锝化学研究Ⅻ.^(99)Tc^m-d,l-PAO类络合物的脑滞留能力与体外稳定性的研究

STUDIES OF TECHNETIUM CHEMISTRY XII. Study of Brain Retention Ability and in Vitro Stability of 99 Tc m d,l PAO Complexes

以９９Ｔｃｍ－ｄ，ｌ－ＨＭＰＡＯ的晶体数据为基础，采用量子化学中的ＩＮＤＯ／１方法，对９９Ｔｃｍ－ｄ，ｌ－ＨＭ－ＰＡＯ、９９Ｔｃｍ－ｄ，ｌ－ＣＢＰＡＯ、９９Ｔｃｍ－ｄ，ｌ－ＯＣＢＰＡＯ、９９Ｔｃｍ－ｄ，ｌ－ＥＯＣＢＰＡＯ、９９Ｔｃｍ－ｄ，ｌ－ＩＰＯＣＢＰＡＯ进行了结构优化计算，研究了这５种９９Ｔｃｍ－ｄ，ｌ－ＰＡＯ类络合物的脑滞留能力的大小与体外稳定性的关系，验证了实验结果；探讨了９９Ｔｃｍ－ｄ，ｌ－ＰＡＯ类络合物的分子极性及络合物分子与Ｈ２Ｏ分子形成氢键对分子脂溶性的影响。这为合理的药物设计及脑药物滞留机制的研究提供了一定的理论基础。

Based on crystal data of 99 Tc m d,l HMPAO, the structures of 99 Tc m d,l PAO complexes ( 99 Tc m d,l HMPAO, 99 Tc m d,l CBPAO, 99 Tc m d,l OCBPAO, 99 Tc m d,l EOCBPAO, 99 Tc m d,l IPOCBPAO) are optimized. The total energy of molecule, dipolement of molecule,net charge of atom and the molecular orbital energy of HOMO and LUMO are calculated. The results indicate that brain retention ability of 99 Tc m d,l PAO complexes depends on the in vitro instability of the complexes, which are consistent with the results of experiment. The influence of molecular polarity and intermolecular hydrogen bond on molecular lipophilicity of complexes are investigated. The conclusion provides the theoretical basis for studying reasonable drug design and brain retention mechanism.