Highly efficient polarizing agents for dynamic nuclear polarization
Inventors
SAUVEE, Claire • CASANO, Gilles • Ouari, Olivier • Tordo, Paul • AUSSENAC, Fabien • Rosay, Melanie
Assignees
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Publication Number
US-9738657-B2
Publication Date
2017-08-22
Expiration Date
Abstract
The invention relates to compounds of general formula (I) wherein X is C═O or SO2, M is NR2 or O, and Q1 and Q2 are nitroxide-containing radicals, and their use as a Dynamic Nuclear Polarization (DNP) agent for polarizing an NMR-active spin of a nucleus of an analyte in Nuclear Magnetic Resonance (NMR) spectroscopy.
Core Innovation
The invention relates to compounds of general formula (I) that include cyclic nitroxide components Q1 and Q2 and defined structural variables M, X, a, R1, and R2. The disclosure includes optional formation of a substituted 5- or 6-membered heterocyclic ring when X is CO, a is 1, and M is NR2, together with parameterized substituent and bridging motifs for R1 and R2.
The disclosed chemical embodiments include cyclic nitroxide-containing biradicals and related derivatives such as bPyTurea/PyPOL and PEGylated variants, bCTurea, bTamide, Proxurea/TProxamide, PyPOL and PyPOLPEG derivatives, and named embodiments including AMUPOL, PyPOLC6OH, PyPOLPEG2OH, and PyPOLPEG10. The partial content also describes PEG-triazole linked nitroxide compounds, bis-nitroxide heterocycles, and oxyl or oxidanyl nitroxide derivatives.
The patent positions these compounds as Dynamic Nuclear Polarization (DNP) agent candidates for polarizing NMR-active nuclear spins. The provided examples include characterization and preparation of multiple final compounds and intermediates, with reported analytical information and DNP signal enhancement and polarization build-up time for selected biradical compounds.
Claims Coverage
The claim coverage centers on an independent compound claim for general formula (I) with cyclic nitroxide components Q1 and Q2. The provided claim excerpts also include dependent coverage for using the claimed compound as a DNP agent to polarize NMR-active nuclear spins and analyzing by NMR, with further narrowing to MRI or SS-NMR, a stated DNP agent concentration range, and selected named compound embodiments.
General formula (I) with cyclic nitroxide components
A compound of general formula (I) wherein M is NR2 or O, X is CO or SO2, a is 1 or 0, R1 is H or a defined substituted or linked group, R2 is independently defined as R1, and Q1 and Q2 are a cyclic nitroxide of the specified formula.
Optional substituted 5- or 6-membered heterocyclic ring formation
If X is CO, a is 1, and M is NR2, R1 and R2 form together with the group X and the atoms to which they are bound a substituted 5- or 6-membered heterocyclic ring.
Selecting a named bPyTurea/PyPOL or PyPOLPEG embodiment
The compound according to claim 1 is selected from specified bPyTurea/PyPOL and related named derivatives including bPyTureaPEG2, bPyTureaPEG4 (AMUPOL), PyPOLC6OH, PyPOLPEG2OH, and PyPOLPEG10.
DNP agent for polarizing NMR-active nuclear spins
A method that polarizes NMR-active nuclear spins in an analyte by preparing a sample with the analyte and a compound according to claim 1 as a DNP agent, then analyzing it using NMR spectroscopy.
NMR spectroscopy performed as Magnetic Resonance Imaging
The NMR spectroscopy is performed as Magnetic Resonance Imaging (MRI).
NMR spectroscopy performed as solid-state NMR
The NMR spectroscopy is performed as solid-state NMR (SS-NMR) spectroscopy.
DNP agent concentration range
The method uses a DNP agent concentration in the range from about 1 mM to about 200 mM.
The claim coverage is directed to cyclic nitroxide compounds of general formula (I), including optional heterocycle formation and parameterized substituent motifs, together with dependent coverage for DNP-based NMR analysis using the claimed compounds, including MRI or SS-NMR modalities, a stated concentration range, and named bPyTurea/PyPOL-related embodiments.
Stated Advantages
Stability and water solubility are presented for example embodiments.
DNP signal enhancement and polarization build-up time are reported for selected biradical compounds.
Documented Applications
Polarizing NMR-active nuclear spins in an analyte using a DNP agent and analyzing by NMR spectroscopy.
Polarizing NMR-active nuclear spins with NMR spectroscopy performed as Magnetic Resonance Imaging (MRI).
Polarizing NMR-active nuclear spins with NMR spectroscopy performed as solid-state NMR (SS-NMR) spectroscopy.
DNP in liquid-state NMR.
DNP in SS-NMR (solid-state NMR).
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