Free radical induced selenoxide formation in isomeric organoselenium compounds: The effect of chemical structures on antioxidant activity

Article abstract of DOI:10.1039/c9nj02227a

With an aim to understand the effect of structural modifications on antioxidant activity, two structurally isomeric selenium compounds, linear, bis(ethan-2-ol)selenide (SeEOH), and cyclic, dl-trans-3,4-dihydroxy-1-selenolane (DHS), were compared. The antioxidant activity was assigned through their ability to scavenge reactive oxygen species (ROS), where both compounds indicated formation of selenoxides. The ROS identified for the present study are peroxynitrite, hydroxyl (OH) and carbonate (CO₃^-) radicals. The rate constant for the scavenging of both peroxynitrite and the CO₃^- radical was higher for DHS as compared to that for SeEOH. The one-electron oxidation during these reactions indicated the formation of a selenium centred dimer radical cation (Se∴Se)⁺, as the intermediate, which undergoes the disproportionation reaction to form the corresponding selenoxide. Quantitative estimation of selenoxides indicated that cyclic compound DHS produced a higher yield of selenoxides than the linear compound SeEOH due to higher stability of (Se∴Se)⁺. The selenoxides undergo reduction by thiols, thereby regenerating back to the parent compound. The results thereby suggest that formation of selenoxides improves the antioxidant activity of organoselenium compounds and should be considered as an important step in the design of new selenium based antioxidants.

Full text of DOI:10.1039/c9nj02227a

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DOI: 10.1039/C9NJ02227A
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Free radical induced selenoxide formation in isomeric
organoselenium compounds: Role of chemical structure on
antioxidant activity
Received 00th January 20xx,
Accepted 00th January 20xx
a,b
a,b
c
d
b,c
DOI: 10.1039/x0xx00000x
Beena G. Singh* , Pavitra Kumar, P. Phadnis , Michio Iwaoka, and K. Indira Priyadarsini *
With an aim to understand the role of structural modifications on antioxidant activty, two structurally isomeric
selenium compounds, linear, bis(ethan-2-ol)selenide (SeEOH) and cyclic, DL-trans-3,4-dihydroxy-1-selenolane
(DHS) were compared. The antioxidant activity, was assigned through their ability to scavenge reactive oxygen
scavenging (ROS), where both compounds indicated formation of selenoxides. The ROS identified for the present
●
●−
study are peroxynitrite, hydroxyl ( OH) and carbonate (CO
3
) radical. The rate constant for the scavenging of both
●−
peroxynitrite and CO
3
radical was higher for DHS as compared to that for SeEOH. The one-electron oxidation
+
during these reactions indicated formation of selenium centred dimer radical cation (>SeSe<) , as the
intermediate, which undergoes disproportionation reaction to form the corresponding selenoxide. Quantitative
estimation of selenoxides indicated that cyclic compound DHS, produced higher yield of selenoxide than the
+
linear compound SeEOH due to higher stability of (>SeSe<) . The selenoxide undergoes reduction by thiols,
thereby regenerated back to the parent compound. The results thereby suggest that formation of selenoxide
improves the antioxidant activity of organoselenium compounds and should be considered as an important step
in the design of new selenium based antioxidants.
reported that the rate constant for the reaction of various free
radicals and molecular oxidants with biologically relevant
Introduction
1
0
organoselenium compounds is an important parameter.
Organoselenium compounds constitute a unique class of
antioxidants due to their versatile redox properties. Such
compounds exhibit antioxidant properties like free radical
scavenging and glutathione peroxidase (GPx) like catalytic
activity. Studies from several synthetic molecules identified
the role of important structural motifs such as aromaticity, non-
bonding interactions, ring size, and nature of functional groups,
In search of water soluble and low molecular weight
antioxidants/radioprotectors, our group has studied the
hydroxyl ( OH) radical reaction with different classes of
●
11
1
,2
organoselenium compounds by pulse radiolysis technique.

The studies have shown that the initial attack of OH radical
takes place at selenium centre to form hydroxyselenouranyl
3
,4,5
radical adduct (>SeOH) and the fate of this transient depends
on the nature of functional group (hetero atom) attached to the
selenium centre. Of the several compounds screened in our
on the GPx like activity.
Romano et al have found that the
antioxidant activity of aromatic selenocynates is higher than the
aliphatic selenocynates and Rafique et al have showed that 2-
picolylamide-based diselenides having non-bonding interaction
showed higher activity. Engman et al, have reported that the
ring size in cyclic seleno-tocopherols affects their radical
laboratory, trans-3,4-dihydroxyselenolane (DHS)
a water-
6
,7
soluble organoselenium compound, has been found to reduce
●
OH radicals, hydroperoxides and peroxynitrite catalytically
8
through the formation of a stable selenoxide, which is reverted
trapping ability. Similarly, Back et al reported that the GPx
12
back to DHS by thiols. Further, this antioxidant activity was
activity of a five member spirodioxaselenanonane was higher
13
9
also verified under in vitro and in vivo models. In contrast, its
linear analogue bis(ethan-2-ol)selenide (SeEOH) showed low
compared to those with six member ring. Davies et al have
14
GPx like activity and was toxic to cells. Therefore, to
understand the contrasting behaviour, the two structural
analogues have been investigated for their reactivity with ROS
and the yields of products formed were estimated. To further
compliment the observations, quantum chemical calculations
have been carried out. The structures of DHS, SeEOH and their
selenoxides are given in scheme 1.
a.
Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay,
Mumbai-400085, India.
b.
Homi Bhabha National Institute, Anushaktinagar, Mumbai – 400092, India
Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai – 400085
Department of Chemistry, School of Science, Tokai University, Kitakaname,
Hiratsuka-shi, Kanagawa 259-1292, Japan.
c.
d.
†
*Corresponding authors: beenam@barc.gov.in; kindira@barc.gov.in .
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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HO
OH
●-
HO
OH
presence of 10 μM SeEOH. In the absence ofVieS OH, CO
radical decayed by second order kinetics with 2k/εl value of (5.7
w ticle Online
eEAr
DOI: 10.1039/C9NJ02227A
3
Se
O
7
-1
●-
Se
± 0.1) x 10 s at pH 7.4. On addition of 10 μM SeEOH, CO
3
radical decayed very fast and the reaction was found to follow
pseudo-first order kinetics (kobs). The bimolecular rate constant
was estimated from the slope of the linear plot of kobs at
different concentration of SeEOH (10 -100 μM), which was
found to be (6.5 ± 0.3) x 10 M s . Both DHS, SeEOH did not
showed any reaction with NO2 radical, which could be due to
the unfavourable redox potential of these compounds.
Further to understand the mechanism of electron transfer in
these compounds, the nature of the transients produced during
these ROS reactions was investigated as discussed below.
DHS
DHSox
HO
OH
HO
OH
Se
Se
SeEOH
O
8
-1 -1
0
1
2
3
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0
SeEOHox
●
Scheme 1: Structure of 3,4-dihydroxy selenolane (DHS), bis(ethan-2-ol)selenide
SeEOH) and their corresponding selenoxide DHSox and SeEOHox
(
.
Results
Transient studies:
Kinetics of reaction of DHS/SeEOH with different ROS: As
reported earlier, SeEOH and DHS reacted with OH radical with
a bimolecular rate constants of (1.0 ± 0.1) x 10 M s and (9.1
± 0.1) x 10 M s , respectively.
antioxidant activity under different conditions, rate constants
for the reaction of these compounds with peroxynitrite,
carbonate (CO3 ) radical and nitrogen dioxide (NO ) radical,
were studied. Under physiological condition peroxynitrite
readily reacts with CO to form nitroso-peroxocarbonate which
●

The reaction of SeEOH and DHS with OH radical formed two
centered three electron bonded dimer radical cation
1
0
-1 -1
+
9
-1 -1
12,14
(
>Se

Se<) , which decayed by following second order kinetics
To further understand the
5
-1
5 -1
with 2k/εl of (2.7 ± 0.2) x 10 s and (3.9 ± 0.3) x 10 s for DHS
and SeEOH, respectively. Using the reported ε value for
Se<) radical of DHS, and presuming similar value for
SeEOH, the 2k value for DHS and SeEOH was estimated to be
1.6 ± 0.1) x 10 and (2.3 ± 0.2) x 10 M s , respectively. This
indicates that the (>SeSe<) radical of DHS is more stable
compared to that from SeEOH. In case of SeEOH along with the
+
●-
●
2
(>Se

9
9
-1 -1
(
2
+
●
-
●
decomposes to form CO3 radical and nitrogen dioxide NO2
radical, which are important for peroxynitrite induced oxidative
+
18
(>Se
Se<) radical, a species absorbing at 320 nm was
stress.
The reaction between DHS/SeEOH with peroxynitrite, was
studied by employing competition kinetics using
attributed to a carbon centred radical of the type α-(hydroxyl
●
ethyl) seleno methyl radical (HOCH CH SeCH ) or

-reducing
radical (-SeC ). Such radicals are formed by rearrangement of
>Se OH) radical at α-position to the selenium centre followed
by elimination of water and formaldehyde (HCHO) molecules
2
2
2
●
17
Dihydrorhodamine 123 (DHR123) as reference solute.
(

k1
DHR123 Peroxynitrite   R123
(1)
(2)
1
9
via Barton reaction. In case of DHS, no indication for
reducing radical formation was observed.
-
k2
DHS / SeEOH  Peroxynitrite  Products
●-
The relative yield of the radical cations, estimated by ABTS
reaction was found to be 1.8 times higher for DHS than SeEOH.
As reported earlier, the (>SeSe<) radical undergoes radical-
radical disproportionation to form selenoxides, as estimated
below.
The bimolecular rate constant (k ) was estimated by plotting
2
+
(
F0/F)-1 as a function of ((SeEOH or DHS)/DHR123) according to
equation (3):
F0 k2 [SeEOH / DHS]

X
F
k1
[DHR123]
(3)
2
.0
Where, F and F are the intensities of fluorescence of R123 in
0
1000
800
600
400
200
0
absence and in presence of SeEOH/DHS respectively, k (8.2 x
SeEOH
1
3
-1 -1
1
0 M s ) is the bimolecular rate constant for the reaction of
1.5
1
2d
DHS
DHR123 with peroxynitrite. The estimated values for k were
2
2
-1 -1
3
-1 -1
(9.2 ± 0.1) x10 M s and (2.2 ± 0.2) x10 M s for SeEOH and
DHS respectively (Figure S1). The results indicate that DHS
showed higher rate constant in neutralizing peroxynitrite as
compared to SeEOH.
Rate constant for the reaction of DHS with CO radical was
reported to be (1.2 ± 0.2) x 10 M s . In the present study,
SeEOH was tested for its ability to scavenge CO3 and NO2
radicals using pulse radiolysis technique. The kinetics between
SeEOH and CO3 radical was estimated by following the
characteristic decay of CO3 at ~600 nm (ε600 nm=1680 M cm )
in presence of varying concentration of SeEOH. Figure S2 shows
the absorption-time plot of CO3 radical in absence and in
1.0
0.5
0.0
0.2
0.4
0.6
DTT , mM
ox
DTT
●-
3
9
-1 -1 12
DTTox
●-
●
0.0
●
-
4.0
6.0
8.0
10.0
12.0
●-
-1
-1
Time, min.
●
-
2
| J. Name., 2012, 00, 1-3
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Figure 1: HPLC chromatogram generated on treating irradiated aqueous solution (N O
saturated) of 5 mM SeEOH/DHS with 1 mM DTT at pH 7. Inset shows the calibration
curve for DHSox
Å) is slightly more leading to decrease in inter electronic
View Article Online
DOI: 10.1039/C9NJ02227A
repulsion and stabilisation of the two centred three electron
+
+
bond in (>Se
Se<) radical. Additionally, (>SeSe<) of DHS is
stabilized by two non-bonded Se···O interactions from the
hydroxyl functional group, which is not seen in SeEOH.
Product analysis by HPLC :
Formation of selenoxide and formaldehyde products formed
during the reaction of OH radicals with SeEOH/DHS were
identified and quantified by HPLC measurements.
Selenoxide estimation: The HPLC chromatogram for SeEOH and
DHS showed peaks at 4.2 min and 4.0 min, while their
corresponding selenoxides being more polar, were fast eluted
and therefore could not be detected on HPLC directly.
Therefore the selenoxides formation was quantified by
employing their reaction with DTT and monitoring the amount
+
Therefore, (>Se
of SeEOH.

Se<) radical of DHS is more stable than that
●
0
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Se —Se = 3.071 Å
Se —Se =3.035 Å
1
2
14b
1
2
of DTTox formed thereof at 240 nm as described. From this
analysis, it was found that DHS showed higher yield of
selenoxide (0.45 ± 0.04) μmol/J) than SeEOH (0.23 ± 0.02)
μmol/J) (Figure 1). The relative yield of selenoxides is in the
same order as estimated yield of their radical cations within
experimental limits.
Formaldehyde (HCHO) estimation: Formation of HCHO was
confirmed by treating with (2,4-dinitrophenyl)hydrazine (DNPH)
followed by HPLC analysis as described in reference. Using the
calibration curves plotted for the known concentration of HCHO
treated with DNPH, the amount of HCHO formed during -
radiolysis of SeEOH in N O saturated condition was (0.11 ± 0.01)
µmoles/J which corresponding to ~18 % of the total OH radical
Figure 2: Optimized geometries of (>SeSe<) radicals of a) SeEOH and b) DHS using
+
DFT at B3LYP-6/31+G(d,p) level in water.
●
Further the energetics for the initial reaction of OH radical
with these compounds and consequent formation of
+
(>Se

Se<) radical was calculated. The results showed that
●
initial attack of OH radical at Se-centre to form (>Se
radical is more preferred in DHS (∆E=-17.29 kcal/mol) than
SeEOH (∆E=+3.49 kcal/mol). This (>Se OH) generally decays by
proton catalyzed dehydration to form selenium centered
OH)
22

●+
2
radical cation (>Se ) which on reaction with another parent
molecule forms (>SeSe<) . The dimerization process was
found to be more exothermic in DHS (-19.3 kcal/mol) as
compared to SeEOH (-14.9 kcal/mol). These results suggest that
Se<) radical is more favourable in case of
DHS than SeEOH and support the experimental observations.
The preferential formation of (>SeSe<) radical can also be
explained on the basis of HOMO energy values of different
transients involved in its formation. Table 1 lists the HOMO,
LUMO and HOMO-LUMO energy gap in different transients
formed for SeEOH and DHS. The HOMO energy values of DHS
and DHS radical are comparable and therefore an efficient
overlap is expected.
●
+
yield (Figure S3). However no peak corresponding to HCHO-
DNPH was observed in case of DNPH derivatized DHS samples
(irr) indicating absence of any HCHO.
+
formation of (>Se

To explain the differential yield of selenoxides obtained during
reaction with OH radicals and their ROS scavenging activity,

+
quantum chemical calculations were performed and the results
are discussed below.
Quantum chemical calculations: For these studies, ground
state geometry of DHS/SeEOH and different transients
observed during electron transfer process were optimized at

+
B3LYP/6-31+G(d,p) level in water followed by HOMO and LUMO
level calculations.
23
Figure S4 represents the optimized
structures and corresponding HOMO level of SeEOH and DHS.
The HOMO values indicate that the cyclization in DHS
structure leads to introduction of ring strain, causing increase
in ground state energy and its HOMO energy levels. Due to
this, it becomes easier to remove outermost electron
compared to its linear (relaxed) form where HOMO level is
well stabilized.
Compounds
HOMO
eV)
LUMO
(eV)
HOMO-LUMO
Energy gap
(
(eV)
SeEOH
-5.7822
-7.8693
-5.7414
-0.2829
-5.2380
-3.5918
-0.1006
-1.3496
-0.9088
-5.4992
-2.6312

+
(
SeEOH)

+
(
SeEOH)
2
-2.1496
-5.5618
-5.4584
-5.1401
To explain the nature and stability of the resultant
+
(>Se

Se<) radicals of SeEOH and DHS, their geometries were
DHS
-
5.6625
optimized followed by correction for BSSE (basis-set
superposition error) using counter-poise method. Figure 2

+
(DHS)
-6.8081
-6.0489

+
(DHS)
2
represents the optimized ground state structure of
+
(>Se

Se<) radical at B3LYP/6.31+G(d,p) level. The bond
Table 1: HOMO values of SeEOH/DHS and their proposed intermediates formed during
distance between two selenium atoms is less (3.035 Å) in
electron transfer reactions.
+
(>Se
Se<) radical of SeEOH which enhances the inter
electronic repulsion and destabilizes the bond. On the other
hand in (>SeSe<) radical of DHS, Se-Se bond distance (3.071
+
The monomer radical cation of organoselenium compound
tends to undergo irreversible deprotonation to form a carbon
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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centred radical (α-reducing radical) on the carbon adjacent to Additionally, the stability of dimer radical cation of DHS is due
the chalcogen centre. In our earlier work, we have shown that to the direct interaction between selenium and oxygen of DHS
the deprotonation is favoured by the effective overlap between and this prevents deprotonation to form carbon centred
the σ* of the selenium centre with the σ-C-H bond at the α- radical. Thus higher HOMO value coupled with higher stability
position. The energy of such non-bonding interactions can of the intermediate (>Se
theoretically be calculated by employing natural bond orbital selenoxide formation and thereby better antioxidant activity of
View Article Online
DOI: 10.1039/C9NJ02227A
+

Se<) results in higher yield of
2
4
(NBO) analysis. The non-bonding interaction energy (Enb) DHS as compared to SeEOH. The selenoxide being reversible in
indicates the extent of the interactions taking between two presence of thiols, imparts higher antioxidant activity in DHS
orbitals. The optimized structure of (>Se ) derived from than in SeEOH against ROS.
DHS/SeEOH were calculated and the Enb value of DHS and
SeEOH was calculated to be 0.36 kcal/mol and 1.61 kcal/mol,
respectively. From this it can be inferred that the (>Se )
derived from DHS is less prone to undergo irreversible
deprotonation as compared to SeEOH. Further, the energetics
for conversion of (>Se
that this radical in DHS disproportionates in an energetically
favored path (∆E=+31.1 kcal/mol), as compared to SeEOH (∆E=
0
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0
●
+
●
+
Experimental
The organoselenium compounds studied were synthesized as
1
4a,c
per
the
reported
method.
2,2'-azino-bis(3-
+
2
–

Se<) to form selenoxides indicated
ethylbenzthiazoline-6-sulphonic acid-sodium salt) (ABTS ),
DHR123, Diphenylpicrylhydrazine (DNPH), dithiothretol reduced
(DTT) and dithiothretol oxidized (DTT )were purchased from
ox
+
32.5 kcal/mol).
Sigma Aldrich and were of >95% purity. All the other chemicals
and reagents were of “Analar” grade and used as such. The
solutions were freshly prepared for each experiment in
Discussion
-1
nanopure water with a conductivity of 0.1 μS cm , obtained
In the present study two isomeric compounds, DHS and SeEOH from a milipore water purification system. The pH of the
were investigated to understand the effect of small structural solutions was adjusted using monosodium phosphate
alteration on their ROS scavenging activity. DHS/SeEOH were (NaH PO ), disodium phosphate (Na HPO .2H O) and perchloric
2
4
2
4
2
●
●-
examined for their ability to scavenge ROS like ● OH, CO3
acid (HClO4).
radical and peroxynitrite. The rate constants for OH radical Peroxynitrite was prepared by the ozonolysis of 0.1 M sodium
25
reaction for both SeEOH/DHS were comparable. However teh azide solution containing 0.1 M NaOH. For all experiments
rate constant with peroxynitrite, was two times more for DHS stock peroxynitrite solutions were diluted using 10 mM NaOH
as compared to SeEOH. To explain this significantly different and during the experiments, the pH was maintained at 7.4 by
activity by minor change in the structure, detailed mechanism using 70 mM phosphate buffer. The concentration of
of the radical reaction with DHS/SeEOH was studied. The peroxynitrite was estimated by measuring the absorbance at
-1
-1
overall reaction of SeEOH and DHS is depicted in scheme 2.
302 nm (ε302 nm=1705
M
cm ) on UV-Visible
spectrophotometer (Jasco V-639).
Pulse radiolysis studies were carried using 7 MeV electron
beam with 100 ns pulse width and the details of the instrument
is reported. An average dose of 9 Gy as estimated by using
thiocyanate dosimeter (aerated aqueous solution of 10 mM
(
DHS)2
DHS
SeEOH
(SeEOH)2
Does not reacts with
DHS/SeEOH
NO
2
[
ONOO-CO2]
disproportionation
reaction followed
by hydrolysis
475 nm
2
KSCN, Gε
=2.59 x 10-4 m /J) was used for all
CO
3
OH
OH
26
CO
2
experiments. Solutions were saturated with N O to monitor
2
•
●−
the OH radical reaction (G•OH=0.6 µmole/J). Carbonate (CO3
)
2
CO
ONOO
3
DHSox
SeEOHox
radical was generated on pulse radiolyzing N O saturated
2
DHS
SeEOH
solution containing sodium carbonate (0.1M) at pH 7. The
product formed on reaction of OH radical with the
organoselenium compound was quantified by HPLC technique.
For this, N O saturated aqueous solutions of 10 mM SeEOH
●
NO2
Scheme 2: Reaction of DHS and SeEOH with different oxidants

2
On reaction with OH, both the compounds were converted to
their corresponding selenoxide, where DHS produced
significantly higher amount of selenoxide than SeEOH
The experimental results were complimented by calculating the
energetics determined by quantum chemical calculations. The
HOMO energy of DHS is higher than that of SeEOH indicating
6
0
were radiolysed using Co γ-source with a dose rate of 40
Gy/min. The absorbed dose was set in a way that not more
than 10% of the compound undergoes radiolysis. Selenoxide
estimation was performed as per the reported method. In brief,
180 µl of radiolysed samples were treated with 20 µl DTT (10
mM) and incubated for 5 minutes. 20ul of the mixture was
injected to C-18 reverse phase column. The different
compounds were eluted using acetonitrile:water (5:95) mixture
as mobile phase and absorption peaks were detected at 240
nm. The yield of formaldehyde formed during radiolysis of the
organoselenium compound was estimated by derivatizing the
aldehyde with DNPH. The radiated solutions were mixed with 1
the easier oxidation of DHS. The reaction of initial addition of

OH radical on selenium atom to form (>SeOH) adduct is
endothermic in SeEOH (∆E=+3.48 kcal/mol) but exothermic in
DHS (∆E=-17.29 kcal/mol). This (>Se OH) adduct generally
Se<) . The dimerization process was
found to be more exothermic in DHS as compared to SeEOH.

+
decays to form (>Se

4
| J. Name., 2012, 00, 1-3
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mM DNPH dissolved in 10 mM HCl and stirred for 5 minutes. 20
µl of resulted solutions were injected to C-18 reverse phase
column. Acetonitrile:water (60:40) was used as mobile phase
and detector was set at 345 nm.
Reaction of the organoselenium compounds with peroxynitrite
was studied by competition kinetics using dihydrorhodamine
1. a) N. V. Barbosa, C. W. Nogueira, P. A. Nogara, A. F. de
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2
.
(DHR)123 as standard. The fluorescence measurements were
done on Hitachi F-4500 fluorescence spectrophotometer with
excitation and emission wavelength at 510 nm and 536 nm
respectively. Peroxynitrite solution (5 µM) was added to
DHR123 (10 µM) containing 0.1 mM DTPA in 70 mM phosphate
buffer (pH 7.5) in absence and presence of the organoselenium
compound (10-100 µM).
0
1
2
3
4
5
6
7
8
9
0
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2
3
4
5
6
7
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8
9
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1
2
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Malevolti, M. Ambrosi, P. L. Nostro and A. Capperucci.
Chem. Commun. 2019, 55, 5705.
The structures of transients were optimized in vacuo by
regressive variation in starting geometry at B3LYP/6-31++G(d,p)
level (Becke non local model and Lee−Yang−Parr nonlocal
correlation functionals). The geometries obtained were checked
by frequency calculations. The global minima structures were
then further optimized in water at B3LYP/6-31+G(d,p) level in
water using PCM-SMD model. Geometry optimization and
frequency calculations were performed by adopting the
GAMESS suite of programs on a PC-based LINUX cluster
4.
a) S. S. Zade, S. Panda, S. K. Tripathi, H. B. Singh and G.
Wolmershauser, Eur. J. Org. Chem., 2004, 3857.b) R. N.
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K. I. Priyadarsini. RSC Adv., 2015, 5, 66621. c) M.
Raghuraman, P. Verma, A. Kunwar, P. P. Phadnis, V. K. Jain
and K. I. Priyadarsini. Metallomics, 2017, 9, 715.
2
7
platform. The absorption maxima wavelength were calculated
in water by using UCIS model at B3LYP; 6-31-G(d,p) level using
Gaussian 09. The transient’s geometries and molecular orbitals
were visualized using chemissian V4.38 software.
6.
B. Romano, D. Plano, I. E. Juan, A. Palop and C. Sanmartin,
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J. F. Poon, J. Yan, V. P. Singh, P. J. Gates, and L. Engman,
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Conclusions
Two isomeric organoselenium compounds, cyclic compound,
DHS and a linear compound, SeEOH were studied for their
antioxidant ROS scavenging activity, where DHS, a cyclic
compound was found to be much better than its linear isomer
SeEOH. The enhanced activities in DHS have been attributed to
the strain induced in the cyclic structure that elevated the
HOMO energy level and easy oxidation. Further, the cyclic
structure assists in stabilizing the selenium centred dimer
radical cations which favour formation of stable selenoxides,
that can be reversed by the thiols. Thus the cyclic structural
feature of DHS can be used as a molecular design for
developing new organoselenium compounds with enhanced
antioxidant activity.
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2. a) K. Arai, K. Moriai, A. Ogawa and M. Iwaoka, Chemistry
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Conflicts of interest
The authors declare that there is no conflict of interest.
1
2016, 807, 33.
1
4. a) K. Arai, F. Kumakura, M. Takahira, N. Sekiyama, N.
Acknowledgements
The authors acknowledge the LINAC team, RPCD, BARC and
Computer Division, BARC for the support for radiolysis and
computing facility.
Kuroda, T. Suzuki, and M. Iwaoka, J. Org. Chem., 2015, 80,
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Notes and references
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New Journal of Chemistry
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DOI: 10.1039/C9NJ02227A
Table of contents entry
Free radical induced
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selenoxide
isomeric
formation
organoselenium
in
compounds: Role of chemical
(DHS)2
DHS
structure
activity
in
antioxidant
SeEOH
(SeEOH)
2
NO
2
Does not reacts with
DHS/SeEOH
Beena G. Singh*, Pavitra
Kumar, P. Phadnis, Michio
disproportionation
reaction followed
by hydrolysis
2
[ONOO-CO ]
OH
OH
CO
3
CO
2
Iwaoka,
and
K.
Indira
2
ONOO
Priyadarsini
Formation of selenoxide improves
the antioxidant activity of
organoselenium compounds and
should be considered as an
important marker in the design of
new selenium based antioxidants .
CO3
DHSox
SeEOHox
DHS
SeEOH
NO
2