However, other studies have reported contradictory results: Merchat et al. (1996) concluded that the number of charges does not affect the activity of the PS against both bacterial Gram types [23]. Caminos et al. (2006) showed that the photodynamic activity of a tricationic CDK assay porphyrin combined with trifluoromethyl group was higher for an E. coli strain than the one observed with the corresponding tetracationic porphyrin [24]. Banfi et al. (2006) also concluded that a dicationic porphyrin was more efficient than the corresponding tetracationic derivatives against Gram (+) Staphylococcus aureus and Gram (-) E. coli and Pseudomonas aeruginosa [21]. However, our results suggest

that the number of positive charges affects the PI process. Two of the tricationic PS are the GS-7977 most efficient ones, although they have quite different partition coefficients. Comparing the photoinactivation rate of Tri-Py+-Me-PF and Tri-Py+-Me-CO2Me with the photoinactivation rate of tetracationic Tetra-Py+-Me, the results suggest that a high number of positive charges and a hydrophilic character can decrease the PI

efficiency, as shown by other studies (Jori, personal communication). On the other hand, the meso-substituent groups can play an important role on bacterial PI process. In fact, it has Fosbretabulin purchase been shown that positive charges combined with highly lipophilic groups might increase the amphiphilic character of the PS, enhancing its

affinity to bacteria [25, 27], and consequently increasing the photocytotoxic activity [24]. However, in the present study no direct correlation could be established between the PI pattern and the partition coefficients of the PS. Probably, other interactions, not accounted by log PB/W, such as the combined effect of the cationic charge and the amphiphilic character of the macrocycle is responsible for the photodynamic efficiency [19, 20, 34]. In our case, the results obtained with Tri-Py+-Me-PF and Tri-Py+-Me-CO2Me against E. coli were significantly different (p = Carbachol 0.000, ANOVA) from those obtained with the other tricationic porphyrin Tri-Py+-Me-CO2H. Tri-Py+-Me-PF, and Tri-Py+-Me-CO2Me caused a reduction below the detectable limits (~7 log) after a light dose of 21.6 J cm-2 on E. coli while Tri-Py+-Me-CO2H produced only a ~5 log survivors reduction after 64.8 J cm-2. A possible explanation for this behaviour can be the presence of the acid group in the Tri-Py+-Me-CO2H porphyrin. This acid group can be ionized when dissolved in PBS buffer and the global charge of the porphyrin decreases and, consequently, the efficiency of inactivation decreases. On the other hand, the Tri-Py+-Me-CO2Me, that has the acid group protected, shows a significantly higher (p < 0.000, ANOVA) inactivation rate for E. coli than Tri-Py+-Me-CO2H.