Photochemical Mechanisms in Photosensitization B

PHOTOCHEMICAL MECHANISMS IN PHOTOSENSITIZATION B. Pouyet, R. Chapelon

To cite this version:

B. Pouyet, R. Chapelon. PHOTOCHEMICAL MECHANISMS IN PHOTOSENSITIZATION. Jour- nal de Physique Colloques, 1987, 48 (C7), pp.C7-247-C7-251. 10.1051/jphyscol:1987755. jpa- 00227059

HAL Id: jpa-00227059 https://hal.archives-ouvertes.fr/jpa-00227059 Submitted on 1 Jan 1987

HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. JOURNAL DE PHYSIQUE Colloque C7, supplQment au n012, Tome 48, decembre 1987

PHOTOCHEMICAL MECHANISMS IN PHOTOSENSITIZATION

B. POWET and R. CHAPELON Laboratoire de Photochimie Appliquee, Universite Claude Bernard, Lyon I, 43, Bd du 11 novembre 1918, F-69622 Villeurbanne Cedex, France

Abstract -

Action of light in chemical transformations can be classified in two main groups : - Direct photochemical reactions :molecules which absorb lightare that which are transformed. - Photosensitized reactions : the light is absorbed by a different molecule to that we wish to transform.

In the second case the sensitizer which absorbs a photon may react in two ways : . Electron transfer. . Energy transfer. So for photo-oxidations it is possible to speak about two types : - Type I photo-oxidations : there is either hydrogen atom abstraction, or electron transfer. - Type I1 photo-oxidations : energy transfer occurs between excited sensitizer and oxygen giving excited singlet oxygen; it is a very reactive species. Rose Bengal, Acridin Orange, Methylene Blue, Chlorophyll and Hematoporphyrin are the most current sensitizers. It is Hematoporphyrin that is employed in phototherapy, in consideration of the two properties : . it is a good sensitizer without important toxicity ; . its life time in carcinogenic cells is longer than in normal cells.

The action of light on Hematoporphyrin in ill cells gives singlet oxygen (strong oxidant) which destroys them. An example of photochemical studies usefulness is given.

Light can bring about or initiate some chemical reactions, but it is necessary that one of the constituants in the reactant media absorbs this light. Then we can have two cases : 1 - The light is absorbed by the studied reactant which is transformed or reacts following this absorption : it is named a direct photochemical reaction. ex : thfljne-ijmgyization C

Article published online by EDP Sciences and available at http://dx.doi.org/10.1051/jphyscol:1987755 CY-248 JOURNAL DE PHYSIQUE

2 - The light is absorbed by a constituant which does not generally participate in the reaction : it is only present to catch a photon and then to initiate the chemical process. It plays as a kind of "catalyst". It makes the reaction sensitive to the light : : this type of situation is called a photosensitized reaction.

visible light +

"2 + (chlorophyll) '6 H12 '6 '2 To understand the route of a photochemical reaction, it is necessary to give a brief and simplified scheme of what happens in a molecule which absorbs a photon. The ground state is the stable state in which the molecules are generally present. For organic molecules this state is a singlet state : that means that spins of elec- trons in the high energy orbital that is occupied are paired. The energy of the absorbed photon is used to energize an electron and cause it to jump to a higher energy level. Two excited electronic states can be obtained. In one, the spin of the electron is not changed : this state is termed an excited singlet state. In the second case, the electron spin is changed and the two electron spins =ow unpairedgivingan excited triplet state. After photoexcitation, the molecule can follow different paths, according to the following state energy diagram (1).

In the case of a photosensitized reaction, the photosensitizer can follow two paths giving : . either, an electron transfer . or, an energy transfer For example, in photo-oxidation with oxygen, it is possible to have : A - Type I photo-oxidation reactions : the photosensitizer transfers an electron to the substrate, or abstracts an hydrogen atom S + h3 - S" (singlet or triplet) s'+ RH-SH' + R' or sf i R'-s+ i R: then radicals react with oxygen B - Type I1 photo-oxidation reactions : the photosensitizer transfers its energy to a molecule of oxygen. S + hv -S' (triplet) s* + o* -S + 0; oxygen in ground state is in a triplet state contrarily to organic molecules. In the excited state, obtained by energy transfer, the oxygen molecule is in a singlet state. Singlet oxygen has special physical properties which allow characterization of it. Moreover it is a very reactive species : It is a strong oxidizing agent. Among the main photosensitizers currently used, there are Rose Bengal, Acridin Orange, Methylene Blue, Chlorophyll and Hematoporphyrin. In the phototherapy treatment it is Hematoporphyrin and its derivatives which are employed, on account of the three following properties (2). 1 - It is a good sensitizer and the quantum yield of singlet oxygen production is about 0.6. 2 - The life time in carcinogenic cells is longer than in normal cells. 3 - It has no toxicity for human organism. With Hematoprophyrin (HP) the scheme of action is like type I1 photo-oxidation (3). HP + hv- l*HP---,HP* 3

The stages shown being very simplified and schematic. Thus singlet oxygen hence produced in tumoral cells, destroys them (4). It has been shown by different authors, that type I photo-oxidation does not occur with Hematoporphyrin and it should be noted that generally it is derivatives of Hematoporphyrin which are used (see conference of Dr. BRAULT) (5) (6). This is due to the difference of the penetration of light into cells and also a better efficiency of singlet oxygen production. Moreover, the agregate state of molecules, which seems to be an important factor, is different in HP and HP derivatives. An absorption spectrum of Hematoporphyrin is given here. Hematoporphyrin derivatives have similar spectra. The first treatments used white light sources, like xenon lamps. More recently the use of lasers allows transportation of light along an optical fiber and selective irradiation of the tumoral sites (7) (8). The wavelength of 630 nm is used and is produced by a dye laser ; this light has a good penetration into the tissues because they have a "window" of absorption between 630 and 900 nm.

Absorption spectrum of H.P. derivatives JOURNAL DE PHYSIQUE

Quantum yield of '0; production

The destruction of these cells by this technique could be effective up to 20 mm depth. Unfortunately the light at 630 nm is only sligthly absorbed by H.P. derivatives and the problem is to find a new molecule which has a good absorption between 630 nm and 900 nm. Phtalocyanin, chlorine ... are the products towards which research is now heading (see conf. of Dr. BRAULT). Of course the true efficiency is found by using "in vivo" experiments, but the knowledge of photochemical behaviors is important to optimize the treatment condi- tions. For example, to avoid or to minimize the risk of erythema it is necessary to

Photochemical effect efficiency A - Rabbit 1 iver B - Rabbit muscle employ the smallest quantit'es1 of H.P. derivatives. A photochemical study of 05 production indicates that the quantum yield varies with the wavelength of irradiation. Taking into account the absorption of tissues and H.P. derivatives, it is seen that the efficiency also varies with wavelength of irradiation. In the same manner, the penetration of light, is more or less important, according to the wavelength used. The conclusion is that a compromise has to be found between wavelength and penetration. For example, in the case of superficial tumors it would be better to irradiate by a light near 530 nm,

Photochemical effect efficiency Wavelength of irradiation 620 nm --530 nm

References - 1 - N.J. TURRO - Modern Molecular Photochemistry. Benjamin/Cummings, Publishing to Menlo Park, 1978. 2 - R. LIPSON, E. BALDES and A. OLSEN, J. Natl. Cancer Inst. 26, 1, 1961. 3 - M.C. BERENBAUM, R. BONNET and P.O. SCOURIDES, Br. J. Cancer, -45, 71, 1982. 4 - T.J. DOUGHERTY, W.R. POTTER and K.R. WEISHAUPT, In Porphyrins in Tumor Photo- therapy, 23, 1984. 5 - C.J. GOMER, Cancer Res., 3,146, 1979. 6 - D. KESSEL, Cancer Res., 5,1318, 1981. 7 - K.R. WEISHAUPT, C.J. GOMER and T.J. DOUGHERTY, Cancer Res., 36, 2326, 1976. 8 - T.J. DOUGHERTY, C.J. GOMER and K.R. WEISHAUPT, Cancer Res., 36, 2330, 1976. 9 - P. MURASECCO, E. OLIVEROS, A.M. GRAUN and P. MONNIFR, Photobiochem. Photobiophys. -9, 193, 1985.