Towards parahydrogen-induced polarization of acetoacetate
Abstract
Hyperpolarized acetoacetate is a promising probe for the detection of redox status inside mitochondria using ¹³ C MRI. In this pilot study we used parahydrogen-induced polarization by means of a side arm hydrogenation (PHIP-SAH) approach for the hyperpolarization of [1,3- ¹³ C ₂ ]acetoacetate. The propargyl [1,3- ¹³ C ₂ ]acetoacetate precursor was synthesized and subjected to homogeneous hydrogenation with parahydrogen. After optimization, the observed ¹ H polarization was 25.5% while achieving 100% chemical conversion of the propargyl moiety, and 80% selectivity to allyl [1,3- ¹³ C ₂ ]acetoacetate product. After hydrogenation, a linear magnetic field sweep was performed for the ¹ H-to- ¹³ C polarization transfer in allyl [1,3- ¹³ C ₂ ]acetoacetate, with maximum observed ¹³ C polarizations: P( ¹³ C-1) = 4.1% and P( ¹³ C-3) = 2.7%. Next, we analyzed the products of allyl [1,3- ¹³ C ₂ ]acetoacetate hydrolysis under different conditions. Alkaline hydrolysis results in the formation of stereoisomeric enolates of allyl [1,3- ¹³ C ₂ ]acetoacetate, which can then be converted into hyperpolarized [1,3- ¹³ C ₂ ]acetoacetate under harsh alkaline conditions with a subsequent decomposition to hyperpolarized [2- ¹³ C]acetone and [ ¹³ C]carbonate. These results expand PHIP-SAH studies beyond pyruvate to the metabolically relevant acetoacetate probe and identify the key chemical factors that currently limit the direct probe production. Beyond the achieved polarization levels, this work provides a useful mechanistic insight into allyl acetoacetate hydrolysis and offers guidance for future PHIP-SAH development of β-ketoacid-derived probes.
Versions
Related
- Parahydrogen-induced 15N polarization of nitrate ion
- Field-induced near-unity spin polarization in a highly emissive organic diradical
- Aggregation-Induced Polarization (AIP) of Racemic and Achiral Organic Molecules Leading to Asymmetric Elliptical Polarization Displaying Optical Rotation
- Purified [1-¹³C]α-Ketoisocaproate Spin-Polarized Up to 39% with Parahydrogen Enables Real-Time Metabolism Studies in Cancer Cells.
- Hyperpolarization of [1‐ 13 C]Ketoisocaproate‐d 2 by Reversible Exchange with Parahydrogen Enables Profiling of Branched‐Chain‐Amino‐Acid Metabolism in Cellulo and in Vivo
BibTeX
@article{sviyazov2026towards,
title = {{Towards parahydrogen-induced polarization of acetoacetate}},
author = {Sergey V. Sviyazov and Ivan A. Trofimov and Nikita V. Chukanov and Nazim R. Mustafin and Philipp R. Groß and Stefan Sell and Dominik von Elverfeldt and Maxim Zaitsev and Cornelius von Morze and Dudari B. Burueva and Oleg G. Salnikov and Igor V. Koptyug and Andreas B. Schmidt},
journal = {Communications Chemistry},
year = {2026},
month = oct,
doi = {10.1038/s42004-026-02213-1},
url = {https://www.nature.com/articles/s42004-026-02213-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Towards parahydrogen-induced polarization of acetoacetate
AU - Sergey V. Sviyazov
AU - Ivan A. Trofimov
AU - Nikita V. Chukanov
AU - Nazim R. Mustafin
AU - Philipp R. Groß
AU - Stefan Sell
AU - Dominik von Elverfeldt
AU - Maxim Zaitsev
AU - Cornelius von Morze
AU - Dudari B. Burueva
AU - Oleg G. Salnikov
AU - Igor V. Koptyug
AU - Andreas B. Schmidt
PY - 2026
DA - 2026/10/07
JO - Communications Chemistry
DO - 10.1038/s42004-026-02213-1
UR - https://www.nature.com/articles/s42004-026-02213-1
AB - Hyperpolarized acetoacetate is a promising probe for the detection of redox status inside mitochondria using ¹³ C MRI. In this pilot study we used parahydrogen-induced polarization by means of a side arm hydrogenation (PHIP-SAH) approach for the hyperpolarization of [1,3- ¹³ C ₂ ]acetoacetate. The propargyl [1,3- ¹³ C ₂ ]acetoacetate precursor was synthesized and subjected to homogeneous hydrogenation with parahydrogen. After optimization, the observed ¹ H polarization was 25.5% while achieving 100% chemical conversion of the propargyl moiety, and 80% selectivity to allyl [1,3- ¹³ C ₂ ]acetoacetate product. After hydrogenation, a linear magnetic field sweep was performed for the ¹ H-to- ¹³ C polarization transfer in allyl [1,3- ¹³ C ₂ ]acetoacetate, with maximum observed ¹³ C polarizations: P( ¹³ C-1) = 4.1% and P( ¹³ C-3) = 2.7%. Next, we analyzed the products of allyl [1,3- ¹³ C ₂ ]acetoacetate hydrolysis under different conditions. Alkaline hydrolysis results in the formation of stereoisomeric enolates of allyl [1,3- ¹³ C ₂ ]acetoacetate, which can then be converted into hyperpolarized [1,3- ¹³ C ₂ ]acetoacetate under harsh alkaline conditions with a subsequent decomposition to hyperpolarized [2- ¹³ C]acetone and [ ¹³ C]carbonate. These results expand PHIP-SAH studies beyond pyruvate to the metabolically relevant acetoacetate probe and identify the key chemical factors that currently limit the direct probe production. Beyond the achieved polarization levels, this work provides a useful mechanistic insight into allyl acetoacetate hydrolysis and offers guidance for future PHIP-SAH development of β-ketoacid-derived probes.
SN - 2399-3669
ER -