Liver-targeted fluorescence/photoacoustic dual-modal probe for early detecting drug-induced hepatic inflammation and autoimmune hepatitis

A method for preparing a liver-targeted fluorescent/photoacoustic bimodal probe, wherein:

• Trifluoromethanesulfonic anhydride is dropwise added to a mixture of hCy-NHBoc and triethylamine in anhydrous dichloromethane in an ice bath under nitrogen atmosphere;
• after stirring for 5 minutes, it is quenched by ice water, an organic layer is separated and directly purified by column chromatography to afford intermediate hCy-Tf-NHBoc as a purple solid;
• subsequently, the intermediate hCy-Tf-NHBoc is added anhydrous dichloromethane containing 25% trifluoroacetic acid;
• after stirring for 5 minutes, the reaction solution is evaporated under reduced pressure and the resulting residue is washed with diethyl ether to afford crude intermediate hCy-Tf-NH2;
• then hCy-Tf-NH2, cholic acid, o-Benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate, 1-Hydroxybenzotriazole and N,N-Diisopropylethylamine are dissolved in N,N-Dimethylformamide;
• after the reaction is complete, the solvent is removed by excess petroleum ether, and the resulting residue is purified by column chromatography to afford the liver-targeted fluorescence/photoacoustic dual-modal probe hCy-Tf-CA as a purple solid,
• the molar ratio of hCy-NHBoc, trifluoromethanesulfonic anhydride and triethylamine is 1:1.2:1.2;
• the volume ratio of methanol to dichloromethane is 1:50 in the first silica gel column chromatography;
• the molar ratio of hCy-Tf-NHBoc to trifluoroacetic acid is 1:536;
• the molar ratio of hCy-Tf-NH2, cholic acid, o-Benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate, 1-Hydroxy benzotriazole and N,N-Diisopropylethylamine is 1:1.2:1.2:1.2:2;
• the volume ratio of methanol to dichloromethane is 1:10 in the second silica gel column chromatography.