Ceftriaxone Synthesis, Characterization And Biological Activity Of Rare Earth Complexes

With wide antimicrobial spectrum,strong bactericidal action and low toxic action, Cephalosporin drugs, commonly used in clinic, are the third-generation broad-spetrum antibiotic, one of which is Ceftriaxone Sodium. Recently, arising of drug-resistant flora have decreased drug's antiseptic activity greatly, so it is very useful to develop a new type of Cephalosporin.Rare earth element has lots of special physiological activities, such as antiseptic, anti-inflammtory,anticoagulant, antivirotic, antineoplasic, et al,and it can be taken in by plant, animal and human body by many means and coordinate with many biomoleculars and drug moleculars. A good many experimental results showed that, rare earth complex has less toxic effect, and has not been found accumulated in vivio by oral medication and external use. Compounding with a ligand which possesses a certain physiological activeness, rare earth complexes will not only be more active, their toxicities also be decreased.To increase antiseptic activity of Cephalosporin drugs and decreaset their side effect, while taking the co-effect of rare earth and drug molecular into account, the thesis synthesized a series of complex of Ceftriaxone, studied their bacteriostasic activity and researched their interactivity with protein. The main work of the thesis is:First,synthesized eight rare earth complexes with Ceftriaxone by the co-precipitation method and determined their composition, [LnL₂ClH₂O]·nH₂O (Ln=La³⁺,Ce³⁺,Pr³⁺,Sm³⁺,Gd³⁺,Dy³⁺,Ho³⁺,Er³⁺,L=C₁₈H₁₇N₈O₇S₃).Then studied the physicochemical property of these complexs, and characterized their structure by element analysis, molar conductivity, thermal spectrum analysis, UV spectroscopy and Infrared spectroscopy and ¹HNMR.Second, an external bacteriostatic experiment was done to test Ceftriaxone and its complexes through K-B paper method. The antibacterial tests indicated that all these complexes have the antibacterial ability against Escherichia coli, Staphy aureus , Proteus .The antibacterial ability of Er complex and Gd complex against Staphy aureus is stronger than the ligand.Only through storing and transporting by plasma, drug entered the human body, can arrive at every section and take into pharmacological action. Serum albumin, capable of combining with drug, being stored and conveying in blood, is the maximum constituent support protein in plasma. The mechanism of interaction between bovine-serum albumin(BSA)and complexes was studied by UV spectroscopy. The apparent binding constant of Ho complex with BSA and the binding sits n of Ho complex with BSA were studied.The results indicate that the main binding force between complexes and BSA is stronger than ligand . This can help enlengthen drug's storage period in plasma, which will enable the drug release slowly in the body.The thesis lay experimental and theoretical ground for related complex studies of rare earth-Cephalosporin drugs, and will promote the research on rare earth complex medicine, as well as the research of functional mechanism between complexes and BSA.