Difluoro Dipyridomethene Boron Complexes: Synthesis, Characterization, and Ab Initio Calculations.

Molecular engineering studies on the meso-cyano difluoro dipyridomethene boron complexes are presented and two series (a and b) of novel fluorophores are extensively studied. Halogenated derivatives were reacted under Suzuki-Miyaura or Sonogashira cross coupling reactions to introduce electron-donating or electron-withdrawing functional groups on positions 1 and 2 of the aromatic ligand. All derivatives were obtained in 14-90% yields and studied in detail by structural, photophysical, and computational analyses. Both series display excellent emissive properties in solution with blue to orange fluorescence emission upon blue light absorption and promising features as solid emitters. All the spectroscopic measurements are supported and confirmed by first-principles theoretical calculations combining TD-DFT and CC2. Series b, featuring an aryl substituent onto position 1 of the aromatic core, showed significantly large Stokes shifts values.

Lysosomes Targeting pH Activable Imaging-Guided Photodynamic Agents.

Photodynamic therapy (PDT) is a photochemistry-based medical treatment combining light at a specific wavelength and a photosensitizer (PS) in the presence of oxygen. Application of PDT as a conventional treatment is limited and clearly the approval in clinics of new PS is challenging. The selective accumulation of the PS in the targeted malignant cells is of paramount importance to reduce the side effects that are typical of the current worldwide approved PS. Here we report a new series of aniline- and iodine-substituted BODIPY derivatives (1-3) as promising lysosome-targeting and pH-responsive theranostic PS, which displayed a significant in vitro light-induced cytotoxicity, efficient imaging properties and low dark toxicity (for 2 and 3). These compounds were obtained in few reproducible synthetic steps and good yields. Spectroscopic and electrochemical measurements along with computational calculations confirmed the quenching of the emissive properties of the PS, while both fluorescence and 1 O2 emission were obtained only under acidic conditions inducing amine protonation. The pKa values and pH-dependent emissive properties of 1-3 being established, their cellular uptake and activation in the lysosomal vesicles (pH≈4-5) were confirmed by their co-localization with the commercial LysoTracker deep red and light-induced cytotoxicity (IC50 between 0.16 and 0.06 µM) against HeLa cancer cells.

Genotoxic effects of chlorinated disinfection by-products of 1,3-diphenylguanidine (DPG): Cell-based in-vitro testing and formation potential during water disinfection.

1,3-diphenylguanidine (DPG) is a commonly used rubber and polymer additive, that has been found to be one of the main leachate products of tire wear particles and from HDPE pipes. Its introduction to aquatic environments and potentially water supplies lead to further questions regarding the effects of disinfection by-products potentially formed. Using different bioassay approaches and NGS RNA-sequencing, we show that some of the chlorinated by-products of DPG exert significant toxicity. DPG and its chlorinated by-products also can alter cell bioenergetic processes, affecting cellular basal respiration rates and ATP production, moreover, DPG and its two chlorination products, 1,3-bis-(4-chlorophenyl)guanidine (CC04) and 1-(4-chlorophenyl)-3-(2,4-dichlorophenyl)guanidine (CC11), have an impact on mitochondrial proton leak, which is an indicator of mitochondria damage. Evidence of genotoxic effects in the form of DNA double strand breaks (DSBs) was suggested by RNA-sequencing results and further validated by an increased expression of genes associated with DNA damage response (DDR), specifically the canonical non-homologous end joining (c-NHEJ) pathway, as determined by qPCR analysis of different pathway specific genes (XRCC6, PRKDC, LIG4 and XRCC4). Immunofluorescence analysis of phosphorylated histone H2AX, another DSB biomarker, also confirmed the potential genotoxic effects observed for the chlorinated products. In addition, chlorination of DPG leads to the formation of different chlorinated products (CC04, CC05 and CC15), with analysed compounds representing up to 42% of formed products, monochloramine is not able to effectively react with DPG. These findings indicate that DPG reaction with free chlorine doses commonly applied during drinking water treatment or in water distribution networks (0.2-0.5 mg/L) can lead to the formation of toxic and genotoxic chlorinated products.