Modulation of water exchange in Eu(III) DOTA-tetraamide complexes: considerations for in vivo imaging of PARACEST agents.
Modulation of water exchange in Eu(III) DOTA-tetraamide complexes: considerations for in vivo imaging of PARACEST agents.
复制标题
DOI：
10.1002/cmmi.279
复制
发表时间：
2009-07
影响因子：
--
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
--
作者：
Mani, Tomoyasu;Tircso, Gyula;Togao, Osamu;Zhao, Piyu;Soesbe, Todd C.;Takahashi, Masaya;Sherry, A. Dean
在过去的二十年里，稀土(III)-DOTA型络合物中水交换的调制引起了人们的极大关注，特别是因为它们作为磁共振成像(MRI)造影剂的应用。LnDOTA-四酰胺络合物表现出异常缓慢的水交换动力学，这一化学性质为基于化学交换饱和转移(CEST)机制的新型造影剂提供了机会。合成了6个具有不同疏水性和不同极性的侧链酰胺臂的DOTA-四酰胺配体，并研究了它们与Eu(III)形成的配合物的水交换特性。结果表明，在Eu(III)络合物的酰胺侧链臂上引入空间位阻，不仅有利于形成一般不利于CEST的单帽扭方反棱镜(TSAP)配位异构体，而且促进了单帽正方反棱镜(SAP)异构体的水交换。然而，将这些大臂上的单一甲基转化为羧基或羧基乙酯，导致水交换速率相当戏剧性地下降，约为50倍。因此，酰胺侧链的空间体积、极性和疏水性都有助于在Eu(III)离子的第二水合球体中组织水分子，这反过来又控制着这些络合物中的水交换。
Modulation of water exchange in lanthanide(III)-DOTA type complexes has drawn considerable attention over the past two decades particularly because of their application as contrast agents for Magnetic Resonance Imaging (MRI). LnDOTA-tetraamide complexes display unusually slow water exchange kinetics and this chemical property offers an opportunity to use these complexes as a new type of contrast agent based upon the chemical exchange saturation transfer (CEST) mechanism. Six new DOTA-tetraamide ligands having side-chain amide arms with varying hydrophobicity and polarity were prepared and the water exchange characteristic of complexes formed with europium(III) complexes were investigated. The results show that introduction of steric bulk into the amide side-chain arms of the europium(III) complexes not only favors formation of the mono-capped twisted square antiprism (TSAP) coordination isomers, the isomer that is generally less favourable for CEST, but also accelerates water exchange in the mono-capped square antiprism (SAP) isomers. However, converting single methyl groups on these bulky arms to carboxyl or carboxyl ethyl esters results in a rather dramatic decrease in water exchange rates, about 50-fold. Thus, steric bulk, polarity, hydrophobicity of the amide side-chains, each contribute to organization of water molecules in the second hydration sphere of the europium(III) ion and this in turn controls water exchange in these complexes.
登录
查看更多内容
影响因子：
2.2
作者：
Ward, KM;Aletras, AH;Balaban, RS
通讯作者：
Balaban, RS
影响因子：
3.3
作者：
Liu, Guanshu;Li, Yuguo;Pagel, Mark D.
通讯作者：
Pagel, Mark D.
影响因子：
4.9
作者：
Aime, S;Barge, A;Puschmann, H
通讯作者：
Puschmann, H
影响因子：
16.6
作者：
Chauvin, Thomas;Durand, Philippe;Toth, Eva
通讯作者：
Toth, Eva
影响因子：
15
作者：
Ratnakar, S. James;Woods, Mark;Sherry, A. Dean
通讯作者：
Sherry, A. Dean