Friday, April 4, 2025
4/4/2025
Cationic Carbone-Boracycles as Far-Red and Near-Infrared Photoactive Agents - Project Summary Photoactive agent-based theranostics play an important role in the development of innovative approaches for tumor diagnosis and treatment. Society stands to benefit greatly if methods to detect and treat cancers at an early stage are enhanced, which often depend on our ability to effectively visualize and send localized energy to specifics regions of the body. The central theme of the proposed project involves the rational design, synthesis, and molecular and photophysical characterization of cationic carbone-boracycles as far-red and near-infrared (NIR) photoactive agents. The innovative approach involves utilizing carbone ligands as both σ- and π-donors, which impart remarkable stability to cationic boron centers, ensuring the molecules remain stable in biologically-relevant conditions and offering advantages for targeting and treating tumors. Various boracycles are being targeted with unique ring fusions and sizes such that they have appropriate electronic structures to make them suitable for potential applications in phototheranostics. Specific aim #1 focuses on the synthesis and functionalization of cationic boron heterocycles that emit in the near-infrared region, enhancing fluorescence/luminescence imaging capabilities and facilitating photodynamic therapy (PDT). This includes the synthesis of stable versions of conjugated cationic boron, nitrogen-acene derivatives and non-conjugated anthanthrene bis-cations. Specific aim #2, which is independent of aim #1, focuses on the development of non-emissive carbone-azulenes as biocompatible NIR absorbers. The hypothesis is that the addition of the azulene unit will permit maximum absorption, such that all of the absorbed light energy will be transformed into heat for potential applications in photothermal therapy (PTT). In aims #1 and #2 the synthesis will be guided by computational chemistry and the photophysical data will be simulated to obtain detailed information regarding the electronic transitions that result in the optical properties. Specific aim #3 involves sophisticated optical measurements to compare the photophysical properties of the newly synthesized compounds, especially those that have undergone nanoencapsulation. These measurements include including absorption and emission, quantum yield measurements, and fluorescence lifetimes. The goal is to screen for compounds with suitable energy properties for biological screening at the MIT Broad Institute. This interdisciplinary approach, combining main-group chemistry, photophysics, and photobiology, highlights the project's innovative nature and potential for groundbreaking advancements in bioimaging and cancer therapy.
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