13 Photodynamic Therapy
449
porphyrin skeleton. Currently, in Japan, porfimer sodium (photofrin) and talaporfin
sodium (Laserphyrin) are approved by the Ministry of Health, Labor and Welfare
and practically used for PDT, as porphyrin-based photosensitizing dyes (Fig. 13.3a)
(Ethirajan et al. 2011). Porfimer sodium, a first-generation photosensitizer, has a
photoabsorption band (λ
abs
max = 630 nm) in a wavelength region relatively favorable to tissue penetration. On the other hand, talaporfin sodium, a second-generation
photosensitizer, has a chlorin skeleton and photoabsorption band (λ
abs
max = 650 nm)
in a wavelength region more tissue-permeable than that of porphyrin-based porfimer
sodium.
Furthermore, because talaporfin sodium shows highly specific accumulation in
tumor tissues and can modestly suppress photosensitivity, it is used as an excellent
photosensitizer for PDT.
So far, much knowledge about the effects of the central metal and substituents of
porphyrin-based photosensitizing dyes on the efficiency of
1 O 2 generation has been
accumulated (Fig. 13.3a) (DeRosa and Crutchley 2002; Bonnett 1995). Tetraphenylporphyrin (H2TPP) without a central metal shows a Φ value of ca. 0.6–0.7 and is
used as a standard photosensitizing dye for porphyrin dyes (Fig. 13.3a). Porphyrin
dyes having diamagnetic metal ions including Zn
2+ , Pd
2+ , and Cd
2+ as the central
metal exhibit high Φ values. In contrast, Φ values of porphyrin dyes with paramagnetic metal ions such as Mn
2+ , Co
2+ , and Cu
2+ are extremely low. Φ correlates
with triplet quantum yield (Φ T ) and triplet state lifetime (τ T ); for example, ZnTPP
(Φ = 0.83) and PdTPP (Φ = 0.88) have high Φ T (0.8–1.0) and long-lived τ T
(10
3
−10
4
μs), whereas CoTPP and CuTPP (Φ = < 0.01) exhibit extremely low
Φ T and short-lived τ T . On the other hand, PtTPPS with Pt
2+ as the central metal has
a low Φ value (0.06), but Pt4TPyP having four pyridyl groups coordinated with
Pt
4+ shows a relatively high Φ value (0.50) (Naik et al. 2014).
It is known as an interesting substituent effect that the Φ values of sulfonated
H 2 TPP (H 2 TPPS, Φ = 0.58) and carboxylated H 2 TPP (H 2 TPPC, Φ = 0.56)
are improved by introduction of silyl groups into H 2 TPPS (H 2 TPPSSi, Φ = 0.66)
and H 2 TPPC (H 2 TPPCSi, Φ = 0.72) (Fig. 13.3a) (Horiuchi et al. 2014). It has
been reported that the Φ value (0.92) of diazaporphyrin (H 2 DAP) is higher than
that of H2TPP (Shinmori et al. 2005).
Porphycene, a structural isomer of porphyrin, is expected as a second-generation
photosensitizer because of the larger ε value (−50,000 M
–1 cm
–1 ) than porphyrin in
the red region above 630 nm. Compared to porphycenes without the central metal
(H 2 TPPo, Φ T = 0.52, Φ = 0.23) and with the central Cu
2+ (CuTPPo, Φ T = 0.35,
Φ = 0.24), a porphycene with Pd
2+ as the central metal (PdTPPo) has a higher
Φ T (0.78) and Φ (0.78) values (Rubio et al. 2005). In addition, bromine-substituted
porphycenes (H2TPrPoBr1–4) show high Φ values (0.49–0.95) (Shimakoshi et al.
2008), resulting from the increased spin–orbit interaction due to the heavy electron
effect of bromine atom (decreased Φ fl ) and enhanced Φ T (Fig. 13.3b).
Rubilin is a porphyrin analogue, and a Se-substituted rubilin, selenium rubilin
(RubSe), has a strong Soret absorption band at 633 nm (ε = 221,000 M
–1 cm
–1 )
and two Q absorption bands at 835 nm (ε = 42,300 M
–1 cm
–1 ) and 1156 nm (ε =
121,000 M
–1 cm
–1 ) (Fig. 13.3b) (Tian et al. 2013). RubSe exhibits pH-dependent
449
porphyrin skeleton. Currently, in Japan, porfimer sodium (photofrin) and talaporfin
sodium (Laserphyrin) are approved by the Ministry of Health, Labor and Welfare
and practically used for PDT, as porphyrin-based photosensitizing dyes (Fig. 13.3a)
(Ethirajan et al. 2011). Porfimer sodium, a first-generation photosensitizer, has a
photoabsorption band (λ
abs
max = 630 nm) in a wavelength region relatively favorable to tissue penetration. On the other hand, talaporfin sodium, a second-generation
photosensitizer, has a chlorin skeleton and photoabsorption band (λ
abs
max = 650 nm)
in a wavelength region more tissue-permeable than that of porphyrin-based porfimer
sodium.
Furthermore, because talaporfin sodium shows highly specific accumulation in
tumor tissues and can modestly suppress photosensitivity, it is used as an excellent
photosensitizer for PDT.
So far, much knowledge about the effects of the central metal and substituents of
porphyrin-based photosensitizing dyes on the efficiency of
1 O 2 generation has been
accumulated (Fig. 13.3a) (DeRosa and Crutchley 2002; Bonnett 1995). Tetraphenylporphyrin (H2TPP) without a central metal shows a Φ value of ca. 0.6–0.7 and is
used as a standard photosensitizing dye for porphyrin dyes (Fig. 13.3a). Porphyrin
dyes having diamagnetic metal ions including Zn
2+ , Pd
2+ , and Cd
2+ as the central
metal exhibit high Φ values. In contrast, Φ values of porphyrin dyes with paramagnetic metal ions such as Mn
2+ , Co
2+ , and Cu
2+ are extremely low. Φ correlates
with triplet quantum yield (Φ T ) and triplet state lifetime (τ T ); for example, ZnTPP
(Φ = 0.83) and PdTPP (Φ = 0.88) have high Φ T (0.8–1.0) and long-lived τ T
(10
3
−10
4
μs), whereas CoTPP and CuTPP (Φ = < 0.01) exhibit extremely low
Φ T and short-lived τ T . On the other hand, PtTPPS with Pt
2+ as the central metal has
a low Φ value (0.06), but Pt4TPyP having four pyridyl groups coordinated with
Pt
4+ shows a relatively high Φ value (0.50) (Naik et al. 2014).
It is known as an interesting substituent effect that the Φ values of sulfonated
H 2 TPP (H 2 TPPS, Φ = 0.58) and carboxylated H 2 TPP (H 2 TPPC, Φ = 0.56)
are improved by introduction of silyl groups into H 2 TPPS (H 2 TPPSSi, Φ = 0.66)
and H 2 TPPC (H 2 TPPCSi, Φ = 0.72) (Fig. 13.3a) (Horiuchi et al. 2014). It has
been reported that the Φ value (0.92) of diazaporphyrin (H 2 DAP) is higher than
that of H2TPP (Shinmori et al. 2005).
Porphycene, a structural isomer of porphyrin, is expected as a second-generation
photosensitizer because of the larger ε value (−50,000 M
–1 cm
–1 ) than porphyrin in
the red region above 630 nm. Compared to porphycenes without the central metal
(H 2 TPPo, Φ T = 0.52, Φ = 0.23) and with the central Cu
2+ (CuTPPo, Φ T = 0.35,
Φ = 0.24), a porphycene with Pd
2+ as the central metal (PdTPPo) has a higher
Φ T (0.78) and Φ (0.78) values (Rubio et al. 2005). In addition, bromine-substituted
porphycenes (H2TPrPoBr1–4) show high Φ values (0.49–0.95) (Shimakoshi et al.
2008), resulting from the increased spin–orbit interaction due to the heavy electron
effect of bromine atom (decreased Φ fl ) and enhanced Φ T (Fig. 13.3b).
Rubilin is a porphyrin analogue, and a Se-substituted rubilin, selenium rubilin
(RubSe), has a strong Soret absorption band at 633 nm (ε = 221,000 M
–1 cm
–1 )
and two Q absorption bands at 835 nm (ε = 42,300 M
–1 cm
–1 ) and 1156 nm (ε =
121,000 M
–1 cm
–1 ) (Fig. 13.3b) (Tian et al. 2013). RubSe exhibits pH-dependent