Refining antimicrobial photodynamic therapy: effect of charge distribution and central metal ion in fluorinated porphyrins on effective control of planktonic and biofilm bacterial forms.

Antibiotic resistance represents a pressing global health challenge, now acknowledged as a critical concern within the framework of One Health. Photodynamic inactivation of microorganisms (PDI) offers an attractive, non-invasive approach known for its flexibility, independence from microbial resistance patterns, broad-spectrum efficacy, and minimal risk of inducing resistance. Various photosensitizers, including porphyrin derivatives have been explored for pathogen eradication. In this context, we present the synthesis, spectroscopic and photophysical characteristics as well as antimicrobial properties of a palladium(II)-porphyrin derivative (PdF2POH), along with its zinc(II)- and free-base counterparts (ZnF2POH and F2POH, respectively). Our findings reveal that the palladium(II)-porphyrin complex can be classified as an excellent generator of reactive oxygen species (ROS), encompassing both singlet oxygen (Φ△ = 0.93) and oxygen-centered radicals. The ability of photosensitizers to generate ROS was assessed using a variety of direct (luminescence measurements) and indirect techniques, including specific fluorescent probes both in solution and in microorganisms during the PDI procedure. We investigated the PDI efficacy of F2POH, ZnF2POH, and PdF2POH against both Gram-negative and Gram-positive bacteria. All tested compounds proved high activity against Gram-positive species, with PdF2POH exhibiting superior efficacy, leading to up to a 6-log reduction in S. aureus viability. Notably, PdF2POH-mediated PDI displayed remarkable effectiveness against S. aureus biofilm, a challenging target due to its complex structure and increased resistance to conventional treatments. Furthermore, our results show that PDI with PdF2POH is more selective for bacterial than for mammalian cells, particularly at lower light doses (up to 5 J/cm2 of blue light illumination). This enhanced efficacy of PdF2POH-mediated PDI as compared to ZnF2POH and F2POH can be attributed to more pronounced ROS generation by palladium derivative via both types of photochemical mechanisms (high yields of singlet oxygen generation as well as oxygen-centered radicals). Additionally, PDI proved effective in eliminating bacteria within S. aureus-infected human keratinocytes, inhibiting infection progression while preserving the viability and integrity of infected HaCaT cells. These findings underscore the potential of metalloporphyrins, particularly the Pd(II)-porphyrin complex, as promising photosensitizers for PDI in various bacterial infections, warranting further investigation in advanced infection models.

Efficient Synthesis of Novel 1,3,4-Oxadiazoles Bearing a 4-N,N-Dimethylaminoquinazoline Scaffold via Palladium-Catalyzed Suzuki Cross-Coupling Reactions.

Two series of novel (symmetrical and unsymmetrical) quinazolinylphenyl-1,3,4-oxadiazole derivatives were synthesized using palladium-catalyzed Suzuki cross-coupling reactions. The presented synthetic methodology is based on the use of bromine-substituted 2-phenyl-4-N,N-dimethylaminoquinazolines and either a boronic acid pinacol ester or a diboronic acid bis(pinacol) ester of 2,5-diphenyl-1,3,4-oxadiazole. The reactions are conducted in a two-phase solvent system in the presence of catalytic amounts of [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), sodium carbonate, and tetrabutylammonium bromide, which plays the role of a phase-transfer catalyst. The luminescence properties of the obtained compounds are discussed in the context of applying these compounds in optoelectronics. Specifically, two highly-conjugated final products: N,N-dimethyl-2-phenyl-6-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4-amine (8f) and 6,6'-(4,4'-(1,3,4-oxadiazole-2,5-diyl)bis(4,1-phenylene))bis(N,N-dimethylquinazolin-4-amine (9f), which contain a 1,3,4-oxadiazole moiety connected to a quinazoline ring by a 1,4-phenylene linker at the 6 position, exhibit strong fluorescence emission and high quantum yields.