Two new zinc phthalocyanine derivatives bearing four 3,5-di-tert-butyl-4-hydroxy-phenyl (ZnPc1) and 3,5-dimethylphenoxy (ZnPc2) have been synthesized and proved by elemental analyses and UV-vis, H-1 NMR, FTIR and MALDI-TOF mass spectra as spectroscopic determination. Thermal stabilities of these neutral Zn-phthalocyanines were performed by thermal gravimetric analysis and, significantly, were found stable up to 373 degrees C for ZnPc1 and 550 degrees C for ZnPc2. In addition, the photostability of the sensitizers was quite successful within 240 min. Furthermore, photodynamic therapy has been investigated using these neutral phthalocyanines. Singlet oxygen generation capacities of ZnPc1 and ZnPc2 were studied using 1,3-diphenyl-iso-benzofuran (50.0 mu M) as a selective singlet oxygen trap in DMSO and both of them demonstrated very high singlet oxygen generation capacity. Photodynamic therapy is of considerable interest for its potential its an antimicrobial therapy on the grounds that the photodynamic activity of these compounds was tested against a Gram-negative bacteria, Escherichia coli and a Gram-positive bacteria, Staphylococcus aureus. Suspensions of the microorganisms were irradiated for 240 min in the presence of ZnPc1 (with hydrophilic group) and ZnPc2 phthalocyanines. In order to simulate solar radiation, we used a 750 W xenon lamp. Minimum photosensitizer concentration was used as 0.1 mg.10 mL(-1) in 1% dimethylsulfoxide/phosphate buffer saline solution (DMSO/PBS). Moreover, the photostability of these compounds has been investigated and the effect of the amount of DMSO tested against selected bacteria. In the dark, with and without Pes, bacterial inactivation did not occur. Bacterial inactivation by light with ZnPc1 was observed in response to Gram-negative bacteria E. coli and Gram-positive bacteria S. aureus, whereas the photoinactivation studies with ZnPc2 have revealed that the lack of its activity is due to its poor affinity for either of the organisms. These results suggest that a neutral amphiphilic photosensitizer may be easily used in an application concerning photoinactivation of bacterial cells as well as ionic photosensitizers. Copyright (c) 2008 Society of Porphyrins & Phthalocyanines.