PHOTOCHEMICAL MECHANISMS IN PHOTOSENSITIZATION

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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�

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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

A b s t r a c t

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A c t i o n o f l i g h t i n chemical transformations can be c l a s s i f i e d i n two main groups :

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D i r e c t photochemical r e a c t i o n s :molecules which absorb l i g h t a r e t h a t which a r e transformed.

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Photosensitized r e a c t i o n s : t h e l i g h t i s absorbed by a d i f f e r e n t molecule t o t h a t we wish t o transform.

I n t h e second case t h e s e n s i t i z e r which absorbs a photon may r e a c t i n two ways :

.

E l e c t r o n t r a n s f e r .

.

Energy t r a n s f e r .

So f o r photo-oxidations i t i s p o s s i b l e t o speak about two types :

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Type I photo-oxidations : t h e r e i s e i t h e r hydrogen atom a b s t r a c t i o n , o r e l e c t r o n t r a n s f e r .

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Type I 1 photo-oxidations : energy t r a n s f e r occurs between e x c i t e d s e n s i t i z e r and oxygen g i v i n g e x c i t e d s i n g l e t oxygen; i t i s a very r e a c t i v e species.

Rose Bengal, A c r i d i n Orange, Methylene Blue, C h l o r o p h y l l and Hematoporphyrin a r e t h e most c u r r e n t s e n s i t i z e r s . It i s Hematoporphyrin t h a t i s employed i n phototherapy, i n c o n s i d e r a t i o n o f t h e two p r o p e r t i e s :

.

^{i t}i s a good s e n s i t i z e r w i t h o u t i m p o r t a n t t o x i c i t y ;

.

i t s l i f e t i m e i n carcinogenic c e l l s i s longer than i n normal c e l l s .

The a c t i o n o f l i g h t on Hematoporphyrin i n ill c e l l s gives s i n g l e t oxygen ( s t r o n g o x i d a n t ) which destroys them. An example o f photochemical s t u d i e s usefulness i s given.

L i g h t can b r i n g about o r i n i t i a t e some chemical r e a c t i o n s , b u t i t i s necessary t h a t one o f t h e c o n s t i t u a n t s i n the r e a c t a n t media absorbs t h i s l i g h t .

Then we can have two cases :

1

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The l i g h t i s absorbed by the s t u d i e d r e a c t a n t which i s transformed o r r e a c t s f o l l o w i n g t h i s absorption : i t i s named a d i r e c t photochemical r e a c t i o n .

ex : t h f l j n e - i j m g y i z a t i o n

C

Article published online by EDP Sciences and available at http://dx.doi.org/10.1051/jphyscol:1987755

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CY-248 JOURNAL DE _PHYSIQUE

2

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The l i g h t i s absorbed by a constituant which does not generally p a r t i c i p a t e in t h e reaction : i t i s only present t o catch a photon and then t o i n i t i a t e the chemical process. I t plays as a kind of " c a t a l y s t " .

I t makes t h e reaction s e n s i t i v e t o the l i g h t : : t h i s type of s i t u a t i o n i s called a photosensitized reaction.

v i s i b l e l i g h t

"2 ⁺ (chlorophyll) 6' H12 ' 6 ⁺ ' 2

To understand the route of a photochemical reaction, i t i s necessary t o give a brief and simplified scheme of what happens in a molecule which absorbs a photon.

The ground s t a t e i s the s t a b l e s t a t e in which the molecules are generally present.

For organic molecules t h i s s t a t e i s a s i n g l e t s t a t e : t h a t means t h a t spins of elec- trons in the high energy o r b i t a l t h a t i s occupied a r e paired.

The energy of the absorbed photon i s used t o energize an electron and cause i t t o jump t o a higher energy level. Two excited electronic s t a t e s can be obtained. In one, the spin of the electron i s not changed : t h i s s t a t e i s termed an excited s i n g l e t s t a t e . In t h e second case, t h e electron spin i s changed and the two electron spins

=ow unpairedgivingan excited t r i p l e t s t a t e .

After photoexcitation, the molecule can follow d i f f e r e n t paths, according t o the following s t a t e energy diagram (1).

In the case of a photosensitized reaction, the photosensitizer can follow two paths giving :

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e i t h e r , an electron t r a n s f e r

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o r , an energy t r a n s f e r

For example, in photo-oxidation with oxygen, i t i s possible t o have :

A

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Type I photo-oxidation reactions : the photosensitizer t r a n s f e r s an electron t o t h e substrate, or a b s t r a c t s an hydrogen atom

S

+

h3

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^S" ( s i n g l e t or t r i p l e t )

s'+ RH-SH'

+

R '

o r

sf

ⁱR'-s+ i R: then radicals react w i t h oxygen

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B

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Type I1 photo-oxidation reactions : the photosensitizer t r a n s f e r s i t s energy t o a molecule of oxygen.

S + hv

-

^S' ( t r i p l e t )

s* + o* -

^S ⁺ ^0;

oxygen in ground s t a t e i s i n a t r i p l e t s t a t e c o n t r a r i l y t o organic molecules. In the excited s t a t e , obtained by energy t r a n s f e r , the oxygen molecule i s in a s i n g l e t s t a t e .

Singlet oxygen has special physical properties which allow characterization of i t . Moreover i t i s a very reactive species : I t i s a strong oxidizing agent.

Among the main photosensitizers currently used, there a r e Rose Bengal, Acridin Orange, Methylene Blue, Chlorophyll and Hematoporphyrin.

In t h e phototherapy treatment i t i s Hematoporphyrin and i t s derivatives which a r e employed, on account of the three following properties ( 2 ) .

1

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I t i s a good s e n s i t i z e r and the quantum yield of s i n g l e t oxygen production i s about 0.6.

2

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The l i f e time in carcinogenic c e l l s i s longer than in normal c e l l s . 3

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I t has no t o x i c i t y f o r human organism.

With Hematoprophyrin (HP) the scheme of action i s l i k e type I1 photo-oxidation ( 3 ) .

l * 3

HP

+

hv- HP---,HP*

The stages shown being very simplified and schematic.

Thus s i n g l e t oxygen hence produced i n tumoral c e l l s , destroys them ( 4 ) .

I t has been shown by d i f f e r e n t authors, t h a t type I photo-oxidation does not occur with Hematoporphyrin and i t should be noted t h a t generally i t i s derivatives of Hematoporphyrin which a r e used (see conference of Dr. BRAULT) ( 5 ) ( 6 ) . This i s due t o the difference of the penetration of l i g h t i n t o c e l l s and a l s o a b e t t e r e f f i c i e n - cy of s i n g l e t oxygen production.

Moreover, the agregate s t a t e of molecules, which seems to be an important f a c t o r , i s d i f f e r e n t in HP and HP derivatives.

An absorption spectrum of Hematoporphyrin i s given here. Hematoporphyrin d e r i v a t i - ves have similar spectra.

The f i r s t treatments used white l i g h t sources, l i k e xenon lamps. More recently the use of l a s e r s allows transportation of l i g h t along an optical f i b e r and s e l e c t i v e i r r a d i a t i o n of t h e tumoral s i t e s ( 7 ) ( 8 ) .

The wavelength of 630 nm i s used and i s produced by a dye laser ; t h i s l i g h t has a good penetration into the t i s s u e s because they have a "window" of absorption between 630 and 900 nm.

Absorption spectrum of H.P. derivatives

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JOURNAL DE PHYSIQUE

Quantum y i e l d o f '0; p r o d u c t i o n

The d e s t r u c t i o n o f these c e l l s by t h i s technique could be e f f e c t i v e up t o 20 mm depth.

Unfortunately the l i g h t a t 630 nm i s o n l y s l i g t h l y absorbed by H.P. d e r i v a t i v e s and t h e problem i s t o f i n d a new molecule which has a good a b s o r p t i o n between 630 nm and 900 nm. Phtalocyanin, c h l o r i n e

...

a r e t h e products towards which research i s now heading (see conf. o f Dr. BRAULT).

O f course t h e t r u e e f f i c i e n c y i s found by u s i n g " i n v i v o " experiments, b u t t h e knowledge o f photochemical behaviors i s i m p o r t a n t t o o p t i m i z e t h e treatment condi- t i o n s . For example, t o a v o i d o r t o minimize t h e r i s k o f erythema i t i s necessary t o

Photochemical e f f e c t e f f i c i e n c y A

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^Rabbit¹^{i v e r}

B

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R a b b i t muscle

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employ t h e s m a l l e s t q u a n t i t ' e s o f H.P. d e r i v a t i v e s . A photochemical study o f

1

05 p r o d u c t i o n i n d i c a t e s t h a t t h e quantum y i e l d v a r i e s w i t h t h e wavelength o f i r r a d i a t i o n . Taking i n t o account t h e a b s o r p t i o n o f t i s s u e s and H.P. d e r i v a t i v e s , i t i s seen t h a t t h e e f f i c i e n c y a l s o v a r i e s w i t h wavelength o f i r r a - d i a t i o n .

I n t h e same manner, t h e p e n e t r a t i o n o f l i g h t , i s more o r l e s s important, according t o t h e wavelength used.

The conclusion i s t h a t a compromise has t o be found between wavelength and penetra- t i o n . For example, i n t h e case o f s u p e r f i c i a l tumors i t would be b e t t e r t o i r r a d i a t e by a l i g h t near 530 nm,

Photochemical e f f e c t e f f i c i e n c y Wavelength o f i r r a d i a t i o n

620 nm

- - 530 nm

References

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1

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N.J. TURRO

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Modern Molecular Photochemistry. Benjamin/Cummings, P u b l i s h i n g t o Menlo Park, 1978.

2

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^R. LIPSON, E. BALDES and A. OLSEN, J. N a t l . Cancer I n s t .

26,

1, 1961.

3

-

M.C. BERENBAUM, R. BONNET and P.O. SCOURIDES, Br. J. Cancer,

-

45, 71, 1982.

4

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T.J. DOUGHERTY, W.R. POTTER and K.R. WEISHAUPT, I n Porphyrins i n Tumor Photo- therapy, 23, 1984.

5

-

C.J. GOMER, Cancer Res.,

3,

146, 1979.

6

-

^D. KESSEL, Cancer Res.,

5,

1318, 1981.

7

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K.R. WEISHAUPT, C.J. GOMER and T.J. DOUGHERTY, Cancer Res.,

36,

2326, 1976.

8

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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.

-