Verdazyl-ribose: A new radical for solid-state dynamic nuclear polarization at high magnetic field

Abstract

Solid-state dynamic nuclear polarization (DNP) using the cross-effect relies on radical pairs whose electron spin resonance (ESR) frequencies differ by the nuclear magnetic resonance (NMR) frequency. We measure the DNP provided by a new water-soluble verdazyl radical, verdazyl-ribose, under both magic-angle spinning (MAS) and static sample conditions at 9.4 T, and compare it to a nitroxide radical, 4-hydroxy-TEMPO. We find that verdazyl-ribose is an effective radical for cross-effect DNP, with the best relative results for a non-spinning sample. Under non-spinning conditions, verdazyl-ribose provides roughly 2× larger C cross-polarized (CP) NMR signal than the nitroxide, with similar polarization buildup times, at both 29 K and 76 K. With MAS at 7 kHz and 1.5 W microwave power, the verdazyl-ribose does not provide as much DNP as the nitroxide, with the verdazyl providing less NMR signal and a longer polarization buildup time. When the microwave power is decreased to 30 mW with 5 kHz MAS, the two types of radical are comparable, with the verdazyl-doped sample having a larger NMR signal which compensates for its longer polarization buildup time. We also present electron spin relaxation measurements at Q-band (1.2 T) and ESR lineshapes at 1.2 and 9.4 T. Most notably, the verdazyl radical has a longer T than the nitroxide (9.9 ms and 1.3 ms, respectively, at 50 K and 1.2 T). The verdazyl electron spin lineshape is significantly affected by the hyperfine coupling to four N nuclei, even at 9.4 T. We also describe 3000-spin calculations to illustrate the DNP potential of possible radical pairs: verdazyl-verdazyl, verdazyl-nitroxide, or nitroxide-nitroxide pairs. These calculations suggest that the verdazyl radical at 9.4 T has a narrower linewidth than optimal for cross-effect DNP using verdazyl-verdazyl pairs. Because of the hyperfine coupling contribution to the electron spin linewidth, this implies that DNP using the verdazyl radical would improve at lower magnetic field. Another conclusion from the calculations is that a verdazyl-nitroxide bi-radical would be expected to be slightly better for cross-effect DNP than the nitroxide-nitroxide bi-radicals commonly used now, assuming the same spin-spin coupling constants.

Dynamic Nuclear Polarization for Sensitivity Enhancement in Biomolecular Solid-State NMR

“…In verdazyl radical, , the electron spin is not stringently centered at a carbon site, but is largely delocalized over a conjugated system of four nitrogens and a central carbon which is carrying negative spin density via the mechanism of spin polarization of its atomic orbitals. , Verdazyl-ribose is well water-soluble and highly biocompatible, and may feature better stability than nitroxide-based radicals under biologically relevant conditions . Its MAS DNP performance is close to that of a nitroxide (see Section ) at 9.4 T, however, best performance is expected at lower fields because the dominating broadening mechanism is (field-independent) HFI to the four 14 N nuclei …”

“…255 Its MAS DNP performance is close to that of a nitroxide (see Section 4.2) at 9.4 T, however, best performance is expected at lower fields because the dominating broadening mechanism is (field-independent) HFI to the four 14 N nuclei. 253 Besides these persistent radicals, MAS DNP has also been performed with radicals introduced by γ-irradiation of glucose or cellulose, besides other materials. 256 This approach avoids the addition of any exogenous PA and is able to create radical sites deep within the bulk of the material enabling DNP even of reactive materials, but its applicability to biologically relevant systems is limited.…”

Verdazyls as Possible Building Blocks for Multifunctional Molecular Materials: A Case Study on 1,5-Diphenyl-3-(p-iodophenyl)-verdazyl Focusing on Magnetism, Electron Transfer and the Applicability of the Sonogashira-Hagihara Reaction

“…Owed to the in general lower toxicity of TMI free compounds, many of these applications are related to the increasingly important field of biochemistry. Similar developments with respect to their application of verdazyl radicals are conceivable, and first results have been obtained in some of the aforementioned fields [ 38 , 107 , 108 , 109 , 110 , 111 , 112 ].…”

Polarising Agents and Spin Tags for Dynamic Nuclear Polarisation (DNP)-Enhanced Solid-State Nuclear Magnetic Resonance (ssNMR) Analysis of Biological Samples

“…The water-soluble monoradical verdazyl-ribose (20) was synthesised in two steps by condensation of 2,4-diisopropylcarbonobis(hydrazide) bis-hydrochloride with ribose [118] and later tested as a potentially useful polarising agent for DNP-ssNMR. With a sample of [ 15 N, 13 C3]-L-alanine at 31 K, a concentration of 40 mM verdazyl-ribose produced DNP enhancement factors of  = 31 and 74 in 13 C spectra with MAS (6.7 kHz) and without MAS, respectively [119].…”