Woods Mark, Kovacs Zoltan, Kiraly Robert, Brücher Ernö, Zhang Shanrong, Sherry A Dean
Department of Chemistry, University of Texas at Dallas, P.O. Box 830660, Richardson, Texas 75083, USA.
Inorg Chem. 2004 May 3;43(9):2845-51. doi: 10.1021/ic0353007.
Addition of a benzyl substituent to the macrocyclic ring of DOTA has a substantial impact on the conformational ring flipping motion of the macrocycle in the resulting LnDOTA complexes. The p-NO2-benzyl substituent in the Ln(p-NO2-Bn-DOTA)- complexes lies in an equatorial position and effectively "locks" the conformation of the ring into the deltadeltadeltadelta configuration. The presence of the p-NO2-benzyl group also increases the population of the square antiprismatic (SAP) coordination isomer for all Ln(p-NO2-Bn-DOTA)- complexes relative to that seen for the respective LnDOTA- complexes. Despite this increase in SAP isomer population, the rate of water exchange in these complexes remains comparatively fast. The kinetic and thermodynamic stabilities of the Ln(p-NO2-Bn-DOTA)- complexes are also slightly lower than the corresponding LnDOTA- complexes but appear to be sufficiently high for in vivo use.
在DOTA的大环上添加苄基取代基会对所得LnDOTA配合物中大环的构象环翻转运动产生重大影响。Ln(p-NO2-Bn-DOTA)-配合物中的对硝基苄基取代基处于赤道位置，并有效地将环的构象“锁定”为δδδδ构型。相对于各自的LnDOTA-配合物，对硝基苄基的存在也增加了所有Ln(p-NO2-Bn-DOTA)-配合物的四方反棱柱体（SAP）配位异构体的比例。尽管SAP异构体比例有所增加，但这些配合物中的水交换速率仍然相对较快。Ln(p-NO2-Bn-DOTA)-配合物的动力学和热力学稳定性也略低于相应的LnDOTA-配合物，但似乎足够高可用于体内。
