Study On The Optical And Photochemical Properties Of Gadolinium Labeled Porphyrin

Photodynamic Therapy(PDT)is considered to be the most promising non-invasive cancer therapy method,which is suitable for individualized precision treatment.In order to realize quantitative implementation of PDT,the distribution of photosensitizer and oxygen in tissue needed to be obtained accurately.Gadolinium(Gd³⁺)labeled porphyrins can not only retain the photosensitivity of porphyrin,but also possess the function of magnetic resonance imaging and oxygen sensing,which can realize the visually detection of photosensitizer and the monitoring of oxygen concentration in tussiue.Thus,Gd³⁺labeled porphyrins have the potential to be used as photosensitizers in PDT.At present,there are several problems in the application of Gd³⁺labeled porphyrins in PDT:(1)The singlet oxygen quantum yield is low;(2)The change of singlet oxygen quantum yield due to hypoxia cannot be monitored quantitatively in real time;(3)The study of physicochemical properties in the aqueous solution is absent.Thus,in this article,the impact factor of singlet oxygen quantum yield for Gd³⁺labeled porphyrins were studied,the method for quantitative monitoring singlet oxygen quantum yield in real time was established and the luminescence kinetics of Gd³⁺labeled porphyrins in aqueous solution was studied.Sinoporphyrin sodium(DVDMS)and Hematoporphyrin monomethyl ether(HMME)were used as matrix,Gd³⁺was applied as the coordination metal cation,to synthesize Gd-DVDMS and Gd-HMME.Fourier transform infrared spectroscopy and UV-vis absorption spectra were monitored to characterize Gd-DVDMS and Gd-HMME,the result showed that Gd³⁺replaced H molecular in N-H of porphyrin ring and finally coordinated with DVDMS and HMME.Based on the above analysis,the chemical structures of Gd-DVDMS and Gd-HMME were shown.The photoluminescence spectra and time resolved spectroscopy of Gd-DVDMS and Gd-HMME in methanol solution were studied,it can be found that Gd-DVDMS and Gd-HMME possess not only fluorescent emission,but also phosphorescence emission.The singlet oxygen quantum yield of Gd-DVDMS and Gd-HMME were measured it can be found that after Gd³⁺labeling to DVDMS and HMME,the singlet oxygen quantum yield of DVDMS and HMME reduced much.The effect of imidazole,a sort of small molecule that introduced in the process of synthesize,on the singlet oxygen quantum yield of Gd-DVDMS was studied.The method for monitoring the dialysis process of imidazole was proposed.The singlet oxygen quantum yield of Gd-DVDMS was first obtained to be as high as 0.97 after dialysis completely.The singlet oxygen quantum yield of Gd-DVDMS under different imidazole concentration were measured,which showed that the singlet oxygen quantum yield of Gd-DVDMS decreased first and then kept constant with the imidazole concentration increase.To find out the reason for the above phenomenon,the photophysical and photochemical process of singlet oxygen generated by Gd-DVDMS was analyzed.Combined with the UV-vis absorption spectra and photoluminescence spectra of Gd-DVDMS under different imidazole concentrations,the reason for the reduced singlet oxygen quantum yield of Gd-DVDMS was proved to be the decrease of interaction between Gd-DVDMS and oxygen molecular by imidazole.The effect of imidazole on the singlet oxygen quantum yield of DVDMS was studied,which proved that the attachment of imidazole to Gd-DVDMS molecule was not for the combination between imidazole and the suspension bond left on the surface of Gd-DVDMS molecule.This work proved that Gd-DVDMS has great potential to be applied in PDT,and provided material for PDT.The method for monitoring singlet oxygen quantum yield by time resolved spectroscopy was established.Through analyzing the photophysical and photochemical process of singlet oxygen generated by Gd-HMME,the relation between phosphorescence lifetime and singlet oxygen quantum yield was established in theory.To obtain the parameters that needed to be measured in the above relation,the triplet radiation transition rate was measured through monitoring the phosphorescence lifetimes of Gd-HMME in variational oxygen content,the singlet oxygen quantum yield of Gd-HMME in different oxygen concentrations was measured with a relative method to acquired triplet quantum yield.Based on the above results,the equation between phosphorescence lifetime and singlet oxygen quantum yield was first established.The method to value the oxygen level in PDT implementation using Gd-HMME as photosensitizer was studied.The relation between phosphorescence lifetime and singlet oxygen quantum yield of Gd-DVDMS and the method for valuing oxygen level were also obtained.Compared the phosphorescence lifetime of Gd-DVDMS with Gd-HMME in low oxygen concentration,it was proved that Gd-HMME was more suitable for clinical application.The research in this section gives a method for quantitative monitoring of singlet oxygen quantum yield by time resolved spectroscopy using Gd³⁺labeled porphyrins as photosensitizer.The luminescence kinetics of Gd-DVDMS in aqueous solution was studied.The UV-vis absorption spectra and photoluminescence spectra of Gd-DVDMS in aqueous solution were monitored,which suggested that the profile and intensity of the UV-vis absorption was not changed with the dissolving time increases,while the fluorescence increases and phosphorescence decreased.In order to find the reason for the above behavior,the physical process of fluorescence and phosphorescence emission of Gd-DVDMS was analyzed.Combined with the time resolved spectroscopy of Gd-DVDMS at 710 nm and 624 nm in different dissolving times,it is proved that the intersystem crossing from first singlet excited state to triplet state of Gd-DVDMS in aqueous solution was impeded.The stability of chemical structure of Gd-DVDMS in aqueous solution was verified,through measuring the time resolved spectroscopy of Gd-DVDMS aqueous solution and Gd-DVDMS in the mixture with DVDMS at 710 nm,it was proved that the chemical structure of Gd-DVDMS in aqueous solution was stable.The probability of directly excitation from the ground state to the triplet state for Gd-DVDMS in aqueous solution was studied,which showed that Gd-DVDMS can be excited by 690 nm excitation light and produce singlet oxygen.This research provided the basis of optical properties study for application of Gd³⁺labeled porphyrins in PDT.