Probe Study For Detecting Lp-PLA₂ And NaBH（OAc）₃-Promoted N-Formylation Using Carbon Dioxide

Cardiovascular and cerebrovascular disease（CVD）is the number one cause of death worldwide,with more deaths due to CVD than any other cause each year.Lipoprotein phospholipase A₂（Lp-PLA₂）is a new inflammatory marker that has attracted widespread attention in recent years and is closely related to atherosclerosis（AS）.The detection of Lp-PLA₂ can directly and accurately reflect the degree of intravascular inflammation and can be used as a dynamic indicator.An increase in the amount of Lp-PLA₂ may indicate an increase in the risk of CVD（linear correlation）,and its detection can determine the progression of atherosclerotic disease.Therefore,by monitoring changes in Lp-PLA₂ levels,we can understand the risk of atherosclerosis-related cardiovascular and cerebrovascular embolism,and take preventive and therapeutic measures in a timely manner.Based on the existing commercial probes for the detection of Lp-PLA₂,this study modified the probes by replacing the phenolic ester bond with a thioester bond or replacing the p-nitrophenol with a halogen-substituted phenol,which is intended to improve the stability of the probe while maintaining the effectiveness of the detection.At the same time,we also replaced p-nitrophenol with fluorescent molecules,which made it possible to replace the original UV spectrophotometry with fluorescence detection,which improved the detection sensitivity.We have designed and synthesized five compounds,optimized the post-treatment methods for these compounds,and tested the validity and stability of Lp-PLA₂.It was found that the stability of compounds A,B,D and E is better than that of the positive control.The stability of compound D is comparable to that of the positive control,and the wavelength change before and after the enzyme can be used for the detection of Lp-PLA₂.The stability of compound E is obviously better than that of the positive control,and the fluorescence changes before and after the action of the enzyme are obvious.It is expected to achieve fluorescence detection instead of ultraviolet spectrophotometry,and it is hopeful to become a probe molecule superior to the positive control.The results of this study provide a reference for the further design of Lp-PLA₂ probes.As a greenhouse gas,carbon dioxide has a wide range of sources and its low price makes it of great significance in the application of organic synthesis.It has been reported that in the presence of catalysts or other special conditions,carboxyl groups,formyl groups,methyl groups,etc.can be formed by carbon dioxide in organic molecules.This work has developed a synthetic method for the formation of formamide using carbon dioxide as a carbon source in a mild environment.The method uses amine and carbon dioxide as raw materials,acetonitrile as solvent,normal pressure,50℃,can be synthesized under the action of sodium triacetoxyborohydride to form carboxamide derivatives.A total of 13 formamide derivatives were synthesized with high yield（40%-97%）,mild conditions and wide range of substrates,providing a research direction for the application of carbon dioxide.