Photoswitching the Cytotoxic Properties of Platinum(II) Compounds

Abstract

The photoactivation of potential anticancer metal complexes is a hot topic of current research as it may lead to the development of more selective drugs. Photoactivated chemotherapy (PACT) with coordination compounds is usually based on a (photo)chemical reaction taking place at the metal center. Herein, a new strategy is exploited that consists of “photomodifying” a ligand coordinated to metal ions. Platinum(II) complexes from photoswitchable 1,2‐dithienylethene‐containing ligands have been prepared, which exhibit two interconvertible photoisomeric forms that present distinct DNA‐interacting properties and cytotoxic behaviors.

Photoactivation of the Cytotoxic Properties of Platinum(II) Complexes through Ligand Photoswitching

“…This precipitate was then poured over a glass filter, washed with cold n-pentane and finally dried under reduced pressure to yield the crude final product 1 as a pale brown solid (27.6 g, 81%). 1 mmol) was carefully added under a nitrogen atmosphere using a syringe to an ice-cooled suspension of zinc dust (5.2 g, 80 mmol) in 150 mL of anhydrous THF. The resulting grey-blue reaction mixture was slowly heated to 50 °C and stirred for 2 h, after which pyridine (3.2 mL, 40 mmol) was added dropwise, producing a brown solution.…”

Photoswitchable anticancer activity via trans–cis isomerization of a combretastatin A-4 analog

“…Very recently, Presa and coworkers have developed Pt(II) complexes with ligands that can be switched between more toxic and less toxic forms depending on the wavelength of light used. 14 One potential problem for the clinical application of each of these light-activated drug systems is that the activated drug can diffuse away from the illuminated site of the tumor, causing unwanted damage to the tissues it encounters. An ideal light-activated drug would automatically revert to a less potent form over time in order to limit this off-target toxicity.…”

Beyond Photodynamic Therapy: Light-Activated Cancer Chemotherapy

“…In contrast, 86 and 87 presumably lead to an unwinding of double helix supercoiled DNA, which decreases its mobility. [122] Overall, this effect is more distinct for the closed forms of the complexes and also more pronounced for complex 87. Subsequently, analogues of CA4 are the most investigated example of this approach.…”

“…irradiation, the open form of the diarylethene switch isomerizes to the closed form, as shown in explained by the fact that the open form is more bulky than the closed form and thus is more sterically hindered to bind to the double helix. [122] In addition, electronic properties of the ligand after ring closure may be favorable for the binding. Next, DNA binding of the complexes was examined by analyzing electrophoretic mobility of plasmid DNA.…”