The Intramolecular Hydrogen Transfer Of HMB And Its Analogue As Well As Their Photosensitization

The intramolecular hydrogen transfer (IHT) of Hypomycin B (HMB), a novel type of perylenequinonoid photosensitizer (PQP), and of its analogue have been investigated by using quantum chemistry method. The relationship between IHT and its photosensitive activity is discussed.PQP, a new type of photosensitizer, has attracted more and more attention recently because of their light-induced antiviral (especially anti-HIV) and antitumor activity. The study on structure-activity relationship indicated that perylenequinone (PQ) is the active center of these compounds. The unique structure of PQPs enables them to isomerize on ground and excited states. It has been found that PQPs' IHT between hydroxyl and carbonyl group is critical for PQP to reserve their photosensitive activity and structural stability.Due to so many possible IHT patterns exsit in PQP, great difficulties are taken to the theoretical study, the experimental research and spectrum analyze. It seems ture that hypocrellin and hypericin would have similar IHT reaction. But in fact, their characteristic of IHT as well as the mechanism of their photosensitive activity is different. Besides, which hydrogen is tranfered on earth is still uncertain.HMB is a natural compound found and researched in our country. It can be abundantly produced by biological fermentation technology, which makes it a potential photosensitizer contrasted to the other PQPs that can only be get from natural eumycete. More important, there is only one intramolecular hydrogen bond (IHB) in HMB, that is to say that HMB has only one IHT pattern. Therefore, HMB is an excellent model compound for the theoretical and experimental research of PQP's IHT and their photosensitive activity. To choose HMB as the research object will solve some diverge in the experimental research and lay a foundation in studying the photo-induced activity.From little molecule system, such as 9-HPO and naphthazarin, we analysed the character of IHT assisted by the molecular resonance. Suitable calculating method was also chosen for the rest study. Then we performed further theory calculation for HMB and its nine model compounds including the active center of HMB. The result was compared with PQ, which was the active center of PQP. In the end of our work, we explored the basic structure of hypericin and hypericin anion to explain the diffrences between hypocrellin and hypericin, and to elucidate the mechanism for their photosensitive activity.Molecular mechanics methods in softwares PCModel and Chem3D are employed to get the initial structure. Further quantum chemistry optimizing was performed with program Gaussian 94. To verify the transition state, we also did frenqunce calculation. As to the excited state, configuration interaction approach in Gaussian program was employed, except the calculation for hypericin with theprogram MOPAC.The most important results are as follows:a.) By the calculation of HMB and its nine model compounds, we found: The energy of these systems and barriers for IHT teaction are mainly determined by the conjugation structure or the resonance mode. The side-chain and side ring have little influence on the barrier of HMB's IHT. The barrier for parallel structures is 33.4~41.6kJ/mol and 15.99-24.77kJ/mol for verse ones, which is so lower than the barrier of common chemistry reactions. The barrier is linear to the change of the atom's charge for most similar systems, and linear to the change of the H-bond length or hydroxyl O-H bond length.b.) Isomerizion, caused by IHT, makes HMB, PQ has an unique ground and excited potential energy surface. On ground state, parallel structure's energy is 17.45kJ/mol lower than versa structure. While on the singlet-excited state, it is 33.51kJ/mol higher. Moreover the barrier on singlet-excited state is only 6.38kJ/mol, which is lower than ground state. So the IHT efficiency is even higher.c.) By the triplet-excited single point energy calculation of structure of the singlet excited state HMB's active center, we found: the energy on trip...