Rational design of dinitroxide biradicals for efficient cross-effect dynamic nuclear polarization.

Chemical Science View Article Online Open Access Article. Published on 13 October 2015. Downloaded on 15/05/2018 13:54:14. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. EDGE ARTICLE Cite this: Chem. Sci., 2016, 7, 550 View Journal | View Issue Rational design of dinitroxide biradicals for efficient cross-effect dynamic nuclear polarization† Dominik J. Kubicki,‡a Gilles Casano,‡c Martin Schwarzwälder,d Sébastien Abel,c Claire Sauvée,c Karthikeyan Ganesan,c Maxim Yulikov,d Aaron J. Rossini,a Gunnar Jeschke,d Christophe Copéret,d Anne Lesage,b Paul Tordo,*c Olivier Ouari*c and Lyndon Emsley*a A series of 37 dinitroxide biradicals have been prepared and their performance studied as polarizing agents in cross-effect DNP NMR experiments at 9.4 T and 100 K in 1,1,2,2-tetrachloroethane (TCE). We observe that in this regime the DNP performance is strongly correlated with the substituents on the polarizing Received 7th August 2015 Accepted 12th October 2015 agents, and electron and nuclear spin relaxation times, with longer relaxation times leading to better enhancements. We also observe that deuteration of the radicals generally leads to better DNP DOI: 10.1039/c5sc02921j www.rsc.org/chemicalscience enhancement but with longer build-up time. One of the new radicals introduced here provides the best performance obtained so far under these conditions. Introduction Dynamic nuclear polarization (DNP)1–3 currently attracts considerable attention as one of the most efficient methods to increase the sensitivity of NMR experiments.4–9 One can increase the intrinsically low polarization of nuclear spins by coupling them to unpaired electrons through means of microwave (MW) irradiation. The theoretical limit of the signal enhancement in that process (3max) equals ge/gn, where ge and gn are the gyromagnetic ratios of the electron and the nucleus, respectively (for instance, 3max is 660 for proton, and 2618 for carbon-13). For in situ higheld solid-state NMR, the unpaired electrons are usually added to the sample in the form of a mono- or biradical, usually derived from tetrathiatriarylmethyl or TEMPO radicals, and the experiment is performed with magic angle spinning (MAS) at temperatures of about 100 K.6,10–12 At these temperatures, currently achievable proton DNP enhancements reach up to around 200 in frozen bulk solutions, and up to 500 in mixtures with dielectric solid particles, in magnetic elds of between 5 and 9.4 T.13–17 These signicant enhancements have allowed investigation of a Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. E-mail: b Université de Lyon, Institut de Sciences Analytiques (CNRS / ENS de Lyon / UCB-Lyon 1), Centre de RMN à Très Hauts Champs, 69100 Villeurbanne, France c Aix-Marseille Université, CNRS, ICR UMR 7273, 13397 Marseille, France. E-mail: ; d ETH Zurich, Department of Chemistry, Laboratory of Inorganic Chemistry, 8093 Zurich, Switzerland † Electronic supplementary information (ESI) available: Additional experimental details, sample compositions and synthetic routes of radicals. See DOI: 10.1039/c5sc02921j ‡ These authors contributed equally to this work. 550 | Chem. Sci., 2016, 7, 550–558 a range of systems such as functionalized porous materials,9,18–21 structural materials,22 polymers,23,24 nanoparticles,9,21,25,26 pharmaceuticals,27–29 and biomolecular structures,30–41 that were otherwise out of reach. Under these conditions there are several mechanisms that might lead to polarization transfer,12,42 but currently the most efficient at 100 K is the cross effect (CE). The cross effect requires two dipolar coupled unpaired electrons to fulll a condition where the difference in Larmor frequencies of the two electrons matches the Larmor frequency of the nucleus. There is currently much interest in improving the existing radicals to make cross-effect transfer more efficient. There have been a series of key steps to this end. The idea of using stable biradicals with limited exibility xes the inter-electron distance and leads to a large dipolar coupling, and was rst realized in 2004 with the introduction of the BTnE43 biradicals and later with TOTAPOL.44 For nitroxide biradicals, the relative orientation of the two radicals is crucial since it denes the probability of matching the cross-effect condition between the two radical centers due to the anisotropy of the g tensor.45,46 As a result the bTbK biradical was introduced, in which the framework is rigid and the two TEMPO moieties, and therefore the corresponding g tensors are nearly orthogonal, the gxx (or gyy) component of one TEMPO being nearly parallel to the gyy (gzz) component of the other, which is the optimal orientation.47 The electron relaxation time is a further key property for DNP efficiency, and recently our group showed how dinitroxide biradicals with increased electron relaxation times give much higher DNP efficiency, and remained active at temperatures up to 200 K. Heavier, more bulky, radicals have longer electronic relaxation times, and we showed that this leads directly to better DNP with the introduction of bCTbK and TEKPol.13,14 This journal is © The Royal Society of Chemistry 2016 View Article Online Open Access Article. Published on 13 October 2015. Downloaded on 15/05/2018 13:54:14. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Edge Article Most of these bTbK-based radicals are not soluble in water. It was shown that surfactant-based micellar systems could be efficiently designed and used to solubilise these radicals in aqueous solvents.48,49 In 2013 Sauvée et al. introduced the inherently water-soluble urea-based PyPol and AMUPol biradicals, which also incorporate the concept of increased bulkiness.17 TEKPol and AMUPol, yielded previously unprecedented proton enhancements of over 200 at 9.4 T and 100 K in bulk solution.14,15 Herein we study a large series of bTurea, PyPol and bTbK derivatives designed specically to establish the ne relationship between structural changes and DNP performance. We nd that structural modications of the radicals based on well-dened backbones can signicantly modulate their DNP efficiency, and lead to sometimes signicant increases in performance. One of the new radicals, TEKPol2 yields slightly higher enhancements than TEKPol, and as such is the best system to date. The present study suggests that in the bTbK series the limit on enhancement at 100 K and 9.4 T may now be primarily associated with other factors than the polarizing agents, such as microwave propagation in the sample.16 Experimental NMR spectroscopy All DNP experiments were carried out on a commercial Bruker Avance III 400 MHz NMR spectrometer equipped with a 263 GHz gyrotron microwave source using a 3.2 mm triple resonance MAS probe at sample temperatures around 100 K with spinning at 8 kHz.50 The sample tempera (...truncated)