Understanding the action mechanisms of self-assembled photosensitizers is very important to determine the requirements that constructing monomers should fulfill to obtain nanostructures with the desired function. Here, the synthesis, supramolecular aggregation tendency, photophysical properties, and antimicrobial photodynamic activity of low-symmetry metal-free phthalocyanine are carefully examined and compared with its metalated counterpart. When exposed to the media with different pH values, striking differences in the self-assembly of these two derivatives were observed. Equilibria between active and inactive forms of this unique supramolecular system were shifted upon change of the microenvironment, influencing its biological activity against Gram-positive and Gram-negative bacteria in planktonic and biofilm states. DFT calculations helped to explain possible differences in the aggregate formation, showing that metal-ligand interaction is a key process behind the higher activity of the metalated derivative. These results point out the importance of intermolecular interactions between photosensitizers, which is essential to guide the design of self-assembled phototheranostic agents with improved performance.
Keywords: antimicrobial photodynamic therapy; bacterial biofilm; pH-responsiveness; phthalocyanine; self-assembly.