Studies On The Synthesis And Photodynamic Antimicrobial Activity Of Water Soluble Phthalocyaninato Photosensitizers

Bacterial infection is one of diseases which seriously threat to human health, and common treatment is antibiotics. Unfortunately, emergence of drug-resistant strains lowered the therapeutic effects of antibiotics with antibiotics abusing. The development of new chemical drugs is a long-term high expense work, also with side effect of drugs. It is crucial to find a way to treat bacterial infections. Photodynamic therapy could be a good option. Photodynamic inactivation of microorganisms is based on that photosensitizer could be localized preferentially in the bacteria, and subsequently activated by low doses of visible light of an appropriate wavelength to generate reactive oxygen species (ROS) such as free radicals or singlet oxygen that are toxic to the target microorganisms. It has been successfully used in anti-tumor therapies because its remarkable advantages involving high selectivity and low toxicity. It attracts new continuous research interest because of their applications in bacterial infections can significantly reduce the resistance of bacteria, especially on skin infection.In PDT, photosensitizer plays an important role. Phthalocyanines attracted many attentions for their facile synthesis and modification. Besides these, it has a sharp Q band absorption in the visible-light region of600-800nm which could penetrate tissues efficiently and eliminate more easily. But, for phthalocyaninato derivatives have poor solubility which restrict their applications, synthesis of novel phthalocyaninato derivatives with good solubility is imperative. Our research works focused on the following two respects:1. Synthesis and photodynamic antimicrobial activity of carboxyl-substituded phthalocyaninato photosensitizersCross-condensation of4-[3,5-Bis(methoxycarbonyl)phenoxy] phthalonitrile (2.1a),4,5-bis[(4-methyloxycarbonyl)phenoxy]phthalonitrile (2.1b) and4,5-bis[(3-methyloxycarbonyl)phenoxy]phthalonitrile (2.1c) respectively, in the presence of Zn(OAc)2-2H2O and1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) followed by transesterification in refluxing n-pentanol afforded three ester-substituted phthalocyanines2.2a-2.2c. After purification by silica-gel c column chromatography, all three compounds2.2a-2.2c have been characterized with MALDI-TOF mass, UV-Vis spectroscopy, fluorescence spectroscopy and’H NMR. Finally through hydrolysis reaction we receive three soluble carboxyl-substituted phthalocyanines2.3a-2.3c. We also research the photodynamic antibacterial activities of compound2.3a-2.3c on Staphylococcus aureus and Escherichia coli. Results suggest that all three compounds have antibacterial activities to some extent, and compound2.3a shows the best which is considered may have a link with less aggregation owe to molecular low symmetry. But the accurate interaction mechanism between photosensitizer and bacterial cells remain further explorations.2. Synthesis, separation and characterization of amphiphilic phthalocyaninato complexes.Cross-condensation of two different phthalonitriles, namely4,5-bis[(4-methyloxycarbonyl)phenoxy]phthalonitrile (3.1a) and4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}phthalonitrile (3.1b), in the presence of Zn(OAc)2·2H2O and1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) followed by transesterification in refluxing n-pentanol afforded six phthalocyaninato zinc(II) complexes modulated with different numbers of pentyloxycarbonyl and/or triethylene glycol monomethyl ether groups. Simple silica-gel column chromatography leads to the successful separation of all these six compounds, namely Zn[Pc(BP)4](3.2a), Zn[Pc(BP)3(TEG)](3.2b), Zn[Pc(BP)2(TEG)2]-opp (3.2c), Zn[Pc(BP)2(TEG)2]-adj (3.2d), Zn[Pc(BP)(TEG)3](3.2e), and Zn[Pc(TEG)4](3.2f). Compound3.2b-3.2e are amphiphilic with triethylene glycol monomethyl ether substituents. In addition to elemental analysis, the six complexes have been characterized with elemental analysis, MALDI-TOF mass, UV-Vis spectroscopy,1H NMR, and2D COSY spectroscopy. The amphiphilic compound3.2b-3.2e have a sharp Q band absorption in UV-Vis spectroscopy, moreover the AABB and ABAB compounds (compound3.2c and3.2d) also have a great value of comparative research. Those all indicate that such series of compounds have potential use in antibacterial photodynamic therapy, and establish theoretical foundations for the next PACT study. The electrochemical properties have also been investigated.