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.
A novel ligand, diethylenetriamine-N,N''-bis(acetyl-isoniazid)-N,N',N''-triacetic acid (H(3)L) 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, (1)H-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 4.34 l.mmol(-1).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 6.08 l.mmol(-1).s(-1) in water solution to 9.09 l.mmol(-1).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)(2-) (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.
Zhang
Ding-Wa
DW
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Yang
Zheng-Yin
ZY
Wang
Bao-Dui
BD
Zhang
Shi-Ping
SP
Yang
Ru-Dong
RD
D003287:Contrast Media / Q000737:chemistry*; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008674:Metals, Rare Earth / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D003287:Contrast Media; D008024:Ligands; D008674:Metals, Rare Earth; D009942:Organometallic Compounds; D012709:Serum Albumin; D012996:Solutions; C514001:diethylenetriamine-N,N''-bis(acetyl-isoniazid)-N,N',N''-triacetic acid; D014867:Water; D004369:Pentetic Acid; D007538:Isoniazid