Tetrapyrrolic metal complexes and functional materials in antimicrobial photodynamic therapy: From molecular targeting and excited-state dynamics to clinical translation

Photodynamic inactivation of microorganisms (PDI) is increasingly viewed not only as a light-triggered antimicrobial modality, but as a coordination chemistry-driven approach in which molecular structure, metal coordination, microbial targeting, excited-state dynamics, and irradiation conditions must be considered together. This Review examines tetrapyrrolic metal complexes and functional materials for PDI, with emphasis on heme-mimetic porphyrinoids, siderophore-guided delivery strategies, and hybrid photodynamic platforms. Rather than merely cataloguing photosensitizers according to structure, the discussion is organized around factors that determine biological performance, including interaction with microbial metal-acquisition pathways, bacterial uptake, metal-dependent photophysics, aggregation control, charge distribution, lipophilicity, and reactive oxygen species (ROS) generation. A central theme is the distinction between receptor-mediated uptake and nonspecific membrane association. Heme-mimetic and siderophore-based approaches are evaluated as mechanistically distinct routes to bacterial targeting that impose different requirements on coordination geometry, ligand topology, and intracellular processing. Gallium porphyrinoids are discussed as iron-deceptive agents that combine heme-pathway recognition with disruption of iron-dependent metabolism, whereas zinc porphyrinoids are treated more cautiously as partial heme-like architectures whose activity often reflects membrane interactions, aggregation state, and favorable photophysics rather than experimentally validated active transport. The Review further examines how metal selection, molecular organization, functional materials, and adjuvant strategies influence photochemical pathways, ROS chemistry, and translational potential. We argue that clinically relevant antimicrobial PDT will depend less on identifying universally superior photosensitizers than on matching coordination design, formulation, light delivery, and material architecture to specific infection environments. This framework provides a mechanistic basis for the development and clinical translation of antimicrobial photodynamic systems.