A newly developed series of amphiphilic and cationic phthalocyanines was designed to determine how quaternization, peripheral substituents, and metal coordination govern photodynamic and sonodynamic performance. All derivatives displayed characteristic Q-band absorption between 673 and 705 nm and fluorescence quantum yields spanning Φf = 0.01–0.26. Quaternization markedly increased emission in Zn(II) complexes (Φf: 0.02 → 0.17), while reducing it in metal-free and In(III) analogues. Singlet oxygen formation was efficient across the series, with ΦΔ = 0.63 for both InPc and QInPc and a twofold increase for ZnPc upon quaternization (ΦΔ: 0.27 → 0.51). The unsubstituted ZnPc was used as a reference. Photodecomposition quantum yields (10⁻⁵–10⁻⁴) indicated that quaternization enhanced photostability for metal-free and Zn(II) derivatives, while minimally affecting the In(III) complex.
The quaternized phthalocyanines demonstrated high antimicrobial potency. In methicillin-resistant Staphylococcus aureus (MRSA) and ESBL-producing Escherichia coli, inactivation reached 4.6 logs, while Gram-negative strains showed 4.5-log reductions. Activity against fluconazole-resistant Candida albicans demonstrated the following: QH₂Pc, QInPc, and QZnPc achieved 3.2-log reductions.
Sonodynamic evaluation confirmed strong ROS formation. Non-quaternized sensitizers accelerated DPBF decay around 4.5-fold, with ZnPc showing the fastest kinetics (k = 0.152 min⁻¹; t₀.₅ = 4.55 min). Quaternized derivatives remained sonodynamically active; QZnPc has the potential to generate ROS efficiently (k = 0.130 min⁻¹) and displayed improved ultrasound stability (t₀.₅ = 59.7 min vs. 11.2 min for ZnPc).
These results establish this family of amphiphilic phthalocyanines as potent, multimodal sensitizers, capable of achieving high-log photodynamic reduction and showing potential for strong sonodynamic ROS output. Their performance, together with clear structure–property relationships, highlights their promise for next-generation antimicrobial therapy.
