Synthesis Of Endoperoxides With Potential Biological Activities By Singlet Oxygen Release

Among reactive oxygen species,singlet oxygen is the most active and has the shortest life span.Because of its reactivity,it can react with lipids,amino acids,nucleic acids,and most cellular components.It has been verified that gelled cyclic aromatic hydrocarbons are a kind of endoperoxides that can react with ¹O₂ to generate stored singlet oxygen,and these compounds can release ¹O₂ in the original ring when heated.Therefore,in this paper,1,4-dimethylnaphthalene,whose structure is relatively easy to be modified and whose solubility is good,was selected as the parent for modification.This paper proposes two ideas for the utilization of singlet oxygen:1.Nowadays,there are many antibiotic-resistant bacteria strains,and even some multi-drug-resistant bacteria,so-called"superbacteria",while photodynamic therapy can effectively kill pathogenic bacteria and produce good effects on drug-resistant strains.It is expected that by designing a structure to release singlet oxygen in a controlled way on demand,singlet oxygen will be placed in a"cage"structure in the form of endoperoxides.In this structure,the trimethylsiloxyl(TMS)group provides the spatial volume and inhibits the ring reduction.When fluoride ions are added,it is found that the fluoride ions remove the TMS group very quickly,and the ring reduction of the endoperoxides can be carried out unimpeded,thus releasing singlet oxygen.2.In view of some cell hypoxia caused by blood loss,we consider designing a singlet oxygen carrier based on the conversion of singlet oxygen to triplet oxygen.In this paper,we choose 1,4-diazabicyclic[2.2.2]octane(DABCO),which can provide a new idea for the problem of cell hypoxia.Corresponding compounds were synthesized for the above-mentioned concept and design,and the following work was mainly carried out:1.Endoperoxides(5-TMS)of 1,4-dimethylnaphthalene were designed and prepared using trimethylchlorosilane to replace the 5-position of the host.The structure characteristics of the compounds were confirmed by ¹H-NMR and ¹³C-NMR,and the UV-Vis absorption and fluorescence emission spectra were studied.The half-life of the endoperoxide was measured at25?and 37?.The results are as follows:t_1/2=97 h(25?);t_1/2=15.6 h(37?),and the change of the ring reduction rate after adding tetrabutylammonium fluoride to introduce fluoride ions is observed by ¹H-NMR.2.DPBF was used to test the UV-Vis absorption of 5-TMS in the presence of tetrabutylammonium fluoride.In addition,fluorescence kinetic spectra and related tests of dissolved oxygen were performed,and the experimental results all proved that the endoperoxide could quickly release singlet oxygen in the presence of fluoride ions.When5-TMS compounds and 2-TMS compounds were applied to Escherichia coli,the microscopic data showed that the antibacterial effect of 5-TMS added with fluoride was higher than that of5-TMS alone and 2-TMS added with fluoride.3.Use DABCO group to modify 1,4-dimethylnaphthalene,synthesize and isolate an unusual 5,8-endoperoxide,confirm the structural characteristics of the compound with¹H-NMR and ¹³C-NMR.The half-life of the endoperoxide was measured at 25?,and the result was:t_1/2=2.3 h.