Synthesis Of Asymmetric Cationic Surfactants And Properties Of Their Mixtures

In recent years, gene therapy as one of the most important areas of the medicine, has been used in clinical practice for cancer and immune deficiency diseases; however, its high toxicity and relatively low efficiency seriously affect the development. Compared to low security of viral vectors, non-viral vectors have become a hot topic because of advantages of low immune response, low toxicity and ease to preparation, etc.In this work, six asymmetric hydrophobic chain cationic surfactants (GHCC12-14、 GHCC12-16、GHCC14-16、GHBC12-14、GHBC12-16、GHBC14-16) are designed and synthesized. By’H-’H spectroscopy alkyl isocyanate can be determined to connect to end position hydroxyl of N, N-dimethyl-1,2-propanediol. The structures of all intermediates and target compounds are characterized by MS and 1H NMR.The γcmc, cmc, HLB and critical packing parameter P of the synthesized asymmetric type cationic surfactants are studied. It is found that the surface tension and cmc decreases as the carbon chain length increases. When the number of carbon chain is 12-14, both γctc and cmc is small, indicating good surface activity.Six symmetric cationic surfactants and six asymmetrical cationic surfactants are mixed with the anionic surfactants (SDBS, SDS and SAS) to prepared vesicles, respectively. By using appearance of morphology, particle size, Zeta potential, conductivity and transmission electron microscopy (TEM), it is found that ions surfactant complex systems can form vesicles, no matter in rich cationic area or rich anion area. The particle size distribution conform the range vesicles between 200～400nm, except X1=0.5; zeta potential is less than-30 mV in anion-rich area and greater than 30 mV in cation-rich region, showing good stability of spontaneous formation vesicles of mixed solution. Meanwhile analysis is made from the viewpoint of Masaniko molecular geometry structure and Israelachvili theory for spontaneous formation of vesicles.Six asymmetric cationic surfactants are used to carry out biological experiments. TEM shows that, except GHBC14-16, asymmetric cationic lipid GHCn-m are able to form liposomes; particle size and zeta potential of asymmetric cationic liposome/DNA complexs shows that particle size 300～400 nm meets the requirements of cell transfection; agarose gel electrophoresis experiment indicate that asymmetric cationic liposome GHCn-m/DNA complexs have good blocking of DNA with the proportion more than 4:1; when GHCn-m/ DNA is 1:1, the asymmetric cationic liposome transfection efficiency of Hela cells is highest, slightly higher than the commodity reagent DOTAP; asymmetric liposomes have large cytotoxicity on Hela cells from its cytotoxicity tests.