Tuning the Optical Properties of Phenanthriplatin: Towards New Photoactivatable Analogues

Abstract

The activity of traditional bifunctional platinum‐based drugs is based on a double binding attack of DNA strands that eventually damages the genetic code. Unfortunately, such therapy comes with severe side effects, which drastically limit its efficiency and more importantly, its large‐scale applicability. One emerging alternative is the use of monofunctional platinum complexes based on phenanthriplatin, a new molecule that develops a potent toxicity in tumorous cells by reacting with one DNA base only. Herein, we use theoretical tools to assess the optical properties of phenanthriplatin as well as a series of analogues in an effort to pave the way to their use in photoactivated chemotherapy. In a first step, the absorption signatures of both isolated and DNA‐embedded drugs are predicted through ab initio calculations. Two nitro derivatives are shown to activate a charge transfer from the DNA to the drug and might consequently initiate a cascade of photodamage events. In a second step, we performed molecular dynamics simulations that reveal that such structural change is enough to perturb the DNA‐binding mode. The biological implications of these results in the framework of the design of novel photoactivatable drugs are discussed.

Tuning the Reactivity and Bonding Properties of Metal Square-Planar Complexes by the Substitution(s) on the Trans-Coordinated Pyridine Ring

“…Complexes with aromatic monodentate ligands having anticancer properties were also reported including those based on pyridine and its derivatives. − To minimize the inactivating interactions with thiols, a sterically hindered complex AMD 473 with 2-picoline (2-methylpyridine) ligand was synthesized . The reactivity of Pt­(II) complexes with 2- and 3-picoline as ligands was experimentally compared by Sadler and co-workers.…”

Platinum(IV)–Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple‐Negative Breast Cancer Models

“…DFT calculations afford theoretical values for these differences supporting the coordination in a monodentate fashion: 277 1 ( PtAu ‐ 3 ), 325 ( PtAu 2 ‐ 4 ), and 316 cm −1 ( PtAu 2 ‐5 ; Figures S26–S28) [41–47] . The Supporting Information includes optimization data.…”

“…DFT calculations afford theoretical values for these differences supporting the coordination in a monodentate fashion: 277 1 (PtAu-3), 325 (PtAu 2 -4), and 316 cm À 1 (PtAu 2 -5; Figures S26-S28). [41][42][43][44][45][46][47] The Supporting Information includes optimization data. All optimizations led to compounds containing monodentate carboxylates (Figure 2).…”

Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs

“…That approach has been shown to provide reliable results for the thermochemistry and kinetics of Pt-based compounds [ 32 , 33 ]. The def2-SVP basis set was used to describe all the atoms, except the Pt centers, where the core electrons were replaced with the effective core potentials def2-ECP to account for scalar relativistic effects without increasing the computational cost [ 34 , 35 ]. For all the calculations, we used an ultrafine grid for numerical density functional theory integration.…”