Preparation Of Functional Complexes And Their Application In Antitumor Activity And Detection Of Heavy Metal Ions

Recent years,functional complexes have been widely used in cancer treatment and heavy metal ion detection because of their unique structural characteristics and performance advantages.At present,complexes as anticancer drugs still face many challenges in clinical application,such as their large side effects and high prices.On the other hand,most of the currently reported complex probes could only output a single signal,such as electrical signals,optical signals.A single signal output will not be self-calibrated in the event of a data error.In addition,the single signal output complexes probes could not be used in complicated and changeable environments.Therefore,it is urgent to further modify the complexes which could bring the breakthrough in anticancer and heavy metal ion detection through functional optimization.The main results including two aspects were listed as follows:（1）Modification of chlorophenoxyacetate complexes and their anticancer studyThis study developed a new strategy for targeted delivery non-noble metal complexes as anticancer drugs.Ten rare earth metal complexes RC₁-RC₁₀ based on2-/3-/4-chlorophenoxyacetic acid with certain anticancer activity were prepared.Then the Si O₂@RC nanoparticles with good biocompatibility were prepared by reverse-phase microemulsion method,and two different target molecules,galactose（gal）and folic acid（FA）were further modified.Their chemical formula was confirmed as[Dy（o-CPA）₃（H₂O）]·H₂O RC₁,[Ho（o-CPA）₃（H₂O）]·H₂ORC₂,2[Er（m-CPA）₃（H₂O）]·3H₂ORC₃,2[Gd（m-CPA）₃（H₂O）]·3H₂O RC₄,[Ce₂（m-CPA）₆（H₂O）₃]·2H₂O RC₅,[Er₂（p-CPA）₆（H₂O）₆]RC₆,[Ho₂（p-CPA）₆（H₂O）₆]RC₇,[Sm（p-CPA）₃（H₂O）]RC₈,[Pr（p-CPA）₃（H₂O）]·3H₂O RC₉和[Ce（p-CPA）₃（H₂O）₂]·2H₂O RC₁₀ through X-ray single crystal diffraction.Their morphology and particle size were further characterized by SEM,TEM and DLS,which indicated that the particle size was about 125 nm.Simultaneously,complexes RC₁-RC₁₀showed inhibition activity on Hep G2 cells with Si O₂-gal/Si O₂-FA showing no significant toxicity to Hep G2 cells or normal 293T cells at high concentration,which proved that these two materials were safe for the construction of complexes RCs.RC₂ and RC₇ with better activity were selected for the next experiment.The anticancer activity against Hep G2 of RC₂/RC₇ and RC₂@Si O₂-gal/RC₇@Si O₂-FA were tested.The results showed that RC₂@Si O₂-gal/RC₇@Si O₂-FA is better than free RC₂/RC₇ at the same concentration.Finally,the activities of RC₂@Si O₂-gal/RC₇@Si O₂-FA on 293T and Hep G2 cells were determined under different concentration gradients.The results showed that the functionally modified complexes showed concentration dependence against Hep G2 cancer cells with no cytotoxity on normal 293T cells.This study provides a new idea for non-noble metal complexes as targeted delivery anticancer drugs.（2）Modification of ferrocene complex and its application in heavy metal ion detectionIn this study,the acetylferrocene and thiazolylferrocene complexes with good electrochemical properties were used as precursors.Rhodamine fluorophores with spectral signal output were grafted to prepare complexes probes with multiple signal outputs.Moreover,the structures of RBFc-1 and RBFc-2 were confirmed by ¹H NMR,¹³C NMR and X-ray single crystal diffraction.Ion titration experiments and competition experiments showed that the complexes probes RBFc-1 could specifically recognize Cu²⁺and RBFc-2could specifically recognize Hg²⁺by fluorescence enhancement and natural light visualization,respectively.Infrared and complexation ratio tests demonstrated that Cu²⁺/Hg²⁺could coordinate with the O,N or S heteroatoms on the RBFc-1/RBFc-2 molecules,causing the rhodamine ring to change from a closed state to an open state,which result the increase in fluorescence intensity with a complex ratio of 1:1.Electrochemical studies showed that the coordination of Cu²⁺/Hg²⁺with O,N or S on the RBFc-1/RBFc-2 molecule could lead to a decrease in the electron cloud density of the ferrocene moiety,which makes it more difficult to redox with the reduction potential moves toward the anode.Both spectroscopy and electrochemical test results demonstrated that RBFc-1/RBFc-2 could specifically recognize the Cu²⁺/Hg²⁺,and thus RBFc-1/RBFc-2 are attributed to multi-channel Cu²⁺/Hg²⁺probes.The design and synthesis of the ferrocene-rhodamine complexes provided the theoretical basis for the highly selective multi-channel ferrocene complex application to the detection of heavy metal ions.In summary,the modification of high-activity,low-toxic phenoxyacetic acid non-noble metal complexes,provides a new strategy for the design,development and utilization of inexpensive complexes anticancer drugs.At the same time,the design,synthesis and mechanism study of the visualization complexes Cu²⁺/Hg²⁺probes not only expand the application range of ferrocene complexes,but also promote the development of multi-channel probes with specific selectivity.Overall,this study provides a theoretical basis and technical support for the development of complexes in the fields of medicinal chemistry and analytical chemistry.