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Nuclear spin polarization enhancing method through dynamic nuclear polarization by using soluble pentacene UPDATE_EN

Foreign code F190009890
File No. 08404-EP
Posted date Aug 26, 2019
Country EPO
Application number 16817869
Gazette No. 3315987
Date of filing Jun 27, 2016
Gazette Date May 2, 2018
International application number JP2016069007
International publication number WO2017002761
Date of international filing Jun 27, 2016
Date of international publication Jan 5, 2017
Priority data
  • P2015-129912 (Jun 29, 2015) JP
  • 2016JP69007 (Jun 27, 2016) WO
Title Nuclear spin polarization enhancing method through dynamic nuclear polarization by using soluble pentacene UPDATE_EN
Abstract An object is to provide a method for enhancing a nuclear spin polarization. Triplet DNP where a pentacene derivative represented by the following formula (A) is used as a polarizing agent enables an effective enhancement in nuclear spin polarization to be achieved. In formula (A), each R independently represents a hydrogen atom (-H), a deuterium atom (-D), or a hydrocarbon group having 1 to 20 carbon atoms which optionally includes at least one atom selected from the group consisting of an oxygen atom, a sulfur atom and a silicon atom, provided that at least one R represents a hydrocarbon group having 1 to 20 carbon atoms which optionally includes at least one atom selected from the group consisting of an oxygen atom, a sulfur atom and a silicon atom.
Outline of related art and contending technology BACKGROUND ART
Nuclear magnetic resonance (hereinafter, abbreviated as "NMR".) is a phenomenon where nuclear spin interacts with an electromagnetic wave in a static magnetic field. A signal intensity of NMR is proportional to a "polarization" representing the degree of nuclear spin alignment. A common polarization, however, is not much more than 10-4 to 10-6%, and it can also be thus said that the signal intensity can be potentially still increased by 10000 times or more.
NMR spectroscopy is one important method in chemical analysis. It, however, is known to be significantly inferior in terms of sensitivity as compared with other analysis methods (such as ultraviolet spectroscopy, infrared spectroscopy, and mass spectrometry). If a low polarization which is one cause of such inferiority can be improved, thereby allowing for measurement of an extremely trace amount of a sample, which has been heretofore difficult to measure in terms of sensitivity.
Also in magnetic resonance imaging (hereinafter, abbreviated as "MRI".) widely used in the medical field, a substance enhanced in polarization can also be used as a contrast agent. Such a contrast agent enables an image, which cannot be taken by conventional MRI, such as a metabolic process image, to be taken.
Dynamic nuclear polarization (hereinafter, abbreviated as "DNP".) has attracted attention as one solution for an enhancement in polarization, as described in References listed below, and has been actively researched in recent years (see, for example, Patent Documents 1, 2 and 3). DNP is performed according to the following procedures (1) to (3), namely, (1) doping of an electron spin resonance-(hereinafter, abbreviated as "ESR".)-active molecule serving as a polarizing agent, with a sample, (2) enhancing of electron spin polarization by a temperature drop or the like, and (3) transferring of the polarization to the nuclear spin by use of a microwave. Thus, electron spin functions to increase the polarization state of nuclear spin, and may be thus referred to as a "polarizing agent". In common DNP, an unpaired electron in a radical is used as a polarizing agent, thereby providing electron spin polarization at 1% or more by use of a low-temperature environment of 100K or less. In NMR signal measurement, however, problems are that [1] a radical molecule causes unnecessary relaxation and/or a reduction in resolution, [2] the maximum gain in principle is 660-fold at most in the case of 1H spin, and furthermore [3] an increase in operational cost is caused due to a recent increase in the price of helium, thereby prohibiting widespread use.
Such problems are due to use of a paramagnetic electron in a radical for a polarizing agent, and there is proposed, in order to solve such problems, use of DNP using electron spin at the photoexcited triplet state for a polarizing agent (hereinafter, abbreviated as "triplet DNP".). This electron spin is characterized by not impairing NMR signal measurement because the polarization rate thereof does not depend on the experimental environment and the photoexcited triplet state thereof is rapidly decayed to the ground state after completion of triplet DNP.
The research products by researchers including the present inventor are published in the following URL, and the effectiveness thereof is indicated from the viewpoint that pentacene can achieve a high signal intensity.
http://resou.osaka-u.ac.jp/ja/research/2014/20140513_1
Scope of claims [claim1]
1. A method for enhancing a nuclear spin polarization by triplet DNP, wherein
a polarizing agent of triplet DNP is a photoexcited triplet electron of a pentacene derivative represented by the following formula (A) and/or a salt thereof:wherein each R independently represents a hydrogen atom (H), a deuterium atom (D), or a hydrocarbon group having 1 to 20 carbon atoms which optionally includes at least one atom selected from the group consisting of an oxygen atom, a sulfur atom and a silicon atom, provided that at least one R represents a hydrocarbon group having 1 to 20 carbon atoms which optionally includes at least one atom selected from the group consisting of an oxygen atom, a sulfur atom and a silicon atom.

[claim2]
2. The method for enhancing a nuclear spin polarization according to claim 1, comprising the following operations (1) to (3):
(1) preparing a composition including a test compound, the pentacene derivative and/or the salt thereof, and a solvent;
(2) irradiating the composition prepared in operation (1) with laser in a magnetostatic field in order to allow the pentacene derivative and/or the salt thereof to be in a photoexcited triplet state; and
(3) subjecting the composition, subjected to operation (2) in a magnetostatic field, to magnetic-field sweep and microwave irradiation in order to perform triplet DNP.

[claim3]
3. The method for enhancing a nuclear spin polarization according to claim 1 or 2, which is a method for enhancing a nuclear spin polarization of a subject for chemical analysis measurement.

[claim4]
4. The method for enhancing a nuclear spin polarization according to claim 1 or 2, which is a method for enhancing a nuclear spin polarization of a contrast agent for MRI.

[claim5]
5. A composition for NMR measurement, comprising a pentacene derivative represented by the following formula (A) and/or a salt thereof:wherein each R independently represents a hydrogen atom (H), a deuterium atom (D), or a hydrocarbon group having 1 to 20 carbon atoms which optionally includes at least one atom selected from the group consisting of an oxygen atom, a sulfur atom and a silicon atom, provided that at least one R represents a hydrocarbon group having 1 to 20 carbon atoms which optionally includes at least one atom selected from the group consisting of an oxygen atom, a sulfur atom and a silicon atom.
  • Applicant
  • OSAKA UNIVERSITY
  • RIKEN
  • Inventor
  • TATEISHI, Kenichiro
  • UESAKA, Tomohiro
  • NEGORO, Makoto
  • KITAGAWA, Masahiro
IPC(International Patent Classification)
Specified countries Contracting States: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

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