Selenophene-Modified Boron Dipyrromethene-Based Photosensitizers Exhibit Photodynamic Inhibition on a Broad Range of Bacteria.

Microorganisms are crucial for human survival in view of both mutualistic and pathogen interactions. The control of the balance could be achieved by use of the antibiotics. There is a continuous arms race that exists between the pathogen and the antibiotics. The emergence of multidrug-resistant (MDR) bacteria threatens health even for insignificant injuries. However, the discovery of new antibiotics is not a fast process, and the healthcare system will suffer if the evolution of MDR lingers in its current frequency. The cationic photosensitizers (PSs) provide a unique approach to develop novel, light-inducible antimicrobial drugs. Here, we examine the antimicrobial activity of innovative selenophene-modified boron dipyrromethene (BODIPY)-based PSs on a variety of Gram (+) and Gram (-) bacteria. The candidates demonstrate a level of confidence in both light-dependent and independent inhibition of bacterial growth. Among them, selenophene conjugated PS candidates (BOD-Se and BOD-Se-I) are promising agents to induce photodynamic inhibition (PDI) on all experimented bacteria: E. coli, S. aureus, B. cereus, and P. aeruginosa. Further characterizations revealed that photocleavage ability on DNA molecules could be potentially advantageous over extracellular DNA possessing biofilm-forming bacteria such as B. cereus and P. aeruginosa. Microscopy analysis with fluorescent BOD-H confirmed the colocalization on GFP expressing E. coli.

Balanced Intersystem Crossing in Iodinated Silicon-Fluoresceins Allows New Class of Red Shifted Theranostic Agents.

Iodination of the silicon-fluorescein core revealed a new class of highly cytotoxic, red-shifted and water-soluble photosensitizer (SF-I) which is also fairly emissive to serve as a theranostic agent. Singlet oxygen generation capacity of SF-I was evaluated chemically, and up to 45% singlet oxygen quantum yield was reported in aqueous solutions. SF-I was further tested in triple negative breast (MDA MB-231) and colon (HCT-116) cancer cell lines, which are known to have limited chemotherapy options as well as very poor prognosis. SF-I induced efficient singlet oxygen generation and consequent photocytotoxicity in both cell lines upon light irradiation with a negligible dark toxicity while allowing cell imaging at the same time. SF-I marks the first ever example of a silicon xanthene-based photosensitizer and holds a lot of promise as a small-molecule-based theranostic scaffold.

Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells.

Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher 1 O2 generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32 % overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors.

Synthesis of N-Bridged Pyrido[4,3-d]pyrimidines and Self-Assembly into Twin Rosette Cages and Nanotubes in Organic Media.

Two N-bridged pyrido[4,3-d]pyrimidine derivatives were synthesized toward realization of a self-assembled bis-rosette cage, in organic media. Starting from commercially available malononitrile dimer and dimethyl 5-aminoisophthalate, the target molecules were synthesized in 11 steps using a convergent approach. The final bridged compounds were characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The hierarchical self-assembly of the nanocages into rosette nanotubes and nanobundles was established by electron microscopy and molecular modelling studies.