Amphiphilic tricationic Zn(II)phthalocyanine provides effective photodynamic action to eradicate broad-spectrum microorganisms

摘要

A novel tricationic Zn(II)phthalocyanine derivative, (NCH3)3 ZnPc~(3+) , was synthesized by ring expansion reaction of boron(III) [2,9(10),16(17)-trinitrosubphthalocyaninato]chloride. First, the reaction of this subphthalocyanine with 2,3-naphthalenedi- carbonitrile and Zn(CH 3 COO) 2 catalyzed by 8-diazabicyclo[5.4.0]undec-7-ene was used to obtain the A 3 B-type nitroph- thalocyanine. After reduction of nitro groups with Na 2 S and exhaustive methylation of amino groups, (NCH3)3 ZnPc~(3+) was formed in good yields. In addition, the tetracationic analog (NCH3)4 ZnPc~(4+) was synthesized to compare their properties. The absorption and fluorescence spectra showed the Q-bands and the red emission, respectively, which are characteristic of the Zn(II)phthalocyanine derivatives in N,N-dimethylformamide. Furthermore, photodynamic activity sensitized by these compounds was studied in the presence of different molecular probes to sense the formation of reactive oxygen species. (NCH3)3 ZnPc~(3+) efficiently produced singlet molecular oxygen and also it sensitized the formation of superoxide anion radi- cal in the presence of NADH, while the photodynamic activity of (NCH3)4 ZnPc~(4+) was very poor, possibly due to the partial formation of aggregates. Furthermore, the decomposition of L-tryptophan induced by (NCH3)3 ZnPc~(3+) was mainly medi- ated by a type II mechanism. Antimicrobial photodynamic inactivation sensitized by these phthalocyanines was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans, as representative microbial cells. In cell suspensions, (NCH3)3 ZnPc~(3+) was rapidly bound to microbial cells, showing bioimages with red fluorescence emission. After 5 min of irradiation with visible light, (NCH3)3 ZnPc~(3+) was able to completely eliminate S. aureus, E. coli and C. albicans, using 1.0, 2.5 and 5.0 μM phthalocyanine, respectively. In contrast, a low photoinactivation activity was found with (NCH3)4 ZnPc~(4+) as a photosensitizer. Therefore, the amphiphilic tricationic phthalocyanine (NCH3)3 ZnPc~(3+) is a promising photosensitizing structure for application as a broad-spectrum antimicrobial phototherapeutic agent.