Aromatic Compound 13C Relaxation Time Extension

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Solution Overview

Problem

Current DNP technology for MRI is limited by the short relaxation time of 13C nuclei, which restricts its application for long-term observations and makes it unsuitable for detailed metabolic studies.

Innovation Solution

Development of an aromatic compound with two adjacent carbon atoms as 13C, where other atoms bonded to these carbon atoms have a spin quantum number of 0, and a hydrogen atom bonded to the 13C nucleus is substituted with a deuterium atom, enhancing the relaxation time of the 13C nucleus.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If DNP method is used to improve polarization rate, then measurement sensitivity is improved by several digits, but polarization is lost in a few seconds to a few tens of seconds due to magnetic field modulation by molecular motion

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidpolarization lifetime
Core Design Contradiction:
Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

The patent changes the chemical structure parameters of the aromatic compound by introducing specific substituents (deuterium atoms, groups with spin-0 nuclei) to modify the relaxation properties of the 13C nuclei, thereby extending polarization lifetime while maintaining measurement sensitivity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite nuclear spin system involving 13C nuclei coupled with spin-0 nuclei (deuterium, 12C, 16O, etc.), where the spin-0 nuclei provide a protective effect that extends the singlet state lifetime without interfering with the 13C NMR signal detection

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If conventional aromatic compounds are used for DNP, then NMR spectroscopy and MRI can be performed, but the relaxation time of 13C nuclei is too short for long-term observations and detailed metabolic studies

Engineering Contradiction:
Improveapplicability for NMR spectroscopy and MRIVSAvoidrelaxation time of 13C nucleus
Core Design Contradiction:
Ease of operationVSDuration of action of stationary object

Solution Approach 1:

The patent systematically varies the substituent parameters on the aromatic ring (different spin-0 groups at different positions) to optimize the relaxation time while maintaining the compound's suitability for NMR spectroscopy and MRI applications

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent segments the molecular environment around the 13C nuclei by introducing specific substituents at different positions on the aromatic ring, creating distinct chemical environments that protect the 13C singlet state from relaxation while maintaining detectability

Inventive Principle:
Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The proposed aromatic compound significantly extends the relaxation time of the 13C nucleus, enabling longer polarization lifetimes and facilitating more extensive and accurate metabolic observations and imaging.

Implementation Method 1

it is known that a singlet state of the nearest-neighbor nucleus spin pair is a long-lived state with respect to this interaction

Methodology Applied
Scientific EffectSinglet state:

Implementation Method 2

A dynamic nuclear polarization (DNP) method is used as a method for improving the measurement sensitivity by improving the polarization rate by several digits

Methodology Applied
Scientific EffectDynamic nuclear polarization:

Implementation Method 3

the Zeeman energy of the nucleus spins is very low even under a strong magnetic field of several teslas (T) to several tens of teslas applied by a superconducting magnet

Methodology Applied
Scientific EffectZeeman energy:

Data Source

PatentEP4556458A1Aromatic compound, mixture, molecular probe for hyperpolarization, metabolite, diagnostic agent, derivatization agent, naphthalene derivative, catechol derivative, and compound
Publication Date: 2025.05.21 NIPPON SANSO CORP
  • EP4556458A1 patent drawingFigure 1~2
  • EP4556458A1 patent drawingFigure 3~4
  • EP4556458A1 patent drawing

AI summary

An aromatic compound is composed of a stable isotope, in which two adjacent carbon atoms are 13C, atomic nuclei of other atoms to which the two adjacent carbon atoms are bonded have a spin quantum number of 0, and a hydrogen atom which has a spin coupling constant and is bonded to the 13C nucleus through a carbon atom is substituted with a deuterium atom. In the aromatic compound, a relaxation time of a 13C nucleus excited by a DNP device is longer than that in the related art.