The use of ruthenium complexes as chemotherapeutic agents has been recently explored as one of the alternatives to conventional treatments. In the present study, two Ru(II) polypyridyl complexes were synthesized and characterized: a strained [Ru(bipy)₂(BC)]Cl₂ (complex 1) where [bipy = 2,2′-bipyridine and BC = bathocuproine] along with the unstrained control [Ru(bipy)₂(phen)]Cl₂ (complex 2) where [phen = 1,10-phenanthroline]. The photophysical and photochemical analyses proved that unlike the photostable complex 2, complex 1 ejected both bipy and BC ligands at a ratio of 3 : 1 respectively. Results showed that the activity of complex 1 was significantly enhanced upon photoactivation. The response was however particularly significant in B16-F10 melanoma cells where phototoxicity index (PI = IC₅₀ dark/IC₅₀ light) was >900. When compared to cisplatin, the photoproducts were more potent against all tested cell lines, implying that the complex acquired significant chemotherapeutic potential upon irradiation. Cellular uptake of complex 1 and the free BC ligand were found to be significantly facilitated as evidenced by 400–600 fold increase in concentration of the compounds inside the cells relative to the extracellular culture medium. Complex 2 exhibited 35 times lower cellular concentration relative to complex 1. Flow cytometry and plasmid DNA gel electrophoresis measurements showed that complex 1 interacts with DNA inducing apoptosis in the dark and either late-apoptosis or necrosis upon irradiation. These findings corroborate the importance of lipophilic ligands such as BC to enhance uptake and subsequently improve the photochemotherapy potential of Ru(II) polypyridyl complexes.

Phthalate esters (PAEs) are plasticizers associated with multiple toxicities; however, no strict regulations have been implemented to restrict their use in medical applications in Lebanon. Our study aimed at assessing the potential risks correlated with phthalate exposure from IV bags manufactured in Lebanon. GC–MS analysis showed that di-(2-ethylhexyl) phthalate (DEHP) is the predominant phthalate found in almost all samples tested with values ranging from 32.8 to 39.7% w/w of plastic. DEHP concentrations in the IV solutions reached up to 148 µg/L, as measured by SPME-GC–MS/MS, thus resulting in hazard quotients greater than 1, specifically in neonates. The toxicity of DEHP is mainly attributed to its metabolites, most importantly mono-(2-ethylhexyl) phthalate (MEHP). The IV bag solution with the highest content in DEHP was therefore used to extrapolate the amounts of urinary MEHP. The highest concentrations were found in neonates having the lowest body weight, which is concerning, knowing the adverse effects of MEHP in infants. Our study suggests that the use of IV bags manufactured in Lebanon could pose a significant risk in hospitalized patients, especially infants in neonatal care. Therefore, Lebanon, as well as other countries, should start imposing laws that restrict the use of phthalates in medical IV bags and substitute them with less toxic plasticizers.

This study validates a rapid LC-MS/MS method for the quantification of Ru(ii) bipyridyl complexes in biological matrices, using selective ligand dissociation.