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The porphyrin handbook - Kadish K.M.

Kadish K.M. The porphyrin handbook - Academic press, 2000. - 368 p.
Download (direct link): kadishsmishgulilard2000.djvu
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destabilization of the HOMO result in a smaller energy gap between the
two orbitals and, consequently, the lowest energy absorption band of a
chlorin is red-shifted relative to a porphyrin. Similar effects account
for the optical spectra of bacteriochlorins.206 As shown in Figure 3,207
the energy gap between HOMO and LUMO increases in this order:
bacteriochlorin < isobacteriochlorin < chlorin < porphyrin. Meanwhile,
the energy required for oxidation parallels the energy of the HOMOs and
decreases in this order:
porphyrin > chlorin > isobacteriochlorin, bacteriochlorin. Thus,
bacteriochlorin has the most red-shifted first absorption band and is
also the least stable. This feature can be further modulated by the
presence or absence of metals as well as of various substituents. For
example, introducing an electron-withdrawing group at peripheral position
can induce a further red shift.
Because of its long-wavelength absorption close to 800 nm, naturally
occurring bacteriochlorophylls are ideal candidates for PDT. However, due
to their unstable nature, synthesis of stable bacteriochlorins has been a
challenge for porphyrin chemists worldwide.
The term bacteriochlorin originates from the bacteriochlorophylls, which
are widespread as pigments in bacterial photosynthesis. Its constitution
was elucidated by Eisner.208 Natural bacteriochlorophyll a 128 has
several photophysical and chemical characteristics that may make it a
better candidate for PDT. It has good singlet oxygen-producing ability
and it absorbs strongly at 780 nm (s > 70,000) near the optimum
wavelength for tissue penetration. Henderson et al. evaluated this
compound for its in vivo photodynamic activity.209 It appeared to be an
effective sensitizer, but was found to be unstable in vivo. Rosenbach-
Belkin et al. prepared serine conjugates of bacteriochlorophyll (Bchl)
and studied their biodegradation.127 The optical absorption spectra of
Bchl-Ser from melanoma extracts included two additional transitions at
525 nm and 680 nm. The 525-nm absorption band characterized the Qx
transition of the
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 36. Some naturally occurring bacteriochlorins.


Bacteriochlorophyll a


Bacteriochlorophyllin a


Bacteriochlorin a
131 Tolyporphin
demetalated product (BPhe), for which the Qy absorption is at 750 nm. The
680 nm absorption pointed to the presence of oxidation products. Beems et
al. also investigated photosensitizing properties of two water soluble
derivatives of bacteriochlorophyll a 128, namely bacteriochlorophyllin a
129 and bacteriochlorin a 130 (Scheme 36).210 Bacteriochlorin a 130 has
an absorption maximum at 765 nm and proved to be effective both in vitro
210 and in vivo. 211
The only naturally occurring bacteriochlorin that is not involved in
photosynthesis is the tolyporphin 131 isolated by Prinsep et al.212 from
the blue-green alga Tolypothrix nodosa. This compound, which enhances the
cytotoxicity of adriamycin or vinblastine in SK-VLB cells at doses as low
as 1 (xg/ml, is characterized as a multidrug resistance-
(MDR) reversing agent. Kishi's group213 synthesized the tolyporphin
chromophore by the extension of the Eschen-moser sulfide
contraction/iminoester cyclization method. However, the long-wavelength
absorption of tolyporphyrin is at 675 nm (e = 22,000), and there is no
report regarding the photosensitizing efficacy of this novel compound.
Most of the naturally occurring bacteriochlorins (e.g., 132) have
absorptions between 760 and 780 nm and are extremely sensitive to
oxidation, resulting in a rapid transformation into the chlorin state 133
which generally has an absorption maximum at or below 660 nm (Scheme 37).
Furthermore, if a laser is used to excite the bacteriochlorin in vivo,
oxidation may result in the formation of a new chromophore absorbing
outside the laser window, reducing its photodynamic efficacy. Due to the
desirable photophysical properties of bacteriochlorins, there has been
increasing interest in the synthesis of stable bacteriochlorins from
bacteriochlorophyll a or other similar tetrapyrrolic systems.
Scheme 37. Conversion of bacteriochlorin to chlorin in the presence of
Me 0 Me
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