Diastereoisomers of l-proline-linked trityl-nitroxide biradicals: synthesis and effect of chiral configurations on exchange interactions.

Chemical Science View Article Online Open Access Article. Published on 05 April 2018. Downloaded on 18/05/2018 10:42:56. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. EDGE ARTICLE Cite this: Chem. Sci., 2018, 9, 4381 View Journal | View Issue Diastereoisomers of L-proline-linked tritylnitroxide biradicals: synthesis and effect of chiral configurations on exchange interactions† Weixiang Zhai,a Yalan Feng,a Huiqiang Liu,a Antal Rockenbauer, *b Deni Mance,c Shaoyong Li,a Yuguang Song,*a Marc Baldus c and Yangping Liu *a The exchange (J) interaction of organic biradicals is a crucial factor controlling their physiochemical properties and potential applications and can be modulated by changing the nature of the linker. In the present work, we for the first time demonstrate the effect of chiral configurations of radical parts on the J values of trityl-nitroxide (TN) biradicals. Four diastereoisomers (TNT1, TNT2, TNL1 and TNL2) of TN biradicals were synthesized and purified by the conjugation of a racemic (R/S) nitroxide with the racemic (M/P) trityl radical via L-proline. The absolute configurations of these diastereoisomers were assigned by comparing experimental and calculated electronic circular dichroism (ECD) spectra as (M, S, S) for TNT1, (P, S, S) for TNT2, (M, S, R) for TNL1 and (P, S, R) for TNL2. Electron paramagnetic resonance (EPR) results showed that the configuration of the nitroxide part instead of the trityl part is dominant in controlling the exchange interactions and the order of the J values at room temperature is TNT1 (252 G) > TNT2 (127 G) Received 28th February 2018 Accepted 5th April 2018 >> TNL2 (33 G) > TNL1 (14 G). Moreover, the J values of TNL1/TNL2 with the S configuration in the nitroxide part vary with temperature and the polarity of solvents due to their flexible linker, whereas the J values of TNT1/TNT2 are almost insensitive to these two factors due to the rigidity of their linkers. The distinct exchange interactions between TNT1,2 and TNL1,2 in the frozen state led to strongly different DOI: 10.1039/c8sc00969d high-field dynamic nuclear polarization (DNP) enhancements with 3 ¼ 7 for TNT1,2 and 40 for TNL1,2 rsc.li/chemical-science under 800 MHz DNP conditions. Introduction Exchange-coupled biradicals have recently attracted tremendous interest owing to their unique physiochemical properties and potential applications in high-frequency dynamic nuclear polarization (DNP),1,2 molecule-based magnetism,3–5 and molecular charge transfer6–8 as well as molecular sensing.9,10 A key point in the design of new biradicals is to control the magnitude and sign of the spin–spin exchange interaction that determines their physiochemical properties and potential applications. The intramolecular exchange interaction of biradicals strongly depends on the number of chemical bonds in the linkage between the two spins, the linker conformation, and a Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. E-mail: ; songyuguang@tmu. edu.cn b Institute of Materials and Environmental Chemistry, Hungarian Academy of Sciences, Department of Physics, Budapest University of Technology and Economics, Budafoki ut 8, 1111 Budapest, Hungary. E-mail: c NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands † Electronic supplementary 10.1039/c8sc00969d information (ESI) This journal is © The Royal Society of Chemistry 2018 available. See DOI: the s/p contributions to the bonding as well as the environment (e.g., temperature and solvent). This exchange interaction can be through-bond and/or through-space, and its value varies by many orders of magnitude due to different linkers between the two radical moieties.11,12 In general, for the biradicals with pconjugated backbones, the exchange interaction is mediated more effectively via through-bond mechanisms. The large exchange interactions have been achieved by enhancing the degree of p-orbital overlap between the spacer and two radical moieties through a conformational constraint to enforce their coplanarity.13–16 Using donor–bridge–acceptor biradical systems, the dependence of magnetic exchange interaction on the degree of p-orbital overlap and torsional rotations between different parts has been well demonstrated.17–19 Comparatively, the exchange interactions in the biradicals with nonconjugated spacers are much weaker and can be through-bond and/or through-space, depending on the exibility of the spacers. Recently, weakly coupled nitroxide biradicals have attracted intense attention as high-eld DNP polarizing agents which boost the sensitivity of solid-state nuclear magnetic resonance spectroscopy.20–27 Nonconjugated linkers were applied in these biradicals and the rigidity and conformation of the linkers were well tailored in order to optimize the through-bond exchange and dipolar interactions and simultaneously realize the Chem. Sci., 2018, 9, 4381–4391 | 4381 View Article Online Open Access Article. Published on 05 April 2018. Downloaded on 18/05/2018 10:42:56. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Chemical Science matching conditions of the EPR frequency. In addition, the supramolecular interaction with host molecules has been an effective approach to modulate the exchange interaction in nitroxide biradicals.28–31 Despite these extensive studies, to the best of our knowledge, there is no related study on the chiral effect of the linker and radical moieties on the exchange interaction of biradicals. In the past few years, we have developed trityl-nitroxide (TN) biradicals which combine two different radical properties into unique molecules.32–36 Similar to other biradicals, the exchange interaction of TN biradicals is a key factor for their applications. We have ne-tuned the exchange interactions of TN biradicals by structural modication of the linkers37 as well as by supramolecular interaction with cyclodextrins.38 The largest DNP enhancement at a high magnetic eld (18.8 T) has been achieved by using these TN biradicals as polarizing agents,35,36 in part due to the lack of nuclear depolarization.39 In the present work, we utilize the chiral effect of the linker and two radical parts to modulate the spin–spin exchange interaction of TN biradicals. The trityl radical has a propeller conguration which affords the right-handed (P) and le-handed (M) helices. Due to the large steric bulk of three aryl groups, the interconversion between the two enantiomeric helices is slow and they are separable at room temperature.40,41 Thus, the conjugation of the trityl radical CT-03 with the racemic mixture of the nitroxide APO through L-proline leads to four enantiomerically pure diastereoisomers (TNT1, TNT2, TNL1 and TNL2, Scheme 1) which were separated by reve (...truncated)