Long‐Lived ¹H Nuclear Spin Singlet in Dimethyl Maleate Revealed by Addition of Thiols

Abstract

Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) have become important techniques in many research areas. One major limitation is the relatively low sensitivity of these methods, which recently has been addressed by hyperpolarization. However, once hyperpolarization is imparted on a molecule, the magnetization typically decays within relatively short times. Singlet states are well isolated from the environment, such that they acquire long lifetimes. We describe herein a model reaction for read-out of a hyperpolarized long-lived state in dimethyl maleate using thiol conjugate addition. This type of reaction could lend itself to monitoring oxidative stress or hypoxia by sensitive detection of thiols. Similar reactions could be used in biosensors or assays that exploit molecular switching. Singlet lifetimes of about 4.7 min for 1 H spins in [D 4 ]MeOH are seen in this system.

Singlet-filtered NMR spectroscopy

“…Nuclear spin singlet states have been explored over the past years for a variety of applications. One research goal with relevant implications for clinical magnetic resonance imaging (MRI) is to preserve nuclear spin hyperpolarization (6)(7)(8)(9)(10)(11)(12). Hyperpolarization methods can transiently enhance NMR signals by more than four orders of magnitude leading to large gains in sensitivity (13)(14)(15)(16)(17).…”

“…Hyperpolarization methods can transiently enhance NMR signals by more than four orders of magnitude leading to large gains in sensitivity (13)(14)(15)(16)(17). Hyperpolarized magnetization decays within T 1 but may be preserved for longer times if stored in a singlet state (6)(7)(8)(9)(10)(11)(12). T S of more than 1 hour was observed so far (10), and molecules in which hyperpolarization can be maintained for a long period of time have been proposed to be used as biosensors (11,12).…”

“…Hyperpolarized magnetization decays within T 1 but may be preserved for longer times if stored in a singlet state (6)(7)(8)(9)(10)(11)(12). T S of more than 1 hour was observed so far (10), and molecules in which hyperpolarization can be maintained for a long period of time have been proposed to be used as biosensors (11,12). Singlet NMR has also been used for the investigation of dynamic phenomena.…”

Collisional cross-section of water molecules in vapour studied by means of 1H relaxation in NMR

“…In supercritical water171819, spin-rotation significantly contributes to NMR relaxation despite the high density. In the context of our attempts to prepare para -water20212223242526 and related spin states in other molecules272829303132, we have measured longitudinal relaxation rates R 1  = 1/ T 1 of gaseous H 2 O and HDO at different temperatures and pressures. To the best of our knowledge, this is the first time that such observations are reported.…”

Versatile pulse sequence device to conserve hyperpolarization for NMR and MRI studies

“…While the group was able to image phantoms, the overall polarization ($1.3%) and short lifetime T LLS $ 4.7s make translation to imaging in vivo challenging (29). Several groups have studied the long lived spin lifetime of dimethyl maleate (30)(31)(32). Although the molecule has a long lifetime (over 4 min) its use in vivo may be limited due poor solubility of the agent in water.…”