80

Chapter 2

Studies on Photochemistry of

Photosensitizing Drugs Trimeprazine

and Fluvoxamine

81

Introduction

Recently, much attention has turned to the problem of biological photosensitization by

drugs. Indeed, despite their excellent therapeutic activity, many drugs can induce

phototoxic, photoallergic and photomutagenic phenomena, strictly related to the drug

photochemical reactivity 1-3. Photosensitization reactions leading to phototoxicity are

generally considered as belonging to either the type I (radical mediated) or type II 4-6

(singlet oxygen mediated).

There are photosensitizing drugs of varied structural variety and significant variations

in the phototoxic mechanisms must be expected depending on the difference in

structural features 7. Moreover, associated with its own chromophoric structural

features, it is the individuality of the drug to follow a typical course of

photodegradation and photosensitization. It is therefore highly desirable to study the

photochemical reaction of each individual photosensitizing drug.

Oxygen is an abundant element with multiple faces. It’s most common and important

one is the molecular form (O2), which is a prerequisite for all aerobic cell

metabolisms. Singlet oxygen (1O2) is an excited state of molecular oxygen and can be

produced by energy transfer (type II reaction) from excited triplet photosensitizers

such as flavins, tetrapyrrols, protoporphyrins, rose bengal, benzophenone and

riboflavin to the molecular oxygen. Several drugs are known act themselves as

potential singlet oxygen sensitizer. Singlet oxygen is very toxic to organisms because

it reacts with important biological molecules such as unsaturated lipids, oxidizable

amino acids, and nucleic acids, particularly guanosine derivatives 8. The resulting

reactions cause destruction of membranes, enzyme inactivation, and mutations, all of

which can lead to cell death. Singlet molecular oxygen involving photochemical

82

reactions are a matter of current interest, mainly due to their important role in the

photosensitization processes and drug phototoxicity 9.

So the studies on singlet oxygen mediated photoreactions of drug are relevant to

understand the mechanism of drug phototoxicity. With this interest herein we have

undertaken the following study:

[A] Photodegradation of Trimeprazine Triggered by Self-Photogenerated

Singlet Molecular Oxygen

[B] Singlet Oxygen Mediated Photooxidation of Fluvoxamine, a Photosensitive

Antidepressant Drug

83

Section [A]

Photodegradation of Trimeprazine

Triggered by Self -Photogenerated

Singlet Molecular Oxygen

84

[A] Photodegradation of Trimeprazine Triggered by Self- Photogenerated

Singlet Molecular Oxygen

Phenothiazines are a class of neuroleptic drugs 10,11 used in the therapy of mental

disorders, in particular in the treatment of various psychoses including schizophrenia

and mania, as well as disturbed behavior and in the short-term, as adjunctive

management of severe anxiety 12,13. Beside several dermatologic side effects, such as

eczema, erythema and exfoliative dermatitis, patients receiving phenothiazines often

experience the occurrence of photosensitivity in terms of both phototoxic and

photoallergic14,15 reactions. Moreover, given the phototoxicity of these drugs 16,17 a

large number of investigations on the photochemical properties of these substances

have been carried out. Several reports also indicate that irradiation of phenothiazines

can produce singlet oxygen 18 but, surprisingly, very few studies have dealt with the

chemical reactivity of singlet oxygen (1O2) with the phenothiazines themselves.

Trimeprazine (N, N, 2-trimethyl-3-phenothiazin-10-yl-propan-1-amine, also known as

Alimemazine) is a tricyclic antihistamine, similar in structure to the phenothiazine

antipsychotics, but differing in the ring-substitution 19 and chain characteristics.

Trimeprazine (1) is in the same class of drugs as chlorpromazine (Thorazine) and

trifluoperazine (Stelazine); however, unlike the other drugs in this class, trimeprazine

(1) is not used clinically as an anti-psychotic 20. It acts as anti-histamine, a sedative

and an anti-emetic (anti-nausea) 21. Trimeprazine (1) is used principally as an anti-

emetic to prevent motion sickness or as anti-histamine in combination with other

medications in cough and cold preparations. It is also used for insomnia and oral

premedication in pediatric day surgery 22. Tricyclic antihistamines are also

structurally-related to the tricyclic antidepressants, explaining the antihistaminergic

85

adverse effects of these two drug classes and also the poor tolerability profile of

tricyclic H1-antihistamines. Interest in the photo reactivity of trimeprazine (1) arises

from the clinical and pharmacological reports of phototoxic effects demonstrated by

this drug 23, 24.

In pursuance of our interest in the photochemical reactions involved in the

phototoxicity of the photosensitizing drugs and their mechanisms, herein we have

examined the photochemical behaviour of the antihistaminic drug trimeprazine (1, a

Phenothiazine derivative) under aerobic condition. Photolysis of trimeprazine (TMPZ,

1) in the presence of oxygen resulted in the formation of two photodegradation

products, identified as (2) and (4) from their spectral (IR, 1H-NMR, 13C-NMR, Mass

spectra) properties (Scheme-2A.1). The products are formed by oxidative

photodegradation of trimeprazine (1) in an irreversible trapping of the self-

photogenerated singlet molecular oxygen (1O2) in the type II photodynamic action of

the drug.

Experimental

Chemicals

All chemicals used were of analytical grade. Pure trimeprazine, 2, 5-dimethylfuran (2,

5-DMF), rose bengal, methylene blue, riboflavin and benzophenone were purchased

from Sigma Aldrich (India).

Apparatus

Photochemical reactions were carried out in quartz fitted immersion well

photochemical reactor equipped with 400W medium pressure mercury vapour lamp

with continuous supply of water. IR spectra were recorded as KBr discs on a Perkin

Elmer model spectrum RXI. 1H-NMR and 13C-NMR spectra were recorded on a

86

Bruker Avance DRX-300 Spectrometer using TMS as internal standard and CD3OD

as solvent. High resolution mass spectra were determined with a VG-ZAB-BEQ9

spectrometer at 70 e V ionization voltage. Column chromatography was performed on

silica gel 60 (70-230 mesh); thin layer chromatography (TLC) was carried on Merck

silica gel 60 F 254 (0.2 mm thick plates).

Photoirradiation procedure

A solution of trimeprazine (1, 275 mg, 0.9 mM) in methanol (400 ml) under aerobic

condition was irradiated for 1 hr in a Rayonet photochemical reactor for the complete

conversion of reactant. Progress of the reaction was monitored by thin layer

chromatography (TLC) (chloroform-methanol, 98:2). At the end of the reaction

formation of two major photoproducts were indicated on TLC and photoproducts

were isolated and purified by column chromatography using dichloromethane-ethyl

ether (1:1, v/v) on a silica gel column. The photoproducts were identified as, N, N 2-

trimethyl-3-(10 H-phenothiazin-10-yl sulfoxide) propan-1-amine (2) and N, 2-

dimethyl-3-(10 H-phenothiazin-10-yl) propan-1-amine (4) from the following

spectral properties:

N, N 2- trimethyl-3-(10 H-phenothiazin-10-yl sulfoxide) propan-1-amine (2):

Yield: 95 mg (34.5%); HRMS calcd. For (M+) C18H22N2OS 314.1453 Found

314.1448; IR (KBr): 3416, 2965, 1388, 1301, 1270, 1209, 1055 (SO), 978, 763 cm-1;

1H-NMR (CD3OD, , ppm): 7.12- 6.9 (m, 8 H, arom), 4.60 (d, J=7.3 Hz, 2 H, H-15),

2.32 (s, 6 H, H-19, H-20), 2.27 (d, J=7.4Hz, 2 H, H-17), 2.13 (m, 1 H, H-16), 1.02 (d,

J=6.0 Hz, 3 H, H-21); 13C-NMR (CD3OD, , ppm): 145.1, 131.0, 128.6, 119.3, 118.2,

62.2, 55.3, 36.1, 32.1, 16.0; MS: m/z: 314 (M+), 298 (M+- 16), 214 (M+- 100).

87

N, 2- dimethyl-3-(10 H-phenothiazin-10-yl) propan-1-amine (4):

Yield: 75 mg (27.2%); HRMS calcd. For (M+) C17H20N2S 284.4191 Found 284.4185;

IR (KBr): 1388, 1301, 1270, 1209, 978, 763 cm-1; 1H-NMR ( CD3OD, , ppm): 7.12-

6.9 (m, 8H, arom), 4.50 (d, J=7.3 Hz, 2 H, H-15), 2.38 ( s, 3 H, H-19), 2.26 (d, J=7.4

Hz, 2 H, H-17), 2.0 (m, 1 H, NH), 1.02 (d, J=6.0 Hz, 3 H, H-20); 13C NMR (CD3OD,

, ppm): 145.2, 131.1, 128.7, 119.4, 118.3, 62.3, 55.4, 36.2, 32.2, 15.9; MS: m/z: 284

(M+), 198 (M+- 86).

Singlet Oxygen detection

In order to confirm the role of singlet oxygen (1O2) as a trigger of trimeprazine (1,

TMPZ) photodecomposition, photolysis was performed under the same experimental

condition but now in the presence of 2, 5-dimethylfuran (2, 5-DMF) which is

normally used as a trap for singlet oxygen (1O2) 25.

Similar experiment was also carried out by using different sensitizers such as

methylene blue, rose bengal, riboflavin, benzophenone to study the effect of triplet

energy of sensitizer on the percentage yields of photoproducts.

Results and discussion

The two major photoproducts, N, N 2- trimethyl-3-(10 H-phenothiazin-10-yl

sulfoxide) propan-1-amine (2) and N, 2-dimethyl-3-(10 H-phenothiazin-10-yl)

propan-1-amine (4), which were obtained on irradiation of trimeprazine (1) in

methanol under oxygen atmosphere, are depicted in scheme-2A.1. The spectral

features correlated to the assigned structure of the products and were done in

comparison with the spectra of the starting drug. The 1H-NMR spectrum of the

photoproduct (4) showed signals similar to those of trimeprazine, except for signals at

2.27 ppm for one of the -CH3 group associated with the N-dimethyl amino nitrogen

88

of starting drug trimeprazine. A new signal in the photoproduct (4) at δ 2.0 ppm was

assigned to the proton of NH. The 13C-NMR spectrum of photoproduct (4) showed

signals similar to those of trimeprazine except for the loss of signal of one of the -CH3

group associated with the N-dimethyl amino nitrogen. The IR spectrum of

photoproduct (2) showed absorption band at 1055 cm-1. That indicates the presence of

sulfoxide group.

The formation of photoproduct has been rationalized in the photosensitized generation

of singlet oxygen by the type II photodynamic action of the drug and subsequent

quenching of the generated singlet oxygen by the drug as proposed in scheme -2A.2.

Photoproduct (2) is formed by simple sulfoxidation of parent compound and

photoproduct (4) is formed through a mechanism in which a charge transfer complex

is formed involving the N-dimethyl amino nitrogen of trimeprazine (1) and 1O2. This

complex, in addition to intersystem crossing process, undergoes -hydrogen

abstraction to form a transient -amino carbon radical (3) and peroxy radical (HO2).

Both of these radical can then undergo electron transfer to produce an iminium cation

leading to the N-demethylation product (4). This mechanism is in agreement with

photodegradation pathway proposed for N-demethylation of trialkylamines 26-28.

89

Scheme-2A.1

S

N

N

hvO2 S

N

N

O(1) (2)

S

N

NH

(4)

90

S

N

NO O

S

N

N CH2

HO2

S

N

N CH2

S

N

NH

S

N

N

1O2

-e-

-HO2

H2O -H+

(1)

(4)

..

(3)

TM PZ (S 0 )hv O2 1O2

(1)

1O2

S

N

N

O(2)

TMPZ(S1) TMPZ(T1)

CH2O

Scheme- 2A.2

91

When trimeprazine (1) was irradiated with singlet oxygen scavenger 2, 5-

dimethylfuran (2, 5 DMF) it compete with drug for singlet oxygen (1O2), and

decreased the availability of singlet oxygen (1O2) therefore slowed down the rate of

photodegradation.

In order to further ascertain the oxidative photodegradation of trimeprazine (1) by its

quenching of the self-photogenerated singlet oxygen, the drug was photolysed under

the same experimental condition, in the presence of well known photosensitized

singlet oxygen generator, where same photoproducts were obtained in different yields.

Rose bengal and methylene blue was much more efficient than riboflavin and

benzophenone in the photosensitized decomposition of (1) (Table-2A.1). This may be

due to the fact that rose bengal and methylene blue, with lower triplet energies,

produce singlet oxygen in large amount 29,30 by type II mechanism 31. On other hand

riboflavin and benzophenone (higher triplet energies) act mainly by type I

photosensitized photooxidation, do not produce significant amount of 1O2 32.

92

Sensitizers Triplet energy (kcal /mole) Yields of photoproducts (%)

(2+4)

Methylene blue 33.5 - 34.0 60.9 (34.3+26.6)

Rose bengal 39.2 - 42.2 59.5 (32.3+27.2)

Riboflavin 57.8 50.4 (26.5+23.9)

Benzophenone 68.6 - 69.1 49.1 (25.1+24.0)

Table 2A.1 Effect of Triplet energies of different sensitizers on the yields of

photoproducts.

93

The present study demonstrated that these photoproducts are formed by irreversible

trapping of self-photogenerated singlet molecular oxygen. The formation of

photoproducts through oxygenation is relevant to understand the mechanism of

photobiological effect of trimeprazine (1).

Usually, the self-sensitized drug photooxidation (or singlet oxygen physical

quenching) is barely considered, although it would be important because if singlet

oxygen (1O2) is quenched, it will not be available to react with other biologically

relevant substrates.

94

Section [B]

Singlet Oxygen Mediated Photooxidation

of Fluvoxamine, a Photosensitive

Antidepressant Drug

95

[B] Singlet Oxygen Mediated Photooxidation of Fluvoxamine, a Photosensitive

Antidepressant Drug

Oximes and their derivatives have found widespread use in synthetic organic

chemistry as protecting groups for carbonyl compounds 33,34. In addition to their

synthetic utility, many oximes are commonly used as pesticides 35 (including the

structurally related carbamates) as photo-initiators 36 and as drugs e.g., as antidotes for

organ phosphorus poisoning 37,38. The photochemical reactions of oximes have

received considerable attention 39-41. A number of pathways are available to oximes in

the excited state and oximes may form a range of reactive intermediates in these

reactions such as excited-state oximes (singlet or triplet), oxime radical cations, or

reactive species (radicals) derived from these such as iminoxyl radicals, which have

the potential to cause cell and tissue damage 42. Photooxidation is a major tool to

generate these reactive intermediates hence photochemical oxidations of oximes

direct or sensitized, by energy or electron transfer, has attracted ever-growing

interest43.

Fluvoxamine (FXM, 5); (E)-5-methoxy-4′-trifluromethyl-valerophenone O-2-

aminoethyl-oxime is a new generation antidepressant drug 44,45. It exerts its

antidepressant effect through a selective inhibition for the reuptake of the

neurotransmitter serotonin by the presynaptic receptors hence it group of selective

serotonin reuptake inhibitors (SSRIs) 46,47. They are replacing the older tricyclic

antidepressants (TCAs) and because the efficacy of the SSRIs does not differ

significantly from that of the TCAs and the SSRIs do not show severe extra pyrimidal

side-effects, SSRIs are more and more becoming the drugs of choice in depression

therapy 48-50 . Although originally developed as an antidepressant, its most widespread

96

application is in the treatment of anxiety disorders, particularly obsessive-compulsive

disorder (OCD) in adults and children 51. In recent years, there have been a number of

studies of fluvoxamine (5) in other anxiety disorders, particularly in social anxiety

disorder (SAD) and its eastern equivalent taijin kyofusho 52. Like the other SSRIs, there

is somewhat less evidence available for efficacy in panic disorder, but fluvoxamine (5)

has significant advantages over the benzodiazepines in day-to-day usage 53.

Fluvoxamine (5) shows efficacy in the group of illnesses some have characterized as

the obsessive compulsive spectrum disorders. Such disorders include a number of

eating disorders, pathological gambling, body dysmorphic disorder and even

compulsive shopping 54. The serotonin syndrome or serotonin-syndrome-like side

effects occur during treatment with fluvoxamine (5). Side effects most commonly

observed with fluvoxamine (5) include nausea, vomiting, drowsiness, insomnia,

dizziness, nervousness, feeling anxious, dry mouth, abdominal pain, constipation,

diarrhea, heart burn, loss of appetite, muscle weakness, pins and needles, abnormal

taste, headache, faster heart beat, sweating, weight gain, weight loss or unusual

bruising. Other side effects which are observed more frequently in children includes

abnormal thoughts or behaviour, cough, increased period pain, nose bleeds, increased

restlessness, infection and sinusitis 55. Sexual side effects with fluvoxamine are less

pronounced than with other SSRIs 56. Despite its useful clinical activity it is also known

to posses phototosensitizing properties that lead to phototoxic responses in human 57. In

continuation of our interest in the photochemical reactions involved in the phototoxicity

of the photosensitizing drugs and their mechanisms and to delineate the underlying

photochemical reaction that may possibly be involved in its phototoxicity, herein we

have examined the photochemical behaviour of fluvoxamine (5) in presence of

97

methylene blue under aerobic condition as dye sensitized formation of singlet oxygen

and its reaction with drug are relevant to understand the phototoxicity of drug 58.

Photosensitized oxidation of fluvoxamine (5) resulted in the formation of two

photodegradation products identified as (6) and (7) from their spectral (IR, 1H-NMR,

13C-NMR, Mass spectra) properties (Scheme-2B.1). The Photoproducts are formed by

the reaction of drug with singlet oxygen produced through type II photodynamic action.

Experimental

Chemicals

All chemicals used were of analytical grade. Fluvoxamine (5) was extracted from

commercial medicament sorest (Ranbaxy Laboratories, New Delhi, India). The purity

of drug, extracted was checked by thin layer chromatography (TLC) and comparing

its melting point with the literature value. 1, 4-diazabicyclo [2.2.2] octane (DABCO),

rose bengal, methylene blue, riboflavin and benzophenone were purchased from

Sigma Aldrich (India).

Apparatus

Photochemical reactions were carried out in quartz fitted immersion well

photochemical reactor equipped with 400W medium pressure mercury vapour lamp

with continuous supply of water. IR spectra were recorded as KBr discs on a Perkin

Elmer model spectrum RXI. 1H-NMR and 13C-NMR Spectra were recorded on a

Bruker Avance DRX -300 Spectrometer using TMS as internal standard and CDCl3 as

solvent. High resolution mass spectra were determined with a VG-ZAB-BEQ9

spectrometer at 70 e V ionization voltage. Column chromatography was performed on

silica gel 60 (70-230 mesh); thin layer chromatography (TLC) was carried on Merck

silica gel 60 F254 (0.2 mm thick plates).

98

Photoirradiation procedure

Irradiation of air-saturated solution of fluvoxamine (5) (210, 0.66 mM) in methanol

with methylene blue as sensitizer was carried out with medium pressure mercury

vapour lamp for 6 h. Progress of the reaction was monitored by thin layer

chromatography (TLC) (chloroform-methanol, 98:2). At the end of the reaction

formation of two photoproducts were indicated on TLC which was isolated and

purified by column chromatography using dichloromethane: methanol (8:2) on a silica

gel column. The photoproducts were identified as, 5-Methoxy-1-(4-(trifluoromethyl)

phenyl) pentan-1-one (6) and 2-nitroethanamine (7) from the following spectral

properties:

5-Methoxy-1-(4-(trifluoromethyl) phenyl) pentan-1-one (6):

Yield: 95 mg (45.23 %); HRMS calcd. For (M+) C13H15F3O2 260.2522 Found

260.2519; IR (KBr): 1715, 1600, 1500, 1210 cm-1; 1H NMR (CDCl3, , ppm): 3.26

(s, 3H, H-6), 2.70 (t, 2H, H-2), 1.62 (m, 2H, H-4), 1.61 (m, 2H, H-3); 13C-NMR

(CDCl3, , ppm): 197.1 (C-1), 139.07 (C-1’), 132.4 (C-4’), 125.28 (C-3’& C-5’),

124.1 (CF3), 73.6 (C-5), 58.2 (C-6), 35.8 (C-2), 29.4 (C-4), 23.02 (C-3); MS: m/z: 260

(M+), 229 (M+-31), 191 (M+- 69), 145 (M+-115).

2-nitroethanamine (7):

Yield: 37 mg (17.6 %); HRMS calcd. For (M+) C2H6N2O2 90.0812 Found 90.0801;

IR(KBr): 3140, 3250 (NH2), 1345 (NO2) cm-1; 1H-NMR (CDCl3, , ppm): 4.66 (m,

2H, H-2), 3.26 (m, 2H, H-1), 2.0 (s, 2H, NH2); 13C-NMR (CDCl3, , ppm): 79.5 (C-

2), 38.5 (C-1); MS: m/z: 90 (M+), 44 (M+- 46), 74 (M+- 16).

99

Similar experiments were carried out by using different combinations of sensitizers

such as methylene blue, rose bengal, riboflavin and benzophenone to study the effect

of triplet energy of sensitizer on the percentage yields of photoproducts.

In order to confirm the role of singlet oxygen (1O2) in this photoreaction, photolysis

was also carried out under nitrogen atmosphere and in presence of 1, 4-diazabicyclo

[2.2.2] octane (DABCO) which is normally used as a singlet oxygen scavenger 59.

Results and Discussion

Irradiation of air-saturated methanolic solution of fluvoxamine (5) with methylene

blue as sensitizer in a water-cooled immersion well type photoreactor equipped with

medium pressure mercury vapour lamp and purification of the crude product by silica

gel column chromatography afforded two photoproducts, 5-Methoxy-1-(4-

(trifluoromethyl) phenyl) pentan-1-one (6) and 2-nitroethanamine (7). (Scheme-2B.1).

The spectral features correlated to the assigned structure of the photoproduct (6) and

were done in comparison with the spectra of the starting drug. The 1H NMR spectrum

of photoproduct (6) was devoid of signals at δ 3.79, 2.84 and 2.0 ppm for substituted

amino ethyl group that was present in the starting drug fluvoxamine; however rest of

the proton signals were similar to that of the parent drug. The 13C NMR spectrum of

photoproduct (6) further supported the loss of the substituted amino ethyl group. A

new signal at 197.1 ppm corresponding to keto group indicated that substituted

amino ethyl group has been replaced by keto group in the product.

The Photoproducts are formed by the reaction of fluvoxamine (5) with singlet oxygen

produced through type II photodynamic action. Formation of photoproducts has been

realized as depicted in scheme-2B.2. Interaction between oxygen and the triplet state

of sensitizer (methylene blue) results in energy transfer yielding singlet oxygen (1O2).

100

The generated singlet oxygen (1O2) would undergo [2 + 2] cycloaddition with the

C=N double bond of the fluvoxamine (5) to gave dioxetane analogues as in the case

of the cycloaddition with olefins 60. The unstable dioxetane analogues could

decompose under the reaction conditions to yield the corresponding carbonyl product

5-Methoxy-1-(4-(trifluoromethyl) phenyl) pentan-1-one (6) and a side product 2-

nitroethanamine (7).

The effect of triplet energies of various sensitizers on the percentage yields of

photoproducts has also been studied. It was observed that rose bengal and methylene

blue was much more efficient than riboflavin and benzophenone in the

photosensitized decomposition of (5) (Table 2B.1). This may be due to the fact that

rose bengal and methylene blue, with lower triplet energies, produce singlet oxygen in

large amount 61, 62 by type II mechanism 63. On other hand riboflavin and

benzophenone (higher triplet energies) act mainly by type I photosensitized

photooxidation, do not produce significant amount of singlet oxygen (1O2) 64. The

participation of 1O2 in the reaction was confirmed by studying the effect of scavenger

on the yield of this photooxidation reaction product. The drastic lowering of the yield

of products in presence of scavenger (DABCO) confirms that singlet oxygen (1O2) is

an active oxidizing species in this photoreaction. Also no reaction was observed on

conducting experiments under nitrogen atmosphere, which further support the

involvement of singlet oxygen (1O2) in this photoreaction.

101

F3C

N

ONH2

OCH3

(5)Fluvoxamine

F3C

O

OCH3

(6)

O2N NH2

(7)

O2

Sens.(Methylene blue)

Scheme-2B.1

102

F3C

CN

ONH2

F3C

C N

OCH3

R

O O

O NH2

F3C

C NR

O O

O NH2R =

R

(5)

(6) (7)

1O2

Sens.hv 1Sens * 3Sens *

Sens 1O2

O2ISC

Scheme-2B.2

103

Sensitizers Triplet energy (kcal /mole) Yields of photoproducts (%)

(2+3)

Methylene blue 33.5 - 34.0 62.8 (45.2+17.6)

Rose bengal 39.2 - 42.2 58.4 (35.2+23.2)

Riboflavin 57.8 47.8 (25.3+22.5)

Benzophenone 68.6 - 69.1 49.1 (24.5+22.0)

Table 2B.1 Effect of Triplet energies of different sensitizers on the yields of

Photoproducts

104

To conclude, the present results have shown that the photooxidation products are

formed by singlet oxygen (1O2) mediated photodynamic action upon sensitized visible

light irradiation of fluvoxamine (5). 5-Methoxy-1-(4-(trifluoromethyl) phenyl)

pentan-1-one (6) was identified as the main photooxidation product.

The investigation of photochemical properties of compounds used in clinical

medicines is of great relevance from photobiological as well as photo medical point of

view since singlet oxygen formation and the ensuing photooxidation of the drug and

biomolecules is one of the main routes for the drug phototoxicity. The present

findings may have an implication to the phototoxic effect of the drug.

105

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