| Abstract [eng] |
One of the main compounds of the cytotoxin class suitable for cancer treatment is tirapazamine (TPZ), which exhibits selective behavior in a hypoxic environment. The use of tirapazamine derivatives in medicine has been widely investigated for several decades. However, the photophysical examination of these compounds remains scarce. In order, to successfully understand their usability, control, modification, and application more studies of tirapazamine optical properties need to be performed both by modifying the molecule itself and by explaining the relaxation mechanisms. The aim of this study was to investigate the influence of polar substituents on the rate of photochemical reactions in tirapazamine and deoxytyrapazamine (dTPZ) and to optimize the fluorescence properties of modified dTPZ. This work was carried out in collaboration with Vilnius University Life Science Center prof. N. Čėno group, synthesis of tirapazamine based compounds was performed by dr. J. Šarlauskas. Were we focused the possibilities to control optical properties of tirapazamine with small polar substituents. In this work, spectroscopic studies of newly synthesized derivatives were performed, firstly to understand in detail the excitation relaxation mechanisms of tirapazamine compounds and secondly to optimize the control of the fluorescence properties of modified desoxytirapazamine compounds. Tirapazamines with intense fluorescence could be used to visualize the stages of cancer treatment or to monitor various enzymatic reactions. The relaxation dynamics of tirapazamine (T2) excitation, which consists of the rapid part of the relaxation (in the range of 1 to 200 ps) related to oxygen cyclization or the formation of triplet states, and the slow part related to the relaxation events of charge transfer (CT) state (2 - 20 ns). We have shown the control of these processes by polar substituents. A large series of modified polar substituents of desoxytirapazamine (T1) compounds was investigated. These substituents have been shown to increase the fluorescence quantum yield of desoxytirapazamine (T1) by 4 times compared to the T1 compound by introducing strong donor groups at the C7 position. Such substituted T1 compounds can be used to monitor the oxygen reduction reaction by fluorescence detection. |
