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 [D4]MeOH are seen in this system.

Symmetry constraints on spin dynamics: Application to hyperpolarized NMR

“…The transformation of total spin magnetization into singlet order, and back again, is an important manipulation in the NMR of long-lived states [13,14,15,16,17,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44] and in parahydrogen-enhanced NMR [18,19,20,21,22,45,46,47,48,49].…”

“…I examine closely the spin dynamical manipulations of four-spin systems, involving long-lived spin states [13,14,15,16,17] and SABRE (Signal Amplification by Reversible Exchange) experiments [18,19,20,21,22]. Such experiments sometimes involve four-spin-1/2 systems of the type A 2 X 2 (two magnetically equivalent pairs) or AA XX (two chemically equivalent but magnetically inequivalent pairs).…”

Singlet NMR methodology in two-spin-1/2 systems

“…However, magnetic equivalence must be imposed in order to convert this precursor into singlet order and to exploit its features. This procedure of switching on and off magnetic equivalence has been dubbed symmetry switching [2] and it has been implemented in a number of ways using: i) field cycling [25,26]; ii) singlet-locking [24] or iii) a chemical reaction [36,42,62]. As will be clearer below, field cycling and chemical reaction are most convenient in weak and strong coupling regimes when ω ∆ is large (larger than a few kHz to give an indicative number).…”

“…Since its discovery in the Levitt group [24,25,26] a number of research groups have investigated the field of singlet NMR over the past 12 years with the purpose of defining and characterising singlet order relaxation properties [3,27,28,29,30], and the conditions for its existence [31,32,33,34], and of developing the methodology to access singlet order in different magnetic regimes [24,26,35,36,37,38,39,9,40,11,41,42,43] and to demonstrate the existence of long-lived singlet order in multiple-spin systems [44,45,46,47,48,49] and in heteronuclear systems [50]. Significant studies on the chemical requirements for obtaining long-lived spin order have been also conducted [17,51,52,53,54] with a record lifetime of 70 min for a 13 C-pair [54], 26 min for a 15 N-pair [51], and 10 min for a 1 H-pair [17] demonstrated.…”

Long-lived nuclear spin states in rapidly rotating CH 2 D groups

“…The population imbalance between the singlet state and the triplet states is called singlet order and is protected against many common relaxation mechanisms [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The relaxation time constant for singlet order is called T S and often exceeds the conventional longitudinal relaxation time T 1 by a large factor [16][17][18][19][20][21][22]. Applications of singlet order to hyperpolarized NMR experiments have been proposed [8,[23][24][25][26][27][28].…”