**5.2 Activity control through the self-quenching of photosensitizers**

DiethoxyP(V)tetrakis(*p*-methoxyphenyl)porphyrins, **Por10** and **Por11**, analogues of above mentioned **Por9**, were synthesized [47]. Their water-solubilities were smaller than that of **Por9**, and these porphyrins form self-aggregation complexes (**Figure 8**). Photoexcited states of **Por10** and **Por11** were effectively quenched through this aggregation (concentration quenching). These phosphorus(V) porphyrins can bind to the hydrophobic pocket of HSA, resulting in dissociation of their self-aggregation states (**Figure 8**). Calculating simulation showed the distance between the tryptophan residue and the porphyrin molecules as follows: 24.4 Å (**Por10**) and 23.5 Å (**Por11**). Fluorescence lifetime of these porphyrins were recovered by the dissociation of self-aggregation. Photoirradiation to these porphyrins binding to HSA induced the oxidation of tryptophan through 1 O2 generation and electron transfer. The axial fluorination of ethoxy chain of central phosphorus atom reduced the *E*red of porphyrin ring. The electron transfer

**Figure 8.**

*Scheme of the activity control of photosensitizers,* **Por10** *and* **Por11***, through the self-aggregation and interaction with HSA.*

rate constant from the tryptophan residue of HSA to **Por11** is larger than that of **Por10**, due to the effect of axial fluorination. The substitution by fluorine, the highest electronegative element, showed the improving effect on photooxidation of protein through electron transfer. However, the fluorination decreased the binding interaction with HSA. In the presence of same concentration of porphyrins, **Por10** exhibits higher damaging activity to HSA under photoirradiation. These results suggest that selective interaction is important for electron transfer-mediated photodamage of biomolecules. These porphyrins demonstrated the photocytotoxicity to HaCaT cells. The IC50 value of **Por11** was lower (stronger cytotoxicity) that **Por10**. Photooxidative activity of **Por11** through electron transfer and enhanced cellular uptake by the fluorination may play the important role in this photocytotoxic effect. Furthermore, **Por10** and **Por11** barely induce cellular DNA damage to HaCaT cells, similarly to **Por8**, **Por9**, and **Por12**. Therefore, their carcinogenic risks are also small. The self-aggregation of photosensitizers can be used to suppress their photosensitizing activity. These results suggest that the PDT activity of self-aggregation photosensitizers can be reversed using association with targeting biomacromolecules, such as protein.
