Synthesis And Characterization Of A Photoactivated Dideoxy Inosine Prodrug And Two Novel Organic Fluorescent Probes

H₂O₂ is a vital member of reactive oxygen species?ROS? in livine system and H 2S serves as a gaseous molecule for cell signaling. Both H 2O2 and H2 S are involved in various physiological and phthological processes. Rapid, sensitive, selective and visualizable detection of H₂O₂ and H2 S is of great significance for physiological / phthological research and diseases diagnosis. Photoactivated prodrug can be prepared by conjugation of a photosensitive carrier with an active drug. Such prodrug can be photocleaved with light of special wavelenghth and release of the active drug can be temporally, spatially and quantitatively. In this way the side effect of the active drug for non-irridiated parts of the body can be effectively avoided.This work mainly covers the following three parts:1. An ELF-97-based fluorescent probe for H₂O₂ was prepared from 5-chlorosalicyl-aldehyde, 4-?bromomethyl?phenylboronic acid and 2-amino-5-chlorobenzamide, and its structure was characterized by 1H NMR, 13 C NMR and MS. Weak fluorescence intensity was observed at 425 nm when the probe solution was excited by 360 nm UV light. After addition of H₂O₂, however, peak emission at 425 nm disappeared while strong peak emission at 515 nm appeared with the same excitation wavelength?360 nm?. The fluorescence intensity at 515 nm is dependent on the concentration of H₂O₂ with the linear response range being 5-45 ?mol/L. The detection limit of H₂O₂ is 0.1 ?mol/L.2. An ELF-97-based fluorescent probe for H2 S was prepared from 5-chlorosalicyl-aldehyde, 4-?bromomethyl?phenylazide and 2-amino-5-chlorobenzamide, and its structure was characterized by 1H NMR and 13 C NMR. Weak fluorescence intensity was observed at 405 nm when the probe solution was excited by 355 nm UV light. Following incubation of the probe solution with 1 mmol/L Na 2S solution for 3 h, no significant change of the fluorescent spectra and intensity was observed indicating that the probe was almost irresponsive to H2 S.3. A lipophilic photosensitive drug carrier was prepared from 7-amino-4-methylcoumarin by nucleophilic substitution, oxidation and reduction, which was then conjugated with the HIV reverse transcriptase inhibitor dideoxyinosine through carbamate bond to afford a photoactivated prodrug. The structure of the prodrug was characterized by 1H NMR, 13 C NMR and MS. The photo-controlled release of dideoxyinosine from the prodrug was evaluated by HPLC. Following irradiation of 100 ?mol/L prodrug solution with 365 nm UV light for 25 min, 87.4% of dideoxyinosine was released from the prodrug.