The solid-state intramolecular cyclization of lisinopril to diketopiperazine was investigated by <i>in situ</i> Fourier transform infrared (FT-IR) microscopy. Using a controllable heating cell, the isothermal transformation was monitored <i>in situ</i> at 147.5, 150, 152.5, 155, and 157.5 °C. The collected time-dependent FT-IR spectra at each isothermal temperature were preprocessed and analyzed using a multivariate chemometric approach. The pure component spectra of the observable component (lisinopril and diketopiperazine) were resolved and their time-dependent relative contributions were also determined. Model-free and various model fitting methods were implemented in the kinetic analysis to estimate the activation energy of the intramolecular cyclization reaction. Arrhenius plots indicate that the activation energy is circa 327 kJ/mol.
Vol. 3, Iss. 9 Virtual Journal for Biomedical Optics
Effendi Widjaja and Wei Jian Tan, "Kinetics of Lisinopril Intramolecular Cyclization in Solid Phase Monitored by Fourier Transform Infrared Microscopy," Appl. Spectrosc. 62, 889-894 (2008)