Constant-adiabaticity radiofrequency pulses for generating long-lived singlet spin states in NMR.

A method is implemented to perform "fast" adiabatic variation of the spin Hamiltonian by imposing the constant adiabaticity condition. The method is applied to improve the performance of singlet-state Nuclear Magnetic Resonance (NMR) experiments, specifically, for efficient generation and readout of the singlet spin order in coupled spin pairs by applying adiabatically ramped RF-fields. Test experiments have been performed on a specially designed molecule having two strongly coupled 13C spins and on selectively isotopically labelled glycerol having two pairs of coupled protons. Optimized RF-ramps show improved performance in comparison, for example, to linear ramps. We expect that the methods described here are useful not only for singlet-state NMR experiments but also for other experiments in magnetic resonance, which utilize adiabatic variation of the spin Hamiltonian.

Excitation of singlet-triplet coherences in pairs of nearly-equivalent spins.

We present approaches for an efficient excitation of singlet-triplet coherences in pairs of nearly-equivalent spins. Standard Nuclear Magnetic Resonance (NMR) pulse sequences do not excite these coherences at all or with very low efficiency. The single quantum singlet-triplet coherences, here termed the outer singlet-triplet coherences, correspond to lines of low intensity in the NMR spectrum of a strongly-coupled spin pair (they are sometimes referred to as "forbidden transitions"), whereas the zero-quantum coherences, here termed the inner singlet-triplet coherences, do not have a direct spectral manifestation. In the present study, we investigated singlet-triplet coherences in a pair of nearly-equivalent carbon spins of the 13C-isotopomer of a specially designed naphthalene derivative with optimized relaxation properties. We propose and compare several techniques to drive the singlet-triplet coherence in strongly coupled spin pairs. First, we study different methods for efficient excitation of the outer singlet-triplet coherences. The achieved conversion efficiency of magnetization to the coherences of interest is close to the theoretically allowed maximum. Second, we propose methods to convert the outer coherences into the inner singlet-triplet coherence. The inner singlet-triplet coherence is insensitive to field inhomogeneity and can be long-lived. By probing this coherence, we perform a very precise measurement of the spin-spin J-couplings. A remarkable property of this coherence is that it can be preserved even in absence of a spin-locking radiofrequency field. Consequently, it is possible to shuttle the sample between different magnetic fields preserving the coherence. This allows one to study the field dependence of the relaxation time, TIST, of the inner singlet-triplet coherence by performing field-cycling experiments. We observed dramatic changes of the ratio TIST/T1 from about 1 (in strong fields) up to 2.4 (in weak fields), which is the evidence of a significant influence of the chemical shift anisotropy on relaxation. We have detected a remarkably long lifetime of the inner singlet-triplet coherence of about 200 s at the magnetic field of 5 mT.

Synthesis of an isotopically labeled naphthalene derivative that supports a long-lived nuclear singlet state.

The synthesis of an octa-alkoxy substituted isotopically labeled naphthalene derivative, shown to have excellent properties in singlet NMR experiments, is described. This highly substituted naphthalene system, which incorporates an adjacent (13)C spin pair, is readily accessed from a commercially available (13)C2-labeled building block via sequential thermal alkynyl- and arylcyclobutenone rearrangements. The synthetic route incorporates a simple desymmetrization approach leading to a small difference in the chemical shifts of the (13)C spin pair, a design constraint crucial for accessing nuclear singlet order.

Real-space imaging of macroscopic diffusion and slow flow by singlet tagging MRI.

Magnetic resonance imaging can be used to study motional processes such as flow and diffusion, but the accessible timescales are limited by longitudinal relaxation. The spatially selective conversion from magnetization to long-lived singlet order in designer molecules makes it possible to tag a region of interest for an extended period of time, of the order of several minutes. Here we exploit this concept of "singlet tagging" to monitor diffusion over a macroscopic scale as well as very slow flow.

Theory of long-lived nuclear spin states in methyl groups and quantum-rotor induced polarisation.

Long-lived nuclear spin states have a relaxation time much longer than the longitudinal relaxation time T1. Long-lived states extend significantly the time scales that may be probed with magnetic resonance, with possible applications to transport and binding studies, and to hyperpolarised imaging. Rapidly rotating methyl groups in solution may support a long-lived state, consisting of a population imbalance between states of different spin exchange symmetries. Here, we expand the formalism for describing the behaviour of long-lived nuclear spin states in methyl groups, with special attention to the hyperpolarisation effects observed in (13)CH3 groups upon rapidly converting a material with low-barrier methyl rotation from the cryogenic solid state to a room-temperature solution [M. Icker and S. Berger, J. Magn. Reson. 219, 1 (2012)]. We analyse the relaxation properties of methyl long-lived states using semi-classical relaxation theory. Numerical simulations are supplemented with a spherical-tensor analysis, which captures the essential properties of methyl long-lived states.

A nuclear singlet lifetime of more than one hour in room-temperature solution.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are supremely important techniques with numerous applications in almost all branches of science. However, until recently, NMR methodology was limited by the time constant T1 for the decay of nuclear spin magnetization through contact with the thermal molecular environment. Long-lived states, which are correlated quantum states of multiple nuclei, have decay time constants that may exceed T1 by large factors. Here we demonstrate a nuclear long-lived state comprising two (13)C nuclei with a lifetime exceeding one hour in room-temperature solution, which is around 50 times longer than T1. This behavior is well-predicted by a combination of quantum theory, molecular dynamics, and quantum chemistry. Such ultra-long-lived states are expected to be useful for the transport and application of nuclear hyperpolarization, which leads to NMR and MRI signals enhanced by up to five orders of magnitude.

A Nuclear Singlet Lifetime of More than One Hour in Room-Temperature Solution.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are supremely important techniques with numerous applications in almost all branches of science. However, until recently, NMR methodology was limited by the time constant T1 for the decay of nuclear spin magnetization through contact with the thermal molecular environment. Long-lived states, which are correlated quantum states of multiple nuclei, have decay time constants that may exceed T1 by large factors. Here we demonstrate a nuclear long-lived state comprising two 13C nuclei with a lifetime exceeding one hour in room-temperature solution, which is around 50 times longer than T1. This behavior is well-predicted by a combination of quantum theory, molecular dynamics, and quantum chemistry. Such ultra-long-lived states are expected to be useful for the transport and application of nuclear hyperpolarization, which leads to NMR and MRI signals enhanced by up to five orders of magnitude.

Enhancement of quantum rotor NMR signals by frequency-selective pulses.

Quantum-rotor-induced polarisation (QRIP) enhancement is exhibited by substances which contain freely rotating methyl groups in the solid state, provided that the methyl groups contain a (13)C nucleus. Strong signal enhancements are observed in solution NMR when the material is first equilibrated at cryogenic temperatures, then rapidly dissolved with a warm solvent and transferred into an NMR magnet. QRIP leads to strongly-enhanced (13)C NMR signals, but relatively weak enhancements of the (1)H signals. We show that the (1)H signals suffer from a partial cancellation of degenerate contributions, which may be corrected by applying a frequency-selective π pulse to the inner peaks of the (13)C multiplet prior to (1)H observation.

Long-lived localization in magnetic resonance imaging.

The longitudinal nuclear relaxation time, T1, sets a stringent limit on the range of information that can be obtained from magnetic resonance imaging (MRI) experiments. Long-lived nuclear spin states provide a possibility to extend the timescale over which information can be encoded in magnetic resonance. We introduce a strategy to localize an ensemble of molecules for a significantly extended duration (∼30 times longer than T1 in this example), using a spatially selective conversion between magnetization and long-lived singlet order. An application to tagging and transport is proposed.

Long-lived nuclear spin states in methyl groups and quantum-rotor-induced polarization.

Substances containing rapidly rotating methyl groups may exhibit long-lived states (LLSs) in solution, with relaxation times substantially longer than the conventional spin-lattice relaxation time T1. The states become long-lived through rapid internal rotation of the CH3 group, which imposes an approximate symmetry on the fluctuating nuclear spin interactions. In the case of very low CH3 rotational barriers, a hyperpolarized LLS is populated by thermal equilibration at liquid helium temperature. Following dissolution, cross-relaxation of the hyperpolarized LLS, induced by heteronuclear dipolar couplings, generates strongly enhanced antiphase NMR signals. This mechanism explains the NMR signal enhancements observed for (13)C-γ-picoline (Icker, M.; Berger, S. J. Magn. Reson. 2012, 219, 1-3).

Recycling and imaging of nuclear singlet hyperpolarization.

The strong enhancement of NMR signals achieved by hyperpolarization decays, at best, with a time constant of a few minutes. Here, we show that a combination of long-lived singlet states, molecular design, magnetic field cycling, and specific radiofrequency pulse sequences allows repeated observation of the same batch of polarized nuclei over a period of 30 min and more. We report a recycling protocol in which the enhanced nuclear polarization achieved by dissolution-DNP is observed with full intensity and then returned to singlet order. MRI experiments may be run on a portion of the available spin polarization, while the remaining is preserved and made available for a later use. An analogy is drawn with a "spin bank" or "resealable container" in which highly polarized spin order may be deposited and retrieved.

Long-lived nuclear singlet order in near-equivalent 13C spin pairs.

Molecules that support (13)C singlet states with lifetimes of over 10 min in solution have been designed and synthesized. The (13)C(2) spin pairs in the asymmetric alkyne derivatives are close to magnetic equivalence, so the (13)C long-lived singlet states are stable in high magnetic field and do not require maintenance by a radiofrequency spin-locking field. We suggest a model of singlet relaxation by fluctuating chemical shift anisotropy tensors combined with leakage associated with slightly broken magnetic equivalence. Theoretical estimates of singlet relaxation rates are compared with experimental values. Relaxation due to antisymmetric shielding tensor components is significant.

TEMPO-mediated electrooxidation of primary and secondary alcohols in a microfluidic electrolytic cell.

A general procedure for the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated electrooxidation of primary and secondary alcohols modified for application in a microfluidic electrolytic cell is described. The electrocatalytic system utilises a buffered aqueous tert-butanol reaction medium, which operates effectively without the requirement for additional electrolyte, providing a mild protocol for the oxidation of alcohols to aldehydes and ketones at ambient temperature on a laboratory scale. Optimisation of the process is discussed along with the oxidation of 15 representative alcohols.