Application Of Chloroperoxidase Modified Electrodes In Organic Catalytic Chlorination Synthesis

Bio-enzyme used as catalysts have a lot of advances in organic synthesis meetingthe requirement of today’s society to protect the environment as well as greenchemistry, such as its high efficiency, non-pollution, mild reaction conditions,stereoselectivity and regioselectivity,. Chloroperoxidase is a special kind ofperoxidase having a variety of different catalytic activities, it can catalyze oxidation,chlorination, epoxidation, or dehydrohalogenation reactions. There have been somereports about CPO using as a catalytic in organic synthesis reaction, but theseapplications are generally in a homogeneous system, need to add a lot of CPO andplus hydrogen peroxide guarantee the conduct of bio-enzyme-catalyzed reaction at thesame time. Our research group in recent years concentrated to immobilize thebiological enzyme on the electrode surface, and then use the modified electrode in situelectro-catalytic generating hydrogen peroxide to drive the catalytic reaction. In thispaper, we tried the catalytic chlorination of active pharmaceutical ingredients on thebasis of the research group preliminary workWe used UV-visible spectrophotometry to detect the biological enzyme catalyticactivity of CPO both in solution phase or immobilized on a glass carbon(GC) surfaceby Didodecyldimethylammonium bromide, one kind of similar biofilm molecules.The results showed that, the activity of CPO immobilized on the GC was slightlylower than the activity of CPO in the solution phase.Cyclic voltammetry measurement results show that the oxidation peak currentand reduction peak current ratio of the CPO fixed on the electrode is approximately1,indicate that this is a quasi-reversible process. Peak current and sweep acceleratedlinear relationship, Suggests that direct electron transfer between the CPO and theelectrode were achieved, and the process is controlled by surface adsorption. Theelectrically active CPO coverage Γ*on the GC surface estimated by about3.82 ×10-10mol cm-2, and O2can be reduced in situ by the modified electrode. Theseresults laid the foundation for subsequent catalytic organic synthesis experiments.The CPO-DDAB/GC modified electrode was used as a working electrode tocatalytic chlorination of bergenin at the potential of-0.6V. The HPLC-MS analysisresult proved the chlorinated product of bergenin, indicating that CPO immobilizedon the electrode can catalyze Bergen in chlorination reaction in the case of thepresence of chlorine ions (KCl as the chlorine source), and a positioning of thechlorinated product was obtained. There are22.49%bergenin been catalyzed tochlorinated products in2hours, and the total turnover number (TTN) of the reactionwas estimated to be13600mol Bergenin/mol CPO, and the reaction equipment andoperation was easier meanwhile.We attempted to catalytic chlorination of vancomycin，a pharmaceuticallyactive ingredient, and used HPLC to detect the product. The results show that we gottwo products, which were considered as one chlorine product and dichloride product.Then we explored different catalytic potentials and found the best catalytic results inthe potential of-0.6V finally. And with the potential negative shift, the first productincreased to a certain amount, and then the second product generated. DDAB andcarbon nanotubes were used to prepare different modified electrodes，and the thecatalytic results revealed that CPO-DDAB/GC modified electrode has a bettercatalytic efficiency and yield reached40.7%after2h, while CPO-SWNTs/GCmodified electrode catalyst the yield was37.9%. Due to vancomycin molecularweight and limited research conditions, it is difficult to confirm whether thechlorination reaction occurs, but also difficult to separate the product. Thereforefurther exploration and research are required.