Biological And Organic Functionalization Of A Polyoxomolybdate For Applications As Antitumor Drug And Gelator

Polyoxometalate (POM) is the early transition metals (most commonly VⅤ, MoⅥ and WⅥ) in their highest oxidation states to form metal-oxygen cluster anions. Owing to its well chemical composition and diverse structure, it has widespread application value and good prospect of development including catalysis, photochromism, electricity, magnetism, and medicinal chemistry. Since1971, when the French scientist Raynaud et al. reported that the polytungstosilicate heteropoly compounds had good antiviral activity, POM has attracted widespread attention in medicinal chemistry. The polyoxomolybdate has good cell activity on human colon cancer, breast cancer and lung cancer, however, it has no choice on malignant cells and normal cells. Thus, cytotoxicity is the biggest bottleneck of the drug research of POMs. Based on obvious cell activity and symmetrical structure of the polyoxomolybdate, which is used as the research object in this dissertation. Novel biomolecule-POM conjugates are created through covalent to impart the selectivity by the synergistic effect coming from both the biological ligands and polyoxomolybdate moiety. In addition, we hope that the conjugates could show outstanding performance on other potential applications.First, the tris-modified Anderson-type POM{MnMo6O18[(OCH2)3CNH2]2}3-(Tris-POM-Tris) was selected due to its potent antitumor activity, and possibility in further organic modification. Through the literature review and selection of biological ligands, biomolecules (cholic acid, dehydrocholic acid, cholesterol, and galactose) were conjugated onto the POM cluster. We hope that biological ligand decorated on POM can well interact with tumor cell receptors by the synergistic effect, resulting site-specific modification. The chemical structures of the conjugates were cautiously confirmed with full FT-IR, ESI-MS,1H NMR and elemental analysis. Then the noncancerous breast epithelial cell (MCF-10A) and breast cancer cells (MCF-7and MDA-MB-231) were selected to test their cancer cell activity. The experimental results show that the bioconjugates of the POM cluster with cholic acid as well as dehydrocholic acid present an enhanced anti-tumor activity and selectivity. In other words, a rational selection of biological ligands is very crucial for creating the candidates of anticancer hybrid drugs. This work presents a new concept to develop novel tumor-cell targeting POM-biomolecule hybrid drugs.Through above results, hybrid products obtained by the synergistic effect not only show the original components of their respective performance, can even show a more superior performance, and able to better applied to daily life. Gel as soft material is widely used in our daily life, such as toothpaste, jelly, glue, etc. The gels contained cholesterol are widely researched, due to the application prospect of building functional soft materials. The driving forces of gel formation are usually weak noncovalent interactions, such as hydrogen-bonding interactions, π-π stacking, and Van der Waals interactions, so most gels possess a lower thermal stability, which may be a major concern in practical applications. Next, we choose cholesterol-POM-cholesterol conjugates as the research object, hope that the thermal stability of organogels can be enhanced through the self-reinforcing supramolecular assemblies. In the experiment, we found the thermal stability of organogel in toluene was greatly enhanced. We performed a close investigation of the structures of supramolecular assemblies in the dried gel samples using TEM, EDX, XRD, and AFM, in order to understand the driving force and mechanism of the enhanced thermal stability of organogels. This work may provide a new, smart approach to the future fabrication of thermostable gels with potential applications as soft materials.Hybrid products obtained through covalent show a more superior performance due to the synergistic effect, however, we find that the current methodology has its defects, such as products are not easy purification, also the yield is low using amidation or esterification. Using cross coupling or Huisgen1,3-dipolar cycloaddition reactions, the metal catalyst residues could have serious influence in POM-based biomedical research. Thus, it is very meaningful to provide a simple, high efficient and ideal synthetic methodology for post-functionalization of POM cluster. Through detailed research, we successfully carried out the post-functionalization of an Anderson-type POM cluster with very different kinds of biological moieties or organic groups by using the Diels-Alder click reaction. The reaction is high efficient and ease to purify, so it is an ideal methodology for the synthesis of novel post-functionalized POM hybrids.