# BODIPY-Based Nanomaterials--Sensing and Biomedical Applications
## 2 Metallic Nanoparticles@BODIPY
### The Relationship of the Chemical Structure on Physicochemical Properties and Activity of BODIPY  
Taking into consideration the results of studies reviewed in this paper, one can conclude some relationships and impacts of the chemical structure of BODIPY derivatives on their medical use as well as physicochemical properties, including fluorescence and binding abilities. The uniqueness of BODIPY is the result of its chemical structure, where a connection of two pyrrole rings with a methylene bridge, also called the \"_meso_\" position is present. In addition, two pyrrole nitrogen atoms can also be linked with a difluoroboron bridge that forms the third ring. Moreover, BODIPY dyes are often symmetrically functionalized with various functional groups within the pyrrole rings or at the _meso_ position to achieve the desired properties.  
The fluorescence emission ability of BODIPY dyes is analyzed in sensing studies. BODIPY derivatives substituted with the phenyl rings in _meso_ position are most often used as fluorophores. The replacement of phenyl with the pentafluorophenyl group significantly increases the fluorescence [59]. The effect is comparable when the BODIPY pyrrole rings are substituted in positions 3 or 5 with styryl groups [64; 65]. However, the amide linkers attached to the pyrrole BODIPY rings can sometimes hamper the fluorescence through the PET phenomenon [60]. BODIPY's peripheral substitution also brings other benefits. In various studies, the BODIPY dyes have been attached to the coated or uncoated metallic nanoparticles by phenyl groups in their _meso_ position [60; 62] or by styryl/alkyl linkers at pyrrole rings [61; 65; 73]. It was also demonstrated that the heteroaromatic pyridyl substituent in the BODIPY periphery allows the dye to be attached directly to the nanoparticle surface [66]. What is more, the phenyl group substituted in _meso_ position can be protonated, which also changes the fluorescence properties under the influence of different pH [67].  
BODIPY dyes with bulky peripheral substituents have been applied in cancer diagnostics [69]. It was possible when the 3,5-dimethyl groups at pyrrole rings were substituted with aromatic ones. It was found that such a change in the chemical structure improves the solubility in common organic solvents used in the preparation of BODIPY/metallic nanoparticle hybrid nanosystems and allows the direct attachment of dyes to the surface of gold nanoparticles. In cancer diagnostics, the fluorophore moiety consists mainly of _meso_-methyl derivatives of dipyrromethene instead of phenyl-substituted ones [70; 72]. Substitution of the 4 th position of the BODIPY pyrrole rings with the halogen atom (mostly iodide) results in an increase of singlet oxygen generation after irradiation of the system. The phenomenon explaining such an effect is commonly called the \"heavy atom effect\". This kind of modification is of great importance for further applications of BODIPY dyes in photodynamic therapy against cancer cells or bacteria strains. The iodide-substituted derivatives reveal no fluorescence ability but instead high efficiency of singlet oxygen production when irradiated with light at proper wavelengths. In addition, the absorbance of dyes is red-shifted in comparison to unsubstituted derivatives. BODIPY dyes representing such structures have been researched in various in vitro cytotoxicity studies against, i.e., human breast adenocarcinoma cells, mouse melanoma, human colon adenocarcinoma, and against _P. aeruginosa_ and _S. aureus_[75; 76; 80; 81; 82].  
A schematic representation of the effects of individual BODIPY structural elements on their physicochemical and spectral properties is shown in Figure 26.