Zhao Jian, Xu Zichen, Lin Jing, Gou Shaohua
Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University , Nanjing 211189, China.
Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University , Nanjing 211189, China.
Inorg Chem. 2017 Aug 21;56(16):9851-9859. doi: 10.1021/acs.inorgchem.7b01355. Epub 2017 Aug 3.
Platinum(IV) complexes are generally thought to be kinetically inert, and are expected to be stable enough to resist premature aquation before entering the cancer cells. Nevertheless, in this work, complex 2 with axial acetato ligands can hydrolyze relatively quickly under biologically relevant conditions with a half-life of 91.7 min, resulting in the loss of the equatorial chlorido ligand. Further study indicated that the fast hydrolysis of complex 2 may be attributed to the strong σ-donor ability of N-isopropyl-1R,2R-diaminocyclohexane, and an increasing σ-donor ability of the amine group can promote the hydrolysis rate of the corresponding platinum(IV) complex. The experiment results were proven by the corresponding DFT calculation. Our study can help to re-evaluate the aqueous properties of the platinum(IV) complexes with axial acetate, which may be less inert to hydrolysis than expected under biologically relevant conditions.
人们普遍认为铂（IV）配合物在动力学上是惰性的，并且预计它们足够稳定，能够在进入癌细胞之前抵抗过早的水合作用。然而，在这项工作中，带有轴向乙酸根配体的配合物2在生物学相关条件下能够相对快速地水解，半衰期为91.7分钟，导致赤道面氯配体的丢失。进一步的研究表明，配合物2的快速水解可能归因于N-异丙基-1R,2R-二氨基环己烷的强σ供体能力，并且胺基σ供体能力的增加可以促进相应铂（IV）配合物的水解速率。实验结果通过相应的密度泛函理论（DFT）计算得到了证实。我们的研究有助于重新评估带有轴向乙酸根的铂（IV）配合物的水性，在生物学相关条件下，它们对水解的惰性可能比预期的要小。
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