The longstanding notion that Pt_((IV))complexes are inert under physiological conditions where there are limited reducing agents is facing a great challenge.Herein,we systematically investigated the hydrolytic stabili...The longstanding notion that Pt_((IV))complexes are inert under physiological conditions where there are limited reducing agents is facing a great challenge.Herein,we systematically investigated the hydrolytic stability of a wide range of unsymmetric Pt_((IV))anticancer prodrugs built upon clinical Pt_((II))drugs.The detailed structure-stability relationship shows that the hydrolytic stability of one certain axial ligand in Pt_((IV))complexes can be dramatically affected by the other five ligands;both the coordination environment of equatorial ligands and the“trans influence”from one axial ligand affect the hydrolytic stability of the counter axial ligand,and the more electronegative axial ligand faces the higher possibility to detach.Inspiringly,this newly discovered structure-stability relationship has been successfully applied to improve the hydrolytic stability of Pt_((IV))complexes that contain axial dichloroacetato ligands.Our discovery represents a significant advancement in the theory of the chemical inertness of Pt_((IV))complexes toward ligand exchange reactions and provides a practical guide for the future design of Pt_((IV))anticancer prodrugs.展开更多
基金the Hong Kong Research Grants Council(Grant No.CityU 11307419,11304318,and 11303320)the National Natural Science Foundation of China(Grant No.21877092 and 22077108)for funding support.
文摘The longstanding notion that Pt_((IV))complexes are inert under physiological conditions where there are limited reducing agents is facing a great challenge.Herein,we systematically investigated the hydrolytic stability of a wide range of unsymmetric Pt_((IV))anticancer prodrugs built upon clinical Pt_((II))drugs.The detailed structure-stability relationship shows that the hydrolytic stability of one certain axial ligand in Pt_((IV))complexes can be dramatically affected by the other five ligands;both the coordination environment of equatorial ligands and the“trans influence”from one axial ligand affect the hydrolytic stability of the counter axial ligand,and the more electronegative axial ligand faces the higher possibility to detach.Inspiringly,this newly discovered structure-stability relationship has been successfully applied to improve the hydrolytic stability of Pt_((IV))complexes that contain axial dichloroacetato ligands.Our discovery represents a significant advancement in the theory of the chemical inertness of Pt_((IV))complexes toward ligand exchange reactions and provides a practical guide for the future design of Pt_((IV))anticancer prodrugs.
