The effect of cucurbituril (CB) nano-caging on the photophysical properties, particularly excited-state proton transfer (ESPT) reaction, of an eminent anti-cancer drug, topotecan (TPT), is demonstrated through steady-state and time-resolved fluorescence measurements. TPT in water (pH 6) exists exclusively as the cationic form (C) in the ground state. However, the drug emission mainly comes from the excited-state zwitterionic form (Z) of TPT, and is attributed to water-assisted ESPT between the 10-hydroxyl group and water, which leads to the transformation of C* to Z* of TPT. In the presence of CB, it is found that selective encapsulation of the C form of TPT results in the formation of a 1:1 inclusion complex (CB:TPT), and the ESPT process is inhibited by this encapsulation process. As a result, C* becomes the dominant emitting species in the presence of CB rather than Z, and fluorescence switching takes place from green to blue. Time-resolved studies also support the existence of CB-encapsulated cationic species as the major emitting species in the presence of the macrocyclic host. Semi-empirical quantum chemical calculations are employed to gain insight into the molecular picture of orientation of TPT in the inclusion complex. It is clearly seen from the optimised structure of 1:1 CB:TPT inclusion complex that both 10-hydroxyl and 9-dimethylaminomethylene groups of TPT lie partly inside the cavity, and thereby inhibit the excited-state transformation of C* to Z* by the ESPT process. Finally, controlled release of the drug is achieved by means of fluorescence switching by introducing NaCl, which is rich in cells, as an external stimulus. Come on in: Inclusion complexation of the anticancer drug, topotecan (TPT), with cucurbituril (CB) is studied by steady-state and picosecond time-resolved techniques. Inside the nanocavity of CB, excited-state proton transfer (ESPT) of TPT is inhibited and fluorescence switches from green to blue (see picture). If NaCl is introduced into the TPT-CB solution, the blue color switches back to green.
All Science Journal Classification (ASJC) codes
- Atomic and Molecular Physics, and Optics
- Physical and Theoretical Chemistry