Design,Synthesis And Application Of Red/Near-infrared Small Molecule And Phosphorescent Iridium(Ⅲ) Complexes In Photodynamic Therapy

Recent statistics indicate an alarming increase in the proportion of cancer-related deaths among all human fatalities.Consequently,the development of novel,efficient,and non-invasive cancer diagnosis and treatment modalities has become a pressing concern.Photodynamic therapy(PDT),with its high specificity,selectivity,and minimal side effects,represents a promising and emerging cancer treatment option.In PDT,photosensitizers play a crucial role in determining the efficacy of the therapy.Photosensitizers can be divided into two types based on their photochemical processes-oxygen-independent Type I and oxygen-dependent Type II photosensitizers.Given that tumors typically exhibit hypoxic microenvironments,the development of oxygen-independent type I photosensitizers has become imperative for improving the effectiveness of PDT.In this paper,we designed and synthesized a fluorescent small molecule and phosphorescent metal iridium(Ⅲ)complexes as red/near-infrared photosensitizers for PDT,and studied the PDT effect of fluorescent small molecules and the relationship between "structure-photophysical properties,electrochemical properties-ROS generation ability-PDT effect" of the iridium(Ⅲ)complexes.This paper mainly includes the following three parts:1.We have developed a fluorescent small molecule photosensitizer,ENBS,with near-infrared excitation and emission wavelengths by introducing hexamethylenediamine to Nile blue and replacing the oxygen atom on the Nile blue heterocycle with a sulfur atom.ENBS exhibits excellent biocompatibility,low dark toxicity,and high phototoxicity,making it a promising candidate for photodynamic therapy(PDT).In the hypoxic state,ENBS generates a significant amount of reactive oxygen species(ROS)upon light exposure,leading to considerable damage to cancer cells.ENBS functions as an oxygen-independent Type I photosensitizer that specifically targets lysosomes and disrupts their integrity,further inducing programmed cell death.Due to its ability to penetrate deep into living tissue,ENBS has the potential to improve the efficacy of PDT in cancer treatment.2.We synthesized six phosphorescent metal iridium(Ⅲ)complexes,Ir1-Ir6,by combining two cyclometallic ligands,which were synthesized by introducing anthraquinone and benzo[b]thiophene into isoquinoline,with three auxiliary ligands,which were synthesized by introducing triphenylamine and alkane chains of different lengths into imidazophenanthrene.The "structure-properties-ROS generating ability-PDT effect" of these complexes were investigated.Ir1,with 2-isoquinoline anthraquinone as the ring metal ligand,showed high cytocompatibility,low dark toxicity,and high phototoxicity.In addition,Ir1 was found to be able to produce a large amount of ROS in vitro,making it an effective Type I photosensitizer.3.During the synthesis process,it was discovered that the iridium(Ⅲ)complexes Ir2 and Ir3,containing anthraquinone groups in the ligand,exhibit piezochromic(PCL)properties.Based on this ligand,we designed and synthesized two additional complexes,Ir7 and Ir8,and found that they also exhibit PCL properties,under external stimuli,the molecular configuration and π-π interaction between molecules of Ir7 and Ir8 may change,resulting in a blue shift of the emission wavelength and an increase in luminescence intensity.