NMR signal enhancement of >50 000 times in fast dissolution dynamic nuclear polarization

Abstract

Herein we report the synthesis and the study as polarizing agent for fast dissolution DNP of a novel mixed biradical with a BDPA and TEMPO radical units covalently bound by an ester group (BDPAesterTEMPO). Such a biradical exhibits an extremely high DNP NMR enhancement > 50000 which constitutes one of the largest signal enhancement observed so far, to the best of our knowledge. Dynamic nuclear polarization (DNP)1 is used for enhancement of nuclear magnetic resonance signals in both solid and liquid samples. , low concentration biological samples 5 or has been used for metabolic imaging applications. 6,7,8 The nature of the polarizing agent has a crucial role in the efficiency of DNP. In the case of dDNP, the effort has been focused in monoradicals, mainly trityl radicals like the well-known Ox63, 2 PTM 9 or BDPA 10 derivatives. The typical mechanism of choice to transfer electron magnetization is the "solid-effect" (SE), 11 and the ideal radical for such a mechanism will be a monoradical with a narrow EPR line like Ox63, however it has been shown to form oligomers that may limit its efficiency. 12 On the other hand, biradicals are of considerable interest as polarizing agents for MAS-DNP experiments. 13,14 The development of high-field MAS-DNP has mainly focused on the cross-effect (CE) mechanism 15,16,17 which is one of the mechanisms for which a large signal enhancement is expected for biradicals, since typical SE enhancements are considerably lower. 13 Up to now, the most successful biradicals so far, used for MAS-DNP in solid-state NMR applications, particularly to study biological solids, new materials and studies of material surfaces 3,4,18 are based on two radicals of the same type (nitroxides) combined in the proper orientation and distance. 14,19,20 It is known that the ideal CE polarizing agent would be a biradical with an EPR spectrum consisting of two sharp lines separated by the Larmor frequency of the nuclei to be polarized, ω 0S1 -ω 0S2 ≈ ω 0I . However, only a few known radicals exhibit spectral narrow lines, e. g. trityl radicals and BDPA radical derivatives, which have similar isotropic g-values. 21 As TEMPO derivatives have a broad line with significant spectral density at a frequency separation matching ω 0I , using a narrow line radical such as trityl or BDPA together with TEMPO could be a reasonable approximation. On the other hand, it is known that for an efficient cross effect mechanism, the dipolar coupling, in conjunction with the J-coupling, leads to the state mixing that is critical for it. 17 Some mixed nitroxide-trityl biradicals had been described as EPR sensors of the redox state of cells 22 or others 23 but had not been tested for DNP. The Griffin group has demonstrated the goodness of using some physical mixtures of two different radical species 13,24,25 and, recently, the use of a mixed biradical for MAS-DNP. 26Under dDNP, the efficiency of TEMPO-based biradicals is not optimal due to the difficulties to efficiently irradiate the full broad EPR lineshape at low temperature...

Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family

“… 21 , 22 In addition to the use of bis-nitroxides, recent efforts have been devoted to the introduction of mixed biradicals for DNP applications, such as trityl-nitroxide 18 , 23 , 24 and BDPA-nitroxide. 25 , 26 …”

BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T

“…38 More recently a BDPA and TEMPO biradical covalently bound by a carboxymethylidene has been prepared and evaluated as a polarizing agent for dissolution DNP. 39 Here we introduce a new family of CE hybrid biradicals in which a BDPA moiety and a nitroxide are chemically tethered. We show that by rationally fine tuning the chemical structures of these BDPA-nitroxide biradicals, their electronic properties can be significantly modulated, and correlations are established with their DNP performance.…”

Hyperpolarized NMR Spectroscopy: d‐DNP, PHIP, and SABRE Techniques

“…The choice of PA is crucial for a successful d ‐DNP experiment (for a list of popular PAs, see Refs ). The solubility, stability, and electron paramagnetic resonance (EPR) parameters of a PA are of great importance for its application in DNP.…”

“…The choice of PA is crucial for as uccessful d-DNP experiment (for al ist of popular PAs, see Refs [9][10][11][12]). The solubility,s tabili- [a] Dr.K.V .…”