studies on photochemistry of photosensitizing...
TRANSCRIPT
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
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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
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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
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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
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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.
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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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