**4. Factors governing the activity control of the photochemical property of the electron donor‐connecting porphyrin**

As mentioned above, the controls of fluorescence intensity and <sup>1</sup> O2 ‐generating activities of the cationic porphyrin connecting to the pyrenyl and anthryl groups by DNA could be suc‐ cessfully established. On the other hand, in the case of phenanthrylporphyrin, the S<sup>1</sup> state of this porphyrin could not be deactivated through intramolecular electron transfer because the electron‐donating property of the phenanthryl moiety was insufficient [56]. To investigate the factors governing the activity control of the electron donor‐connecting porphyrins, two types of electron donor‐connecting porphyrins, *meso*‐(1‐naphthyl)‐tris(*N*‐methyl‐*p*‐pyridinio)por‐ phyrin (1‐NapTPP) and *meso*‐(2‐naphthyl)‐tris(*N*‐methyl‐*p*‐pyridinio)porphyrin (2‐NapTPP) (**Figure 11**), were designed and synthesized [57].

These naphthylporphyrins, 1‐NapTPP and 2‐NapTPP, spontaneously bind to double‐ stranded DNA [57]. The electrostatic force between cationic porphyrins and the anionic DNA strand, as well as the hydrophobic interaction, can be speculated as the driving force of the binding interaction. In the presence of relatively small concentrations of DNA, these naph‐ thylporphyrins aggregate around the DNA strand because their water solubility is relatively low. In the presence of a sufficient concentration of DNA, these naphthylporphyrins can form

**Figure 11.** Structures of 1‐NapTPP (left) and 2‐NapTPP (right). The side‐view structures and the HOMO of these porphyrins were obtained by the DFT calculation at the B3LYP/6‐31G\* level.

a stable complex with the DNA strand. The estimated binding constants were relatively large (more than 10<sup>6</sup> M−1). The binding constants for those of the adenine‐thymine sequence only were larger than those of the guanine‐cytosine‐containing sequences.

**4. Factors governing the activity control of the photochemical property of** 

the cationic porphyrin connecting to the pyrenyl and anthryl groups by DNA could be suc‐

this porphyrin could not be deactivated through intramolecular electron transfer because the electron‐donating property of the phenanthryl moiety was insufficient [56]. To investigate the factors governing the activity control of the electron donor‐connecting porphyrins, two types of electron donor‐connecting porphyrins, *meso*‐(1‐naphthyl)‐tris(*N*‐methyl‐*p*‐pyridinio)por‐ phyrin (1‐NapTPP) and *meso*‐(2‐naphthyl)‐tris(*N*‐methyl‐*p*‐pyridinio)porphyrin (2‐NapTPP)

These naphthylporphyrins, 1‐NapTPP and 2‐NapTPP, spontaneously bind to double‐ stranded DNA [57]. The electrostatic force between cationic porphyrins and the anionic DNA strand, as well as the hydrophobic interaction, can be speculated as the driving force of the binding interaction. In the presence of relatively small concentrations of DNA, these naph‐ thylporphyrins aggregate around the DNA strand because their water solubility is relatively low. In the presence of a sufficient concentration of DNA, these naphthylporphyrins can form

**Figure 11.** Structures of 1‐NapTPP (left) and 2‐NapTPP (right). The side‐view structures and the HOMO of these

porphyrins were obtained by the DFT calculation at the B3LYP/6‐31G\* level.

cessfully established. On the other hand, in the case of phenanthrylporphyrin, the S<sup>1</sup>

O2

‐generating activities of

state of

**the electron donor‐connecting porphyrin**

180 Phthalocyanines and Some Current Applications

(**Figure 11**), were designed and synthesized [57].

As mentioned above, the controls of fluorescence intensity and <sup>1</sup>

Similar to the other electron donor‐connecting cationic porphyrin cases, the calculations by the density functional treatment (DFT) demonstrated that the photoexcited states of these naphthylporphyrins are deactivated through intramolecular electron transfer from their naphthalene moieties to the S1 states of the porphyrin moieties [57]. However, the S<sup>1</sup> state of these porphyrins was hardly quenched by their naphthalene moieties. The ΦΔ values of these naphthylporphyrins are also relatively large without DNA (**Table 3**). The orthogonal position of these naphthalene moieties and the porphyrin rings and the relatively small val‐ ues of −Δ*G* of the intramolecular electron transfer (0.11 and 0.07 eV for 1‐ and 2‐NapTPP, respectively) are not appropriate for electron‐transfer quenching. The relationship between the estimated intramolecular electron transfer rate constants (*k*ET), which are reported in the literature [57], and the driving force (−Δ*G* values) is plotted using the reported values and shown in **Figure 12**. The plots were analyzed by Marcus theory [58, 59] using the following equation:

$$k\_{\rm ET} = \sqrt{\frac{4\,\pi^3}{h^2 \lambda \, K\_y T}} \, V^2 \exp\frac{-(\Delta \, G^\circ + \lambda)^2}{4\lambda \, K\_y T} \tag{6}$$

where *h* is Planck's constant, *λ* is the reorganization energy, *K*B is the Boltzmann constant, *V* is the electronic coupling matrix element, and *T* is the absolute temperature. Observed several components of the *τ*<sup>f</sup> for 1‐ and 2‐NapTPP suggest the different conformations. Therefore, the different *V* values were considered to explain slow electron transfer and relatively fast elec‐ tron transfer. The analyzed values of *V* were significantly smaller than those of other directly connecting electron donor‐acceptor molecular systems [60–62], suggesting that the interaction between the electron donor and the porphyrin ring is small, possibly due to the orthogonal structure. This plot suggests that a −Δ*G* of more than 0.3 eV is required for effective quenching through electron transfer in these types of porphyrin systems.


The fluorescence properties and the ФΔ values were examined in a 10‐mM sodium phosphate buffer (pH 7.6). These values were reported in the literature [57].

**Table 3.** Fluorescence and photosensitized 1 O2 ‐generating activities of 1‐NapTPP and 2‐NapTPP in the absence or presence of DNA.

**Figure 12.** Relationship between the electron transfer rate and the driving force. The plots of 1‐NapTPP (slow) and 2‐NapTPP (slow) were calculated by using the components of their long fluorescence lifetime. These curves were calculated by the Marcus equation using two appropriate values of *V*. This relationship is reported in the literature [57].

#### **5. Conclusions**

Naturally occurring photosensitizers, berberine and palmatine, demonstrate important pho‐ tochemical properties. In aqueous solution, the S<sup>1</sup> state of these compounds was rapidly quenched through an intramolecular electron transfer. These compounds bind to a DNA strand through electrostatic interaction, resulting in inhibition of electron transfer‐mediated quenching. This interaction makes the fluorescence emission and <sup>1</sup> O2 generation by these compounds possible. A similar mechanism can be applied to the cationic porphyrin. TMPyP cationic porphyrins can be incorporated into the cell nucleus and can photosensitize guanine‐ specific oxidation by <sup>1</sup> O2 generation, leading to apoptosis. Therefore, the electron donor‐con‐ necting TMPyP porphyrins can be considered as model photosensitizers for theranostics. For example, PyTPP and AnTPP were designed and synthesized. The activity control of fluo‐ rescence and 1 O2 generation by these cationic porphyrins could be successfully established. However, the activity control of phenanthrene‐ and naphthalene‐connecting porphyrins is insufficient because of their slow intramolecular electron transfer rate. These results suggest that a driving force of more than 0.3 eV is required for sufficiently fast electron transfer in similar porphyrin types. These studies demonstrate the possibility of porphyrin theranostics through control of the S1 state of the porphyrin ring by the electron‐donating moiety and inter‐ action with DNA, one of the most important target biomacromolecules for cancer therapy.
