Design,synthesis And Activities Of Antitumor Photosensitizers Zinc Phthalocyanine Derivatives

With increase of cancer incidence and mortality,cancer has become the number one killer of humans.Photodynamic therapy?PDT?is a cancer treatment method that emerged in the 1970s.It has achieved remarkable results in the treatment of various tumors such as lung cancer,esophageal cancer and breast cancer.Photodynamic therapy has the characteristics of low toxicity,micro-trauma,reproducibility and high selectivity.Photodynamic therapy is highly concerned by researchers.Light,photosensitizer,and oxygen are the three major elements of PDT,and photosensitizers are the key.The maximum absorption wavelength and Selectivity of photosensitizers affect the efficacy of photodynamic therapy.This paper designed and synthesized four zinc phthalocyanine photosensitizers.The specific work is as follows:?1?Using zinc phthalocyanine as the core and introducing different substituents on the pericyclic ring,four new photosensitizers were designed including2,9,16,23-tetrakis??4,4-bis-methyl?piperazinyl?zinc phthalocyanine iodide?1a?,2,9,16,23-tetrakis?N,N,-trimethylamineethoxy?zinc phthalocyanine iodide?1b?,2,9,16,23-tetrakis??4-methyl?piperazinyl?zinc phthalocyanine?2a?,2,9,16,23-tetrakis?N,N-bis-methyl?zinc phthalocyanine?2b?.?2?The target compound was synthesized by nucleophilic substitution,cyclization and methylation with 4-nitrophthalonitrile as starting material.The structure of the target compound was confirmed by ¹H NMR and HRMS.?3?The photophysical properties of the four target compounds,such as UV-visible absorption spectrum,fluorescence emission spectrum,ability to generate singlet oxygen,and photothermal conversion ability,were studied and compared.The Q band maximum absorption of four compound are 710 nm?1a?,682 nm?1b?,723nm?2a?and 683 nm?2b?.The Q-band maximum absorption peak wavelength of the target compounds 1a and 2a is greater than 700 nm,and has a stronger tissue penetrating ability.The fluorescence quantum yield??_F?and singlet oxygen quantum yield??_??of the target compound were calculated by using unsubstituted zinc phthalocyanine?ZnPc,?F=0.20,??=0.67?as reference and DMSO as solvent.The?F of target compound are 0.08?1a??0.22?1b??0.16?2a?and 0.35?2b?;?_?are 0.81?1a??0.71?1b??0.76?2a?and 0.68?2b?.Photothermal conversion efficiency of four target compounds are 32.8%?1a??48.8%?1b??26.8%?2a?and 30.1%?2b?.?4?The interaction of the compound with CT-DNA was investigated by using ultraviolet visible absorption and fluorescence.The binding constant?K?obtained by usingultraviolet visibleare 3.95×10⁵ L/mol?1a?,3.76×10⁵ L/mol?1b?,2.23×10⁵ L/mol?2a?,1.46×10⁵ L/mol?2b?;and calculatedby usingfluorescence are 3.23×10⁵ L/mol?1a?3.58×10⁵ L/mol?1b?,2.53×10⁵ L/mol?2a?,1.98×10⁵ L/mol?2b?.The result show that the fourcompound may bind with CT-DNA in a mode including outside groove-face binding.In thispaper using N atom substitutedthe O atom connected to phthalocyanine ring,the maximum absorption peak wavelength of the Q-band maximum absorptionwavelength of the target compounds 1a and 1b is greater than 700 nm,and has a stronger tissue penetrating ability.Because N atom has stronger nucleophilic ability,it usingNa₂CO₃replaced K₂CO₃reduce the risk of operation.In summary,fourpericyclic ring modified and unreported zinc phthalocyanines were designed and synthesized,its photophysical and photochemical properties and the interaction of the compound with CT-DNA was investigated.The research of this thesis provides a theoretical basis for the design of phthalocyanine photosensitizers.