Theoretical Study on Reactions of Triplet Excited State Thioxanthone with Indole

In the present work, a theoretical study on the deactivation of triplet excited (T1) state thioxanthone (TX) by indole (INH) was performed, based on density functional theory calculations. Three feasible pathways, namely direct electron transfer from INH to T1 state TX, electron transfer followed by proton transfer from INH.+ to TX.−, and H-atom transfer from nitrogen of INH to keto oxygen of T1 state TX, were proposed theoretically to be involved in T1 state TX deactivation by INH.


Introduction
Thioxanthone (TX) and its derivatives are efficient photosensitizers, which have attracted much attention in recent years owing to their broad spectrum of antitumor activities and great potential to be developed as novel antitumor agents [1][2][3]. It has been reported that photoexcited TX can cause DNA damage [4]. It is known that photosensitization involves two mechanisms, i.e., direct reaction with substrates (e.g., DNA, amino acids and proteins) (Type I) or damage via intermediacy of oxygen (through energy or electron transfer processes with molecular oxygen to generate toxic reactive oxygen species) (Type II). As the relatively long-lived triplet excited (T 1 ) state is mainly responsible

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for the photosensitization reactions, exploring the deactivating processes of TX will be helpful to understand its photosensitization properties. The indole moiety exists in many bioorganic compounds like the amino acid tryptophan and in tryptophan-containing proteins. Therefore, in the present work, the energetics describing the deactivation of the T 1 state TX by INH have been investigated using quantum chemical calculations.

Results and Discussion
Upon irradiation, ground (S 0 ) state TX is initially excited to singlet excited (S 1 ) state, which may then reside in the T 1 state through intersystem crossing: According to the electronic parameters of TX and INH (   [5,6], which verifies the calculation methods. As INH possesses higher E T1 relative to TX, the direct energy transfer based deactivation pathway is unfeasible. Moreover, it is worth mentioning that as E T1 of TX is higher than the energy needed to bring 3 O 2 to singlet excited state ( 1 O 2 ), 1.05 eV ( which may be involved in the DNA photooxidation by TX [4]: The second deactivating pathway is direct electron transfer between T 1 state TX and INH (Equations 3 and 4). Table 1 lists the theoretically estimated electronic parameters to characterize the molecular electron-donating or electron-withdrawing potentials for TX and INH. The feasibility of pathway (3) relies on the summation of AEA T1 of TX and AIP of INH, which is negative (Table 1). Thus, it can be inferred that the direct electron transfer from INH to T 1 state TX is favorable. In contrast, the electron transfer from T 1 state TX to INH (Equation 4) is theoretically unfeasible because of the positive value of total reaction energy (summation of AIP T1 of TX and AEA of INH). In previous study, the electron transfer-based DNA oxidation by photoexcited TX has been reported [4]. The electron transfer process has also been reported to be involved in the deactivation of T 1 state TX by amines or indolic derivatives [7,8].
In addition, based on the experimentally identified formations of the radical species, TXH . and IN . , it was proposed that the electron transfer is followed by proton transfer (Equation 5) during the deactivation of T 1 state TX by indolic derivatives [8]. Therefore, the electron transfer followed by proton transfer accounts for an important deactivating pathway: Moreover, there may exist another deactivating pathway which may result in the formation of TXH . and IN . , that is, the H-atom transfer from the quencher to T 1 state TX as represented in the following equation: To explore the feasibility of this pathway, the bond dissociation enthalpy (BDE) and H-atom affinity (HAA), which have been widely employed to measure the molecular H-atom-donating and H-atom-abstracting ability, respectively [9], of TX and INH are calculated ( Table 1). The BDE of N-H bond in INH is calculated to be 4.04 eV. The keto oxygen is the most favored position to accept a H-atom for TX, and the corresponding HAA is estimated as -4.56 eV. Therefore, it can be inferred that the H-atom transfer process from INH to T 1 state TX is feasible as shown in Scheme 1. Through the H-atom transfer from INH to T 1 state TX, TXH . and IN . are formed, and the two radical species have both been observed experimentally during the reactions of T 1 state TX with indolic derivatives [8]. Furthermore, photoinitiated free radical polymerization is widely employed in various industrial applications [10]. TX and its derivatives are important photoinitiators, exhibiting high photoinitiation efficiency and the H-atom abstraction of T 1 state TX from H-atom donors accounts for one important free radical generation pathway.

Conclusions
To summarize, according to quantum chemical calculations, three postulated pathways, i.e., direct electron transfer, electron transfer followed by proton transfer and direct H-atom transfer, may be involved in T 1 state TX deactivation by INH. The present findings provide insight into the photosensitization characteristics of excited state TX.