Vibrational spectra, DFT calculations, and conformations of 5′-chloro-1-isopropyl-7-azaindirubin-3′-oxime

For centuries Danggui Longhui Wan has been used to treat chronic ailments, such as myelocytic leukemia. In the 1960s, the active ingredient in Danggui Longhui Wan was isolated and identified as indirubin. Indirubin has shown potent inhibition of cyclin-dependent kinase through binding to the ATP-binding site. However, indirubin shows poor solubility and low absorption, hence many derivatives have been developed to enhance these properties. One such derivative is 5′-chloro-1-isopropyl-7-azaindirubin-3′-oxime (CIADO), investigated in the current work. Infrared and Raman spectra were collected and compared with predicted spectra using density functional theory. Based on theoretical calculations, the most stable form of CIADO isomer is found to be cis (Z) and trans (E) with respect to the ring system linkage and the 3′-oxime functional group respectively. Also observed were two distinct internal rotational minima for the 1-isoprooyl group separated by a large energy barrier. The presence of two distinct isopropyl conformations observed in our calculations was confirmed with temperature-dependent IR experiments. Assignment of experimental vibrational modes was carried out based on functional group displacement observed in the calculations.