Synthesis Neutral Rare Earth Complexes of Diethylenetriamine-N,N-bis(acetyl-isoniazid)-N,N',N'-triacetic Acid as Potential Contrast Enhancement Agents for Magnetic Resonance Imaging

摘要

A novel ligand,diethylenetriamine-N,N"-bis(acetyl-isoniazid)-N,N",N''-triacetic acid (H_3L)has been synthesized from diethylene triamine pentaacetic acid (DTPA)and isoniazid.Ligand and its five neutral rare earth (RE=La,Sm,Eu,Gd,Tb)complexes holding promise of magnetic resonance imaging (MRI)were characterized on the basis of elemental analysis,molar conductivity,~1H-NMR spectrum,FAB-MS,TG-DTA analysis and IR spectrum.The relaxivity (R_1)of complexes and Gd(DTPA)~(2-)used as a control were determined.The relaxivity of LaL,SmL,EuL,GdL,TbL and Gd(DTPA)~(2-)were 0.14,1.66,3.14,6.08,2.79 and 4.341 centre dot mmol~(1)centre dot s~(-1),respectively.The spin-lattice relaxivity of GdL was larger than that of Gd(DTPA)~(2-).The relaxivity of GdL had also been investigated in human serum albumin (HSA)solution,the relaxivity of GdL was enhanced from 6.081 centre dot mmol~(-1)centre dot s~(-1)in water solution to 9.091 centre dot minol~(-1)centre dot s~(-1)in HSA solution.In addition,thermodynamics stability constant of GdL complex was determined,the thermodynamic stability constant of GdL complex (K_(GdL)=10~(20.84))was a few larger than that of Gd(DTPA)~(K_(Gd.DTPA)=10_(20.73)).The results showed that complex of GdL may be a prospective MRI contrast agent with low osmotic pressure due to non-ion complex,high spin-lattice relaxivity,good stability and binding affinity for the serum protein.