| There are many kinds of natural active components with complex structure and composition,and a variety compounds often coexist,so how to efficiently and simultaneously extract and purify target components is a hot topic in academia and industry.Magnetism is an important basic property of substances,which has shown great potential in the field of drug research.However,the innovative application of it in the field of natural products still needs further development,and the status that a large number of traditional technologies and common organic solvents dominate urgently needs to be improved.For example,a series of magnetic compounds with novel structure,special properties and promising prospects can be obtained by combining Fe3+ with natural active components;meanwhile,magnetic separation technology can be introduced into the preparation process of these compounds.In addition,it is also an important way to promote the green and multifunctional extraction methods in this industry to use green solvents instead of traditional solvents,and make it magnetic.In this paper,a new strategy of magnetization of natural products is proposed,isoquinoline alkaloids,which are easy to form salt with hydrochloric acid and further combine with anions containing Fe3+,are selected as the research object.Firstly,magnetic compounds with novel structure were synthesized,including magnetic isoquinoline([Isoquin·H]+[Fe Cl4]-),magnetic berberine([Ber·H]+[Fe Cl4]-),magnetic tetrahydroberberine([THBer·H]+[Fe Cl4]-),magnetic palmatine([Pal·H]+[Fe Cl4]-),magnetic tetrahydropalmatine([THPal·H]+[Fe Cl4]-)and magnetic tetrahydropapavine([THPap·H]+[Fe Cl4]-).Then the structure of them was confirmed by ultraviolet-visible,fourier transform infrared spectrometer,mass and raman spectra.Moreover,polarity and solubility about them were determined,and the results were compared with the original alkaloids.Furthermore,Apelblat equation is suitable to correlate the solubility of them in water,and the square of correlation coefficient(R2)is more than 0.99.Then,the vibrating specimen magnetometer(VSM)and Gouy method were used to measure the magnetic properties of the obtained compounds in solid status,and the results showed that these magnetic alkaloids are paramagnetic because of the iron in their anionic part,and the magnetic susceptibility are in the range of 2~4×10-5 emu/g,and their magnetic susceptibility follows the order of[Isoquin·H]+[Fe Cl4]->[THPap·H]+[Fe Cl4]->[THPal·H]+[Fe Cl4]->[THBer·H]+[Fe Cl4]->[Pal·H]+[Fe Cl4]->[Be r·H]+[Fe Cl4]-,moreover,the 6 kinds of magnetic alkaloids(solid powder)can be adsorbed by magnet,and the adsorption amount is positively correlated with the magnetic susceptibility.In addition,the magnetic response of their solution was investigated.It was found that magnetic field can drive the droplet to move,and the higher the magnetic susceptibility,the higher the moving rate.Furthermore,the gradient change of the magnetic alkaloid concentration and the difference of the distribution under external magnetic field were investigated,and the results provide the possibility for the application of this magnetization technology in the separation process of alkaloids.Based on the above research,a new emulsion liquid membrane extraction-in situ magnetization-magnetic separation(ELME-ISM-MS)method was developed to extract,separate and recover various compounds(alkaloids,flavonoid and saccharides)from Mahonia bealeias(Fort.)Carr.in a hyphenated way.Stable water-in-oil-in-water emulsion was prepared,and a systematic study on the preparation process was carried out;then it was used in the above integrated operation,and water-soluble compounds(e.g.berberine hydrochloride)remained in feed phase;other compounds with weaker polarity(e.g.rutin)entered into the membrane phase,and the lipid-soluble alkaloids(e.g.tetrahydroberberine)reacted with the derivatization reagents of Fe Cl3 and HCl in the internal phase.Then phase behaviors,transmembrane process and separation mechanism were all investigated systematically,and the yields of berberine,tetrahydroberberine,rutin and polysaccharides were 67.78,1.40,12.58 and 9.88 mg/g,separately.Such a continuous,highly-efficient and low consumed multifunctional process can benefit sustainable preparation of natural products,which realized extraction,enrichment,separation,purification and recovery simultaneously.Compared with the original alkaloids,whether the magnetic products have special physiological activities is another question and it is worth investigation.So,four types of biological activities(antibacterial,lipid-lowering,antioxidant and anti-tumor)were investigated.It was found that the activity increased after the magnetic derivatization,which revealed another important significance of the magnetic derivatization strategy,i.e.,it may make the activity of product higher.And the [Ber·H]+[Fe Cl4]-had the best antibacterial effect on Staphylococcus aureus and Escherichia coli,with the MIC of 200 and 800 μM,and the MBC of 800 and > 800 μM,respectively.But in the study of lipase inhibition activity,[Pal·H]+[Fe Cl4]-had the strongest activity with IC50 of 429 m M.Through the investigation of the mechanism,it was found that the inhibitory effect of magnetic alkaloids on lipase are reversible,and the type of inhibition was a mixture of competitive and non-competitive type.In the study of antioxidant activity,[Isoquin·H]+[Fe Cl4]-had the highest activity,IC50 was 1.11 mg/m L.Moreover,in anti-tumor studies,[Ber·H]+[Fe Cl4]-has the strongest inhibitory effect on colon cancer cells(COLO205,HCT15,HCT116,SW480),lung adenocarcinoma cell(H1975)and human epidermal cancer cell(A431),and the IC50 values were 9.02,38.41,5.80,29.91,11.28 μM,respectively.On this basis,the structure-activity relationship was analyzed.In addition,a series of magnetofluids based on hydrophobic deep eutectic solvents were also prepared,which had good magnetic response,and the density and viscosity were measured.Then,a multiphase dynamic extraction system was constructed with it and another green solvent—IL([Bmim]Br)aqueous solution,and this system was applied to the simultaneous extraction and separation of active components from Tartary buckwheat.The results showed that the extraction rate of flavonoids in ionic liquid aqueous phase was 41.17 mg/g,and the oil in magnetic fluids phase was 95.03%.Through kinetic and thermodynamic analysis,it was found that the extraction process of the two substances conforms to the pseudo-first-order kinetic model,and the higher the temperature is,the higher the extraction rate.Then ethyl acetate was used to recover flavonoids from ionic liquid aqueous solution and oil was recovered by D101 macroporous resin.Finally,the DPPH scavenging activity of the product was studied.It was found that the antioxidant activity of flavonoids obtained from ionic liquid aqueous solution was stronger than that obtained by traditional solvent(70% ethanol solution),and the antioxidant activity of oil was far weaker than that of flavonoids.In this method,two different types immiscible green solvents can be used to efficiently extract and purify lipophilic and hydrophilic natural products at the same time,and hydrophobic magnetic fluid can be rapidly separated from ionic liquid aqueous solution under the action of external magnetic field.The use of magnetic separation makes this method time-saving.In summary,the research realizes the combination of magnetic science,separation science,green chemistry and natural medicine chemistry,which not only expands the research objects of physics and chemistry,but also enriches the research methods of natural active components,and has a substantial promoting effect on the development of many disciplines. |
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