Dynamics of different steps of the photopyrolytic cycle of an eminent anticancer drug topotecan inside biocompatible lyotropic liquid crystalline systems

Abstract

In the present work, we have explored the dynamics of different steps of photopyrolytic processes of an eminent anticancer drug topotecan (TPT) inside the biocompatible reverse hexagonal (H_II), gyroid (Ia3d) cubic and diamond (Pn3m) cubic lyotropic liquid crystalline (LLC) phases. Both steady state and time-resolved area normalized emission spectrum (TRANES) demonstrate the generation of an excited state zwitterionic (Z*) form of TPT in all LLC phases attributed to an excited state intermolecular proton transfer (ESPT) process from TPT (C* form) to the nearby water molecules. Using a kinetic model, we have calculated the dynamics of different steps, namely, proton transfer, recombination and dissociation of photopyrolytic processes of TPT inside different LLC phases. The calculated proton transfer dynamics of TPT are found to be severely retarded inside LLC phases compared to bulk water (32 ps), and they follows the order H_II < Ia3d < Pn3m < H₂O. The combined effect of slower solvation, hampered ‘Grotthuss’ proton transfer and the topological influence of LLC phases are believed to be responsible for the slower and different extent of ESPT dynamics. Geminate recombination dynamics are also found to be slower (nanosecond time scale) and follow the order H_II < Ia3d < Pn3m. Slower geminate recombination dynamics mainly arise due to the lower dielectric constant and reduced water channel diameter of the LLC phases. The dissociation dynamics of TPT also get modulated inside LLC phases, and they are believed to be governed mainly by the topological influence and dielectric constant of the LLC phases.