1. 不對稱二亞胺鋅/銅化合物的密度泛函理論計算研究2. 順鉑氫化合物中間體是否存在?結合實驗與密度泛函理論計算之研究

Abstract

Part A The N,N′-substituted β-diketiminato ligands have been attracting increasing interest over the past several decades, mainly due to their suitability as sterically crowded spectator ligands to stabilize coordinatively unsaturated metal centers and unusual oxidation state. The N,N`-substituted β-diketiminato ligands can act as a biomimetic ligand to bind copper ion and perform chemical biomimetic reaction such as a metalloenzymes does. And the β-diketiminato Zn(II) complexes are important catalysts to the ring-opening polymerization of lactide (LA). Among these researches, most of catalysis design focus on the symmetric β-diketiminato ligand, however, there were less attention on the study of asymmetric β-diketiminato ligands. The beginning design of the asymmetric β-diketiminato ligand is to have a better ability to donate electron to metal, and at a bigger steric effect, easy to form a monomer complexes. That is why we extend bidentate ligand to tridentate′s one. But the experiment results do not match the expectations generated by our design, the tridentate metal complex can also form dimer structure which has been confirmed by the crystal structure. From the X-ray crystal result, we can get different structure by using same ligand and same electron configuration of metal ions. Therefore, in this thesis, we investigate the influence factor of the crystal structure of the asymmetric β-diketiminato zinc/copper complexes using density functional theory (DFT). Part B Cisplatin, Pt(NH3)2Cl2, is one of the most widely used anticancer drugs nowadays. It has been successfully applied to the treatment of various cancers such as testicular, ovarian and cervical cancer. In the early literature study shows, prior to binding with DNA, cisplatin has to undergo a hydrolysis reaction in which one or two chlorides are replaced by water molecules. It is generally accepted that the target of cisplatin is DNA: it prefers binding to the N7 sites of two consecutive guanines, leading to intrastrand cross links and the subsequent cell apoptosis. Essentially study related to the radiation of cisplatin in the course of treatment have been proved that the chemoradiation therapy has a synergistic effect. That is why cisplatin has been used in the clinical treatment for many years. During chemoradiation therapy, cisplatin isn’t the majority molecular that received radiation exposure but water. When the water has been excited by radiation , hydrated electrons are formed. The previously DFT research in our lab found that the behavior of cispaltin is different between the existence of hydrated electrons or not. If cisplatin solution contain hydrated electrons, it will get diffent reaction from the literature’s one. Hydrated electrons will make cisplatin become cisplatin radical, and cisplatin radical will react with DNA. It can abstract hydrogen atoms from the C–H bonds of the ribose moiety and the methyl group of thymine, which in turn leads to DNA strand breaks and cross-link lesions. HPt(NH3)2Cl (cisplatin hydride) will form being byproducts. If we can prove the existence of cisplatin hydride, we can support the previously research.