Synthesis, characterization and structures of 2-(3,5-dimethylpyrazol-1-yl) ethylseleno derivatives and their probable glutathione peroxidase (GPx) like activity

Article abstract of DOI:10.1039/c0ob00807a

A series of 2-(3,5-dimethylpyrazol-1-yl)ethylseleno derivatives has been synthesized. The glutathione peroxidase like catalytic activity of these compounds has been studied in a model system, in which reduction of hydrogen peroxide with dithiothreitol (DTT^red), in the presence of an organoselenium compound was investigated by ¹H NMR spectroscopy. All these compounds exhibit GPx like catalytic activities and the catalytic reaction proceeds through a selenoxide intermediate, identified by ⁷⁷Se{ ¹H} NMR spectroscopy.

Full text of DOI:10.1039/c0ob00807a

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PAPER
Synthesis, characterization and structures of
2-(3,5-dimethylpyrazol-1-yl)ethylseleno derivatives and their probable
glutathione peroxidase (GPx) like activity†
Ananda S. Hodage,a Prasad P. Phadnis,a Amey Wadawale,a K. I. Priyadarsinib and Vimal K. Jain*a
Received 1st October 2010, Accepted 14th January 2011
DOI: 10.1039/c0ob00807a
A series of 2-(3,5-dimethylpyrazol-1-yl)ethylseleno derivatives has been synthesized. The glutathione
peroxidase like catalytic activity of these compounds has been studied in a model system, in which
reduction of hydrogen peroxide with dithiothreitol (DTTred), in the presence of an organoselenium
compound was investigated by 1H NMR spectroscopy. All these compounds exhibit GPx like catalytic
1
activities and the catalytic reaction proceeds through a selenoxide intermediate, identified by 77Se{ H}
NMR spectroscopy.
Accordingly, mono- and di-selenides substituted with func-
tional groups containing heteroatoms have been synthesized and
Introduction
characterized.7–12 These molecules fall into two broad categories,
viz. (i) compounds containing a covalent Se–N bond (e.g. ebselen)
and (ii) molecules containing heteroatoms (N or O) which may
either have weak Se ◊ ◊ ◊ X (X = N, O) non-bonding interactions
or are capable of coordinating with selenium at different stages of
its catalytic reaction. Selenoethers, like bis(hydroxypropyl)selenide
and related derivatives, exhibit high antioxidant activity as GPx
mimics.13 Our recent studies on (HOOCCH2CH2Se)2 have shown
promising antioxidant activity and low toxicity in mice models.14–17
With this background, our group has conceived the synthesis of
new organoselenium compounds containing 3,5-dimethylpyrazole
fragments (I) such that these compounds would exhibit GPx
mimicking activity. Results of this work are reported herein.
Selenium has been recognized as an essential trace element and
its deficiency has been linked to many diseases.1,2 In biological
systems, selenium exists in the form of selenoproteins, where it
is primarily present in the form of selenocyteine (Sec) which is a
higher analogue of cysteine. Selenium in the Sec residue acts as a
strong nucleophile in catalytic reactions. Glutathione peroxidase
(GPx) is one of the important selenoproteins that protects the cell
from peroxides by catalyzing their reduction in the presence of a
thiol cofactor, glutathione.3–5
Recently selenium compounds have been evaluated as a new
class of antioxidants that show reactivity towards reactive oxygen
species (ROS) produced during oxidative stress. With the growing
importance of selenium in health, over the last decade interest in
selenium research has been directed at the design and development
of low molecular weight organoselenium compounds that emulate
GPx activity. One such synthetic organoselenium compound,
ebselen, has been identified as an effective GPx mimic, antioxidant,
radioprotector and as an anti-inflammatory agent.6 The promising
pharmacological properties of ebselen have prompted researchers
to design newer organoselenium compounds containing het-
eroatoms like N, O, etc.
Experimental
aChemistry Division, Bhabha Atomic Research Centre, Trombay, Mum-
bai 400 085, India. E-mail: jainvk@barc.gov.in; Fax: +91-22-2550-5151;
Tel: +91-22-2559-5095
Materials and methods
bRadiation and Photochemistry Division, Bhabha Atomic Research Centre,
Trombay, Mumbai 400 085, India
Elemental selenium (99.99%), sodium borohydride, superhy-
dride (LiBEt3H), 2-bromoacetic acid, 3-bromopropionic acid, 4-
bromobutyric acid and 2-bromoethylamine hydrobromide were
purchased from commercial sources (Aldrich/Fluka). Selenium
reagents (Li2Se and Li2Se2) were prepared freshly by the re-
ported method.18 The compounds [dmpzCH2CH2Br],19 [2-(4-
OTs)C6H4CHO],20 [2-HOCH2C6H4OTs],21 [2-ClCH2C6H4OTs]22
and di-2-pyridyldiselenide (py2Se2)23 were prepared according
† Electronic supplementary information (ESI) available: Synthesis and
characterization data of compounds 4–14, synthesis of dmpzCH2CH2Br
1
and other experimental details, 1H NMR, 77Se{ H} NMR and LC-MS of
the 2-(3,5-dimethylpyrazol-1-yl)ethylseleno derivatives (1–14) and kinetic
analysis data as well as the cif files of the single crystal X-ray diffraction
analyses of compounds 3 and 4 are available. CCDC reference numbers
784803 and 784804. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c0ob00807a
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1
dmpz), 13C{ H} NMR: d 11.1, 13.4 (each s, Me), 28.5 (1JC–Se = 78.0
to known procedures. All reactions were carried out under a
nitrogen atmosphere. Solvents were purified and dried by standard
procedures24 and were distilled prior to use. The purity of the
organoselenium compounds was tested initially by thin layer
chromatography (TLC) followed by column chromatography on
silica gel 60/120 mesh size.
Elemental analyses were carried out on a Flash EA 1112
Series CHNS Analyzer. NMR spectra were recorded on a Bruker
Avance-II 300 MHz spectrometer operating at 300.13 (1H), 75.47
Hz, SeCH2), 48.9 (NCH2), 105.0 (C-4 dmpz), 139.0, 147.8 (each
s, C-3, 5 dmpz); 77Se{ H} NMR: d 293.5 ppm. MS (IT) m/z: 427
1
[M + Na]+, 407 [M + H]+, 203 [dmpzCH2CH2Se]+.
dmpzCH2CH2SeCH2COOH (3). To a yellow solution of
(dmpzCH2CH2Se)2 (0. 41 g, 1.01 mmol) in 50 ml ethanol, sodium
borohydride (0.081 g, 2.13 mmol) was slowly added under a
◦
brisk flow of nitrogen at 0 C. The colorless solution of sodium
selenolate obtained was stirred for 30 min and then a solution of
1-bromoacetic acid (0.296 g, 2.13 mmol) in ethanol (15 ml) was
added drop wise at room temperature with constant stirring. The
reaction mixture was stirred for a further 30 min. The solvent was
evaporated in vacuo. The white residue was dissolved in distilled
water (50 ml) and extracted with diethylether (3 ¥ 50 ml). The ether
extract was dried in vacuo to give a white solid which was purified
by column chromatography with a ethylacetate–hexane mixture
(50 : 50) to give a white solid (0.37 g, 70%). It was recrystallized
from a ethylacetate–hexane mixture (50 : 50) to yield colorless
crystals, m.p. 125–126 ◦C. Anal. Calcd. for C9H14N2O2Se1: Calcd.:
C, 41.39; H, 5.40; N, 10.73%. Found: C, 41.52; H, 5.42; N,
10.90%. IR cm-1: 3585 (u OH), 1715 (u CO). NMR spectral data
(CDCl3): 1H NMR: d 2.23, 2.27 (each 3H, s, –CH3); 3.09 (2H, s,
–SeCH2CO), 3.15 (2H, t, J = 7.2 Hz, –SeCH2), 4.35 (2H, t, J =
1
1
1
(13C{ H}) and 57.25 MHz (77Se{ H}). 1H and 13C{ H} NMR
chemical shifts were relative to an internal chloroform peak
(d = 7.26 ppm for 1H and d = 77.0 for 13C{ H} NMR). The
1
1
77Se{ H} NMR chemical shifts were relative to an external
diphenyl diselenide (Ph2Se2) in CDCl3 (d = 463.0 ppm relative
to Me2Se (0 ppm). A 90◦ pulse was used in every case. The mass
spectra were recorded on a MS-500 Ion Trap (IT) Varian mass
spectrometer at Sophisticated Analytical Instrumentation Facility
(SAIF), Indian Institute of Technology-Bombay, Mumbai. IR
spectra were recorded on a Bomem MB-102 IR spectrome-
ter.
Synthesis
(dmpzCH2CH2)2Se (1). To a suspension of selenium powder
(0.691 g, 8.75 mmol) in THF (75 ml) a slight excess of LiBEt3H
(super hydride) 1 M solution (18.5 ml) in THF, was added carefully
at room temperature with magnetic stirring. Vigorous reaction of
the selenium with LiBEt3H resulted in the formation of a white
suspension of Li2Se, to which dmpzCH2CH2Br (3.23 g, 15.9 mmol)
was added. The reactants were stirred for a further 6 h. The solvent
was evaporated in vacuo and the residue was dissolved in distilled
water (50 ml). Extraction with diethylether (3 ¥ 50 ml) followed by
evaporation of the organic phase in vacuo gave a yellow oil which
was purified by column chromatography using an ethylacetate–
hexane mixture (10 : 90) to yield a pale yellow oil (2.21 g, 85%).
NMR spectral data (CDCl3): 1H NMR: d 2.12, 2.17 (each 3H, s,
–CH3), 2.76 (2H, t, J = 7.0 Hz, –SeCH2), 4.07 (2H, t, J = 7.0 Hz,
7.2 Hz, –NCH2), 5.84 (1H, s, H-4 dmpz); 13C{ H} NMR: d 11.0,
1
12.8 (each s, Me), 23.0 (1JC–Se = 68.0 Hz), 23.8 (1JC–Se = 69.0 Hz,
SeCH2), 48.5 (NCH2), 105.5 (C-4 dmpz), 139.7, 147.8 (each s, C-3,
5 dmpz), 174.0 (CO); 77Se{ H} NMR: d 198.0 ppm. MS (IT) m/z:
1
263 [M+H]+, 203 [dmpzCH2CH2Se]+.
The unsymmetrical 3,5-dimethylpyrazole based monoselenide
derivatives (Scheme 1) were synthesized (ESI†) by applying the
same strategy as adopted for the synthesis of 3.
X-ray crystallography. Single crystal X-ray data for
dmpzCH2CH2Se(CH2)nCOOH (n = 1 or 2) were collected at room
temperature (298 2 K) on a Rigaku AFC 7S diffractometer
˚
using graphite monochromated Mo–Ka (l = 0.71069 A radiation
so that qmax = 27.5◦. The unit cell parameters (Table 1) were deter-
mined from 25 reflections measured by a random search routine.
The intensity data were corrected for Lorenz, polarization and
absorption effects with an empirical procedure.25 The structures
were solved by direct methods using SHELX-9726 and refined
by full-matrix least squares methods. The non-hydrogen atoms
were refined anisotropically. The hydrogen atoms were fixed in
their calculated positions. The molecular structures were drawn
by ORTEP.27
1
–SeCH2CH2), 5.70 (1H, s, H-4 dmpz); 13C{ H} NMR: d 10.9, 13.2
(each s, Me), 23.1 (1JC–Se = 66.0 Hz, SeCH2–), 48.7 (CH2N), 104.7
1
(C-4 dmpz), 138.8, 147.4 (each s, C-3, 5 dmpz); 77Se{ H} NMR: d
139.6 ppm. MS (IT) m/z: 327 [M + H]+, 203 [dmpzCH2CH2Se]+.
(dmpzCH2CH2Se)2 (2). To a suspension of selenium powder
(0.555 g, 7.03 mmol) in THF (75 ml) a LiBEt3H (super hydride)
1 M solution (7.03 ml, 7.03 mmol) in THF, was added carefully
at room temperature with magnetic stirring. Vigorous reaction of
the selenium with LiBEt3H resulted in the formation of a dark
brown solution of Li2Se2 to which dmpzCH2CH2Br (1.0 g, 4.92
mmol) was added and stirred for a further 4 h. The solvent was
evaporated in vacuo and the residue was dissolved in distilled
water (50 ml). Extraction with diethylether (3 ¥ 50 ml) followed by
evaporation of the organic phase in vacuo gave a yellow solid which
was purified by column chromatography using an ethylacetate–
hexane mixture (10 : 90). The yellow solid was recrystallized from
diethylether–hexane mixture (50 : 50) at room temperature to yield
yellow crystals of the title compound (0.9 g, 90%), m.p. 72–73 ◦C.
Anal. Calcd. for C14H22N4Se2: Calcd. C, 41.59; H, 5.49; N, 13.86%.
Found: C, 41.61; H, 5.45; N, 13.15%. NMR spectral data (CDCl3):
1H NMR: d 2.19, 2.23 (each 3H, s, –CH3), 3.26 (2H, t, J = 7.2
Hz, –SeCH2), 4.28 (2H, t, J = 7.2 Hz, –NCH2), 5.77 (1H, s, H-4
Glutathione peroxidase (GPx) activities. The catalytic activity
of organoselenium compounds as mimics of GPx was tested by the
method reported by Iwaoka et al.,13c,28 in which the reduction of
hydrogen peroxide, using DTTred (reduced dithiothreitol) as a thiol
1
cofactor, was monitored by H NMR spectroscopy. In a typical
experiment DTTred (23.1 mg, 0.15 mmol) and an organoselenium
compound (0.015 mmol) as a catalyst were dissolved in CD3OD
(0.5 ml) in a glass vial and the reaction was initiated by addition
of freshly standardized H2O2 (47.6%) (9.15 ml, 0.15 mmol). At
this point the reaction is considered to be at zero time. The
progress of the reaction was monitored by 1H NMR spectroscopy.
The relative concentration of the thiol (DTTred, d 3.67 ppm for
CH protons) and disulfide (DTTox, d 3.49 ppm for CH protons)
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Scheme 1 Synthetic routes for preparation of 2-(3,5-dimethylpyrazol-1-yl)ethylseleno derivatives.
was estimated by integrating the respective resonances. The time
Results and discussion
required for 50% oxidation of the DTTred to DTTox was calculated,
which in turn was a measure of 50% reduction of the H2O2 by
the cofactor thiol (DTTred). For control, a similar experiment
was performed in the absence of a catalyst, i.e. organoselenium
compound.
Synthesis
Reactions of 1-(2-bromoethyl)-3,5-dimethylpyrazole with Li2Se
and Li2Se2, prepared by the treatment of selenium powder in THF
with a stoichiometric amount of superhydride (LiBEt3H) afforded
Table 1 Crystallographic and structural refinement data for dmpzCH2CH2SeCH2COOH (3) and dmpzCH2CH2SeCH2CH2COOH (4)
Compound
dmpzCH2CH2SeCH2COOH(3)
dmpzCH2CH2SeCH2CH2COOH(4)
Chemical formula
Formula weight
Color of crystal
Crystal size
C9H14N2O2Se
261.18
colorless
0.2 ¥ 0.1 ¥ 0.05
Orthorhombic/Pna21
8.370(3)
11.000(4)
12.192(3)
90.00
1122.4 (7)
4
C10H16N2O2Se
275.21
colorless
0.20 ¥ 0.15 ¥ 0.10
Monoclinic/P121/n1
13.200(5)
11.169(5)
7.993(4)
92.12(4)
1177.5(9)
Crystal system
˚
a (A)
˚
b (A)
˚
c (A)
b
3
˚
V (A )
Z
4
Dc (g cm-3)
1.546
1.552
m(Mo–Ka) mm-1/F (000)
Limiting indices
3.324/528
-10 £ h £ 6;
-8 £ k £ 14;
0 £ l £ 15
3.06–27.47
1343
3.172/560
-9 £ h £ 17;
0 £ k £ 14;
-10 £ l £ 10
2.93–27.51
2708
q range for data collection
No. of reflections collected
No. of independent reflections
Data/Restraints/Parameters
R indices [I > 2 s (I)]
R indices (all data):
788
1595
1343/1/130
R1 = 0.0400, wR2 = 0.0965
R1 = 0.1054, wR2 = 0.1178
0.000
2708/0/140
R1 = 0.0372, wR2 = 0.0775
R1 = 0.1006, wR2 = 0.0977
0.000
(D/s)max
-3
-3
-3
-3
˚
˚
˚
˚
(Dr)max, (Dr)min
0.447e A , -0.371e A
0.436e A , -0.415e A
Goodness-of-fit on F2
0.984
1.000
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mono-, (dmpzCH2CH2)2Se (1) and di-, (dmpzCH2CH2Se)2 (2)
selenides respectively in good yields. The reductive cleavage of
the Se–Se bond in the latter (2) with a methanolic solution of
sodium borohydride gave dmpzCH2CH2SeNa which was treated
in situ with a variety of organic halo compounds yielding a
series of asymmetric monoselenides (3–14) (Scheme 1). The
dmpzCH2CH2Sepy (13) was synthesized by a reaction between
pySeNa and dmpzCH2CH2Br in ethanol. All the compounds
were purified by column chromatography using ethylacetate–
hexane mixtures as an eluent and were characterized by elemental
analysis mass and NMR (1H, 13C{ H}, 77Se{ H}) spectroscopies.
All the compounds are air and moisture stable and are soluble
in polar organic solvents like methanol, ethylacetate, chloroform,
etc.
selenium atom. The observed angles are in◦the range reported
for RR¢Se compounds (e.g., Me2Se (96.48 (8) ,33 Se(CH2COOH)2
(98.17 (7)◦,29 Se(CH2CH2COOH)2 (96.48 (8)◦,34 pySeCH2COOH
(99.67 (9)◦32).
Both 3 and 4 are associated through hydrogen bonding. In
both the molecules the hydroxyl proton makes a bond with the
˚
pyrazolyl nitrogen (N(2)) (~1.74 A) of the adjacent molecule
rather than the carbonyl oxygen atom. In 3 the hydrogen bonding
results in an infinite zigzag chain while such bonding in 4
leads to dimerization. Organoselenium compounds containing a
terminal carboxylic acid group show various degrees of association
through hydrogen bond interactions. The four parallel hydrogen
bonds in Se(CH2COOH)2 result in a dimeric structure.29 In
contrast the higher homologue Se(CH2CH2COOH)2 adopts an
infinite chain structure formed by hydrogen bonds between the
terminal carboxylic acid groups.34 A similar infinite zigzag chain is
formed in pySeCH2COOH but with a different mode of hydrogen
bonding.32 In this structure, the pyridyl nitrogen of one unit is
hydrogen bonded with the carboxyl group of another molecule.
1
1
Molecular structures
The crystal and molecular structures of dmpzCH2-
CH2Se(CH2)nCOOH (n = 1 (3) and 2 (4) were established
by single crystal X-ray diffraction analyses. Selected bond lengths
and angles are given in Table 2, while ORTEP drawings with
crystallographic numbering scheme are shown in Fig. 1 and 2.
The Se–C distance associated with the dmpzCH2CH2 fragment is
slightly shorter than the one connected with the (CH2)nCOOH
˚
The N(2) ◊ ◊ ◊ Se(1) distances in 3 and 4 are 4.99 and 5.03 A,
respectively which are much longer than the sum of their van
˚
der Waals radii (3.5 A) indicating the absence of any non-covalent
interactions.
˚
moiety. The two Se–C distances (~1.95 A) in the two molecules
Catalytic properties as mimics of GPx
are, however, within the range reported for several aliphatic
selenoethers.29–32 The C–Se–C angles (~98◦) in the two molecules
are similar and represent a ‘V’-shaped configuration around
For evaluating GPx like activity, the reaction was performed
in CD3OD by 1H NMR spectroscopy as reported by Iwaoka
et al.28 In the 1H NMR spectra, the resonances at d = 2.63,
3.67 ppm, due to DTTred, decreased with a concomitant increase
of the signals at d = 2.87, 3.03, 3.49 ppm, due to DTTox, with
reaction time. The time required to convert DTTred to DTTox by
50% (t50) indicated the catalytic efficacy of the organoselenium
compounds. For dmpzCH2CH2SeCH2CH2NH2·2HCl (12) (0.015
mmol), when used as a catalyst, the oxidation of DTTred was
50% completed within 103 min (t50 = 103 min). The best activity
was found when dmpzCH2CH2SeCH2CH2NH2 (11) was used as
a catalyst at a very low concentration, 0.0016 mmol, where the
time required for 50% conversion of DTTred was found to be
12 min. The comparison of the GPx mimicking capacities of
the tested organoselenium compounds is shown in Fig. 3. The
t50 values estimated from these plots for various organoselenium
compounds are summarized in Table 3. From these results, it is
evident that 11 is the most active organoselenium compound in
reducing hydrogen peroxide, with their relative activities in the
order of 11 > 12 > 5 > 4 > 1> 13 > 3 > 2. The high activity
of 11 and 12 in methanol could be due to the presence of an
amino group which either acts as a good base catalyst for the GPx
reaction illustrated in Scheme 2 or the basicity produced by amino
groups in the reaction solution may facilitate the easy conversion
of DTTred to DTTox. Although non-bonding interactions between
N(2) of the dmpz and selenium are not observed, such interactions
may exist either in the intermediate or in selenoxide, which may
possibly stabilize the intermediate, thereby inducing GPx like
activity.
Table 2 Selected bond lengths (A) and bond angles (◦) for
˚
dmpzCH2CH2Se(CH2)nCOOH[n = 1 (3) and 2 (4]
dmpzCH2CH2-
SeCH2COOH(3)
dmpzCH2CH2-
SeCH2CH2COOH(4)
Bond lengths
Se(1)–C(1)
Se(1)–C(8)
C(1)–C(2)
C(2)–N(1)
N(1)–N(2)
N(1)–C(3)
N(2)–C(5)
C(8)–C(9)
C(9)–O(1)
C(9)–O(2)
C(9)–C(10)
C(10)–O(1)
1.944(8)
1.956(9)
1.473(9)
1.468(8)
1.356(9)
1.361(10)
1.347(12)
1.480(12)
1.206(12)
1.328(11)
—
1.944(4)
1.952(4)
1.503(6)
1.461(4)
1.358(4)
1.356(5)
1.336(5)
1.512(5)
—
—
1.506(6)
1.197(5)
1.315(5)
—
—
C(10)–O(2)
Bond angles
C(1)–Se(1)–C(8)
Se(1)–C(1)–C(2)
C(1)–C(2)–N(1)
C(2)–N(1)–C(3)
C(2)–N(1)–N(2)
N(2)–N(1)–C(3)
N(1)–N(2)–C(5)
Se(1)–C(8)–C(9)
C(8)–C(9)–O(1)
C(8)–C(9)–O(2)
O(1)–C(9)–O(2)
C(9)–O(2)–H(2)
C(8)–C(9)–C(10)
C(9)–C(10)–O(1)
C(9)–C(10)–O(2)
O(1)–C(10)–O(2)
C(10)–O(2)–H(2)
98.0(4)
112.9(5)
113.5(6)
127.4(9)
120.2(9)
112.2(7)
103.9(9)
111.3(6)
122.7(9)
112.9(9)
124.4(9)
109.5
97.90(18)
113.6(3)
111.6(3)
127.9(3)
119.8(3)
111.9(3)
105.2(3)
109.4(3)
—
—
—
—
112.4(3)
124.5(4)
112.5(4)
123.0(4)
109.5
—
—
—
—
The redox reaction shown in Scheme 2 is proposed to proceed
through the intermediacy of selenoxide formation.28 Since similar
reaction intermediates are expected to be involved in the GPx ac-
—
1
tivity of our compounds, the reactions were followed by 77Se{ H}
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Fig. 1 ORTEP diagram of dmpzCH2CH2SeCH2COOH (3) and the inset shows the hydrogen bonding exhibited in the molecule.
Fig. 2 ORTEP diagram of dmpzCH2CH2SeCH2CH2COOH (4) and the inset shows the hydrogen bonding exhibited in the molecule.
NMR spectroscopy. The chemical shift values for some selected se-
lenoxides of 2-(3,5-dimethylpyrazol-1-yl)ethylseleno compounds
signal for 12 (d = 119.7 ppm) on treating the solution with
DTTred
.
1
are given in Table 4. As is evident from Fig. 4 that the 77Se{ H}
NMR resonance in D2O for 12 (d = 119.7 ppm) is highly deshielded
on treatment with one mole equivalent of H2O2, indicating the
formation of the corresponding selenoxide (d = 816.0 ppm). The
latter signal disappeared with a concomitant appearance of the
Conclusions
A series of 2-(3,5-dimethylpyrazol-1-yl)ethylseleno derivatives
having N atoms in proximity to selenium have been synthesized,
2996 | Org. Biomol. Chem., 2011, 9, 2992–2998
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Table 3 Comparative data of GPx-like catalytic activities of organosele-
nium compounds
t50 in min (by 1H NMR
in CD3OD)
Compound
Blank
(dmpzCH2CH2)2Se
(dmpzCH2CH2Se)2
dmpzCH2CH2SeCH2COOH
dmpzCH2CH2SeCH2CH2COOH
dmpzCH2CH2SeCH2CH2CH2COOH
dmpzCH2CH2SeCH2CH2NH2
dmpzCH2CH2SeCH2CH2NH2·2HCl
dmpzCH2CH2SePy
—
> 300
> 300
> 300
> 300
160
(1)
(2)
(3)
(4)
(5)
154
(11)
(12)
(13)
12a
103
> 300
a Concentration of (11): 0.0016 mmol
1
Fig.
4
77Se{ H} NMR spectra (in D2O) of (a) dmpzCH2CH2-
SeCH2CH2NH2·2HCl (12) and (b) its oxidation with H2O2 to the
corresponding selenoxide.
monoselenides, substituted with functional groups like –COOH
and –NH2 groups, the GPx mimicking activity increases because
of their inductive effect, which facilitates selenoxide formation. In
addition, these functionalities enhance solubility in protic solvents.
Supplementary data
Crystallographic data for the structural analyses have been
deposited with the Cambridge Crystallographic Data Centre,
CCDC Nos. 784803 (dmpzCH2CH2SeCH2COOH) and 784804
(dmpzCH2CH2SeCH2CH2COOH). Copies of this information
may be obtained free of charge from: The Director, CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [fax: (int. code)
+44 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk or www:
http://www.ccdc.cam.ac.uk].
Fig. 3 Percentages of residual DTTred as a function of the reaction time
in the oxidation of DTTred with H2O2 in the presence of organoselenium
catalysts in CD3OD. Reaction conditions: [DTTred]0 = [H2O2]0 = 0.15 mmol
and [selenide] = 0.015 mmol, at 25 ◦C. *Concentration of (11) = 0.0016
mmol.
Acknowledgements
We thank Drs. T. Mukherjee, S. K. Sarkar and D. Das for
encouragement of this work. One of the authors (ASH) is grateful
to Board of Research in Nuclear Sciences (BRNS), Department of
Atomic Energy (DAE) for a Junior Research Fellowship awarded
to him. We are also grateful to BRNS for the research grant
under the Prospective Research Fund (PRF) Scheme (Grant No.
BRNS/2007/38/5).
Scheme 2 Reduction of H2O2 with DTTred catalyzed by organoselenium
compounds.
purified and characterized. These compounds showed promising
GPx activity. The GPx mimicking reactions proceed through the
intermediacy of selenoxide formation. It is also evident that in
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