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

Patent metadata

Field	Value
Publication number	US-11001593-B2
Application number	US-201414784472-A
Country	US
Kind code	B2
Filing date	Apr 15, 2014
Priority date	Apr 15, 2013
Publication date	May 11, 2021
Grant date	May 11, 2021

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), SO 2 , 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.

First claim

The invention claimed is:

1. A biradical compound of the formula below:

wherein
two nitroxide units are held by a rigid linkage, and
Z 1 and Z 2 , 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 being a phenyl group optionally substituted with one or more groups R4, in which R4 is a phenyl.

2. The biradical compound of claim 1 , wherein the biradical compound is labelled isotopically with one of deuterium, carbon 13, and nitrogen 15.

3. The biradical compound of claim 1 , which is 22,41-dinitroxyl-3,19,26,38-tetraphenyl-22,41 diazaheptaspiro [5.1.2.2.1.5.1.5.1.2.2.1.5.1] hentetracontane, 22,41-dinitroxyl-2,4,18,20,25,27,37,39-octaphenyl-22,41 diazaheptaspiro [5.1.2.2.1.5.1.5.1.2.2.1.5.1] hentetracontane, or 22,41-dinitroxyl-3,19,26,38-tetra-p-biphenyl-22,41 diazaheptaspiro [5.1.2.2.1.5.1.5.1.2.2.1.5.1] hentetracontane, the spirocyclohexyl in each compound being substituted with one or two groups R3, R3 being a phenyl group optionally substituted with one or more groups R4, in which R4 is a phenyl.

4. A paramagnetic compound comprising at least one nitroxide unit contained in the biradical compound of claim 1 .

5. A composition comprising at least one biradical compound of claim 1 , or at least one paramagnetic compound of claim 4 .

6. The composition of claim 5 , comprising at least one biradical compound of claim 3 .

7. A method of polarization of a sample, comprising a step of bringing the sample into contact with a polarizing agent, wherein the polarizing agent is a biradical compound of the formula below:

wherein
two nitroxide units are held by a rigid linkage, and

Z 1 and Z 2 , 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 being a phenyl group optionally substituted with one or more groups R4, in which R4 is a phenyl;
or the polarizing agent is a paramagnetic compound having at least one nitroxide unit contained in the biradical compound.

8. A method of nuclear magnetic resonance analysis, particle physics, or medical imaging, comprising polarization of a sample, in which the sample is brought into contact with a polarizing agent, wherein the polarizing agent is a biradical compound of the formula below:

wherein
two nitroxide units are held by a rigid linkage, and

Z 1 and Z 2 , 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 being a phenyl group optionally substituted with one or more groups R4, in which R4 is a phenyl;
or the polarizing agent is a paramagnetic compound having at least one nitroxide unit contained in the biradical compound.

Assignees

• Univ Aix Marseille
• Centre Nat Rech Scient
• Bruker Biospin
• Ecole Normale Superieure Lyon
• Eth Zuerich
• Univ Claude Bernard Lyon
• Univ Claude Bernard Lvon 1

Inventors

• Ouari Olivier
• Tordo Paul
• Casano Gilles
• Rosay Melanie
• Aussenac Fabien
• Coperet Christophe
• Lesage Anne
• Rossini Aaron
• Emsley Lyndon
• Zagdoun Alexandre

Classifications

• G01R33/282

  Means specially adapted for hyperpolarisation or for hyperpolarised contrast agents, e.g. for the generation of hyperpolarised gases using optical pumping cells, for storing hyperpolarised contrast agents or for the determination of the polarisation of a hyperpolarised contrast agent · CPC title

• C07D491/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title

• G01N24/08

  by using nuclear magnetic resonance (G01N24/12 takes precedence) · CPC title