The Solvent Effect Of The Photosensitizer Photosensitivity And Photosensitivity Reaction Mechanism

The quality of photosensitizer is a key factor for the efficiency of photodynamic therapy (PDT). In recent years, much research attention has been focused on a novel type of photosensitizer, perylenequinonoid derivatives (PQD). Experimental evidences have suggested that PQD have the potential to replace PhotofrinⅡas the latest photodynamic medicine due to its light-induced antitumor, antifungal and antiviral activities.It has been proposed that the mechanism of photosensitization of the compounds is related to the photoinduced proton or hydrogen atom transfer. So we have mainly studied the process of hydrogen atom transfer up to now. It has been found that there is an intersection between S1 and T1 potential energy profiles. And the photosensitization of PQP may originate from the intersection. The IPT reaction of perylenequinonoid photosensitizers and the effect of the substitutions in gaseous environment have been studied.As we all known the process of the hydrogen atom transfer occur in solution, but we studied the process in gaseous environment. Considering the practice condition, we perform the hydrogen atom transfer in solution.Employing the ab initio methods in the Gaussian 98 package programs, we firstly investigated the IPT processes of PQ in different solvents and discussed the IPT mechanisms of different substituted PQ in aqueous solution. The results may be invoked to direct the experiment to synthesize new type of excellent photosensitizers. The most important results are as follows:i. Taking PQ as the model compound, HF/6-31G(d) and SCRF methods have been employed to explore the solvent effect of PQ. It was found firstly that, the polar solvents lowered the barriers and were propitious to the IPT. Secondly, the dipole moment of the molecule in the polar solvents is higher than in the gas. It is concluded that the hydrogen atom transfer is easier in polar solvent than in nonpolar solvent; the larger the polarity is the easier the process to occur. ii. HF/6-31G(d) and SCRF methods have been employed to explore the solvent effect of the different substitutions of PQ in IPT process. It was revealed firstly, the height of IPT barriers correlated not only with the variance of charge for labile hydrogen but also with the dipole moment, so they became the effective and simple parameters to theoretically characterize PQP's IPT barrier. Finally, it was found that the IPT barrier of the subsititutions at the R4 place was lower in the polar solvent.By now, although the process of hydrogen atom transfer has been studied absolutely, the mechanism of the photosensitization has not been solved. According to mechanism of the photosensitizer, the photosensitization mechanisms of the hypocrellin A (HA) have been explored by using density functional theory (DFT) and time-dependent DFT to study behaviors of excited state. The solvent effects have been taken into consideration by employing the self-consistent reaction field (SCRF) method with polarized continuum model (PCM).i. The energy transfer from excited triplet HA to triplet oxygen can take place, which is a source of the formation of singlet oxygen.ii. The electron transfer can occur between two triplet states of HA in aqueous solution. Once the HA?- is formed, the HA anion radical may in turn donate its excess electron to molecule oxygen to produce superoxide anion in aqueous solution.iii. The direct transfer of electron from HA to molecule oxygen to form superoxide anion is impossible at present calculated conditions.The photosensitizing mechanism of the NA and the effects of halogen substitution on the phototoxic reactions have been explored. The main results are as follows:i. In oxygen-free media, the photo-damage of NA and halogen substitutes to DNA is more likely arises from NAS?+ rather than from T1 state of NAS.ii. In oxygen media, the de-excitation energies of NA and the halogen substituted NA are enough to provide a good source of singlet oxygen. For NA and the substituted NA in the triplet state can't be able to oxidize by O2. So they cannot generate superoxide anion radicals by a direct process. But in water when the NA is reduced, the oxidizing power of O2 is enough to extract an electron from the drug. However the reduced halogen substitutes cannot generate the superoxide anions in all solvents. We thus conclude that the effects of the halogen substitution on the formation of superoxide radical anion are negative. But they are similar to NA on the singlet oxygen yield.