Synthesis,Characterization And Properties Of Metal Complexes And EDTA, DTPA Derivatives Of4-aminosalicylic Acid

Magnetic resonance imaging (MRI) is one of the most advanced techniques of clinical diagnosis which has been widely used in checking diseases in vivo.In order to increase the contrast degree between normal tissue and lesion tissue, contrast agent is often used in MRI diagnosis. And Gd-DTPA (DTPA is diethylene triamine pentaacetic acid) as the contrast agent is used the earliest and most extensive in clinical. Because Gd-DTPA is used as salts of sodium or meglumine, some problems are caused, such as high osmotic pressure, poor selectivity. Therefore, in order to obtain contrast agents which have high relaxation, low toxicity with tissue selective, a lot of research work has been done based on the synthesis of DTPA derivatives of amide and ester, so it is becoming a focuse in this resaerch area.In this thesis, ethylenediamine tetraacetic acid (EDTA) and diethylene triamine pentaacetic acid (DTPA) derivatives were prepared by acylation reaction of dianhydride of EDTA and DTPA with4-amino salicylic acid. Four complexes were synthesized by the reaction of these ligands with Mn2+and Gd3+. The chemical compositions and structures of two ligands and four complexes were confirmed by modern analytical techniques such as nuclear magnetic resonance(NMR), infrared spectrum (IR), ultraviolet spectrum (UV), elemental analysis and so on. The UV spectra and fluorescence spectrum of L1, L2with Mn2+、Gd3+were investigated. And the relaxivities and antibacterial activities were also studied.(1) Two new compounds L1and L2have been synthesized by acylation reaction of dianhydride of EDTA and DTPA with4-amino salicylic acid and characterized by elemental analysis.1H-NMR spectrum, mass spectrometry and IR spectrum. The chemical compositions and structures of them were confirmed to be C24H26N4O12and C28H33N5O14. and the processes of synthesis of the two ligands were optimized. The experimental results showed, when the molar ratio of reactants between anhydride(EDTAA. DTPAA) and4-acetylamino salicylic acid (PAS) is1:2, the reaction time is about24h and the reaction temperature is at30℃, the yields reached over65%.(2) The interactions between the compounds (L1. L2) and five metal ions (Cu2+. Mn2+, Gd3+, Sm3+, Eu3+) were researched by UV spectra and fluorescence spectrum, and the stable constants of the two compounds with Mn2+and Gd3+were determined,respectively. The results showed that the UV characteristic absorption peaks of the compounds (L1, L2) have obvious hypochromic effect after adding Cu2+, Mn2+, Gd3+, Sm3+, and Eu3+, and among them Mn2+was the most obvious. Under the same conditions, the fluorescence quenching effect of Cu2+was the most significant too. The conditional stability constants of four complexes had already been determined which were KMn-L1=1.17×1010; KGd-L1=4.10×109; KMn-L2=3.21×109and KGd-L2=1.38x107, respectively.(3) Four complexes were synthesized by the coordination reaction of the two ligands(L1, L2) and Mn2+, Gd3+. The chemical compositions of these six complexes were basic confirmed by elemental analysis, IR spectrum, chemistry titrimetric method and TG-DTA, which were GdC24H3oN4O15、MnC24H29N4O14、GdC28H36N5O17and MnC28H35N5O16. Through the analysis of the complexes, the results indicate that the complexes which were coordinated between Gd3+and the ligands (L1, L2) may contain three water molecules, and if it was Mn2+, may two. Oxygen atoms of COO’, two oxygen atoms of amide and the nitrogen atoms on the skeleton involved in coordination.(4) The longitudinal relaxation times T1of three different concentrations of Gd-L2and Gd-DTPA were tested by inversion recovery. The research results indicated that the relaxivity R1of the Gd complex was8.530L· mmol-1· s-1. which was more greater than small molecular weight complex Gd-DTPA (4.081L· mmol-1·s-1). Compared with the same concentration complex of Gd-DTPA, the contrast imaging diagram in vivo of complex Gd-L2are clearer, and the relaxation property improvement is obvious.(5) The vitro antibacterial activities of the two ligands and four complexes were tested by using filter paper method and antibacterial effects of the compounds were evaluated. The preliminary results showed that the order of antibacterial effects of the complexes were greater than the two ligands. For the same bacteria, the antibacterial effects of the complexes were as follows:Gd-complexes>Mn-complexes.