Phthalocyanines (PCs) are of great interest as second-generation photosensitizers for antimicrobial photodynamic therapy (aPDT). They have strong absorption in the red and near-infrared region, high singlet oxygen quantum yield, and excellent photochemical stability. Although there are many experimental studies on the antimicrobial activity of PCs, the relationship between their molecular structure and their quantum-chemical properties is not yet fully understood. In this review, the influence of the molecular geometry and of stereochemical modifications of phthalocyanine derivatives on their optimized conformational energy and on their permanent dipole moment is investigated by means of density functional theory (DFT) calculations. Non-planar distortions, peripheral substitutions, and asymmetric functionalizations are focus points of the study. The influence of structural asymmetry on the charge distribution and molecular stability is especially discussed. The results show that an increased structural asymmetry leads to an increase in the dipole moment of the PC by a redistribution of the electron density, to a decrease in the conformational strain, and to an increase of the energetic stability. The quantum-chemical calculated descriptors like dipole moment, conformational energy, aggregation, membrane affinity, solubility, and the interactions with the bacterial cell envelope allow new insights into the photodynamic efficiency, into the aggregation, and into the antimicrobial activity of PCs. The strategy of optimization of the dipole moment and of the conformational energy leads to photosensitizers with improved photodynamic efficiency, low aggregation, and high antimicrobial activity. The results of this study can be used as predictive quantum-chemical descriptors for the design of new PC-based antimicrobial agents for the treatment of periodontal disease and of other oral biofilm-associated infections.
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