In vitro monitoring of ring opening of leflunomide: A surface enhanced Raman scattering and DFT based approach

The in vitro mechanism of ring opening of leflunomide resulting in the formation of a metabolite A771726 has been studied by time series surface enhanced Raman spectra using NaOH buffer at pH ∼10. The decomposition of leflunomide into A771726 through NO bond cleavage was identified by the Raman signature of CN bond of A771726. The experimental results have been correlated with theory by transition state calculations of the reaction using different basic catalysts; OH−, formate and formate + water and water alone. The reaction barrier energy is found to be lowest with OH− as a catalyst.