Aggregation-Driven Photoinduced α-C(sp3)-H Bond Hydroxylation/C(sp3)-C(sp3) Coupling of Boron Dipyrromethene Dye in Water Reported by Near-Infrared Emission.

Molecular aggregation is a powerful tool for tuning advanced materials' photophysical and electronic properties. Here we present a novel potential for the aqueous-solvated aggregated state of boron dipyrromethene (BODIPY) to facilitate phototransformations otherwise achievable only under harsh chemical conditions. We show that the photoinduced symmetry-breaking charge separation state can itself initiate catalyst-free redox chemistry, leading to selective α-C(sp3)-H bond activation/Csp3-Csp3 coupling on the BODIPY backbone. The photoproduction progress was tracked by monitoring the evolution of the strong Stokes-shifted near-infrared emission, resulting from selective self-assembly of the terminal heterodimeric photoproduct into well-ordered J-aggregates, as revealed by X-ray structural analysis. These findings provide a facile and green route to further explore the promising frontier of packing-triggered selective photoconversions via supramolecular engineering.

Metal-binding cyclodextrins: Synthesis and complexation with Zn2+ and Ga3+ cations towards antimicrobial applications.

Highly resistant bacteria producing metallo-ß-lactamases (MBLs) to evade ß-lactam antibiotics, constitute a major cause of life-threatening infections world-wide. MBLs exert their hydrolytic action via Zn2+ cations in their active center. Presently, there are no approved drugs to target MBLs and combat the associated antimicrobial resistance (AMR). Towards this issue, we have prepared a family of cyclodextrins substituted with iminodiacetic acid (IDA) on their narrow side, while the wider side is either unmodified or per-2,3-O-methylated. The molecules form strong coordination complexes with Zn2+ or Ga3+ cations in aqueous solution. Free and metal-complexed compounds have been thoroughly characterized regarding structures, pH-dependent ionization states, distribution of species in solution, pKa values and metal-binding constants. At neutral pH the multi-anionic hosts bind up to four Zn2+ or Ga3+ cations. In vitro, 50 µΜ of the compounds achieve complete re-sensitization of MBL-producing Gram-negative clinical bacterial strains resistant to the carbapenems imipenem and meropenem. Moreover, the radioactive complex [67Ga]Ga-ß-IDACYD prepared, displays high radiochemical purity, sufficient stability both overtime and in the presence of human plasma apo-transferrin, thus providing an invaluable tool for future biodistribution and pharmacokinetic studies of ß-IDACYDin vivo, prerequisites for the development of therapeutic protocols.

A guanidino-γ-cyclodextrin superdimer generates a twin receptor for phosphate dimers assembled by anti-electrostatic hydrogen bonds.

Octakis-6-guadinidino-γ-cyclodextrin (gguan) hydrochloride in the presence of phosphates crystallises from aqueous solution in the unprecedented form of a superdimer (dimer-within-a-dimer). The self-assembly exposes four circular octa-guanidinium regions that bind and stabilise discrete H-bonded phosphate anion dimers. The small (∼2 nm) gguan-phosphate assembly is preorganised and stable in aqueous solution, as demonstrated by DLS and NMR experiments.

Increased antibiotic efficacy and noninvasive monitoring of Staphylococcus epidermidis biofilms using per-cysteamine-substituted γ-cyclodextrin - A delivery effect validated by fluorescence microscopy.

Limited and poor delivery of antibiotics is cited as one reason for the difficulty in treating antibiotic-resistant biofilms associated with chronic infections. We investigate the effectiveness of a positively charged, single isomer cyclodextrin derivative, octakis[6-(2-aminoethylthio)-6-deoxy]-γ-CD (γCys) to improve the delivery of antibiotics to biofilms. Using multiphoton laser scanning microscopy complemented with super-resolution fluorescence microscopy, we showed that γCys tagged with fluorescein (FITC) is uniformly distributed throughout live S. epidermidis biofilm cultures in vitro and results suggest it is localized extracellularly in the biofilm matrix. NMR spectroscopic data in aqueous solution confirm that γCys forms inclusion complexes with both the antibiotics oxacillin and rifampicin. Efficacy of γCys/antibiotic (oxacillin and rifampicin) was measured in the biofilms. While treatment with γCys/oxacillin had little improvement over oxacillin alone, γCys/rifampicin reduced the biofilm viability to background levels demonstrating a remarkable improvement over rifampicin alone. The strong synergistic effect for γCys/rifampicin is at this stage not clearly understood, but plausible explanations are related to increased solubility of rifampicin upon complexation and/or synergistic interference with components of the biofilm. The results demonstrate that designed cyclodextrin nanocarriers, like γCys, efficiently deliver suitable antibiotics to biofilms and that fluorescence microscopy offers a novel approach for mechanistic investigations.