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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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porphycene actually has stability comparable with that of porphyrins.
Evidently, the slightly strained porphycene is stabilized by the presence
of strong NH-N hydrogen bonds.
Tetra-n-propyl-porphycene 240 was the first porphyrin isomer evaluated
for potential use as a photosensitizer for PDT. In 1989, Guardiano et al.
243 found that this compound was selectively transported by serum
lipoproteins and
43 / Porphyrins as Photosensitizers in Photodynamic Therapy
197
Scheme 56. Porphycene derivatives.
240 R1 = R2 = H' 253 R1 = OH, 259
241 R1 = H, R2 = OH R2 = R3 = CH3 260
242 R1 = H, R2 = OCH3 254 jf 261

II
:
243 R1 = H, R2 = 0CH2(C6H4)C02H R2 = R3 = OCH3 262
244 R1 = H, R2 = OCOCH3 255 X 263

II
CM
C?L
II
.
245 R1 = H, R2 = 0C0(CH2)3C02(CH3)3 R3 = CH3 264
246 R1 = H, R2 = 0C0CH2NHC02C(CH3)3 256 R1 = R2 = OCH3, 265
247 R1 = H, R2 = 0C0(CH2)3NHC02C(CH3)3 R3 = CH3 266
248 R1 = H, R2 = NH2 257 R1 = R2 267
249 R1 = H, R2 = NHCOCH3 = R3 = OC2H5 268
250 R1 = H, R2 = NHC0(CH2)3C02H 258 R1 = R2 269
251 R1 = H, R2 = NHC0(CH2)3C02CH3 = R3 = phenyl 270
252 R1 = CH2N(CH3)2, R2 = H 271
272
273
274
' =R2 = H ' = H, R2 = OH ' = H, R2 = OCH3 ' = H, R2 = 0(CH2)5CH3 ' = H,
R2 = OCOCH3 1 = H, R2 =0C0CH2NHC02C(CH3)3 = H, R2 = NH2 = H, R2 = NHCOCH3
= H, R2 = NHC0(CH2)3C02H = H, R2 = NHC0(CH2)3C02CH3 = H, R2 =
N[CO(CH2)3CO]
= H, R2 = OCO(C6H4)carotenyl = H, R2 = OCO(CH2)4CH3 = H, R2 =
OCO(CH2)7CH3 = H, R2 = OCO(CH2),6CH3 = CH2N(CH3)2, R2 = H
275
276
277
was delivered to tumor tissue with good efficiency and selectivity (tumor
vs normal tissue: 16.7). Since it has a large absorbance in the 630-640-
nm region and is an efficient generator of singlet oxygen ( = 0.36),
this compound represents a potential candidate as a PDT drug.
Since the discovery of porphycene, several related derivatives 240-278
have been synthesized with the intention of optimizing these sensitizers
in response to the requirements of PDT, such as in vivo transport,
specificity of localization in tumor tissue, optical absorption in the
long-
wavelength region, and as so-called fast-acting photosensitizers (Scheme
57). Among these derivatives, some have proven to be effective as in vivo
antitumor agents.244-248
Braslavsky et al.249 reported the photophysical properties of certain
porphycene derivatives and it was found that with few exceptions (such as
carotenyl porphycene 270 and porphycenes 276 and 277 in which steric
strains introduced by (bis)benzo annelation and crowding with adjacent
alkyl substituents force the conjugated ring system out of plane),
porphycenes possessing unperturbed 18- aromaticity and are efficient
singlet oxygen generators.
198
Pandey and Zheng
284
285
286
Among these porphycene derivatives, carboxybenzo-porphycene 275
attracted particular attention because of its extremely fast-acting PDT
efficacy.250 This photosensitizer produced complete tumor remission when
tumors were irradiated only 5 minutes after drug injection, the shortest
injection-irradiation time interval reported so far. Probably, the quick
delivery of the drug to the target cells is diffusion controlled. Such
diffusion to the cells may be advantageous over carrier-mediated delivery
since the drug distribution should be relatively unhampered by the
heterogeneous tumor blood flow which characterizes partially necrotic
neoplasm. Thus, a "swift PDT" protocol was suggested with such fast-
acting photosensitizers. Drug injection and tumor irradiation require no
more time than a typical therapeutic session with conventional
techniques. Although these results are very interesting, fast-acting
photosensitizers are generally not desirable.
The simple protocol for construction of porphycenes also led to the
assembly of six additional structural isomers 281-286 as shown in Scheme
57.251 However, only hemipor-phycene and corrphycene are stable enough to
be synthesized. Octaethyl-hemiporphycene 281 and octaethyl-corrporphycene
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