Borinic acids as hydrogen peroxide-responsive probes. Design and new synthetic methodologies. – BoriProbe

This proposal targets the development of innovative probes for hydrogen-peroxyde (H2O2) detection.
Reactive Oxygen Species (ROS) such as H2O2 are involved at low concentration in cell signaling, but at higher concentrations they are responsible for oxidative stress, causing lesions associated with aging, cancer, and neurodegenerative diseases such as Alzheimer’s or Parkinson’s.
The main objectives of this project will be the design of efficient synthetic strategies towards new types of specific and sensitive molecular probes for imaging one of the ROS, hydrogen peroxide (H2O2). We will also evaluate the kinetics, physicochemical, photochemical and biological properties of these probes.
The major challenge in this field is to significantly improve the reactivity of current, boronic acid-based probes.
In this context, we envisioned that borinic acids could be a solution. Due to stereoelectronic effects, borinic acids could be more prone to oxidation compared to their boronic acid analogs. In preliminary studies, we have confirmed this hypothesis using newly synthetized non-symmetrical borinic acids, as well as a model fluorescent probe based on a coumarin scaffold.
However, access to arylborinic acid is in general poorly exemplified in the literature, compared to their boronic acid analogs, partially because they suffer from difficult and challenging synthetic access and purification. Most synthetic approaches are similar which limits the scope and the available chemical space with this scaffold
Thus, this project aims at developing borinic acid chemistry and investigating the use of these groups as triggers for probe activation via the synthesis and full characterization of new borinic acid-based probes, and their validation in cellular models. In vivo validation, as well as further applications to smart drug release and theranostics, do not fall within the range of this project but might be of strong interest as potential outcomes in the future.