Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT

Abstract

This minireview is devoted to honoring the memory of Dr. Thomas Dougherty, a pioneer of modern photodynamic therapy (PDT). It compiles the most important inputs made by our research group since 2012 in the development of new photosensitizers based on BODIPY chromophore which, thanks to the rich BODIPY chemistry, allows a finely tuned design of the photophysical properties of this family of dyes to serve as efficient photosensitizers for the generation of singlet oxygen. These two factors, photophysical tuning and workable chemistry, have turned BODIPY chromophore as one of the most promising dyes for the development of improved photosensitizers for PDT. In this line, this minireview is mainly related to the establishment of chemical methods and structural designs for enabling efficient singlet oxygen generation in BODIPYs. The approaches include the incorporation of heavy atoms, such as halogens (iodine or bromine) in different number and positions on the BODIPY scaffold, and also transition metal atoms, by their complexation with Ir(III) center, for instance. On the other hand, low‐toxicity approaches, without involving heavy metals, have been developed by preparing several orthogonal BODIPY dimers with different substitution patterns. The advantages and drawbacks of all these diverse molecular designs based on BODIPY structural framework are described.

BODIPY‐Based Photosensitizers as Potential Anticancer and Antibacterial Agents: Role of the Positive Charge and the Heavy Atom Effect

“…The molecule in the triplet state can interact with the molecular oxygen in the triplet state, leading to the formation of very reactive singlet oxygen species. [4,17] In vitro photodynamic anticancer activity…”

“…Thus, the derivatives with heavy atoms, usually at 2 and 6 positions of the BODIPY core, form a long‐lived, high‐yield triplet excited state for an efficient singlet oxygen production. Recently, several heavy atom‐free BODIPY dyes with enhanced intersystem crossing and efficient 1 O 2 generation have also been prepared [16–19] …”

“…Recently, several heavy atom-free BODIPY dyes with enhanced intersystem crossing and efficient 1 O 2 generation have also been prepared. [16][17][18][19] High lipophilicity of BODIPYs, resulting in low solubility in aqueous media, can be overcome by the introduction of some hydrophilic moieties to the structure. The ionizable substituents, including ammonium groups and acid residues such as carboxylic, phosphonic, or sulfonic acids, are commonly used to increase the water-solubility.…”

Carbon Nanodots in Photodynamic Antimicrobial Therapy: A Review

“…Alternatives such as photothermal therapies have promise but do not share the spatial resolution possible with APDT [ 20 ]. Accordingly, an emphasis has been placed on optimizing the properties of photosensitizing molecules for antimicrobial applications, particularly in tuning the photophysical properties of those agents [ 21 ] for maximized ROS quantum yields [ 22 , 23 ]. By optimizing these characteristics, it is possible to improve the efficiency of light utilization by the photosensitizer, and even to select for activation wavelengths that are themselves not inherently harmful, unlike short-wavelength ultraviolet light (UV-C) [ 24 ].…”

Alkynyl N-BODIPYs as Reactive Intermediates for the Development of Dyes for Biophotonics

“…However, the development of photonic systems that can be efficiently applied to biophotonics is not an easy task since many requisites need to be fulfilled within the same system: good photonic properties (high fluorescence or/and singlet oxygen generation, photostability), specificity (cell permeability and organelle recognition), biocompatibility (solubility, low dark toxicity), etc. In this context, monochromophoric organic dyes have advantages related to accessibility and biocompatibility and, especially, the possibility of modulating key properties by chemical modifications [8][9][10][11].…”