Photodynamic　antimicrobial　chemotherapy　(PACT)　uses　non-traditional　mechanisms　(free　radicals)　and　is　a　highly　advocated　method　with　promise　of　inactivating　drug-resistance　bacteria　for　local　infections.　However,　there　is　no　related　drug　used　in　clinical　practice　yet.　Therefore,　new　photosensitizers　for　PACT　are　under　active　development.　Here,　we　report　the　synthesis　of　a　series　of　photosensitizers　with　variable　positive　charges　(ZnPc(TAP)4n+,　n = 0,　4,　8,　12)　and　their　inactivation　against　Gram-positive　(Staphylococcus　aureus)　and　Gram-negative　(Escherichia　coli)　bacteria.　The　binding　kinetics　of　ZnPc(TAP)4n+　to　bacteria　were　measured　by　flow　cytometer.　Reactive　oxygen　species　(ROS)　generation　mechanism　of　the　photosensitizers　was　studied.　The　toxicity　of　these　compounds　to　human　blood　cells　was　also　evaluated.　These　compounds　showed　negligible　toxicity　against　human　erythocytes　but　potent　bactericidal　effects.　The　compound　with　8　positive　charges,　ZnPc(TAP)48+,　turned　out　to　have　the　strongest　antibacterial　effect　among　this　series　of　compounds,　giving　IC50　value　of　59 nM　at　a　light　dosage　of　5 J/cm2　toward　E.　coli.　For　a　multi-resistant　E.　coli　strain,　ZnPc(TAP)48+　decreased　the　bacteria　load　by　1000-fold　at　a　concentration　of　1 μM.　Interestingly,　ZnPc(TAP)412+,　instead　of　ZnPc(TAP)48+,　exhibited　the　highest　amount　of　binding　to　bacteria.　Flow　cytometry　studies　showed　that　all　PSs　have　fast　binding　onto　bacteria,　reaching　saturated　binding　within　5 min.　Mechanistically,　ZnPc(TAP)412+　generated　ROS　primarily　via　Type　I　mechanism,　while　ZnPc(TAP)44+　or　ZnPc(TAP)48+　created　ROS　by　both　type　I　and　type　II　mechanisms.　ZnPc(TAP)4n+　are　highly　potent,　rapid-acting　and　non-toxic　photosensitizers　capable　of　inactivating　bacteria.　©　2017,　Springer-Verlag　Berlin　Heidelberg.