Real-time reaction monitoring of Azide-Alkyne cycloadditions us-ing benchtop NMR-based Signal Amplification by Reversible Ex-change (SABRE)

Abstract

Rufinamide is new antiepileptic drugs (AED), relatively well absorbed in the lower dose range, and is currently being used in antiepileptic medications, as well as containing a triazole structure. Triazoles are heterocycles containing three nitrogen atoms in a five-membered aromatic ring. 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 like 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.