Design And Synthesis Of A Novel Light-controlled NO Donor

Nitric Oxide(NO)is an active small molecule that can participate in regulating several physiological and pathological processes.NO is present in large quantities in mammals,but its autosynthesis in organisms is affected by various factors,and the accumulation of large amounts of NO can have toxic side effects and lead to apoptosis,so the control of NO concentration is of great importance.NO donors are exogenous sources of NO,among which,light-controlled NO donors play a role in physiology and pathology by precisely controlling the concentration and location of NO release in organisms through light.In this study,three novel light-controlled NO donors,TBQ-NO,AQE-NO and BMP-NO,were designed and synthesized to address the shortcomings of NO itself such as difficult to quantify and short half-life,and their photoresponsiveness,release kinetics,photostability and interference resistance were verified by using UV-Vis absorption spectroscopy and fluorescence spectroscopy.Details are as follows:1)Two light-controlled NO donors TBQ-NO and AQE-NO with aminoquinoline derivatives as fluorophores were designed and synthesized in this work.By comparison,it was found that TBQ-NO itself fluoresced weakly,and after releasing NO under 365 nm light irradiation,the fluorescence signal was enhanced,which was 3.75 times higher than that before light release;AQE-NO itself has very weak fluorescence,and after releasing NO under 365 nm light irradiation,the fluorescence signal was significantly enhanced and was 11 times higher than that before light release.However,two peaks appeared in the fluorescence emission of TBQ-NO,which proved that the release process was accompanied by the occurrence of side reactions.In contrast,AQE-NO had only one peak and the fluorescence intensity at 535 nm showed a linear relationship with the light exposure time,which could better track the NO release process.Subsequently,the release mechanism of AQE-NO was further verified by using mass spectrometry analysis,and the anti-interference ability was tested.Meanwhile,cellular experiments confirmed that AQE-NO is capable of visualizing the detection and targeted release of NO in living cells,which is promising for further applications in bioimaging and disease diagnosis and treatment.2)In this work,we designed and synthesized a light-controlled NO donor BMP-NO with morpholine as the lysosomal targeting group and 1,8-naphthalimide as the fluorophore.The donor itself fluoresced weakly,and after 365 nm light irradiation,the extremely unstable N-nitroso bond breaks and NO is released,while fluorescence is recovered.NO is released within 70 min,and after release,the fluorescence signal at 570 nm was significantly enhanced,the fluorescence signal at 570 nm was significantly enhanced,which was 67 times higher than that before light release.To verify the successful release of NO,the mechanism was verified by using a commercial reagent for NO detection and further validated by mass spectrometry analysis.In addition,BMP-NO was tested for photostability and proved to be very stable within 2 hours.Finally,several anti-interference substances with different properties were selected to test the anti-interference ability of BMP-NO,and the results demonstrated that the presence of interference substances did not interfere with the release of NO from BMP-NO.In summary,BMP-NO has good photosensitivity,photostability and anti-interference properties,and has promising further applications in bioimaging as well as in the diagnosis and treatment of diseases.