Synthesis And Photodynamic Antimicrobial Chemotherapy Of A Series Of Cationic Zinc Phthalocyanines

Photodynamic antimicrobial chemotherapy(PACT)is one of the promising techniques to address the prevalent challenge of antibiotic resistance.In PACT,photosensitizer(PS)absorbs light with appropriate wavelength and transfers energy to the molecular oxygen,ultimately leading to the generation of reactive oxygen species(ROS)which creates toxicity to the nearby microorganism.Unlike antibiotics,photosensitizers can destroy bacteria efectively at multiple targeting sites through binding to the extracellular or intracellular localizations,thus,inactivate microorganisms without inducing the appearance of drug-resistant pathogens.Structure and property of photosensitizer play a critical role in the effectiveness of PACT.Metallophthalocyanine is an effective photosensitizer but suffers problem of poor aqueous solubility.To improve water solubility and bioavailability of PS,a series of cationic zinc phthalocyanines containing different positive charges(the stoichiometric ratio of ZnPc(TAP)4 and CH3I was 1:4,1:8,1:12 respectively)was synthesized,given the names as Pc-4,Pc-8,Pc-12,and evaluated for PACT efficacy against Gram-positive(S.aureus)and Gram-negative(E.coli)bacteria.These compounds were shown as potent photosensitizers(PSs)against the bacterial strains giving IC50 value up to 59 nM at a light dose of 5 J/cm2.The Pc-8 turned out to be the best PS among this series.Importantly,the PS inactivated effectively a drug-resistant strain of bacteria.In addition,binding kinetics and interaction mechanism of the PSs with bacteria were studied and the PSs showed saturated binding to bacteria within 5 minutes.The ROS producing mechanism of the series was also studied and found to depend on the positive charges.Safety of these PSs to human blood cells was also demonstrated.The results showed this series of positive zinc phthalocyanines are potent photosensitizers to inactivate drug-resistant bacteria.