Synthesis And Properties Of Polyamine Zinc Phthalocyanine And Its Water-soluble Derivatives

Photodynamic therapy(PDT)is a well-established modality for the treatment of a variety of localized tumors,including skin,lung and other tumors.It utilizes the combined action of three individually nontoxic components,namely,a photosensitizer,light,and molecular oxygen,to reach the tumor treatment.Having a number of advantageous characteristics such as good physiological compatibility and excellent photosensitive antitumor activity,phthalocyanines have emerged as a promising class of photosensitizers for PDT.Based on the research productions and existing problems of phthalocyanines used as photosencitizer for PDT,to further enhance the therapeutic efficacy and solubility in water,we report herein a new series of zinc(II)phthalocyanines containing polyamines moieties,including their design,preparation,characterization,basic photophysical and phtochemical properties,in vitro photodynamic and anticancer activity,the results are as follows:1)Five phthalocyanine-polyamine conjugates precursors were designed and prepared.The precursors synthesized included:N-tritylethane-1,2-diamine(Al),4-((2-(tritylamino)ethylamino)methyl)phenol(A2),4-(4-((2-(tritylamino)ethylamino)methyl)phenoxy)phthalonitrile(A3),4-((2-(diethylamino)ethylamino)methyl)phenol(B2),4-(4-((2-(diethylamino)ethylamino)methyl)phenoxy)phthalonitrile(B3).B2 and B3 have not been reported,while compounds A1-A3 were synthesized with new methods.Six zinc phthalocyanines substituted with different polyamine moieties and their water-soluble derivatives have been prepared.They are 2(3),9(10),16(17),23(24)-tetra-(((2-(tritylamino)ethylamino)methyl)phenoxy)phthalocyaninato-zinc(?)(ZnPc1),2(3),9(10),16(17),23(24)-tetra-(((2-aminoethylamino)methyl)phenoxy)phthalocyaninato-zinc(?)(ZnPc2)and 2(3),9(10),16(17),23(24)-tetra-(((2-(diethylamino)ethylamino)methyl)phenoxy)phthalocyaninato-zinc(?)(ZnPc4),quaternized 2(3),9(10),16(17),23(24)-tetra-(((2-aminoethylamino)methyl)phenoxy)phthalocyaninato-zinc(?)(ZnPc3),quaternized 2(3),9(10),16(17),23(24)-tetra-(((2-(diethylamino)ethylamino)methyl)phenoxy)phthalocyaninato-zinc(?)(ZnPc6)and hydrochloride derivative of 2(3),9(10),16(17),23(24)-tetra-(((2-(diethylamino)ethylamino)methyl)phenoxy)phthalocyaninato-zinc(?)(ZnPc5).ZnPc2 to ZnPc6 are new compounds that have not been reported.All of the compounds synthesized have been characterized with UV-Vis spectra,IR spectra,NMR,EDS and elemental analyses.2)The solubility of prepared Pcs was studied.The results showed that the water-soluble derivatives not only have good water solubility but also have oil solubility,show amphipathic property to some degree.3)The studies of absorption spectra,photo stability,aggregate and fluorescence properties of the six Pcs show that water-soluble quaternized derivatives have low aggregate degree and high intensity of fluorescence,while reduced photostability in water;the water-soluble hydrochloride derivative has good photostability and high intensity of fluorescence,meanwhile high aggregate degree.4)The studies of the photosensitivity and in vitro anticancer activity of the six Pcs show that both the two water-soluble derivatives have high efficiency in generating reactive oxygen and high in vitro anticancer activity.5)Comprehensive studies of the properties of the Pcs showed that phthalocyanine-polyamine conjugates especially their water-soluble quaternized and hdrochloride derivatives are of particular interest because of their better photosensitivity and in vitro anticancer activity,have potential to be used as photosensitizer for PDT.