At eam of researchers from Takuya Kurihara at Institute of Science and Engineering, Kanazawa University, Tokushima University, QIQB( Center for Q uantum Information and Quantum Biology), Osaka University, Osaka University's Premium Research Institute for Human Metaverse Medicine (PRIMe), Center for Computational Sciences, University of Tsukuba have developed a cocrystallization (*2) technique to increase the variety of molecules to which triplet DNPs (*1) are applicable. Furthermore, they enabled triplet DNPs of multiple molecules including urea, an MRI molecular probe (*3), at room temperature.
The research team focused on DNPs using photo-excited triplet electron spins (triplet DNPs), which can align their spins at room temperature through quantum mechanical processes induced by light and microwave irradiation. Although triplet DNP has been studied for a long time, there are stili ssues to be solved in applying this technique, and the types of molecules to which it can be applied have been limited. In this study, we developed a co-crystallization technique as a method to dramatically increase the types of molecules to which triplet DNP can be applied. We developed a cocrystal composed of an analyte, coformer, and a polarization source, which is the source of sensitivity enhancement, and reailzed triplet DNPs of multiple molecules including urea, an MRI molecular probe, at room temperature.
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These findings are expected to lead to ultra-sensitive MRI that enables precise cancer diagnosis and treatment decisions, which have been difficult with conventional methods, by combining the cocrystallization technology proposed in this study with MRI in the future.
These results were published in the online edition of the Journal of theAmericanChemical Society on May 17, 2024 at 10:00 (Japan time).
Figure: Schematic representation of cocrystals as matrices for spin polarization using triplet-DNP.
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*1: Triplet DNP
This is a type of DNP. The methods are that the detection sensitivity of NMR can be increased by transferring the electron spin bias of the photo-excited triplet of a molecule to nuclear spin. Scince the electron spin polrization is independent of tempereture and magnetic field strength, DNP can be performed in mild environments (e.g., room temperature without agat and in low magnetic fields of 0.1 to 0.6 T, where the resonance frequency of the electron spin is in the microwave region).
*2: Cocrystal
Cocrystals are crystals in which multiple types of molecules are assembled through hydrogen bonds or π-π bonds. In this work, we focused on various types of cocrystals and showed that triplet DNPs can be formed.
*3: MRI molecular probes
This means a type of molecular sensor that changes its NMR or MRI signal in response to the in vivo environment or reaction.
*4: NMR (Nuclear Magnetic Resonance)
When a nuclear spin is subjected to an electrostatic magnetic field, it performs precessional motion (pendulum motion) around the magnetic field like a top. When an electromagnetic wave of the frequency of this precession (for example, a 17 MHz electromagnetic wave for hydrogen nuclear spins in a 0.4 Tesla magnetic field) is applied, the angle of the precession changes in resonance with the electromagnetic wave, and this can be observed from the emitted electromagnetic wave. This phenomenon is called nuclear magnetic resonance (NMR). Since the frequency varies depending on the type of atomic nucleus and molecular structure, the analysis of these electromagnetic waves can be used to study molecular structure information. This is called NMR spectroscopy and is an indispensable method for chemical analysis.
*5: MRI (Magnetic Resonance Imaging)
The frequency of the precession of spins and the frequency of resonant electromagnetic waves are proportional to the strength of the static magnetic field. MRI is a method of imaging the distribution of the amount of water molecules and other substances contained in the human body by analyzing the resonant electromagnetic waves using a gradient magnetic field. It is an indispensable analysis method for diagnosis of injuries and diseases, research on brain functions, and so on.
*6: Polarization ratio
The energy levels of hydrogen nuclear spins and electron spins in a static magnetic field are split into the energy of the state in which the spins are parallel to the magnetic field and the energy of the state in which they are antiparallel. The polarizability is defined as the difference in the number of occupied spins with each energy divided by the total number of spins. In thermal equilibrium under typical conditions, the polarizability is proportional to the magnetic spin rotation ratio and the magnetic field strength, and inversely proportional to temperature. Since the magnetic rotation ratio of electron spins is 660 times larger than that of hydrogen nuclear spins, the polarizability of electron spins is 660 times larger than that of hydrogen nuclear spins under the same environment.
*7: Dynamic Nuclear Polarization (DNP)
In an ordinary molecule, two electrons with opposite spin directions form a pair, and the absorption and emission of electromagnetic waves due to electron spin are canceled. However, in molecules called radicals, unpaired electrons exist stably. When a sample containing a small amount of such radicals is irradiated with microwaves that resonate with the electron spins, the angle of the electron spins' swinging motion changes. When the frequency at which the nuclear spins resonate is included in the rate at which the angle changes, the polarization rates of the electron spins and nuclear spins are exchanged. This alignment of nuclear spins is called dynamic nuclear polarization. In principle, DNP using electron spins in thermal equilibrium can increase the signal intensity by up to 660 times compared to hydrogen nuclear spins. Since the lower the temperature, the greater the polarization of the electron spins in thermal equilibrium, conventional DNP is performed at cryogenic temperatures in order to achieve higher sensitivity.
Click here to see the press release【Japanese only】
Journal：Journal of the American Chemical Society
Researcher's Information: Takuya Kurihara
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