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Several copper‐ligands, including 1,10‐phenanthroline (Phen), have been investigated for anticancer purposes based on their capacity to bind excess copper (Cu) in cancer tissues and form redox active complexes able to catalyse the formation of reactive oxygen species (ROS), ultimately leading to oxidative stress and cell death. Glutathione (GSH) is a critical compound as it is highly concentrated intracellularly and can reduce and dissociate copper(II) from the ligand forming poorly redox‐active copper(I)‐thiolate clusters. Here we report that Cu‐Phen2 speciation evolves in physiologically relevant GSH concentrations. Experimental and computational experiments suggest that at pH 7.4 mostly copper(I)‐GSH clusters are formed, but a minor species of copper(I) bound to one Phen and forming ternary complexes with GSH (GS−Cu‐Phen) is the redox active species, oxidizing quite efficiently GSH to GSSG and forming HO⋅ radicals. This minor active species becomes more populated at lower pH, such as typical lysosomal pH 5, resulting in faster GSH oxidation and HO⋅ production. Consistently, cell culture studies showed lower toxicity of Cu‐Phen2 upon inhibition of lysosomal acidification. Overall, this study underscores that sub‐cellular localisation can considerably influence the speciation of Cu‐based drugs and that minor species can be the most redox‐ and biologically‐active. [ABSTRACT FROM AUTHOR]

Graphene is the newest form of elemental carbon and it is becoming rapidly a potential candidate in the framework of nano‐bio research. Many reports confirm the successful use of graphene‐based materials as carriers of anticancer drugs having relatively high loading capacities compared with other nanocarriers. Here, the outcomes of a systematic study of the adsorption behavior of FDA approved PtII drugs cisplatin, oxaliplatin, and carboplatin on surface models of pristine, holey, and nitrogen‐doped holey graphene are reported. DFT investigations in water solvent have been carried out considering several initial orientations of the drugs with respect to the surfaces. Adsorption free energies, calculated including basis set superposition error (BSSE) corrections, result to be significantly negative for many of the drug@carrier adducts indicating that tested layers could be used as potential carriers for the delivery of anticancer PtII drugs. The reduced density gradient (RDG) analysis allows to show that many kinds of non‐covalent interactions, including canonical H‐bond, are responsible for the stabilization of the formed adducts. [ABSTRACT FROM AUTHOR]

The outcomes of DFT‐based calculations are here reported to assess the applicability of two synthesized polypyridyl Ru(II) complexes, bearing ethynyl nile red (NR) on a bpy ligand, and two analogues, bearing modified‐NR, in photodynamic therapy. The absorption spectra, together with the non‐radiative rate constants for the S1 – Tn intersystem crossing transitions, have been computed for this purpose. Calculations evidence that the structural modification on the chromophore destabilizes the HOMO of the complexes thus reducing the H‐L gap and, consequently, red shifting the maximum absorption wavelength within the therapeutic window, up to 620 nm. Moreover, the favored ISC process from the bright state involves the triplet state closest in energy, which is also characterized by the highest SOC value and by the involvement of the whole bpy ligand bearing the chromophore in delocalising the unpaired electrons. These outcomes show that the photophysical behavior of the complexes is dominated by the chromophore. [ABSTRACT FROM AUTHOR]

A detailed computational exploration of the most relevant steps of iodido Pt(IV) complexes reduction and Pt(II) drugs mechanism of action and eventual deactivation is presented here inspired by the recent findings on iodido Pt(II) complexes and surprising re‐evaluation of their cytotoxic activity. Pt(II) and Pt(IV) model systems are investigated and compared with cisplatin and its Pt(IV) derivative. Both monodeprotonated ascorbic acid and l‐cysteine are used as reducing agents in the inner‐sphere reduction mechanism of Pt(IV) complexes. Aquation mechanism of iodido Pt(II) complexes, interaction with guanine and sulfur containing compounds and reaction with the model protein hen egg white lysozyme are explored, due to a detected different behavior with respect to classical platinum drugs. The outcomes of such exploration allow to shed light on the role that the increased soft character together with bridging and leaving abilities of iodide over chloride could play in determining the cytotoxic profile of iodido Pt drugs. [ABSTRACT FROM AUTHOR]