Triplet dynamic nuclear polarization of pyruvate via supramolecular chemistry.

Dynamic nuclear polarization (DNP) significantly improves the sensitivity of magnetic resonance imaging, and its most important medical application is cancer diagnosis via hyperpolarized 13C-labeled pyruvate. Unlike cryogenic DNP, triplet-DNP uses photoexcited triplet electrons under mild conditions. However, triplet-DNP of pyruvate has not been observed because of incompatibility of the hydrophobic polarizing agent with hydrophilic pyruvate. This work demonstrates that supramolecular complexation with ß-cyclodextrin can disperse 4,4'-(pentacene-6,13-diyl)dibenzoate (NaPDBA), a pentacene derivative with hydrophilic substituents, even in the presence of high sodium pyruvate concentrations. The polarization of photoexcited triplet electron spins in NaPDBA was transferred to the 13C spins of sodium pyruvate via triplet-DNP of 1H spins in water and 1H-to-13C cross-polarization. This provides an important step toward the widespread use of ultra-sensitive MRI for cancer diagnosis.

Polarizing agents beyond pentacene for efficient triplet dynamic nuclear polarization in glass matrices.

Triplet dynamic nuclear polarization (triplet-DNP) is a technique that can obtain high nuclear polarization under moderate conditions. However, in order to obtain practically useful polarization, large single crystals doped with a polarizing agent must be strictly oriented with respect to the magnetic field to sharpen the electron spin resonance (ESR) spectra, which is a fatal problem that prevents its application to truly useful biomolecular targets. Instead of this conventional physical approach of controlling crystal orientation, here, we propose a chemical approach, i.e., molecular design of polarizing agents; pentacene molecules, the most typical triplet-DNP polarizing agent, are modified so as to make the triplet electron distribution wider and more isotropic without loss of the triplet polarization. The thiophene-modified pentacene exhibits a sharper and stronger ESR spectrum than the parent pentacene, and state-of-the-art quantum chemical calculations revealed that the direction of the spin polarization is altered by the modification with thiophene moieties and the size of D and E parameters are reduced from parent pentacene due to the partial delocalization of spin densities on the thiophene moieties. The triplet-DNP with the new polarizing agent successfully exceeds the previous highest 1H polarization of glassy materials by a factor of 5. This demonstrates the feasibility of a polarizing agent that can surpass pentacene, the best polarizing agent for more than 30 y since triplet-DNP was first reported, in the unoriented state. This work provides a pathway toward practically useful high nuclear polarization of various biomolecules by triplet-DNP.

Generation and Transfer of Triplet Electron Spin Polarization at the Solid-Liquid Interface.

The photoexcited triplet state of dyes can generate highly polarized electron spins for sensing and dynamic nuclear polarization. However, while triplets exhibit long spin-lattice relaxation times (T1) on the microsecond scale in solids, the polarization quickly relaxes on the nanosecond scale in solution due to the rotational motion of chromophores. Here, we report that the immobilization of dye molecules on a solid surface allows molecular contact with a liquid while maintaining high polarization and long T1 as in a solid. By adsorbing anionic porphyrins on cationic mesoporous silica gel, porphyrin triplets exhibit high polarization and long T1 at the solid-liquid interface of silica and toluene. Furthermore, porphyrin triplets on the solid surface can exchange spin polarization with TEMPO radicals in solution. This simple and versatile method using the solid-liquid interface will open the door for utilizing the photoinduced triplet spin polarization in solution, which has been mainly limited to the solid-state.

Singlet fission as a polarized spin generator for dynamic nuclear polarization.

Singlet fission (SF), converting a singlet excited state into a spin-correlated triplet-pair state, is an effective way to generate a spin quintet state in organic materials. Although its application to photovoltaics as an exciton multiplier has been extensively studied, the use of its unique spin degree of freedom has been largely unexplored. Here, we demonstrate that the spin polarization of the quintet multiexcitons generated by SF improves the sensitivity of magnetic resonance of water molecules through dynamic nuclear polarization (DNP). We form supramolecular assemblies of a few pentacene chromophores and use SF-born quintet spins to achieve DNP of water-glycerol, the most basic biological matrix, as evidenced by the dependence of nuclear polarization enhancement on magnetic field and microwave power. Our demonstration opens a use of SF as a polarized spin generator in bio-quantum technology.

Dynamic Electron Polarization Lasting More Than 10 µs by Hybridizing Porphyrin and TEMPO with Flexible Linkers.

Dynamic electron polarization (DEP), induced by quenching of photoexcited species by stable radicals, can hyperpolarize electron spins in solution at room temperature. Recently, development of technologies based on electron spin polarization such as dynamic nuclear polarization (DNP) has been progressing, where it is important to design molecules that achieve long-lasting DEP in addition to high DEP. Hybridization by linking dyes and radicals is a promising approach for efficient DEP, but strong interactions between neighboring dyes and radicals often result in the rapid decay of DEP. In this study, we introduce a flexible linker into the hybrid system of porphyrin and TEMPO to achieve both efficient DEP and long-lasting DEP. The structural flexibility of the linker switches the interaction between the radical and the triplet, which promotes the DEP process by bringing the radical and the triplet into close proximity, while avoiding abrupt relaxation due to strong interactions. As a result, the new hybridized system exhibits a larger DEP than the unlinked system, while at the same time achieving a DEP lasting more than 10 µs.

Porphyrins as Versatile, Aggregation-Tolerant, and Biocompatible Polarizing Agents for Triplet Dynamic Nuclear Polarization of Biomolecules.

Triplet dynamic nuclear polarization (triplet-DNP) achieves nuclear spin polarization at moderate temperatures by using spin polarization of photoexcited triplet electrons. The applications of triplet-DNP for biomolecules have been hampered because acenes, the only polarizing agents used so far, tend to aggregate and lose their polarization in biomolecular matrices. Here, we report for the first time use of porphyrins as polarizing agents of triplet-DNP and propose a new concept of aggregation-tolerant polarizing agents. Sodium salts of tetrakis(4-carboxyphenyl)porphyrin (TCPPNa) can be dispersed in amorphous as well as crystalline biomolecular matrices, and importantly, it can generate polarized triplet electrons even in a slightly aggregated state. Triplet-DNP of crystalline erythritol containing slightly aggregated TCPPNa can achieve more than 120-fold signal enhancement. Because TCPPNa is also the first biocompatible triplet-DNP polarizing agent, this work provides a crucial step forward for the biological and medical applications of triplet-DNP.