Author's introduction .......................................... xi
PART I Introduction ............................................ 1
1 Light ........................................................ 3
1.1 Electromagnetic radiation in everyday life .............. 3
1.2 Radiation and tissue .................................... 5
1.3 Light, electrons and molecules .......................... 6
1.4 Photoreaction ........................................... 9
1.5 Dental/plastics curing ................................. 11
1.6 Photoaging/photofading/photobleaching .................. 12
References .................................................. 12
2 Dyes and stains ............................................. 13
2.1 Dye use ................................................ 13
2.2 Textile dyeing and biological staining ................. 14
2.3 Biological stains and biomedical photosensitisers ...... 17
2.4 The human factor ....................................... 19
2.5 Dyes and drug development .............................. 22
2.6 Dyes and stains and photosensitiser design ............. 25
References .................................................. 25
3 Photosensitisers and photosensitisation ..................... 27
3.1 Photosensitiser action ................................. 29
3.2 The photodynamic effect and cell death ................. 31
3.3 Photosensitising drug discovery ........................ 32
3.4 Fitness for purpose .................................... 36
3.5 Organic versus inorganic photosensitisers .............. 40
References .................................................. 41
PART II Chemistry of photosensitisers ......................... 43
4 Azines ...................................................... 45
4.1 Acridines .............................................. 47
4.2 Acridine synthesis ..................................... 50
4.3 Rationale .............................................. 52
4.4 Acridines in photodynamic therapy ...................... 52
4.5 Phenanthridines ........................................ 53
4.6 Phenaziniums ........................................... 54
4.7 Phenoxaziniums ......................................... 58
4.8 Phenothiazinium derivatives ............................ 63
4.9 Reduction-oxidation activity ........................... 65
4.10 Hydrophilicity-lipophilicity .......................... 65
4.11 Molecular planarity ................................... 66
4.12 Benzannelated derivatives ............................. 67
4.13 Synthetic approaches .................................. 69
References .................................................. 74
5 Triarylmethanes and xanthenes ............................... 81
5.1 Triarylmethanes ........................................ 81
5.2 Victoria blue series ................................... 83
5.3 Structure and photoproperties in triarylmethanes -
extending the long-wavelength absorption ............... 84
5.4 Synthesis .............................................. 91
5.5 Xanthene derivatives ................................... 93
5.6 Biological uses ........................................ 97
5.7 Rhodamines ............................................. 99
5.8 Rosamines ............................................. 103
5.9 Pyrylium compounds .................................... 105
5.10 Pyronines ............................................. 107
References ................................................. 108
6 Porphyrins ................................................. 113
6.1 Central metals ........................................ 116
6.2 Meso compounds ........................................ 116
6.3 Amino derivatives ..................................... 120
6.4 Hetero-porphyrins ..................................... 127
6.5 Chlorins .............................................. 128
6.6 Benzoporphyrin derivative ............................. 132
6.7 Temoporfin ............................................ 134
6.8 Tookad ................................................ 135
6.9 Purpurins ............................................. 135
6.10 Texaphyrins ........................................... 136
6.11 Porphycenes ........................................... 137
6.12 5-Aminolaevulinic acid ................................ 137
6.13 Esters ................................................ 139
References ................................................. 141
7 Phthalocyanines ............................................ 147
7.1 General features ...................................... 148
7.2 Phthalocyanine synthesis .............................. 150
7.3 Photosens ............................................. 154
7.4 Naphthalocyanines ..................................... 155
7.5 Hetero-fused systems .................................. 159
7.6 Silicon derivatives ................................... 161
7.7 Photoantimicrobial activity ........................... 162
References ................................................. 165
8 Cyanines ................................................... 169
8.1 Synthesis ............................................. 172
8.2 Merocyanine 540 ....................................... 176
8.3 N,N'-Bis(2-ethyl-l,3-dioxolane)kryptocyanine .......... 178
8.4 Indocyanine green ..................................... 179
8.5 Structural improvement ................................ 182
8.6 Squaric and croconic acid derivatives ................. 183
8.7 Functional cyanines ................................... 186
References ................................................. 187
9 Natural product photosensitisers ........................... 191
9.1 Condensed aromatic pigments: perylene- and
phenanthroperylenequinones ................................. 192
9.2 Hypericin-type photosensitisers ....................... 193
9.3 Hypocrellins .......................................... 194
9.4 Anthraquinones ........................................ 197
9.5 Psoralens (furocoumarins) ............................. 199
9.6 Isoquinoline alkaloid photosensitisers ................ 204
9.7 Riboflavin ............................................ 206
9.8 Terthiophenes ......................................... 207
References ................................................. 208
PART III Applications ......................................... 211
10 Photodynamic therapy in oncology ........................... 213
10.1 Photosensitisers for use in photodynamic therapy ...... 216
10.2 Indications for photodynamic therapy .................. 217
10.3 Skin .................................................. 218
10.4 Head and neck ......................................... 220
10.5 Gastrointestinal tract ................................ 221
10.6 Breast ................................................ 221
10.7 Lung .................................................. 222
10.8 Genitourinary tract and prostate ...................... 223
10.9 Brain ................................................. 223
10.10 Haematological disease (leukaemia and lymphoma) ...... 224
10.11 Targeting/formulation ................................ 224
10.12 Liposomes ............................................ 225
10.13 Biomolecular conjugation ............................. 226
10.14 Dendrimers ........................................... 227
10.15 Nanoparticles ........................................ 229
10.16 Magnetic targeting ................................... 230
10.17 Light in photodynamic therapy ........................ 231
References ................................................. 233
11 Antimicrobial application - photodynamic antimicrobial
chemotherapy ............................................... 237
11.1 Antimicrobial and photoantimicrobial action ........... 238
11.2 Applications .......................................... 244
11.3 Blood ................................................. 247
11.4 Thionin/light 4 + low-dose UVB for the
decontamination of platelet concentrates .............. 249
11.5 The cellular problem .................................. 250
11.6 A role for photodynamic antimicrobial chemotherapy
in tropical medicine? ................................. 252
References ................................................. 254
12 Non-oncological applications ............................... 259
12.1 Age-related macular degeneration ...................... 259
12.2 Atherosclerosis ....................................... 260
12.3 Endometreosis ......................................... 262
12.4 Port wine stain ....................................... 262
12.5 Arthritis and autoimmune disorders .................... 262
12.6 Photodynamic diagnosis ................................ 263
12.7 Photocytotoxics and photochemical internalisation ..... 264
References ................................................. 266
Index ......................................................... 269
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