Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland.
Int J Mol Sci. 2021 Jul 26;22(15):7973. doi: 10.3390/ijms22157973.
Besides the well-known functions performed by vitamin B (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cancer cells. The present study was aimed at determining the possibility of the formation of CblCN conjugates with Pd(II) complexes. A key aspect was their stability, which we attempted to tune by appropriate choice of ligands. Syntheses, spectroscopic analysis of postreaction systems and kinetic investigations of conjugate formation reactions, have been complemented by DFT modelling. The obtained results showed that ligand charge, geometry and electron affinity may have a significant impact on carrier binding and release leading to the activation of the Pd(II) complex. This provides a rationale to expect that with appropriate composition of the coordination sphere, it will be possible to extend the spectrum of less toxic inorganic chemotherapeutics.
除了维生素 B(CblCN)在人体生化过程中众所周知的功能外,人们越来越关注其作为跨膜药物载体的可能性,这种载体能够增强无机细胞抑制剂在癌细胞中的积累。本研究旨在确定 CblCN 与 Pd(II) 配合物形成缀合物的可能性。一个关键方面是它们的稳定性,我们试图通过适当选择配体来调整其稳定性。我们通过 DFT 建模补充了配合物的合成、反应后体系的光谱分析以及缀合物形成反应的动力学研究。所得结果表明,配体电荷、几何形状和电子亲和力可能对载体结合和释放产生重大影响,从而导致 Pd(II) 配合物的激活。这为我们提供了一个理由,即通过适当组成配位体,有可能扩大毒性较小的无机化疗药物的应用范围。