大环希夫碱顺磁配合物作为新型造影剂磁共振成像分析

Fifty new complexes have been synthesized in this subject, six complexes processing high relaxivity(R1) in them are discovered, for example, a-oxo-pent-anedioic acid benzoyl hydrazone-Gd: R1=8.05mmol-1·L·s-1; a-oxo-pent-anedioic acid isonicotinoyl hydrazone-Gd: R1=10.22,; a-oxo-pentanedioic acid-2,4-dinitrobenzene hydrazone-Gd: R1=6.58; a-oxo-g-ethoxycarbonyl-butanoic acid thiosemicarbazone-Gd: R1=8.10; aminotriethanoic acid-Gd: R1=9.31, and aminotriethanoic acid-Mn: R1=8.52. The animal toxicity experiment shows a-oxo-pentanedioic acid benzoyl hydrazone-Gd: LD50=536.1 mg/kg, two complexes of aminotriethanoic acid: LD50>1000. In adition, biological and pharmacological activity of other complexes has been studied, the inhibitory rate of La(HPBI)3·3.5H2O and Eu(HPBI)3·3.5H2O（HPBI=1-phenyl-3-methyl-5-hydroxy-4-pyrazolyl phenyl ketone iso-nicotinoyl hydrazone）for Leukemia cells ( L1210 ) is 87.1% and 78.5%, respectively，LD50 of them is 348.9, 279.1 mg/kg. The studied result on the subject shows that polycarboxylic hydrazone paramagnetic complexes used as magnetic resonance imaging (MRI) contrast agent would appear good developing foreground, but the macrocyclic Schiff base metal complexes are poor soluble in water, they can not become good MRI contrast agent.

磁共振成像技术对肿瘤、心脑血管疾病等恶性病变的早期诊断极为有效。但不成熟的MRI造影剂理论制约了该技术的发展。本课题拟合成水溶性好的多羧基大环希夫碱顺磁配合物作为研究MRI造影剂的目标分子，测定其结构、系统研究其构效关系和靶向识别规律，总结弛豫视肱馕凰康墓叵担⒄饫嘈滦蚆RI造影剂提供必要的理论依据和参考数据。