A new family of neutral chiral cyclometalated platinum­(II) complexes with formula [Pt­(κ2-(C^N))­Cl­(κ1-(L))], where (C^N) = 2-phenylpyridinate and (L) = 2-(2-pyridyl)­benzimidazole (L1) or (N-(CH2)-Ar-(2-(2-pyridyl)­benzimidazole) ligands; (Ar = phenyl (L2), naphthyl (L3), pyrenyl (L4)), have been synthesized and completely characterized. The unexpected κ1 coordination mode of the 2-(2-pyridyl)­benzimidazole-derived ligands has been confirmed by spectroscopic techniques and X-ray diffraction. The aromatic moieties on the ligands in the new platinum­(II) complexes have a remarkable influence on the cytotoxicity and in the binding mode to DNA. [Pt-L1]–[Pt-L4] complexes internalized more than cisplatin in the SW480 cancer cells even though only [Pt-L1] and [Pt-L2] display high cytotoxicity. 1H NMR and 13P­{1H}­NMR pointed out that [Pt-L1] and [Pt-L2] complexes bind covalently to dGMP, while the electrophoresis assays and CD experiments indicate that only [Pt-L2] is able to covalently interact with DNA, inducing the same conformational changes in the plasmid DNA as cisplatin. Although the complex [Pt-L4] intercalates into DNA, probably through the pyrenyl moiety, no biological activity is observed.

No abstract

In the present study, a comparative human toxicity assessment between newly developed Mn3O4 nanoparticles with enhanced electrochemical properties (GNA35) and their precursor material (Mn3O4) was performed, employing different in vitro cellular models representing main exposure routes (inhalation, intestinal and dermal contact), namely the human alveolar carcinoma epithelial cell line (A549), the human colorectal adenocarcinoma cell line (HT29), and the reconstructed 3D human epidermal model EpiDerm. The obtained results showed that Mn3O4 and GNA35 harbour similar morphological characteristics, whereas differences were observed in relation to their surface area and electrochemical properties. In regard to their toxicological properties, both nanomaterials induced ROS in the A549 and HT29 cell lines, while cell viability reduction was only observed in the A549 cells. Concerning their skin irritation potential, the studied nanomaterials did not cause a reduction of the skin tissue viability in the test conditions nor interleukin 1 alpha (IL- 1 α) release. Therefore, they can be considered as not irritant nanomaterials according to EU and Globally Harmonized System of Classification and Labelling Chemicals. Our findings provide new insights about the potential harmful effects of Mn3O4 nanomaterials with different properties, demonstrating that the hazard assessment using different human in vitro models is a critical aspect to increase the knowledge on their potential impact upon different exposure routes.

In the present study, a comparative human toxicity assessment between newly developed Mn3O4 nanoparticles with enhanced electrochemical properties (GNA35) and their precursor material (Mn3O4) was performed, employing different in vitro cellular models representing alveolar, oral and dermal exposure routes, namely the human alveolar carcinoma epithelial cell line (A549), the human colorectal adenocarcinoma cell line (HT29), and the reconstructed 3D human epidermal model EpiDerm™ (RhE). The obtained results showed that Mn3O4 and GNA35 harbour similar morphological characteristics, while differences were observed in relation to their thermal stability and electrochemical properties. In regard to their toxicological properties, both nanomaterials induced oxidative stress in the A549 and HT29 cell lines that have demonstrated that manganese oxide nanoparticles reduce the cell viability in A549 cells while they do not produce any negative effect on that of HT29 cells. On the other hand, it was observed that Mn3O4 and GNA35 induce oxidative stress in both cell lines. Finally, it was noticed that none of the nanoparticles caused a reduction of the viability on the skin tissue so that they could not be classified as irritants. Our findings demonstrate that the evaluation of the toxicity of nanoparticles using different models is a critical aspect to increase the knowledge on their potential impact on human health.

No abstract