Design And Photophysical Properties Of Activatable Organic Photosensitizer And Application Research

Activable photosensitizers can effectively improve the accuracy and effectiveness of treatment.Activable intersystem crossing is an important strategy for designing activatable photosensitizers.The intersystem crossing refers to the non-radiative transition process from the single excited state to the triplet excited state of the molecule.The excited state dynamics research can intuitively analyze the intersystem crossing process,which has extraordinary guiding significance for the rational design of the activatable photosensitizer.However,the focus of research on activatable photosensitizers is mostly on one-time activation or enhancement of intersystem crossing,and there is little systematic work on the excited state dynamics of materials.To this end,this paper designed a series of materials with 1,4-bis(phenylethynyl)benzene as the Conjugated backbone,and analyzed the relationship between the structure and the intersystem crossing through femtosecond transient absorption spectroscopy and quantum chemical calculation.On this basis,designed two activatable photosensitizers can be used for application research,which reversely validates the results of theoretical research.(1)In the first work of this paper,four 1,4-bis(phenylethynyl)benzene derivatives(PE1-PE4)with similar structures were designed.Although their chemical structures are close,their photophysical properties are very different,especially intersystem crossing.In order to explore the reason behind this phenomenon,the transient absorption spectra of the four materials were tested and analyzed,the evolution process of their excited states was analyzed,and the causes of the difference of intersystem crossing were analyzed by quantum chemical calculations.The molecular geometries was optimized,and the relationship between the intersystem crossing efficiency of the material and the molecular geometries was discovered.The conjugate backbone twist induced intersystem crossing(CBT-ISC)was proposed.(2)In the second work,based on the theory of CBT-ISC and previous research by Quli Fan's group,an activatable photosensitizer(PE4?WP5)was designed using the method of nesting the host and guest,The transient absorption spectrum of PE4?WP5 at different p H is analyzed.It was verified that the change of singlet oxygen yield was caused by intersystem crossing inhibition / activation.Further,the application of PE4?WP5 in vitro cell experiments showed that it has excellent p H selectivity,proving that the strategy can be used as a way to design activatable photosensitizers,and the theory of CBT-ISC has been verified in practice.(3)On the basis of previous work,the third work designed a photosensitizer(PE5)with a p H-reversible intersystem crossing.The isoelectric point(p H = 6.0)of the photosensitizer is very close to the tumor microenvironment.Tests show that PE5 has a higher singlet oxygen yield(48%)at the isoelectric point.On the contrary,PE5 has a very low singlet oxygen yield(5%)in the general biological environment(p H = 7.4).The consumption of ADMA confirmed that reversibility of this change is very stable.Moreover,its excellent selectivity was also verified in vitro cell experiments.The photodynamic therapy effect is activated(p H = 6.0),and it is turned off at p H = 7.4.The most exciting thing is that these characteristics are within the reasonable prediction of CBT-ISC theory,which provides a good sample for the design of reversible intersystem crossing based on CBT-ISC in the future.