Jeong Hye Jin, Min Sein, Baek Juhee, Kim Jisu, Chung Jean, Jeong Keunhong
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
Department of Chemistry, Seoul Women's University, Seoul 01797, South Korea.
ACS Meas Sci Au. 2023 Jan 10;3(2):134-142. doi: 10.1021/acsmeasuresciau.2c00065. eCollection 2023 Apr 19.
Rufinamide, possessing a triazole ring, is a new antiepileptic drug (AED) relatively well-absorbed in the lower dose range (10 mg/kg per day) and is currently being used in antiepileptic medications. Triazole derivatives can interact with various enzymes and receptors in biological systems via diverse non-covalent interactions, thus inducing versatile biological effects. Strain-promoted azide-alkyne cycloaddition (SPAAC) is a significant method for obtaining triazoles, even under physiological conditions, in the absence of a copper catalyst. To confirm the progress of chemical reactions under biological conditions, research on reaction monitoring at low concentrations is essential. This promising strategy is gaining acceptance for applications in fields such as drug development and nanoscience. We investigated the optimum Ir catalyst and magnetic field for achieving maximum proton hyperpolarization transfer in triazole derivatives. These reactions were analyzed using signal amplification by reversible exchange (SABRE) to overcome the limitations of low sensitivity in nuclear magnetic resonance spectroscopy, when monitoring copper-free click reactions in real time. Finally, a more versatile copper-catalyzed click reaction was monitored in real time, using a 60 MHz benchtop NMR system, in order to analyze the reaction mechanism.
鲁非酰胺含有一个三唑环，是一种新型抗癫痫药物（AED），在较低剂量范围（每天10毫克/千克）内吸收相对良好，目前正在抗癫痫药物中使用。三唑衍生物可通过多种非共价相互作用与生物系统中的各种酶和受体相互作用，从而产生多种生物学效应。应变促进的叠氮化物-炔烃环加成反应（SPAAC）是一种在无铜催化剂的情况下，甚至在生理条件下获得三唑的重要方法。为了确认生物条件下化学反应的进程，低浓度反应监测的研究至关重要。这种有前景的策略在药物开发和纳米科学等领域的应用正逐渐得到认可。我们研究了在三唑衍生物中实现最大质子超极化转移的最佳铱催化剂和磁场。通过可逆交换信号放大（SABRE）分析这些反应，以克服实时监测无铜点击反应时核磁共振光谱灵敏度低的局限性。最后，使用60兆赫兹台式核磁共振系统实时监测了一种更通用的铜催化点击反应，以分析反应机理。
