Unfortunately, these complexes had to be later discarded because of their low stability in the dark. Therefore, iodo-based photolabile Pt(IV) complexes which, upon lightĮxposure, undergo photolytic reactions to give active Pt(II) species have been developed. To address the passive activation of Pt(IV) prodrugs, the choice of photoactivated Pt(IV) prodrugs seems to be a promising chemotherapeutic strategy. However, prolonged hydrolysis and less stability against bio-reducing agents are problems still to be overcome. Owing to the availability of bio-reducing agents, mainly proteins, in all cell types, Pt(IV) prodrugs can be reduced to their cytotoxic active Pt(II) analogues in both cancer and normal cells. To overcome these problems, octahedral, low-spin d6 and coordinatively saturated Pt(IV) complexes have been examined because of their substitution inertness towards off-target biomolecules. Since these drugs are structurally related to cisplatin, the unfortunate problems that are associated with cisplatin are more or less the sameįor them.
All calculations were carried out with both the CAM-B3LYP and B3LYP functionals we generally find the former to perform best in comparison with experimental spectra.įollowing the serendipitous discovery of the anticancer drug, cisplatin, numerous platinum(II) complexes have been synthesized and some of them, such as carboplatin, oxaliplatin, nedaplatin, heptaplatin and lobaplatin, have been clinically approved either locally or worldwide.
Since the investigated complexes are activated with light of wavelengths above 300 nm, employing a method with explicit inclusion of spin-orbit coupling may be crucial to rationalize the activation mechanism. Yet the underlying transitions can be strongly influenced by spin-orbit coupling introduced in the 4c framework: while this can affect both intense and less intense transitions in the spectra, the effect is most pronounced for weaker transitions at lower energies, above 300 nm. Large differences are found between spectra calculated within 4c and NR frameworks, while the most intense features (found at higher energies below 300 nm) can be reasonably well reproduced within a SR framework.
#Concept destruction platinum series#
We carried out TD-DFT calculations with a systematic series of non-relativistic(NR), scalar-relativistic (SR), and four-component (4c) Hamiltonians. A first step is usually to rationalize their UV-vis spectra for which time-dependent density functional theory (TD-DFT) is an indispensable tool. We report the first investigation of relativistic effects on the UV-vis spectra of two prototype complexes for so-called photo-activated chemotherapy (PACT), trans-trans-trans- and cis-trans-cis-.In PACT, design of new drugs requires in-depth understanding of the photo-activation mechanisms. We hope this review can help to facilitate the design and development of novel photoactivatable Pt(IV) anticancer prodrugs. In this review, we will focus on the development of the coordinated ligands in such Pt(IV) prodrugs and discuss the effects of diverse ligands on their photochemistry and photoactivity as well as the future evolution directions of the ligands. The coordinated ligands to the Pt center have been proved to be pivotal in determining the function and activity of the photoactivatable Pt(IV) prodrugs. These photochemotherapeutic prodrugs have high dark-stability under physiological conditions, while they can be activated by visible light restrained at the disease areas, as a consequence showing higher spatial and temporal controllability and much more safety than conventional chemotherapy. Photoactivatable Pt(IV) anticancer prodrugs with the structure of, where N1 and N2 are non-leaving nitrogen donor ligands, L1 and L2 are leaving ligands, and A1 and A2 are axial ligands, have attracted increasing attention due to their promising photo-cytotoxicity even to cisplatin-resistant cancer cells.