Cross-correlated relaxation in the NMR of near-equivalent spin pairs: Longitudinal relaxation and long-lived singlet order.

The evolution of nuclear spin state populations is investigated for the case of a 13C2-labeled triyne in solution, for which the near-equivalent coupled pairs of 13C nuclei experience cross-correlated relaxation mechanisms. Inversion-recovery experiments reveal different recovery curves for the main peak amplitudes, especially when the conversion of population imbalances to observable coherences is induced by a radio frequency pulse with a small flip angle. Measurements are performed over a range of magnetic fields by using a sample shuttle apparatus. In some cases, the time constant TS for decay of nuclear singlet order is more than 100 times larger than the time constant T1 for the equilibration of longitudinal magnetization. The results are interpreted by a theoretical model incorporating cross-correlated relaxation mechanisms, anisotropic rotational diffusion, and an external random magnetic field. A Lindbladian formalism is used to describe the dissipative dynamics of the spin system in an environment of finite temperature. Good agreement is achieved between theory and experiment.

Robust parahydrogen-induced polarization at high concentrations.

Parahydrogen-induced polarization (PHIP) is a potent technique for generating target molecules with high nuclear spin polarization. The PHIP process involves a chemical reaction between parahydrogen and a target molecule, followed by the transformation of nuclear singlet spin order into magnetization of a designated target nucleus through magnetic field manipulations. Although the singlet-to-magnetization polarization transfer process works effectively at moderate concentrations, it is observed to become much less efficient at high molar polarization, defined as the product of polarization and concentration. This strong dependence on the molar polarization is attributed to interference due to the field produced by the sample magnetization during polarization transfer, which leads to complex dynamics and can severely affect the scalability of the technique. We address this challenge with a pulse sequence that suppresses the influence of the distant dipolar field, while simultaneously achieving singlet-to-magnetization polarization transfer to the desired target spins, free from restrictions on the molar polarization.

Efficient Parahydrogen-Induced 13C Hyperpolarization on a Microfluidic Device.

We show the direct production and detection of 13C-hyperpolarized fumarate by parahydrogen-induced polarization (PHIP) in a microfluidic lab-on-a-chip (LoC) device and achieve 8.5% 13C polarization. This is the first demonstration of 13C-hyperpolarization of a metabolite by PHIP in a microfluidic device. LoC technology allows the culture of mammalian cells in a highly controlled environment, providing an important tool for the life sciences. In-situ preparation of hyperpolarized metabolites greatly enhances the ability to quantify metabolic processes in such systems by microfluidic NMR. PHIP of 1H nuclei has been successfully implemented in microfluidic systems, with mass sensitivities in the range of pmol/s. However, metabolic NMR requires high-yield production of hyperpolarized metabolites with longer spin life times than is possible with 1H. This can be achieved by transfer of the polarization onto 13C nuclei, which exhibit much longer T1 relaxation times. We report an improved microfluidic PHIP device, optimized using a finite element model, that enables the direct and efficient production of 13C-hyperpolarized fumarate.

Squeezing formaldehyde into C60 fullerene.

The cavity inside fullerene C60 provides a highly symmetric and inert environment for housing atoms and small molecules. Here we report the encapsulation of formaldehyde inside C60 by molecular surgery, yielding the supermolecular complex CH2O@C60, despite the 4.4 Å van der Waals length of CH2O exceeding the 3.7 Å internal diameter of C60. The presence of CH2O significantly reduces the cage HOMO-LUMO gap. Nuclear spin-spin couplings are observed between the fullerene host and the formaldehyde guest. The rapid spin-lattice relaxation of the formaldehyde 13C nuclei is attributed to a dominant spin-rotation mechanism. Despite being squeezed so tightly, the encapsulated formaldehyde molecules rotate freely about their long axes even at cryogenic temperatures, allowing observation of the ortho-to-para spin isomer conversion by infrared spectroscopy. The particle in a box nature of the system is demonstrated by the observation of two quantised translational modes in the cryogenic THz spectra.

NMR spectroscopy of a 18O-labeled rhodium paddlewheel complex: Isotope shifts, 103Rh-103Rh spin-spin coupling, and 103Rh singlet NMR.

Despite the importance of rhodium complexes in catalysis, and the favorable 100% natural abundance of the spin-1/2 103Rh nucleus, there are few reports of 103Rh nuclear magnetic resonance (NMR) parameters in the literature. In part, this is the consequence of the very low gyromagnetic ratio of 103Rh and its dismal NMR sensitivity. In a previous paper [Harbor-Collins et al., J. Chem. Phys. 159, 104 307 (2023)], we demonstrated an NMR methodology for 1H-enhanced 103Rh NMR and demonstrated an application to the 103Rh NMR of the dirhodium formate paddlewheel complex. In this paper, we employ selective 18O labeling to break the magnetic equivalence of the 103Rh spin pair of dirhodium formate. This allows the estimation of the 103Rh-103Rh spin-spin coupling and provides access to the 103Rh singlet state. We present the first measurement of a 18O-induced 103Rh secondary isotope shift as well as the first instance of singlet order generated in a 103Rh spin pair. The field-dependence of 103Rh singlet relaxation is measured by field-cycling NMR experiments.

The 103Rh NMR spectroscopy and relaxometry of the rhodium formate paddlewheel complex.

The nuclear magnetic resonance (NMR) spectroscopy of spin-1/2 nuclei with low gyromagnetic ratio is challenging due to the low NMR signal strength. Methodology for the rapid acquisition of 103Rh NMR parameters is demonstrated for the case of the rhodium formate "paddlewheel" complex Rh2(HCO2)4. A scheme is described for enhancing the 103Rh signal strength by polarization transfer from 1H nuclei, which also greatly reduces the interference from ringing artifacts, a common hurdle for the direct observation of low-γ nuclei. The 103Rh relaxation time constants T1 and T2 are measured within 20 min by using 1H-detected experiments. The field dependence of the 103Rh T1 is measured. The high-field relaxation is dominated by the chemical shift anisotropy mechanism. The 103Rh shielding anisotropy is found to be very large: |Δσ| = 9900 ± 540 ppm. This estimate is compared with density functional theory calculations.

Correction: Terahertz spectroscopy of the helium endofullerene He@C60.

Correction for 'Terahertz spectroscopy of the helium endofullerene He@C60' by Tanzeeha Jafari et al., Phys. Chem. Chem. Phys., 2022, 24, 9943-9952, https://doi.org/10.1039/D2CP00515H.

Ne, Ar, and Kr oscillators in the molecular cavity of fullerene C60.

We used THz (terahertz) and INS (inelastic neutron scattering) spectroscopies to study the interaction between an endohedral noble gas atom and the C60 molecular cage. The THz absorption spectra of powdered A@C60 samples (A = Ar, Ne, Kr) were measured in the energy range from 0.6 to 75 meV for a series of temperatures between 5 and 300 K. The INS measurements were carried out at liquid helium temperature in the energy transfer range from 0.78 to 54.6 meV. The THz spectra are dominated by one line, between 7 and 12 meV, at low temperatures for three noble gas atoms studied. The line shifts to higher energy and broadens as the temperature is increased. Using a spherical oscillator model, with a temperature-independent parameterized potential function and an atom-displacement-induced dipole moment, we show that the change of the THz spectrum shape with temperature is caused by the anharmonicity of the potential function. We find good agreement between experimentally determined potential energy functions and functions calculated with Lennard-Jones additive pair-wise potentials with parameters taken from the work of Pang and Brisse, J. Chem. Phys. 97, 8562 (1993).

A combined inelastic neutron scattering and simulation study of the 3He@C60 endofullerene.

The 3He@C60 endofullerene consists of a single 3He atom entrapped inside a C60 fullerene cage. The confining potential, arising from the non-covalent interaction between the enclosed He atom and the C atoms of the cage, is investigated by inelastic neutron scattering. These measurements allow us to obtain information in both energy (ω) and momentum (Q) transfers in the form of the dynamical structure factor S (Q, ω). Simulations of the S (Q, ω) maps are performed for a spherical anharmonic oscillator model. Good agreement between the experimental and simulated data sets is achieved.

The Aharonov-Anandan phase and geometric double-quantum excitation in strongly coupled nuclear spin pairs.

The Aharonov-Anandan phase is a contribution to the phase acquired by the cyclic evolution of a quantum state, which depends only on the geometric properties of its trajectory. We report the study and the exploitation of the Aharonov-Anandan phase by nuclear magnetic resonance interferometry techniques in homonuclear spin-1/2 pairs in the near-equivalence limit. We introduce a new method for engineering effective zero-quantum Hamiltonians with an arbitrary phase in the transverse plane. We use this method to generate a variety of cyclic zero-quantum paths, enabling direct study of the geometric Aharonov-Anandan phase to probe the rotational characteristics of the zero-quantum subspace. We show that the geometric Aharonov-Anandan phase may be used for efficient double-quantum excitation in strongly coupled spin pairs. We find that geometric double-quantum excitation outperforms the standard method by a factor of 2 in experiments performed on a typical case involving near-equivalent spin pairs.

Symmetry-based singlet-triplet excitation in solution nuclear magnetic resonance.

Coupled pairs of spin-1/2 nuclei support one singlet state and three triplet states. In many circumstances, the nuclear singlet order, defined as the difference between the singlet population and the mean of the triplet populations, is a long-lived state that persists for a relatively long time in solution. Various methods have been proposed for generating singlet order, starting from nuclear magnetization. This requires the stimulation of singlet-to-triplet transitions by modulated radiofrequency fields. We show that a recently described pulse sequence, known as PulsePol [Schwartz et al., Sci. Adv., 4, eaat8978 (2018)], is an efficient technique for converting magnetization into long-lived singlet order. We show that the operation of this pulse sequence may be understood by adapting the theory of symmetry-based recoupling sequences in magic-angle-spinning solid-state nuclear magnetic resonance (NMR). The concept of riffling allows PulsePol to be interpreted by using the theory of symmetry-based pulse sequences and explains its robustness. This theory is used to derive a range of new pulse sequences for performing singlet-triplet excitation and conversion in solution NMR. Schemes for further enhancing the robustness of the transformations are demonstrated.

Cross-correlation effects in the solution NMR spectra of near-equivalent spin-1/2 pairs.

The nuclear magnetic resonance (NMR) spectra of spin-1/2 pairs contain four peaks, with two inner peaks much stronger than the outer peaks in the near-equivalence regime. We have observed that the strong inner peaks have significantly different linewidths when measurements were performed on a 13C2-labelled triyne derivative. This linewidth difference may be attributed to strong cross-correlation effects. We develop the theory of cross-correlated relaxation in the case of near-equivalent homonuclear spin-1/2 pairs, in the case of a molecule exhibiting strongly anisotropic rotational diffusion. Good agreement is found with the experimental NMR lineshapes.

31P spin-lattice and singlet order relaxation mechanisms in pyrophosphate studied by isotopic substitution, field shuttling NMR, and molecular dynamics simulation.

Nuclear spin relaxation mechanisms are often difficult to isolate and identify, especially in molecules with internal flexibility. Here we combine experimental work with computation in order to determine the major mechanisms responsible for 31P spin-lattice and singlet order (SO) relaxation in pyrophosphate, a physiologically relevant molecule. Using field-shuttling relaxation measurements (from 2 µT to 9.4 T) and rates calculated from molecular dynamics (MD) trajectories, we identified chemical shift anisotropy (CSA) and spin-rotation as the major mechanisms, with minor contributions from intra- and intermolecular coupling. The significant spin-rotation interaction is a consequence of the relatively rapid rotation of the -PO32- entities around the bridging P-O bonds, and is treated by a combination of MD simulations and quantum chemistry calculations. Spin-lattice relaxation was predicted well without adjustable parameters, and for SO relaxation one parameter was extracted from the comparison between experiment and computation (a correlation coefficient between the rotational motion of the groups).

Synthesis and 83Kr NMR spectroscopy of Kr@C60.

Synthesis of Kr@C60 is achieved by quantitative high-pressure encapsulation of the noble gas into an open-fullerene, and subsequent cage closure. Krypton is the largest noble gas entrapped in C60 using 'molecular surgery' and Kr@C60 is prepared with >99.4% incorporation of the endohedral atom, in ca. 4% yield from C60. Encapsulation in C60 causes a shift of the 83Kr resonance by -39.5 ppm with respect to free 83Kr in solution. The 83Kr spin-lattice relaxation time T1 is approximately 36 times longer for Kr encapsulated in C60 than for free Kr in solution. This is the first characterisation of a stable Kr compound by 83Kr NMR.

Deuteron-Decoupled Singlet NMR in Low Magnetic Fields: Application to the Hyperpolarization of Succinic Acid.

The reaction of unsaturated substrates with hydrogen gas enriched in the para spin isomer leads to products with a high degree of nuclear singlet spin order. This leads to greatly enhanced NMR signals, with important potential applications such as magnetic resonance imaging (MRI) of metabolic processes. Although parahydrogen-induced polarization has the advantage of being cheap, compact, and mobile, especially when performed in ultralow magnetic fields, efficiency is lost when more than a few protons are involved. This strongly restricts the range of compatible substances. We show that these difficulties may be overcome by a combination of deuteration with the application of a sinusoidally modulated longitudinal field as a well as a transverse rotating magnetic field. We demonstrate a six-fold enhancement in the 13 C hyperpolarization of [1-13 C, 2,3-d2 ]-succinic acid, as compared with standard hyperpolarization methods, applied in the same ultralow field regime.

Terahertz spectroscopy of the helium endofullerene He@C60.

We studied the quantized translational motion of single He atoms encapsulated in molecular cages by terahertz absorption. The temperature dependence of the THz absorption spectra of 3He@C60 and 4He@C60 crystal powder samples was measured between 5 and 220 K. At 5 K there is an absorption line at 96.8 cm-1 (2.90 THz) in 3He@C60 and at 81.4 cm (2.44 THz) in 4He@C60, while additional absorption lines appear at higher temperature. An anharmonic spherical oscillator model with a displacement-induced dipole moment was used to model the absorption spectra. Potential energy terms with powers of two, four and six and induced dipole moment terms with powers one and three in the helium atom displacement from the fullerene cage center were sufficient to describe the experimental results. Excellent agreement is found between potential energy functions derived from measurements on the 3He and 4He isotopes. One absorption line corresponds to a three-quantum transition in 4He@C60, allowed by the anharmonicity of the potential function and by the non-linearity of the dipole moment in He atom displacement. The potential energy function of icosahedral symmetry does not explain the fine structure observed in the low temperature spectra.

Weak nuclear spin singlet relaxation mechanisms revealed by experiment and computation.

Nuclear spin singlet states are often found to allow long-lived storage of nuclear magnetization, which can form the basis of novel applications in spectroscopy, imaging, and in studies of dynamic processes. Precisely how long such polarization remains intact, and which factors affect its lifetime is often difficult to determine and predict. We present a combined experimental/computational study to demonstrate that molecular dynamics simulations and ab initio calculations can be used to fully account for the experimentally observed proton singlet lifetimes in ethyl-d5-propyl-d7-maleate in deuterated chloroform as solvent. The correspondence between experiment and simulations is achieved without adjustable parameters. These studies highlight the importance of considering unusual and difficult-to-control mechanisms, such as dipolar couplings to low-gamma solvent nuclei, and to residual paramagnetic species, which often can represent lifetime limiting factors. These results also point to the power of molecular dynamics simulations to provide insights into little-known NMR relaxation mechanisms.

Direct Production of a Hyperpolarized Metabolite on a Microfluidic Chip.

Microfluidic systems hold great potential for the study of live microscopic cultures of cells, tissue samples, and small organisms. Integration of hyperpolarization would enable quantitative studies of metabolism in such volume limited systems by high-resolution NMR spectroscopy. We demonstrate, for the first time, the integrated generation and detection of a hyperpolarized metabolite on a microfluidic chip. The metabolite [1-13C]fumarate is produced in a nuclear hyperpolarized form by (i) introducing para-enriched hydrogen into the solution by diffusion through a polymer membrane, (ii) reaction with a substrate in the presence of a ruthenium-based catalyst, and (iii) conversion of the singlet-polarized reaction product into a magnetized form by the application of a radiofrequency pulse sequence, all on the same microfluidic chip. The microfluidic device delivers a continuous flow of hyperpolarized material at the 2.5 µL/min scale, with a polarization level of 4%. We demonstrate two methods for mitigating singlet-triplet mixing effects which otherwise reduce the achieved polarization level.

Tuning of pH enables carbon-13 hyperpolarization of oxalates by SABRE.

Nuclear spin hyperpolarization transforms typically weak NMR responses into strong signals paving the way for low-gamma nuclei detection within practical time-frames. SABRE (Signal Amplification by Reversible Exchange) is a particularly popular hyperpolarization technique due to its simplicity but the pool of molecules it can polarize is limited. The recent advancement in the form of co-ligands has made SABRE applicable towards molecules with O-donor sites e.g. pyruvate, a key step towards its potential clinical application. Here we explore the SABRE hyperpolarization of another compound with an alpha-keto motif, namely oxalate. We show that hyperpolarization of oxalate may be achieved by adjusting the pH in the presence of sulfoxide co-ligands. The SABRE effect for oxalate in methanol solutions is most effective for the mono-protonated form, which is dominant in the solution around pH ∼2.8. The polarization levels become markedly lower at both higher and lower pH. Employing 50% enriched pH2 we achieve up to 0.33% net 13C polarization in mono-protonated oxalate. In an alternative procedure we show that the hyperpolarization effect in oxalates can also be realised by synthesizing an esterified version of it, without any substantive pH implications. Further, the procedures to create hyperpolarized singlet orders in such substrates are also investigated.

Experimental determination of the interaction potential between a helium atom and the interior surface of a C60 fullerene molecule.

The interactions between atoms and molecules may be described by a potential energy function of the nuclear coordinates. Nonbonded interactions between neutral atoms or molecules are dominated by repulsive forces at a short range and attractive dispersion forces at a medium range. Experimental data on the detailed interaction potentials for nonbonded interatomic and intermolecular forces are scarce. Here, we use terahertz spectroscopy and inelastic neutron scattering to determine the potential energy function for the nonbonded interaction between single He atoms and encapsulating C60 fullerene cages in the helium endofullerenes 3He@C60 and 4He@C60, synthesized by molecular surgery techniques. The experimentally derived potential is compared to estimates from quantum chemistry calculations and from sums of empirical two-body potentials.