Universität Heidelberg, Anorganisch-Chemisches Institut, INF 270, D-69120 Heidelberg, Germany.
Dalton Trans. 2013 Aug 21;42(31):11066-73. doi: 10.1039/c3dt51049b.
A QSPR scheme for the computation of lipophilicities of ⁶⁴Cu complexes was developed with a training set of 24 tetraazamacrocylic and bispidine-based Cu(II) compounds and their experimentally available 1-octanol-water distribution coefficients. A minimum number of physically meaningful parameters were used in the scheme, and these are primarily based on data available from molecular mechanics calculations, using an established force field for Cu(II) complexes and a recently developed scheme for the calculation of fluctuating atomic charges. The developed model was also applied to an independent validation set and was found to accurately predict distribution coefficients of potential ⁶⁴Cu PET (positron emission tomography) systems. A possible next step would be the development of a QSAR-based biodistribution model to track the uptake of imaging agents in different organs and tissues of the body. It is expected that such simple, empirical models of lipophilicity and biodistribution will be very useful in the design and virtual screening of positron emission tomography (PET) imaging agents.
建立了一个用于计算 ⁶⁴Cu 配合物脂溶性的 QSPR 方案，该方案使用了 24 种四氮大环和双吡啶基 Cu(II)配合物及其实验可获得的 1-辛醇-水分配系数作为训练集。方案中使用了尽可能少的具有物理意义的参数，这些参数主要基于分子力学计算中可用的数据，使用了为 Cu(II)配合物建立的成熟力场和最近开发的用于计算波动原子电荷的方案。所开发的模型也应用于独立验证集，并被发现能够准确预测潜在的 ⁶⁴Cu PET（正电子发射断层扫描）系统的分配系数。下一步可能是开发基于 QSAR 的生物分布模型，以跟踪成像剂在体内不同器官和组织中的摄取。预计这种简单的、经验性的脂溶性和生物分布模型将在正电子发射断层扫描（PET）成像剂的设计和虚拟筛选中非常有用。
