Design of Photosensitizers based on a Singlet Oxygen Reservoir for Antibacterial Applications – CaROS

The project is divided into three parts:
1) Synthetic route: Preparation and characterization of new photosensitizers through the development of innovative synthetic methodologies.
2) Analytical investigations by NMR spectroscopy and determination of the characteristics of the prepared photosensitizers to select the most relevant compounds for biological tests.
3) Antibacterial test of the most relevant photosensitizers.

Until now, the results described below have been obtained by our consortium:
1) Development of an innovative methodology for the preparation of phenalenone-based photosensitizers.
2) Design of new heterocycles able to capture, store and release singlet oxygen.
3) Synthesis of bifunctional photosensitizers having a unit capable of producing singlet oxygen under illumination (phenalenone) and a module able to capture and store singlet oxygen under illumination which will be released by thermolysis in the dark.

In view of the results, the future works are shown below:
1) Applications of the photosensitizers to antibacterial photodynamic therapy under continuous or intermittent illumination.
2) Development of multiple singlet oxygen traps.

Unusual Oxidative Dealkylation Strategy toward Functionalized Phenalenones as Singlet Oxygen Photosensitizers and Photophysical Studies. P. De Bonfils, E. Verron, C. Sandoval-Altamirano, P. Jaque, X. Moreau, G. Gunther, P. Nun, V. Coeffard,* J. Org. Chem. 2020, 85, 10603-10616 (Selected for the Front Cover).

Singlet oxygen is an excited state of molecular oxygen which has found valuable applications in synthetic chemistry, materials science and photomedicine such as antibacterial photodynamic therapy (APDT). Photosensitizers containing a molecular architecture able to trap, store and release singlet oxygen are highly expected to overcome the challenge of oxygen depletion in APDT. The aim of CaROS project is to prepare via an innovative synthetic route a new family of photosensitizers based on reversible singlet oxygen binding. Photophysical and antibacterial studies will be performed to determine the therapeutic potential of the newly formed photosensitizers. The project is expected to be facilitated by preliminary results and should lead to ground-breaking results both in synthetic chemistry and in the development of new agents aiming at mitigating the threat of antimicrobial resistance.