Recent Advances in Zinc(II)-Complexes for Antibacterial Photodynamic Therapy.

Abstract

Antimicrobial resistance (AMR) has emerged as a global health crisis, underlining the need for alternative therapeutic strategies beyond conventional antibiotics. In this regard, antibacterial photodynamic therapy (aPDT) has gained increasing attention as a non-invasive approach that utilizes light-activated photosensitizers to generate targeted reactive oxygen species (ROS), leading to rapid bacterial inactivation with minimal resistance development. Among various photosensitizers, Zn(II) complexes have shown promising potential due to their favorable biocompatibility, photophysical properties, and tunable coordination chemistry. Unlike heavy-metal photosensitizers, Zn(II) complexes owe their photophysical performance to extended macrocyclic π-systems rather than metal spin-orbit coupling, making them uniquely suited for biocompatible aPDT. This review critically examines recent advances in Zn(II)-based complexes as photosensitizers, including phthalocyanines, porphyrins, chlorins, and curcumin systems, highlighting structure-activity relationships (SARs), ROS generation mechanisms, and antibacterial efficacy against both Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. Key design strategies such as cationic functionalization, polymer conjugation, and hybridization with antimicrobial peptides are discussed. Additionally, current limitations, including aggregation, limited penetration, translational challenges, and future perspectives for clinical translation are also outlined. This review aims to provide a comprehensive framework for the rational design of next-generation Zn(II)-photosensitizers for effective aPDT.