Phenolic hydrogen abstraction by the triplet excited state of thiochromanone: A laser flash photolysis study

Article abstract of DOI:10.1590/S0103-50532010000600017

Triplet ketones are known to oxidize biological substrates which can lead to damage of several biomolecules such as amino acids, nucleosides and DNA. As part of our systematic study on the interaction between carbonyl compounds and phenols, the triplet reactivity of thiochromanone (1) towards substituted phenols, in acetonitrile, was investigated employing the laser fash photolysis technique. The quenching rate constants ranged from (1.1 ± 0.1) × 10⁸ L mol^-1 s^-1 (4-cyanophenol) to (5.8 ± 1.0) × 10⁹ L mol^-1 s^-1 (hydroquinone). A Hammett plot for the reaction of triplet 1 with phenols containing polar substituents resulted in a reaction constant ρ =-0.90. This negative value observed for the reaction constant ρ is in accord with a mechanism in which the hydrogen transfer from phenols to the triplet carbonyl involves a coupled electron/proton transfer.

Full text of DOI:10.1590/S0103-50532010000600017

J. Braz. Chem. Soc., Vol. 21, No. 6, 1071-1076, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Phenolic Hydrogen Abstraction by the Triplet Excited State of Thiochromanone:
A Laser Flash Photolysis Study
Alessandra M. Ribeiro,a Ada Ruth Bertotib and José Carlos Netto-Ferreira*,a,b
aDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de
Janeiro, 23851-970 Seropédica-RJ, Brazil
bInstituto de Química, Universidade Federal da Bahia, Campus de Ondina,
40170-490 Salvador-BA, Brazil
O estado excitado triplete de cetonas pode oxidar substratos biológicos acarretando danos a
diversas biomoléculas como aminoácidos, nucleosídeos e mesmo DNA. Como parte de nossos
estudos acerca da interação entre carbonilas e fenóis, foi investigada a reatividade do estado excitado
triplete de tiocromanona (1) frente a fenóis, em acetonitrila, empregando a técnica de fotólise por
pulso de laser de nanossegundo. As constantes de velocidade de supressão obtidas variaram de
(1,1 0,1) × 108 L mol-1 s-1 (4-cianofenol) a (5,8 1,0) × 109 L mol-1 s-1 (hidroquinona). Um gráfico
de Hammett para a reação do triplete de 1 com uma série de fenóis contendo substituintes polares
resultou em uma constante de reação r = -0,90. Este valor negativo para a constante de reação r
está plenamente de acordo com um mecanismo envolvendo uma transferência acoplada elétron/
próton no processo de transferência de hidrogênio do fenol para a carbonila triplete.
Triplet ketones are known to oxidize biological substrates which can lead to damage of several
biomolecules such as amino acids, nucleosides and DNA. As part of our systematic study on the
interaction between carbonyl compounds and phenols, the triplet reactivity of thiochromanone (1)
towards substituted phenols, in acetonitrile, was investigated employing the laser flash photolysis
technique. The quenching rate constants ranged from (1.1 0.1) × 108 L mol-1 s-1 (4-cyanophenol)
to (5.8 1.0) × 109 L mol-1 s-1 (hydroquinone). A Hammett plot for the reaction of triplet 1 with
phenols containing polar substituents resulted in a reaction constant r = -0.90. This negative value
observed for the reaction constant r is in accord with a mechanism in which the hydrogen transfer
from phenols to the triplet carbonyl involves a coupled electron/proton transfer.
Keywords: thiochromanone, laser flash photolysis, triplet excited state, hydrogen donors
Introduction
of the former as well as the low oxidation potential of
the later.4,16 Experimentally, this coupled electron/proton
transfer mechanism ultimately results in the formation of
the ketyl-aryloxyl radical pair.
In the last few years the phenolic hydrogen abstraction
by carbonyl compounds in the triplet excited state has
been extensively studied employing experimental and
theoretical methods.1-16 The mechanism for this process
is now well established and involves the initial formation
of a hydrogen-bonded exciplex in the triplet excited state,
followed by electron transfer and, subsequently, an ultra-
fast proton transfer.4,9-16 DFT calculations clearly showed
that for the triplet complex (exciplex) ketone-phenol the
hydrogen transfer is predominantly occurring.8 The very
fast quenching rate constants of triplet carbonyls towards
phenols is consequence of both the low reduction potential
Triplet ketones are known to oxidize biological
substrates such as amino acids, nucleosides and DNA.
Due to this, topical or systemic administration of drugs
containing the carbonyl chromophore can lead to sever side-
effects upon exposure to sunlight.17 This photosensitization
process involves direct interaction between the triplet
excited state of the sensitizer (the triplet carbonyl) and
the biological substrate through the formation of an
encounter complex. This species leads to an electron
transfer reaction followed by a proton transfer, resulting in
the formation of the corresponding radical pair sensitizer/
biological substrate with the consequent damage of several
*e-mail: jcnetto@ufrrj.br

1072
Phenolic Hydrogen Abstraction by the Triplet Excited State of Thiochromanone
J. Braz. Chem. Soc.
biomolecules18-21 and, for the DNA case, this process
can be responsible for photogenotoxicity.22-25 Of special
importance is the effect of triplet carbonyl compounds
on the photoxidative process of tyrosine and tryptophan,
nucleic acid constituents containing a phenol or an indole
group, respectively, since this type of reaction can result in
high photoallergic activity when several drugs containing
the carbonyl group are employed.26-28
Thiochromanone derivatives have broad biological
activity including antibacterial29 and antifungal activity
against three Candida species, three Cryptococcus
strains, Torulopsis glabrata and Trichosporon cutaneum,
which are important pathogens to man and cause a
variety of chronic superficial and systemic diseases.30
More recently,31 it has been demonstrated that several
3-substituted thiochromanones also show several other
antifungal activity.
The ground state absorption spectrum of
thiochromanone, in acetonitrile, shows bands in the UV
(l = 264, 286 nm) and in the visible region (l = 348 nm)
of the electromagnetic spectrum. Its phosphorescence
spectrum, in 2-methyltetrahydrofuran at 77 K, is relatively
intense and shows very little vibrational progression, as
expected for pp* aromatic ketones32 and already reported
in the literature.33 This phosphorescence spectrum shows
maxima at 438 and 470 nm and from the emission at
438 nm (0-0 band) a triplet energy of 65.3 kcal mol-1 could
be calculated.33
To the best of our knowledge, the only study that has
been reported so far relative to the photoreactivity of
thiochromanone deals with its photodehydrogenation in
methanol leading to 4-thiochromone.34 In the present work
we show results concerning the photochemical reactivity
of the triplet excited sate of thiochromanone (1) towards
phenol and its derivatives containing polar substituents,
employing the laser flash photolysis technique.
4-chlorophenol, 4-fluorophenol, 4-bromophenol,
4-cyanophenol, 4-tert-butylphenol, hydroquinone, and
resorcinol, all from Aldrich, were used as received.
Nanosecond laser flash photolysis
Samples were irradiated with the 3rd harmonic
of Nd-YAG Surelite laser (lexc = 355 nm, ca. 4-6 ns,
e ≥ 40 mJ/pulse), and employing a detection system
from Luzchem (Mini-system model mLPF112). Sample
concentration (ca. 1 mmol L-1, in acetonitrile) resulted in
an absorbance of ca.0.3 at the excitation wavelength. Stock
solutions for the quenchers were prepared in acetonitrile.
Quenching procedure involved the addition of microliters
of stock solution of the quencher to the sample contained
in a Suprasil quartz cell of 10 mm × 10 mm. Samples were
deaerated for 30 min before irradiation by using oxygen-
free nitrogen.
Results and Discussion
Laser excitation (l = 355 nm) of a deoxygenated
solution of thiochromanone (1), in acetonitrile, resulted
in the formation of a transient showing absorption bands
at lmax = 420, 480, 540 and 580 nm (Figure 1A) and a
lifetime (τT) of 1.6 μs (Figure 1B). This transient was
readily quenched by b-carotene, a well-known triplet
acceptor (ET = 19 kcal mol-1; Fisc=0),35,36 for which we
obtained a quenching rate constant (kq), in acetonitrile,
of (1.1 0.1) × 1010 L mol-1 cm-1. The quenching process
followed equation 1:37
kobs = ko + kq[Q]
(1)
where: ko is the triplet decay rate constant in the absence of
quencher, kq is the triplet decay rate constant in the presence
of the quencher and [Q] is the quencher concentration in
mol L-1.
The pp* character for the thiochromanone triplet state18
was further confirmed by laser flash photolysis experiments
employing hydrogen donors such as 2-propanol and
1,4-cyclohexadiene, in acetonitrile. Attempted quenching
of 1 by 2-propanol did not result in any observable decrease
in its triplet lifetime, even at a 2-propanol concentration of
up to 1.0 mol L-1. This lead us to estimate an upper limit of
105 L mol-1 s-1 for this quenching rate constant. On the other
hand, when quenching experiments were performed with
the very efficient hydrogen donor 1,4-cyclohexadiene, a rate
constant of (7.3 0.1) × 106 L mol-1 s-1 was obtained. For
comparison, hydrogen abstraction rate constants for triplet
aromatic ketones of np* character from 1,4-cyclohexadiene
Experimental
Materials
Acetonitrile (spectroscopic grade, VETEC) was
employed as received. Thiochromanone, b-carotene,
2-propanol, 1,4-cyclohexadiene, phenol, 3-chlorophenol,

Vol. 21, No. 6, 2010
Ribeiro et al.
1073
quinone,1 1,2-aceanthrylenedione,3 and 1,2-diketopyracene4
values of -1.48; -1.04 and -0.90, respectively, were
observed.
In all cases, the proposed mechanism involves the
intermediacy of a hydrogen-bonded exciplex between the
carbonyl triplet and the phenol. Since the partially protonated
triplet is more easily reduced by the partially ionized phenol,
the hydrogen-bonding interaction is responsible for reducing
the threshold for electron transfer from phenol to triplet
ketone. After exciplex formation, the net hydrogen-atom
abstraction occurs in the form of an initial electron transfer
followed by a fast proton transfer (a coupled electron/
proton transfer mechanism). It is worth to note that the
triplet state basicity as well as the reduction potential of the
carbonyl group play a very important role in the quenching
by the hydrogen-bonded exciplex mechanism Therefore,
the enhanced basicity of the carbonyl triplet having pp*
configuration results in a more favorable hydrogen transfer
when compared to that of the n,p* state.
Figure 1. A: Triplet-triplet absorption spectra for thiochromanone (1), in
acetonitrile, recorded 1.1 (), 14.3 () and 27.3 ms (♦) after the laser pulse.
B: decay for the transient generated as in graphA and monitored at 440 nm.
are in the order of 108 L mol-1 s-1,38 whereas for pp* ketones6
kq ca. 106 L mol-1 s-1.
Linear Stern-Volmer plots (Figure 2) employing
equation 1 were obtained from quenching studies of
thiochromanone triplet by phenols containing polar
substituents (Table 1). A linear Hammett plot (Figure 3),
employing the rate constants listed in Table 1 and following
equation 2, resulted in a value for the reaction constant of
r = -0.90 (r = 0.835), similar to those obtained for other
aromatic ketones or a-diketones.
Figure 2. Quenching plots for the triplet excited state of thiochromanone
(1) by several phenols, in acetonitrile. lexc = 355 nm; lmon = 440 nm.
+
log kqX/kqH = s r
(2)
where: kqX is the quenching rate constant for a substituted
+
phenol, kqH is the quenching rate constant for phenol, s is a
Hammett constant, which depends solely on the nature and
position of the substituent, and r is the reaction constant,
which depends on the reaction under investigation and the
conditions under which it takes place.
Thus, for acenaphthenone a value of r = -1.5
was obtained,1 whereas for the a-diketones acenaphtheno-
Figure 3. Hammett plot for the hydrogen abstraction reaction of triplet 1
by phenols, in acetonitrile (R = 0.835).

1074
Phenolic Hydrogen Abstraction by the Triplet Excited State of Thiochromanone
J. Braz. Chem. Soc.
Table 1. Second order quenching rate constants for thiochromanone (1),
in acetonitrile
Quencher
kq / (L mol-1 s-1)
(3.0 0.2) × 108
(2.3 0.2) × 108
(5.3 0.6) × 108
(1.7 0.2) × 108
(6.1 0.4) × 108
(1.3 0.2) × 109
(1.1 0.1) × 108
(2.6 0.1) × 108
(5.8 1.0) × 109
(1.2 0.1) × 109
Phenol
3-Chlorophenol
4-Chlorophenol
4-Bromophenol
4-Fluorophenol
4-Methoxyphenol
4-Cyanophenol
4-terc-Butylphenol
Hydroquinone
Resorcinol
the character of their excited state. This mechanism, shown
in Scheme 1, involves an initial electron transfer from
the phenol to the excited ketone, through an intermediate
exciplex, followed by an ultrafast proton transfer, which
ultimately results in the formation of the radical pair ketyl/
phenoxyl.1-8 In support to this mechanism, Figure 4 shows
a representative spectrum obtained after laser irradiation
of a deoxygenated solution of thiochromanone (1) in the
presence of 1.4 × 10-3 mol L-1 of 4-methoxyphenol, in
The Hammett equation39,40 expresses a general
quantitative relation between the nature of a given
substituent and the reactivity of the reaction center, with
the validity of equation 2 being restricted to substituents
in the meta- and para-positions of the benzene ring. The
reaction constant (r) measures the susceptibility of the
reaction to the influence of the substituent. Based on r
values, the transition state characteristic with respect to a
developing charge can be obtained. For r > 1, a negative
charge is built in the transition state, whereas for r < 0 the
reaction develops a positive charge in the transition state.
Thus, the negative values for r in the hydrogen abstraction
reaction of triplet ketones from phenols containing polar
substituents cited above are fully in accord with the
proposed mechanism for this reaction, independently of
Figure 4. Absorption spectrum for the transients generated upon laser
excitation of thiochromanone in the presence of 1.4 × 10-3 mol L-1 of
4-methoxyphenol, in acetonitrile, recorded 13 ms after the laser pulse.
*3
+
.
δ
O
H
-
.
O
S
OH
O
S
δ
hν
+
ACN
exciplex
electron transfer
+
-
.
.
O
OH
OH
O
.
.
proton transfer
+
+
S
S
Scheme 1.

Vol. 21, No. 6, 2010
Ribeiro et al.
1075
acetonitrile. In this spectrum the absorptions relative to
triplet 1 were substituted for new ones in the 340-440 nm
region, which can be associated to a mixture of the ketyl
radical 2 derived from the thiochromanone triplet, as
well as to the 4-methoxyphenoxyl radical, which shows
absorption at 405 nm41 (Scheme 1). Formation of the radical
pair aryloxyl/ketyl was found for all phenols employed in
this work.
7. Netto-Ferreira, J. C.; Lhiaubet-Vallet, V.; Bernardes, B.;
Ferreira, A. B. B.; Miranda, M. A.; Photochem. Photobiol.
2009, 85, 153.
8. de Lucas, N. C.; Elias, M. M.; Firme, C. L.; Correa, R.
J.; Garden, S. J.; Netto-Ferreira, J. C.; Nicodem, D. E.;
J. Photochem. Photobiol., A 2009, 201, 1.
9. Pérez-Prieto, J.; Boscá, F.; Galian, R. E.; Lahoz, A.; Domingo,
L. R.; Miranda, M. A.; J. Org. Chem. 2003, 68, 5104.
10. Das, P. K.; Encinas, M. V.; Scaiano, J. C.; J. Am. Chem. Soc.
1981, 103, 4154.
Conclusions
11. Turro, N. J.; Engel, R.; J. Am. Chem. Soc. 1969, 91, 7113.
12. Biczók, L.; Bérces, T.; Linschitz, H.; J. Am. Chem. Soc. 1997,
119, 11071.
In conclusion, it was demonstrated by laser irradiation
of thiochromanone (1), in acetonitrile, the formation
and characterization of its triplet excited state. Absolute
rate constants were measured for the phenolic hydrogen
abstraction by this triplet, from which a Hammett plot
could be obtained. The negative value observed for the
reaction constant r (-0.90) is in complete accordance with
the proposed mechanism for this type of reaction, which
involves a coupled electron/proton transfer.
13. Leigh, W. J.; Lathioor, E. C.; St Pierre, M. J.; J. Am. Chem. Soc.
1996, 118, 12339.
14. Miranda, M. A.; Lahoz, A.; Boscá, F.; Metni, M. R.;
Abdelouahab, F. B.; Castell, J. V.; Pérez-Prieto, J.; Chem.
Commun. 2000, 2257.
15. Miranda, M. A.; Lahoz, A.; Matínez-Mañez, R.; Boscá, F.;
Castell, J. V.; Pérez-Prieto, J.; J. Am. Chem. Soc. 1999, 121,
11569.
Acknowledgments
16. Lathioor,E.C.;Leigh,W.J.;Photochem.Photobiol.2006,82,291.
17. Boscá, F.; Marín, M. L.; Miranda, M.A.; Photochem. Photobiol.
2001, 74, 637.
Financial support from Fundação de Amparo à Pesquisa
do Estado da Bahia (FAPESB) and Financiadora de Estudos
e Projetos (FINEP) are gratefully acknowledged. We thank
Prof. Cristina Maria Quintella for making available the laser
flashphotolysisfacilitiesattheUniversidadeFederaldaBahia.
A. M. R. thanksCoordenaçãodeAperfeiçoamentodoPessoal
doEnsinoSuperior(CAPES)foragraduatefellowship.A.R.B.
thanks Conselho Nancional de Desenvolvimento Científico
e Tecnológico (CNPq) for a graduate fellowship. J. C. N.-F.
thanks CNPq/FAPESB for a Visiting Professor fellowship at
the Universidade Federal da Bahia.
18. Quintero, B.; Miranda, M. A.; Ars Pharm. 1998, 41, 27.
19. Miranda, M. A.; Castell, J. V.; Hernández, D.; Gómez-Lechón,
M. J.; Boscá, F.; Morera, I. M.; Sarabia, Z.; Chem. Res. Toxicol.
1998, 11, 172.
20. Boscá, F.; Miranda, M. A.; J. Photochem. Photobiol., B 1998,
43, 1.
21. Lhiaubet-Vallet, V.; Sarabia, Z.; Hernández, D.; Castell, J. V.;
Miranda, M. A.; Toxicol. in Vitro 2003, 17, 651.
22. Cadet, J. ; Berger, M. ; Douki, T. ; Ravanat, J. L.; Rev. Physiol.
Biochem. Pharmacol. 1997, 131, 1.
23. Lhiaubet, V. ; Paillous, N. ; Chouini-Lalanne, N.; Photochem.
Photobiol. 2001, 74, 670. 24. Chouini-Lalanne, N. ; Defais,
M. ; Paillous, N.; Biochem. Pharmacol. 1998, 55, 441.
25. Sortino, S.; Condorelli, G.; De Guidi, G.; Guiffrida, S.;
Photochem. Photobiol. 1998, 68, 652.
References
1. deLucas, N. C.;Netto-Ferreira, J. C.; J. Photochem. Photobiol.,A
1998, 116, 203.
2. Silva, M. T.; Netto-Ferreira, J. C.; J. Photochem. Photobiol., A
2004, 162, 225.
26. Lahoz, A. ; Hernández, D.; Miranda, M. A.; Pérez-Prieto, J. ;
Morera, I. M. ; Castell, J. V.; Chem. Res. Toxicol. 2001, 14,
1486.
3. Serra, A. C. S.; de Lucas, N. C.; Netto-Ferreira, J. C.; J. Braz.
Chem. Soc. 2004, 15, 481.
27. Miranda, M. A. ; Pérez-Prieto, J. ; Lahoz, A. ; Morera, I. M. ;
Sarabia, Z. ; Martinez-Mañez, R.; Castell, J. V. ; Eur. J. Org.
Chem. 1999, 497.
4. de Lucas, N. C.; Correa, R. J.;Albuquerque,A. C. C.; Firme, C.
L.; Garden, S. J.; Bertoti, A. R.; Netto-Ferreira, J. C.; J. Phys.
Chem. A 2007, 111, 1117.
28. Pérez-Prieto, J.; Boscá, F.; Galian, R. E.; Lahoz, A.; Domingo,
L. R.; Miranda, M. A.; J. Org. Chem. 2003, 68, 5104.
29. Nakazumi, H. ; Ueyama, T. ; Kitao, T.; J. Heterocycl. Chem.
1985, 22, 1593.
5. Netto-Ferreira, J. C.; Bernardes, B.; Ferreira,A. B. B.; Miranda,
M. A.; Photochem. Photobiol. Sci. 2008, 7, 467.
6. Netto-Ferreira, J. C.; Lhiaubet-Vallet, V.; Bernardes, B.;
Ferreira, A. B. B.; Miranda, M. A.; Phys. Chem. Chem. Phys.
2008, 10, 6645.
30. Nakib, T. A.; Bezijiak, V.; Meegan, M. J.; Eur. J. Med. Chem.
1990, 25, 455.

1076
Phenolic Hydrogen Abstraction by the Triplet Excited State of Thiochromanone
J. Braz. Chem. Soc.
31. Liu, Y.; Luo, W.; Sun, L.; Guo, C.; Drug Discov. Ther. 2008,
36. Kumar, C.V.; Chattopadhay; Das, P. K. ; J. Am. Chem. Soc.
1983, 105, 5143.
2, 216.
32. Turro, N. J.; Ramamurthy, V.; Scaiano, J. C.; Principles of
Molecular Photochemistry - An Introduction, University
Science Books: California, 2009.
37. Stern, O.; Volmer, M.; Physik. Z. 1919, 20, 183.
38. Scaiano, J. C.; Encinas, M. V.; J. Am. Chem. Soc. 1981, 103,
6393.
33. Loutfyi, R.; Still, I. W. J.; Thompson, M.; Leong, T. S.; Can. J.
Chem. 1979, 57, 638.
39. Hammett, L. P.; J. Am. Chem. Soc. 1937, 59, 96.
40. Hammett, L. P.; Trans. Faraday Soc. 1938, 34, 156.
41. Shukla, D.; Schepp, N. P.; Mathivan, N.; Johnston, L. J.; Can.
J. Chem. 1997, 75, 1820.
34. Couture, A.; Lablache-Combier, A.; Min, T. Q.; Tetrahedron
Lett. 1977, 2873.
35. Bensasson, R.; Land, E. J.; Mavdinas, B.; Photochem.
Photobiol. 1976, 23, 189.
Received: October 13, 2009
Web Release Date: March 11, 2010