NMR experiments are also performed on powdered samples to obtain solution-like ²³Na NMR spectra. Our attempts at crystallizing various solvates of SN have led to the characterization of the first crystal structure for the heminonahydrated form. The composition of commercial SN is also investigated and it is shown that Aleve® is composed of approximately 80% monohydrate solvate. Density-functional theory calculations, using the gauge-including projector-augmented-wave formalism, allow for the assignment of ²³Na NMR peaks to specific sodium sites in the reported X-ray crystal structure.

Boron–boron J coupling constants are unique probes of electronic structure: a solid-state NMR and molecular orbital study

Diboron compounds are a part of a relatively unexplored, yet immensely useful, class of compounds. Their main use is for β-boration reactions where a boron center is rendered nucleophilic with the use of a metal catalyst or a Lewis base (alkoxide, amine, or NHC) to form a sp2–sp3 diboron compound. The reactivity of these reagents is largely dictated by the nature of the B–B bond (strength and polarity); however, no experimental methods have been used to directly probe both of these quantities. We demonstrate that unprecedented experimental information regarding the B–B bond may be obtained using 11B solid-state NMR spectroscopy. For example, the 11B quadrupolar coupling constants can be understood on the basis of the polarization of the B–B bond. 11B double-quantum-filtered (DQF) J-resolved NMR spectroscopy was applied to easily and accurately measure J(11B,11B) coupling constants with high precision. These are shown to be well correlated with the orbital energy of the B–B σ-bonding natural bond orbital as well as the hybridisation states of the boron atoms in the bond. An increase in the p character of the bond by electron-donating ligands or via the formation of a sp2–sp3 diboron compound weakens the bond, increases the bond length, and decreases the J(11B,11B) coupling constants. These experiments provide a detailed experimental characterization of the B–B bond and may be useful in understanding the reactivity of diboron compounds and in designing new systems. The potential applicability of 11B DQF J-resolved NMR spectroscopy towards analyzing complex mixtures of diboron compounds and towards measuring 11B J coupling across multiple intervening bonds is also investigated and shows much promise.

Symmetry-Amplified J Splittings for Quadrupolar Spin Pairs: A Solid- State NMR Probe of Homoatomic Covalent Bonds

Chemically informative J couplings between pairs of quadrupolar nuclei in dimetallic and dimetalloid coordination motifs are measured using J-resolved solid-state NMR experiments. It is shown that the application of a double-quantum filter is necessary to observe the J splittings and that, under these conditions, only a simple doublet is expected. Interestingly, the splitting is amplified if the spins are magnetically equivalent, making it possible to measure highly precise J couplings and unambiguously probe the symmetry of the molecule. This is demonstrated experimentally by chemically breaking the symmetry about a pair of boron spins by reaction with an N-heterocyclic carbene to form a β-borylation reagent. The results show that the J coupling is a sensitive probe of bonding in diboron compounds and that the J values quantify the weakening of the B–B bond which occurs when forming an sp2–sp3 diboron compound, which is relevant to their reactivity. Due to the prevalence of quadrupolar nuclei among transition metals, this work also provides a new approach to probe metal–metal bonding; results for Mn2(CO)10 are provided as an example.