Olivier Maury

The rational design of activatable photosensitizers (aPSs) uncaged by specific disease biomarkers is currently booming due to their positive attributes to achieve targeted photodynamic therapy (PDT). In this context, we present here the synthesis and detailed photophysical characterization of a novel class of hetero‐rosamine dyes bearing sulfur or selenium as bridging heavy atom and 4‐pyridyl meso ‐substituent as optically tunable group. The main feature of such photoactive platforms is the spectacular change of their spectral properties depending on the caging/decaging status of their 4‐pyridyl moiety (cationic pyridinium vs . neutral pyridine). The preparation of two alkaline phosphatase (ALP)‐responsive probes (named Valkyrie probes) was achieved through formal N ‐quaternarization with 4‐phosphoryloxybenzyl, the traditional recognition moiety for this important diagnostic enzyme. Bio‐analytical validations including fluorescence/singlet oxygen phosphorescence enzyme assays and RP‐HPLC‐fluorescence/‐MS analyses have enabled us to demonstrate the viability and effectiveness of this novel photosensitizer activation strategy. Since sulfur‐containing Valkyrie probe also retains high fluorogenicity in the orange‐red spectral range, this study highlights meso ‐pyridyl‐substituted S‐pyronin scaffolds as valuable candidates for the rapid construction of molecular phototheranostic platforms suitable for combined fluorescence diagnosis and PDT.

This study presents the synthesis, the spectroscopic and electrochemical properties of new bis‐ and tetra‐substituted azaboron‐dipyrromethene (aza‐BODIPY) dyes substituted by different electron donating groups connected to the aza‐BODIPY core through a thiophene unit. In line with theoretical calculations, experimental measurements point out the positive impact of the thiophene group that behave as a secondary donor group leading to an enhancement of the intramolecular charge transfer process in comparison to previously reported aza‐BODIPY dyes. This heterocycle has also been found to tune the oxidative potential and to stabilize the electro‐generated species.