Rigid dinitroxide biradical compounds used as improved polarizing agents for dynamic nuclear polarization techniques

Inventors

Ouari, Olivier • Tordo, Paul • CASANO, Gilles • Rosay, Melanie • AUSSENAC, Fabien • Coperet, Christophe • Lesage, Anne • Rossini, Aaron • Emsley, Lyndon • Zagdoun, Alexandre

Assignees

Eidgenoessische Technische Hochschule Zurich ETHZ • Universite Claude Bernard Lvon 1 • Aix Marseille Universite • Centre National de la Recherche Scientifique CNRS • Ecole Normale Superieure de Lyon • Bruker Biospin SAS • Universite Claude Bernard Lyon 1

Abstract

The present invention relates to a dinitroxide biradical compound of general formula (I): In formula (I), A is a carbon, an ammonium, or a phosphonium; each of A1 to A6 is a single bond, O, N, N(O), S, S(O), SO2, C(O), or a (C1-C4) alkyl chain; and Z1 and Z2 are selected from R1 and R2 in combination, so that there is always at least one R2 group that is substituted with R3 group. In Z1 and Z2, R1 is an H, an aryl, or a heteroaryl; R2 is an alkyl chain, an alkenyl chain, an alkynyl chain, a cycloalkyl, a heterocycloalkyl, an aryl, or a heteroaryl; and R3 is an alkyl chain, an alkenyl chain, an alkynyl chain, a cycloalkyl, a heterocycloalkyl, an aryl, a heteroaryl, an ether, an ester, or an azide. When Z1 and Z2 are combined together with the same carbon atom of the nitroxide ring to which they are bonded, they form a spirocycloalkyl or a spiroheterocycloalkyl, the spirocycloalkyl or the spiroheterocycloalkyl being substituted with R3.

Core Innovation

The invention relates to rigid dinitroxide biradical polarizing agents for dynamic nuclear polarization (DNP). The compounds are defined by a broad general formula (I) in which two nitroxide units are held by a rigid linkage, and the nitroxide ring carbon is substituted with a spirocycloalkyl or spiroheterocycloalkyl group through variables including Z1, Z2, and R groups.

In the described structures, Z1 and Z2, combined together with the same carbon atom of the nitroxide unit to which they are bound, form a spirocyclohexyl substituted with one or two groups R3. R3 is a phenyl group, optionally substituted with one or more groups R4, with R4 being a phenyl. The variables A/A1-A6, Z1/Z2, and R1/R2/R3 with optional R4 allow solubilizing, reactive, photosensitizing, and isotopic labeling groups.

Preferred embodiments identify specific polarizing agents, including TEKPol derivatives such as bPhCTbK/TEKPol, TEKPol2, and TEKPol3. Comparative efficacy data are described using DNP MAS 13C amplification factors ε versus reference bTbK, together with EPR spectra and performance tables for the TEKPol derivatives.

Claims Coverage

The independent claims cover three inventive features: a biradical compound, a method of polarization using that polarizing agent, and methods of nuclear magnetic resonance analysis, particle physics, or medical imaging in which a sample is polarized using that polarizing agent.

The claim set centers on the specified dinitroxide biradical architecture with a rigid linkage and a spirocyclohexyl substitution formed by Z1 and Z2 on the nitroxide-bound carbon, where R3 is phenyl and R4 is phenyl. This polarizing agent is then used to polarize a sample for DNP-related polarization and for methods directed to nuclear magnetic resonance analysis, particle physics, or medical imaging.

Stated Advantages

Documented Applications