科研之友
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摘要
Diazido PtIV complexes are inert stable prodrugs that can be photoactivated to produce PtII species with promising anticancer activity. Our studies of the photochemistry of PtIV complexes, [Pt(X)2(Y)2(Z)2]0/-1 (X=N-ligands (NH3, pyridine, etc.)/S(CH3)2/H-, Y=(pseudo)halogen (N3-, I-), Z=OR-, R=H, Ac) by time-dependent density functional theory (TDDFT) show close agreement with spectroscopic data. Broad exploration of cis/trans geometries, trans influences, the nature of the OR- and (pseudo)halogen ligands, electron-withdrawing/donating/delocalising substituents on the N-ligands, and intramolecular H bonds shows that: 1) the design of platinum(IV) complexes with intense bands shifted towards longer wavelengths (from 289 to 330 nm) can be achieved by introducing intramolecular H bonds involving the OH ligands and 2-hydroxyquinoline or by iodido ligands; 2) mesomeric electron-withdrawing substituents on pyridine result in low-energy absorption with significant intensity in the visible region; and 3) the distinct makeup of the molecular orbitals involved in the electronic transitions for cis/trans-{Pt(N3)2} isomers results in different photoproducts. In general, the comparison of the optimised geometries shows that PtIV complexes with longer Pt?L bonds are more likely to undergo photoreduction with longer-wavelength light. The novel complex trans,trans,trans-[Pt(N3)2(OH)2(NH3)(4-nitropyridine)] with predicted absorption in the visible region has been synthesised. The experimental UV/Vis spectrum in aqueous solution correlates well with the intense band in the computed spectrum, whereas the overlay in the low-energy region can be improved by a solvent model. This combined computational and experimental study shows that TDDFT can be used to tune the coordination environment for optimising photoactive PtIV compounds as anticancer agents.
- 出版日期2012-8
