Structural Modification And Photosensitization Of New Photoinduced Bioactive Compounds

The intramolecular pronton transfer (IPT) of a novel type of perylenequinonoid photosensitizer (PQP)--Hypomycin A (HMA) have been investigated employing quantum chemistry method to shed light on the IPT mechanisms of PQP. The photophysical and photochemical characters of halogen and cysteamine substituted PQP, together with Al3+-complexed PQ, have also been studied.PQP, such as hypocrellin A (HA), hypocrellin B (HB) and hypericin (HYP) have attracted considerable attention owing to their excellent properties of photosensitization. PQP have strong intramolecular hydrogen bonds in their molecules. The unique structure enables them to isomerize both in the ground state and the excited states by means of IPT. Previous researches demonstrated that IPT played a significant role in the photosensitization of PQP. While owing to the good symmetry of the molecular skeleton of PQP, which proton is transferred during the reaction is still an open question. Typical PQP contain at least two identical hydroxyl groups, therefore, it is difficult to distinguish whether the IPT process is stepwise or concerted. The above questions obstruct the further understanding of the photosensitization of PQP.PQP have poor water solubility and show weak absorption in the therapeutic window, in which tissue penetration is maximal. These disadvantages limit their PDT applications clinically. Much work has been done on site-directed chemical modifications to optimize properties of red absorption, water solubility, tissue distribution and toxicity, while there have not systematic study on the regulation of substitution effect on photophysical and photochemical properties of PQP.Recently, a novel type of photosensitizer-hypomycin A (HMA) was isolated from the mycelia of Hypomyces sp.. Similar to the structure of typical PQP, HMA has a hydroxyl group peri to a carbonyl group at each end, but its structural skeleton is different in that the bond of C11-C12 is single rather than double. Therefore, the environment around the transferable hydrogen at both sides is different so that the IPT process of H14 and H17 may be distinguishable by theoretical calculation. Moreover, the various IPT fashions of HMA facilitate making clear the role of two transferable hydrogens as well as the structural effect on IPT process.Employing ab initio, CIS and TDDFT methods in the Gaussian 98 package programs, we firstly investigated the different IPT processes of HMA and discussed the IPT mechanisms of PQP. The photophysical and photochemical properties of the halogenand cysteamine substituted PQP, together with Al-complexed PQ were also studied. The results may be invoked to direct the experiment to synthesize new type of excellent photosensitizers.The most important results are as follows:i. According to the calculated results for HMA, it was revealed firstly, isomer I and II are the most stable geometries in the ground and singlet excited state, respectively. Secondly, the IPT barriers of 1II were very near to those of PQ, while the IPT barriers of IIV got approximately 17kJ/mol higher in the ground state and 28 kJ/mol higher in the singlet excited state than those of IH; the reaction rate constants suggested that the PQP' s IPT observed in the experiment was in the singlet excited state. Thirdly, the height of IPT barrier correlated not only with the variance of charge for labile hydrogen, the change of H-bond' s length, the change of O-O bond' s length, the change of O-H bond' s length, but also with the reactant molecular H-bond' s length; the correlations were same in the ground and singlet excited state; thus the H-bond' s length became an effective and simple parameter to theoretically characterize PQP' s IPT barrier. Finally, the dipole moment increased during H14 transfer while it decreased during HI 7 transfer both in the ground and singlet excited state.ii. Taking hypomycin B (HMB) as the model compound, HF/6-31G and TD-B3LYP/6-31G methods have been employed to explore the effect of chlorine, bromine and iodine substitutions on molecular proper...