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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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66,000) as well as a good singlet oxygen quantum yield (0.65). Smith and
coworkers197'198 prepared a series of azachlorins 111, 112 from 110 via
the Diels-Alder reaction. Azachlorin 111, upon further subjecting to a
series of reactions, produced the azabacteriochlorin 114 (Scheme 31). In
preliminary screening, these compounds did not show any significant in
vivo photosensitizing activity.198
Aimed at mimicking the lipophilic properties of the active fractions of
Photofrin Montforts and coworkers synthesized some geminally dialkylated
chlorins, the so-called "tailor-made" chlorins 116,117.199-202 chiorins
with geminal dialkyl substitution in the saturated pyrrole ring were
easily obtained from the red blood pigment heme via Claisen rearrangement
and functionalized in the 3 position by reaction of the double bond
(Scheme 32). Photophysical studies of some novel chlorins 116-118
revealed a high quantum yield for singlet oxygen formation ( = 0.69 and
0.58) with long wavelength absorption at 660 nm. These characteristics
make them potential candidates for PDT. However, there has been no report
regarding their in vitro or in vivo biological efficacy.
An alternate approach for the preparation of chlorin 120, obtained by
Ni(II)-promoted intramolecular migration of the corresponding (N-
methoxycarbonylmethyl)porphyrin 119, was reported by Smith et al. (Scheme
33).203 However, several attempts to prepare the corresponding free-base
analogues were unsuccessful, and these compounds could not be evaluated
for in vivo activity.
Scheme 29. Conversion of tetraphenylporphyrins into the corresponding
101a H2(o-THPP) 102a H2(o-THPC)
101b H2(m-THPP) 102b H2(m-THPC)
101c H2(p-THPP) 102c H2(p-THPC)
Pandey and Zheng
Scheme 30. w'c-Dihydroxy-chlorins and ketochlorins.
PMe = CH2CH2C02CH3 PH = CH2CH2C02H
Scheme 31. Chlorins from mono-azaporphyrins.
PMe = CH2CH2C02CH3
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
3-Acetyl-deuteroporphyrin IX dimethyl ester
3-(1-Hydroxymethyl) deuteroporphyrin IX dimethyl ester
pMe pM
116 R1 = Heptyl, R2 = H
117 R1 = H, R2 = Heptyl
PMe = CH2CH2C02CH3
Scheme 33. Nickel(ll)-promoted rearrangements of some N-substituted
120a M = Ni 120b M = 2H
Another chlorin synthetic methodology worth mentioning is the formation
of spirochlorin 122 and allylidenechlorin 123 by the reaction of
bromovinylporphyrin 121 with tetra-
cyanoethlene, reported by Kai et al.204 Because of the presence of an
exocyclic allylidene moiety that plays a role in extending the conjugated
system of the chlorin macrocycle and the electron-withdrawing groups
conjugated with its 1,3-diene system, such chlorins showed a remarkable
bathochromic shift (~ 70 nm) with a high molar extinction coefficient
(Scheme 34).
A rare example of a direct chlorin synthesis was recently reported by
Bums et al.205 This approach 1,9-diformyldi-pyrromethane 124 was
condensed with dipyrromethane monocarboxylic acid 125 to afford the
porphodimethene 126 under controlled oxygen-free conditions. Upon
metalation with Zn(II), quantitative tautomerization of 126 produced
metallochlorin 127 as a single isomer (Scheme 35).
Pandey and Zheng
Scheme 34. Novel spirochlorin from 2-bromovinyl H2(OEP). Br
Scheme 35. Direct synthesis of chlorins from dipyrromethanes.
V. Bacteriochlorin-Based Photosensitizers
So far, chlorin-type photosensitizers derived from various porphyrins and
from pyropheophorbide a or purpurin-18 methyl ester have been discussed.
These sensitizers have a strong absorption near 700 nm, which almost
doubles the tissue-penetration distance of the incident light compared
with Photofrin (630 nm). However, an ideal sensitizer should absorb light
at or near 800 nm, not only because of its deeper tissue penetration, but
also due to the availability of cheaper diode lasers for sensitizer
The light-absorption properties of chlorins relative to porphyrins,
particularly their first optical transitions, are a direct consequence of
the saturation of a peripheral CfJ-CfJ bond. The loss of one double bond
destabilizes the system of a chlorin, and the highest occupied
molecular orbital (HOMO) rises in energy; thus the molecule becomes
easier to oxidize. The smaller system has little effect on the lowest
unoccupied orbital (LUMO) so that analogous chlorins and porphyrins
exhibit similar reduction potentials with the exception of
isobacteriochlorin. However, the invariance of the LUMO and the
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