Insights Towards Optimizing Palladium-Catalyzed Bioorthogonal Reactions

Abstract

Despite large amounts of research investigating the mechanism and kinetics of the Suzuki-Miyaura reaction in organic solvent, very little research has been completed to investigate this mechanism or kinetic properties in aqueous solvent. Due to properties of the Suzuki-Miyaura reaction which are favourable to bioorthogonal reaction, I first investigated a method to study the kinetics of the Suzuki-Miyaura in water using NHC/Pd complexes that had been designed to facilitate cross-coupling in aqueous environments. I also designed a prototype assay for testing these catalysts that could be adapted for high-throughput screening. Synthesis towards a fluorescent probe for a high-throughput screen was also started. I determined that UV-Vis spectroscopy was not suitable for studying the Suzuki-Miyaura reaction in aqueous conditions, and that studying this reaction with fluorescent probes looks more promising.