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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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V Pyrrole N Po ""IFPyrrole N Po
-f 2() -V'':-4" 2u(")..........................................-jf-
-jf- ctiu(")''
I' U

PN N V n n27
f V/ f v
>=N N-S H. /SN N-4
Porphyrin Chlorin
Isobacteriochlorin Bacteriochlorin
585 nm 610 nm 602
nm 755 nm
Figure 3. Energy level diagram for the HOMOs arrd LUMOs of porphyrin,
chlorin, isobacteriochlorin and bacteriochlorin complexes of Zn(ll).
Reproduced with permission from: . K. Chang et al., Proc. Natl. Acad.
Sci. USA, 1981, 78, 2653).
cross-conjugated and are not required to maintain aroma-ticity. Thus,
reduction of one or both of these crossconjugated double bonds (to give
chlorins and bacterio-chlorins, respectively) maintains much of the
aromaticity, but the change in symmetry results in bathochemically
shifted Q bands with high extinction coefficients (Figure 3).86'87
Generally, the longest wavelength extinction coefficients (e) for
porphyrin, chlorin and bacteriochlorin are at "5000, 45,000 and 75,000 M
'em-1, respectively. Nature uses these optical properties of the reduced
porphyrins to harvest solar energy for photosynthesis with chlorophylls
and bacteriochlorophylls as both antenna and reaction-center pigments.88-
90 The long wavelength absorption of these natural chromophores clearly
led to explorations of their uses as photosensitizers in PDT.
It is believed that part of the chemical complexity of Photofrin is due
to the instability of the benzylic secondary hydroxy group towards the
strong reaction conditions used in its manufacturing process.78 91 Thus,
a large number of hematoporphyrin analogues have been synthesized by
several research groups by introducing a variety of substituents at
different positions of the macrocycle.92-95
Moan and coworkers have reported a series of hematoporphyrin dialkyl
ethers 1 (Scheme 2) and observed that the sensitizing efficiency
increased with decreasing polarity.92 Hematoporphyrin diamyl ether was
more efficient than HpD and was slightly less effective than Photofrin.
Pandey et al.93 also observed that the di-phytyl ether derivative of
hematoporphyrin 2 was nearly as active as Photofrin in vivo. However, the
related phytyl ester derivatives 3 and protoporphyrin 4 did not show any
photosensitizing activity. A few years later, Woodbum et al94 and Reiss
and coworkers95 reported a series of hematoporphyrin derivatives
substituted at the 3 and 8 positions (IUPAC nomenclature) of the
macrocycle with ether, thioether, ester and amino functions 5. Some of
these analogues were found to be biologicaly active.
Hill et al.96 were the first to report an interesting approach to
combine PDT with boron neutron capture therapy (BNCT)97 and later studied
the selective tumor uptake of a boronated protoporphyrin 6 in mice
bearing an implanted intracerebral glioma. They found this compound to be
selectively localized in tumor at ratios as high as 400:1 relative to
normal brain, indicating that this compound may be used as a potential
drug for PDT and boron neutron capture therapy (BNCT). Another approach
to overcoming the problem of HpD's chemically complex nature was the use
of pure porphyrins such as isohematoporphyrin 7 and
43/Porphyrins as Photosensitizers in Photodynamic Therapy
Scheme 2. Hematoporphyrin-based photosensitizers
R 0. Me
Me Me
Yy (
-NH >
SN HN v_ -Me
,R2 pR2
1 R = different alkyl group P*2 = CH2CH2C02H
2 R1 = different alkyigroups-
up to
phytyl P92 = CH2CH2C02Me R
P'"' p1
3 R1 = R2 = CH(OH)Me PR3 = CH2CH2Phytyl
4 R1 = R2 = vinyl
PR3 = CH2CH2C02Phytyl
5 R1 = vinyl, ether,ester,
amino groups PR2 = CH2CH2CONH(CH2)2N(CH3)2
7 R = H, R = H
8 R1, R2 = various substituents
the corresponding alkyl ether analogues 8 which are both isomerically
pure due to the presence of primary hydroxyl groups.
Among synthetic porphyrins, meso-5,10,15,20-tetraarylpor-phyrins [e.g.,
H2 (TPP) 9] are the most readily available. The tumor-localizing
properties of tetrasulfonated meso-
tetraphenylporphyrin H2(TPPS4) 10 have been known for a long time,98 but
only a low photochemical efficiency in cells as well as in a tumor model
was reported, regardless of its high singlet oxygen yield ( = 0.84, in
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