Postmodification via Thiol-Click Chemistry Yields Hydrophilic Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization
Postmodification via Thiol-Click Chemistry Yields Hydrophilic Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization
复制标题
通过硫醇点击化学进行后修饰产生亲水性三苯甲基氮氧化物双自由基，用于生物分子高场动态核极化
DOI：
10.1021/acs.jpcb.0c08321
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Yangping Liu
中科院分区：
文献类型：
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作者：
Weixiang Zhai;Aless;ra Lucini Paioni;Xinyi Cai;Siddarth Narasimhan;João Medeiros-Silva;Wenxiao Zhang;Antal Rockenbauer;Markus Weingarth;Yuguang Song;Marc Baldus;Yangping Liu
动态核极化 (DNP) 是增强核磁共振 (NMR) 信号强度的强大方法，可在生命和材料科学中实现前所未有的应用。最终目标是将 DNP 增强型固态 NMR 的使用扩展到超高磁场，其中集成了最佳光谱分辨率和灵敏度。三苯甲基硝基氧 (TN) 双自由基引起了人们对高场 DNP 的极大兴趣，但迄今为止它们在复杂（生物）分子中的应用受到限制。在这里，我们报告了一种用于合成亲水性 TN 双自由基的新型后修饰策略，以改善其在生物分子应用中的用途。最初，合成了三个带有氨基酸连接体的 TN 双自由基（称为 NATriPols 1-3）。 EPR 研究表明，氨基酸连接体的 α 位是这些双自由基的理想修饰位点，因为它们的电子-电子磁相互作用受到该位置取代基的轻微影响。基于这一发现，我们合成了在 α 位添加二硫化吡啶的 NATriPol-4。通过硫醇点击化学对 NATriPol-4 进行后修饰，以定量方式产生各种 TN 双自由基，包括亲水性 NATriPol-5。有趣的是，在18.8 T NATriPols 下，甘油/水基质中13 C, 15 N-脯氨酸的DNP 增强与其疏水性成反比。重要的是，与 TEMTriPol-1 和 AMUPol 相比，亲水性 NATriPol-5 和 NATriPol-3 在包括球状可溶性蛋白和膜靶向肽在内的生物分子中的应用显示出显着改善的性能。我们的工作为一步合成具有可调物理化学性质的新型极化剂提供了一种有效的方法，从而加快了超高磁场下生物分子应用的新型双自由基的优化。
Dynamic nuclear polarization (DNP) is a powerful method to enhance nuclear magnetic resonance (NMR) signal intensities, enabling unprecedented applications in life and material science. An ultimate goal is to expand the use of DNP-enhanced solid-state NMR to ultrahigh magnetic fields where optimal spectral resolution and sensitivity are integrated. Trityl-nitroxide (TN) biradicals have attracted significant interest in high-field DNP, but their application to complex (bio)molecules has so far been limited. Here we report a novel postmodification strategy for synthesis of hydrophilic TN biradicals in order to improve their use in biomolecular applications. Initially, three TN biradicals (referred to as NATriPols 1–3) with amino-acid linkers were synthesized. EPR studies showed that the α-position of the amino-acid linkers is an ideal modification site for these biradicals since their electron–electron magnetic interactions are marginally affected by the substituents at this position. On the basis of this finding, we synthesized NATriPol-4 with pyridine disulfide appended at the α-position. Postmodification of NATriPol-4 via thiol-click chemistry resulted in various TN biradicals including hydrophilic NATriPol-5 in a quantitative manner. Interestingly, DNP enhancements at 18.8 T of NATriPols for13C,15N-proline in a glycerol/water matrix are inversely correlated with their hydrophobicity. Importantly, applications of hydrophilic NATriPol-5 and NATriPol-3 to biomolecules including a globular soluble protein and a membrane targeting peptide reveal significantly improved performance compared to TEMTriPol-1 and AMUPol. Our work provides an efficient approach for one-step synthesis of new polarizing agents with tunable physicochemical properties, thus expediting optimization of new biradicals for biomolecular applications at ultrahigh magnetic fields.