Study On The Synthesis And Application Of Functional Magnetic Materials On Benzophenanthridine Alkaloids

Sanguinarine?SA?and chelerythrine?CHE?are the main benzophenazine alkaloids isolated from Macleaya cordata?Willd?R.Br.?M.cordata?.At the same time,they possess a wide array of pharmacological activities which have great application prospects in cancer treatment,so it is of great significance to study the separation and preparation development of these two alkaloids.However,the contents of SA and CHE in M.cordata are relatively low and it is inefficient and polluting to separate them by traditional methods.At present,functional magnetic materials have been studied as excellent separation materials for separation and targeted drug delivery due to their magnetism and surface functionality.Two kinds of functional materials including magnetic molecularly imprinted polymers?MMIPs?and magnetic-thermosensitive hydrogels were synthesized in this study.One is magnetic molecularly imprinted polymer for alkaloid separation,the other is magnetic-thermosensitive hydrogel for drug-loading and release.The main contents are as follows:?1?The SA-magnetic molecularly imprinted polymers?SMs?were prepared by molecular imprinted technology using functional Fe₃O₄@SiO₂ as a magnetic support,SA as template,4-vinylpyridine as functional monomer,and ethylene glycol dimethacrylate as cross-linker.The obtained SMs were well characterized with TEM,FT-IR,XRD,TGA,and VSM.The adsorption capacity and selectivity of SMs were also studied.The obtained SMs were core-shell spherical morphologies with an average diameter of 300 nm.The adsorption experiments showed that the SMs exhibited high adsorption capacity towards SA(Q_max=12.24 mg/g).The calculated parameters of adsorption isotherms and kinetics suggested that the adsorption process matched the Langmuir adsorption isotherm and pseudo-second-order kinetics model.The selectivity experiment showed that the SMs displayed higher selective adsorption capacity for SA compared to its reference compounds.Moreover,the SMs were applied to enrich SA from the extraction wastewater of M.cordata,which could extract about 65.17%SA.The SMs possess a great potential as aborsent for rapid,cost-effective,and efficient separation of SA from the extraction wastewater of M.cordata.?2?A novel type of MMIPs was successfully prepared for selective enrichment and isolation of CHE from M.cordata.The CHE-MMIPs?CMs?were prepared using functional Fe₃O₄@SiO₂ as a magnetic support,CHE as template,methacrylic acid?MAA?as functional monomer,and ethylene glycol dimethacrylate as cross-linker.The density functional theory at the B3LYP/6-31G?d,p?level with Gaussian 09 software was applied to calculate the interaction energies of CHE,MAA and the complexes formed from CHE and MAA in different ratios.The structural features and morphological characterizations of the synthesized polymers were performed by FT-IR,XRD,TEM,TGA and VSM.The adsorption experiments were carried and revealed that the CMs possessed rapid kinetics,high selectivity,high binding capacity to CHE(Q_max=7.96 mg/g).And the adsorption process was in good agreement with Langmuir adsorption isotherm and pseudo-second-order kinetics models by calculating the parameters of adsorption isotherms and kinetics.Furthermore,the CMs were successfully employed as adsorbents for extraction and enrichment of CHE from M.cordata,which could extract about 69.51%CHE.The results indicated that the CMs were suitable for the selective adsorption of CHE from complex samples such as natural medical plants.?3?Dual-responsive composite hydrogels were synthesized via a free radical polymerization of thermo-responsive poly?N-isopropylacrylamide-co-acrylamide??P?NIPAm-co-Am??in the presence of functional Fe₃O₄@SiO₂ magnetic nanoparticles.The resulting composite hydrogels?MHs?were characterized by SEM,FT-IR,XRD,TGA,DSC and VSM.The properties of swelling and temperature-sensitive were also studied.Results indicated that the MHs had obvious thermosensitive properties.With the increase of the amide group,the LCST of the MHs move toward high temperature.CHE was chosen as a model drug and the controlled-release properties of the MHs in different temperatures?25 ^oC,37 ^oC,45 ^oC?and alternating magnetic field were investigated.The controlled drug release mechanism of the MHs were also analyzed.The results of drug release experiments showed that the cumulative drug release rate of the MHs at 45°C was85.73%,where the cumulative release rate at 25°C was only 27.52%.These results indicated that high temperature was beneficial to drug release.And the cumulative drug release rate could reach87.88%under intermittent magnetic field condition,which was better than that of under continuous magnetic field condition.It can be concluded that the MHs are promising for applications in multi-modal cancer therapy combing hyperthermia with radio-or chemotherapy.