**2.2 Axially RPy-bonded polycationic Sb-porphyrins**

*The Universe of Escherichia coli*

**Figure 1.**

to O2, which leads to the formation of reactive oxygen such as <sup>1</sup>

absorption band in the visible-light region [8–11].

*Typical structure of porphyrin sensitizer (P type).*

ing cells and bacteria. Preliminary studies on the photodynamic action for biological systems started in the 1930s by PDI of phages using methylene blue [6, 7]. PDI of bacteria has received considerable attention as a methodology leading to the medical application of infection therapy beyond antimicrobial resistance. Among the large variety of photosensitizers developed for PDI over the last 60 years, porphyrins and metalloporphyrins became attractive sensitizers owing to their strong

In the case of porphyrin sensitizers, their solubilities in water are an important characteristic for handling them as aqueous solutions, since porphyrin derivatives, in general, are poorly soluble in water. The most popular method to improve the solubility in water is the introduction of ionic groups to the porphyrin ring. Especially, the introduction of an alkylpyridinium (RPy) group into porphyrins is a useful method to make porphyrins water-soluble [12, 13]. A typical RPy-bonded porphyrin is represented by *meso*-tetra[4-(1-methyl-pyridinium)] porphyrin (TMP). The first application of TMP to PDI was reported by Ben Amor et al. in 1998 [14]. For the last two decades, a variety

We have interested in axially RPy-bonded tricationic P-porphyrins and their PDI activity [22–26]. It is advantageous that the water solubilization is easily achieved through the modification of the axial ligands of P-porphyrins. It is expected that polycationic porphyrins have strong binding affinities to DNA [27–32]. In this chapter, drug resistance of *E. coli* was discussed based on PDI activity of a variety of P- and Sb-porphyrin sensitizers with different number of ionic valence and different hydrophobic character. The typical structure of the porphyrin sensitizer is

of RPy-bonded porphyrins have been prepared and studied for PDI [15–21].

**2.1 Axially RPy-bonded tricationic P-porphyrins: (RPy3)2P(Tpp)3+**

The preparation of tricationic bis[3-(1-alkyl-4-pyridinio)propoxo] tetraphenylporphyrinatophosphorus(V) complex, (RPy3)2P(Tpp)3+ (Tpp = tetraphenylporphyrinato group), was performed as follows [22]. Dichloro(tetraphenylporphyrinato)phosphorus chloride ([Cl2P(Tpp)]Cl [33], 300 mg) was reacted with 3-(4-pyridyl)-1-propanol (5.0 mL) in MeCN (30 mL) at reflux temperature

shown in **Figure 1**, and they are named P-type porphyrin.

**2. Materials and methods**

O2, thereby inactivat-

**122**

Axially RPy-bonded polycationic Sb-porphyrins were prepared using dibromo(tetraphenylporphyrinato)antimony bromide ([Br2Sb(Tpp)]Br) as the starting material [34]. The partial methanolysis of [Br2Sb(Tpp)]Br (1.077 g) was performed in MeOH-MeCN (1:1, 160 mL) in the presence of pyridine (0.75 mL) at 80°C until the Soret band shifted from 427 to 423 nm. Bromo(methoxo)- (tetraphenylporphyrinato)antimony bromide ([MeO(Br)Sb(Tpp)]Br, 520 mg) was formed in 61% yield [35]. An MeCN (20 mL) solution of [Br2Sb(Tpp)]Br (150 mg) and [MeO(Br)Sb(Tpp)]Br (180 mg) was heated with 3-(4-pyridyl)- 1-propanol (3.7 mL) at refluxing temperature for about 24 h until the Soret band


*a Z = charge of the complex.*

*b n = carbon number of the alkyl chain on the Ap.*

*c Molar absorption coefficient for the Soret and the Q bands in MeOH solution.*

*d CW = water solubility in mM. <sup>e</sup>*

*Broadening of UV spectra occurred.*

#### **Table 1.**

*PDI of E. coli with cationic porphyrins.*

shifted to 418 nm, respectively. Thus, bis[3-(4-pyridyl)propoxo]tetraphenylporphyrinatoantimony (V) bromide ((Py3)2Sb(Tpp)+ , 83 mg) and 3-(4-pyridyl) propoxo(methoxo)tetraphenylporphyrinatoantimony (V) bromide (Py3Sb(Tpp)<sup>+</sup> , 90 mg) were obtained in 50% and 43% yields, respectively. (Py3)2Sb(Tpp)+ (50 mg) was reacted with 1-bromohexane (0.5 mL) in MeCN (13 mL) at reflux temperature for about 24 h to give bis[3-(1-hexyl-4-pyridinio)-1-propoxo]-5,10,15,20 tetraphenylporphyrinatoantimony (V) tribromide ((HexPy3)2Sb(Tpp)3+, 20 mg, 35%). The reaction of (Py3Sb(Tpp)+ , 50 mg) with MeI and 1-bromohexane (0.5 mL in MeCN (13 mL) at reflux temperature for about 24 h gave α-(methoxo)-β-[3(1- -methyl-4-pyridinio)-1-propoxo]-5,10,15,20-tetraphenylporphyrinatoantimony (V) dibromide (MePy3Sb(Tpp)2+, 25 mg, 42%) and α-(methoxo)-β-[3 (1-hexyl-4-pyridinio)-1-propoxo]-5,10,15,20-tetraphenyl-porphyrinatoantimony (V) dibromide (HexPy3Sb(Tpp)2+, 20 mg, 25%), respectively [24].
