Synthesis, characterization, structures and antioxidant activity of nicotinoyl based organoselenium compounds

Article abstract of DOI:10.1016/j.jorganchem.2012.04.014

A series of nicotinoyl based organoselenium compounds, [2-NC ₅H₃(3-COOH)Se]₂ (1), [2-NC₅H ₃(3-CO)Se-Se] (2), [2-NC₅H₃(3-CONH ₂)Se]₂ (3), [2-NC₅H₃(3-CONHPh)Se] ₂ (4), [2-NC₅H₃(3-CONHpyrimidine)Se] ₂ (5), [2-NC₅H₃(3-CONHPh)SeBr] (6) and [2-NC₅H₃(3-CONHPh)SeI] (7) have been synthesized and characterized by absorption, IR, NMR (¹H, ¹³C{ ¹H}, ⁷⁷Se{¹H}) and mass spectrometry. The crystal structures of [2-NC₅H₃(3-CO)Se-Se] (2) and [2-NC₅H₃(3-CONHPh)Se]₂ (4) have been determined. The structure of (4) revealed the existence of two intra-molecular Se?X (X = O and N) interactions, as a result of this, C-Se-Se-C torsion angle is unusually large (180°). The GPx mimicking activity of these compounds has been evaluated using methods based on ¹H NMR spectroscopy and HPLC. Free radical scavenging ability of the compounds was examined by DPPH and deoxyribose assay. All these studies indicated that the compound (3) not only showed highest GPx activity but also has a very good free radical scavenging ability thus making it a novel structure for development of nicotine based antioxidants.

Full text of DOI:10.1016/j.jorganchem.2012.04.014

Journal of Organometallic Chemistry 713 (2012) 42e50
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis, characterization, structures and antioxidant activity of nicotinoyl based
organoselenium compounds
,
C. Parashiva Prabhu a, Prasad P. Phadnis a, Amey P. Wadawale a, K. Indira Priyadarsini b, Vimal K. Jain a
*
a Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India
b Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of nicotinoyl based organoselenium compounds, [2-NC5H3(3-COOH)Se]2 (1), [2-NC5H3(3-CO)SeeSe]
(2), [2-NC5H3(3-CONH2)Se]2 (3), [2-NC5H3(3-CONHPh)Se]2 (4), [2-NC5H3(3-CONHpyrimidine)Se]2 (5), [2-
NC5H3(3-CONHPh)SeBr] (6) and [2-NC5H3(3-CONHPh)SeI] (7) have been synthesized and characterized by
absorption, IR, NMR (1H, 13C{1H}, 77Se{1H}) and mass spectrometry. The crystal structures of [2-NC5H3(3-CO)
SeeSe] (2) and [2-NC5H3(3-CONHPh)Se]2 (4) have been determined. The structure of (4) revealed the exis-
tence of two intra-molecular Se/X (X ¼ O and N) interactions, as a result of this, CeSeeSeeC torsion angle is
unusually large (180ꢀ). The GPx mimicking activity of these compounds has been evaluated using methods
based on 1H NMR spectroscopy and HPLC. Free radical scavenging ability of the compounds was examined by
DPPH and deoxyribose assay. All these studies indicated that the compound (3) not only showed highest GPx
activity but also has a very good free radical scavenging ability thus making it a novel structure for devel-
opment of nicotine based antioxidants.
Received 10 February 2012
Received in revised form
27 March 2012
Accepted 10 April 2012
Keywords:
Organoselenium compound
Nicotinamide
Antioxidant
GPx activity
X-ray structure
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
compounds containing a covalent SeeN bond (e.g. IIeIV) [7e9],
(ii) compounds exhibiting weak intra-molecular Se/N or Se/O
Selenium is an essential micronutrient for animals and humans
and exists in the form of selenoenzymes. Glutathione peroxidase
(GPx) is one of the major mammalian selenoenzymes [1,2]. GPx is
an antioxidant enzyme that catalyzes the reduction of harmful
hydroperoxides by using two molecules of glutathione (GSH) as
a cofactor [3]. Having recognized the role of GPx enzymes in
biochemical reactions, considerable efforts have been made to
design and develop low-molecular weight organoselenium
compounds, which can emulate the activity of naturally occurring
selenoenzymes, GPx. Since the discovery of GPx like catalytic
activity in a synthetic organoselenium compound, ebselen (I)
[4,5], there is a growing interest in developing new classes of
organoselenium compounds that exhibit GPx mimicking activity
[3,6]. Accordingly, different groups have studied several families of
GPx active organoselenium compounds. These compounds can
readily be recognized by one of the following features, (i)
interactions (e.g. VeVIII) reported by Wilson [10], Tomoda [11],
Mugesh [12,13], Singh [6,14], Wirth [15] and Jain [16] (iii) hetero-
cyclic diselenides, e.g. 2-pyridyl diselenide (IX) [17] and (iv)
compounds, both mono and diselenides, derived from alky groups
bearing eOH, eNH2, eCOOH substituent at terminal positions
(XeXIII) [18e21] (Scheme 1).
Nicotinic acid (vitamin B3) and nicotinamide are important
bio-molecules and are involved in a wide range of biological
processes including energy production, synthesis of fatty acids,
etc. They are precursors for the coenzymes NAD (nicotinamide
adenine dinucleotide) and NADP (nicotinamide adenine dinucle-
otide phosphate). They are important cofactors in numerous
enzymatic redox reactions [22]. Nicotinamide has shown anti-
inflammatory [23], chemo- and redox-sensing and antioxidant
[24e27] activities.
With the above perspective, an intriguing idea could be to
develop organoselenium compounds as antioxidants based on
nicotinoyl group and the resulting compounds may show signifi-
cant enhancement of GPx catalytic activity. Thus in pursuance of
our interest on organoselenium compounds as antioxidant and
radio-protectors we have designed and synthesized a series of
* Corresponding author. Tel.: þ91 22 2559 5095; fax: þ91 22 2550 5151.
E-mail addresses: kindira@barc.gov.in (K. Indira Priyadarsini), jainvk@
barc.gov.in (V.K. Jain).
0022-328X/$ e see front matter Ó 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2012.04.014

C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
43
O
O
O
OH
NPh
Se
Se
N-Me
Se
NPh
Se
III
N-Ac
Back et al.9
(I) ebselen
II
(IV)
O
Et
R
R
N
N
OMe
2
R = H, Me, Et, Pr
R’ = Me, Ey, Pr
R, R’ = Me or C-
Hx
Se)2
Se)2
Se
Singh14
(V)
(VII) Wirth15
(VI)
Wilson10, Tomoda11, Singh6, Mugesh12,13
Se
N
N
Se
HOOC
2
OH
N
Se)2
Se)2
(XI) Jain and Priyadarsini20
(X) Back et al18
(VIII) Jain16
(IX) Jacob et al17
Se
HO
Se
HO
OH
2
(XII) Back et. al.19
(XIII) Iwaoka et al.21
Scheme 1.
nicotinoyl based organoselenium compounds and evaluated their
antioxidant properties. The results of this work are reported
herein.
recorded on a JASCO FT IR-6100 spectrometer. NMR spectra were
recorded on a Bruker Avance-II 300 MHz spectrometer operating at
300.13 (1H), 75.47 (13C{1H}) and 57.25 MHz (77Se{1H}). 1H and 13C
{1H} NMR chemical shifts were relative to internal dmso peak
(d
¼ 2.49 ppm for 1H and
d
¼ 39.5 for 13C{1H} NMR). The 77Se{1H}
2. Experimental
NMR chemical shifts were relative to external diphenyl diselenide
(Ph2Se2) in CDCl3
d
463.0 ppm relative to Me2Se (0 ppm). A 90ꢀ
2.1. Materials and methods
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.
Elemental selenium (99.99%), sodium borohydride, 2-
chloronicotinic
acid,
thionyl
chloride,
aniline,
2-
aminoepyrimidine, hydrogen peroxide (30%), glutathione (GSH)
and reduced dithiothreitol (DTTred), 1,1-diphenyl 2-picryl hydrazyl
(DPPH), thiobarbituric acid (TBA), 2-deoxyribose, trichloro acetic
2.2. Synthesis of organoselenium compounds
acid (TCA), ethylenediaminetetraacetic acid (EDTA),
D-mannitol,
butylated hydroxytoluene (BHT), -ascorbic acid were obtained
L
2.2.1. Synthesis of [2-NC5H3(3-COOH)Se]2 (1)
from commercial sources (Sigma/Aldrich). The compounds 2-
chloro-3-nicotinoyl chloride [28], 2-chloro-3-nicotinamide, 2-
To a THF solution of Na2Se2 (prepared from selenium metal
(3.50 g, 44.32 mmol) and sodium borohydride (1.75 g, 46.26 mmol)
in refluxing THF (100 ml) under nitrogen), solid 2-chloronicotinic
acid (6.96 g, 44.17 mmol) was added with stirring and the
contents were refluxed for 3 h. After cooling to room temperature,
the solvent was evaporated under reduced pressure and the
residue was treated with water (50 ml). The aqueous phase was
extracted with chloroformemethanol (80:20). Combined organic
phases were washed with sodium bicarbonate (5% aq.) followed by
water, dried over anhydrous sodium sulphate and filtered. The
filtrate was concentrated in vacuum and the residue was column
chromatographed using chloroformemethanol mixture (70:30 v/
v). The solvents from the eluted solution were evaporated in
vacuum to yield a greenish yellow solid (2.78 g, 31%), m.p.
218e220 ꢀC (decomp). Anal. for C12H8N2O4Se2; Calcd: C, 35.84; H,
2.00; N, 6.97%. Found C, 35.64; H, 2.18; N, 6.92%. UVevis (in MeOH)
chloro-3-(N-phenyl)nicotinamide,
2-chloro-3-(N-pyrimidine)
nicotinamide were prepared by literature methods. Disodium
diselenide (Na2Se2) was prepared by reduction of selenium metal
with stoichiometric quantity of sodium borohydride in refluxing
water or THF under a nitrogen atmosphere as a brown solution
[29]. Freshly prepared solutions were used in situ. All syntheses
were carried out under a nitrogen atmosphere in dry solvents.
Solvents were purified and dried by standard procedures and were
distilled prior to use. The purity of organoselenium compounds
was tested initially by thin layer chromatography followed by
column chromatography on silica gel (60/120 mesh size) using
solvent mixtures as eluents.
Elemental analyses were carried out on a Thermo Fisher EA 1112
CHNS analyzer. Electronic spectra were recorded in methanol on
a Jasco UVevis spectrometer model V-630 PC. IR spectra were
(
lmax in nm): 220, 275, 393. IR in KBr (y
cmꢁ1): 3375 (OH), 1645

44
C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
(CO). 1H NMR (dmso-d6)
d
: 7.07 (dd, 7.5, 4.5 Hz, H-5, py); 8.06 (dd,
138.6 (CeSe), 142.4, 163.0 (py); 167.9 (CO). 77Se{1H} NMR (dmso-
d6)
352 ppm. Mass (m/z) 552 (Mþ): 276 (1/2 Mþ or
1.8, 7.5 Hz, H-4 py); 8.29 (dd, 1.5, 4.8 Hz, H-6, py). 13C{1H} NMR
d:
(dmso-d6)
d
; 119.0, 133.4 (CeSe), 136.9, 149.5, 162.1 (CeCOOH);
NC5H3(CONHPh)Se).
169.0 (CO). 77Se{1H} NMR (dmso-d6)
d: 506 ppm. Mass (m/z):
402 (Mþ), 236 (Se2C5H4N).
2.2.5. Synthesis of [2-NC5H3(3-CONHpyrimidine)Se]2 (5)
To a THF solution of Na2Se2 (prepared from selenium metal
(1.45 g, 18.36 mmol) and sodium borohydride (700 mg,
18.50 mmol) in 50 ml refluxing THF), 2-chloro-3-(N-pyrimidine)
nicotinamide (4.30 g, 18.32 mmol) in THF was added with stirring
under a nitrogen atmosphere. The reaction mixture was refluxed
for 2 h. The solvent was evaporated under vacuum. The residue was
treated with water (40 ml) and the product was extracted with
chloroform. Organic phase was washed with sodium bicarbonate
(5% aqueous) followed by water, dried over anhydrous sodium
sulphate and filtered. The filtrate was concentrated under vacuum
and the residue was chromatographed using ethyl acetateehexane
(30:70) mixture. The eluted solution on vacuum drying afforded
a brown solid (yield 2.64 gm 52%), m.p. 222e224 ꢀC (decomp). Anal.
for C20H14N8O2Se2; Calcd: C, 43.18; H, 2.54; N, 20.14% Found C,
43.00; H, 2.18; N, 20.20%. UVevis (in MeOH) (lmax in nm): 250, 298,
2.2.2. Synthesis of [2-NC5H3(3-CO)SeeSe] (2)
To a brown THF solution of Na2Se2 (prepared from selenium
metal (2.42 g, 30.65 mmol) and sodium borohydride (1.16 g,
30.66 mmol) in refluxing THF (80 ml)) solid 2-chloro-3-nicotinoyl
chloride (2.70 g, 15.34 mmol) was added and the contents were
refluxed for 3 h under a nitrogen atmosphere with stirring. The
residue was treated with water (50 ml). After aqueous work-up and
extraction with chloroform, the crude product was column chro-
matographed using ethyl acetate-petroleum ether mixture (10:90
v/v). After the solvents evaporation, saffron coloured crystals of the
title compound were obtained (863 mg, 21%), m.p. 120e122 ꢀC.
Anal. for C6H3N1O1Se2; Calcd : C, 27.40; H, 1.15; N, 5.32%. Found;
C, 27.66; H, 1.19; N, 5.31%. UVevis (in MeOH) (lmax in nm): 282, 375.
IR in KBr (
y d: 7.28 (d,d, 8, 6 Hz,
cmꢁ1): 1767 (CO). 1H NMR (dmso-d6)
CH-5, py); 8.11 (d, 6 Hz, CH-4 py); 8.77 (br, C-6, py); 13C{1H} NMR
356, 370. IR in KBr (
d6)
: 7.23 (t, H-5 py) þ H-4 (pyrimidine); 8.04 (d, 6 Hz, py); 8.30 (d,
7 Hz, py); 8.68 (d, 5 Hz, H-3, 5; pyrimidine); 12.62 (br, NH). 13C{1H}
NMR (dmso-d6) : 123.6, 128.5 (CeSe), 140.5, 157.5 (py ring), 166.1
(CO), 110.3, 148.2, 152.1, 156.1 (pyrimidine carbons). 77Se{1H} NMR
(dmso-d6)
: 355 ppm. Mass (m/z), 557 (Mþ), 278 (1/2 Mþ).
y
cmꢁ1): 3112 (NH), 1670 (CO). 1H NMR (dmso-
(dmso-d6)
d
: 120.7, 128.4 (CeSe), 136.9, 155.1, 167.5 (CeCO); 195.4
d
(CO). 77Se{1H} NMR (dmso-d6)
(SeeCO). Mass (m/z): 263 (Mþ).
d: 439 ppm (SeeC5H3N), 628
d
2.2.3. Synthesis of [2-NC5H3(3-CONH2)Se]2 (3)
d
To an aqueous solution of Na2Se2 (prepared from selenium
metal (1.00 g, 12.66 mmol) and NaBH4 (434 mg, 11.47 mmol) in
60 ml distilled water) was added a solution of 2-chloro-3-
nicotinamide (2.00 g, 12.77 mmol) with stirring under a nitrogen
atmosphere. The reaction mixture was refluxed for 2 h with stir-
ring. After cooling to room temperature, product was extracted
with a chloroformemethanol (3:1 ratio) mixture. The organic
phase was separated, washed with sodium bicarbonate solution
followed by water, dried over anhydrous sodium sulphate, and
filtered. The filtrate was concentrated under vacuum and the
residue was column chromatographed with chloroformemethanol
(90:10) mixture. The solution on evaporation afforded yellow
powder (yield 216 mg, 8%; due to degradation during column
purification product yield was significantly reduced), m.p.
126e128 ꢀC. Anal. for C12H10N4O2Se2; Calcd: C, 36.02; H, 2.52; N,
14.00%. Found C, 34.64; H, 2.73; N, 13.47%. UVevis (in MeOH) (lmax
2.2.6. Synthesis of [2-NC5H3(3-CONHPh)SeBr] (6)
To a stirred dichoromethane solution (35 ml) of [2-NC5H3(3-
CONHPh)Se]2 (2.50 g, 4.52 mmol), a carbon tetrachloride solution
of bromine was added drop wise till the light brown colour of
bromine persisted. The reactants were stirred for 3 h at room
temperature whereupon a yellow precipitate formed which was
filtered through a sintered funnel and washed thoroughly with
carbon tetrachloride and dried under vacuum (yield 3.06 g, 95%),
m.p. 205e207 ꢀC. Anal. for C12H9BrN2O1Se; Calcd: C, 40.48; H, 2.55;
N, 7.85%. Found; C, 41.30; H, 2.92; N, 7.77%. UVevis (in MeOH) (lmax
in nm): 268, 333. IR in KBr (
(dmso-d6)
: 7.27 (t, Ph þ py); 7.44 (t); 7.56 (d); 7.94 (t); 8.47 (d, py);
8.99 (d, py); 11.24 (s, NH). 13C{1H} NMR (dmso-d6)
: 120.0, 123.6,
124.6, 129.3, 133.6 (CeSe), 138.6, 139.1, 150.9 (C-3), 164.0 (CO). 77Se
{1H} NMR (dmso-d6) : 768 ppm. Mass (m/z): 356 (Mþ); 276
y
cmꢁ1): 3250 (NH), 1626 (CO). 1H NMR
d
d
d
in nm): 326, 402. IR in KBr (
(dmso-d6) : 7.28 (d, d, 6 Hz, CH-5, py); 8.35, 7.84 (NH2); 8.16 (d,
7.5 Hz, py); 8.49 (d, 5 Hz, py); 13C{1H} NMR (dmso-d6)
: 119.7, 128.1
(CeSe),135.5, 151.5, 160.5 (C-3, py); 168.2 (CO). 77Se{1H} NMR
(dmso-d6)
: 525 ppm. Mass (m/z): 400 (Mþ).
y
cmꢁ1): 3250 (NH2), 1671 (CO). 1H NMR
(M ꢁ Br); 197 (NC5H3CONHPh).
d
d
2.2.7. Synthesis of [2-NC5H3(3-CONHPh)SeI] (7)
To a stirred dichloromethane solution (35 ml) of [2-NC5H3(3-
CONHPh)Se]2 (2.00 g, 3.62 mmol), a carbon tetrachloride solution
of iodine was added drop wise till the purple colour of iodine
persisted. The reactants were stirred for 3 h at room temperature
whereupon a brown solid was precipitated which was filtered
through a sintered funnel, washed with carbon tetrachloride and
dried under vacuum (yield 2.84 g, 97%), m.p. 201e203 ꢀC. Anal. for
C12H9IN2OSe; Calcd : C, 35.76; H, 2.25; N, 6.95%. Found: C, 35.76; H,
2.25; N, 6.86%. UVevis (in MeOH) (lmax in nm): 240, 282. IR in KBr
d
2.2.4. Synthesis of [2-NC5H3(3-CONHPh)Se]2 (4)
To an aqueous solution of Na2Se2 (prepared from selenium
metal (1.46 g, 18.46 mmol) and NaBH4 (704 mg, 18.61 mmol) in
150 ml water), 2-chloro-3-(N-phenyl)nicotinamide (4.30 g,
18.48 mmol) was added in small instalments with stirring under
a nitrogen atmosphere. The reactants were refluxed with stirring
for 3 h, whereupon yellow crystals of the title compound were
formed. The crystals were filtered through a sintered funnel and
washed thoroughly with distilled water followed by ethyl
acetateehexane (1:1) mixture and dried in vacuo (2.78 g, 55%),
m.p. 217e219 ꢀC. Anal. for C24H18N4O2Se2; Calcd: C, 52.19; H,
3.28; N, 10.14% Found C, 52.02; H, 3.49; N, 10.30%. UVevis (in
(y d: 7.16 (t, 7.2 Hz,
cmꢁ1): 3214 (NH), 1637 (CO). 1H NMR (dmso-d6)
CH-4, Ph); 7.35e7.42 (m, Ph þ py); 7.32 (d, 7.8 Hz, CH-2,6, Ph); 8.29
(d.d, 7,1.5 Hz, CH-4, py); 8.52 (d, d, 6,1.5 Hz, CH-6, py); 10.60 (s, NH).
13C{1H} NMR (dmso-d6)
d: 120.1, 122.2, 124.5, 126.2, 128.9, 129.4,
136.0, 136.7, 151.7(CO), 153.4. 77Se{1H} NMR (dmso-d6)
Mass (m/z): 403 (Mþ); 246, 237.
d: 524 ppm;
MeOH) (lmax in nm): 230, 313, 407. IR in KBr (
y
cmꢁ1): 3177 (NH),
1651 (CO). 1H NMR (dmso-d6)
d
: 7.11 (t, 8 Hz, H-4, Ph); 7.24 (t,
2.3. GPx like catalytic activity
7 Hz, H-5, py); 7.36 (t, 8 Hz, H-3, 5, Ph); 7.69 (d, 8 Hz, H-2, 6, Ph);
8.01 (d, 6 Hz, 1H, py); 8.32 (d, 6 Hz, 1H, py); 12.14 (s, NH). 13C{1H}
NMR (dmso-d6) d: 116.5, 124.4, 138.9, 140.7 (Ph); 119.9, 129.3,
The GPx like catalytic activity of these compounds has been
evaluated by HPLC and 1H NMR spectroscopy. In HPLC assay GPx

C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
45
like activity was monitored by following the ratio of the depletion
in the concentration of glutathione reduced (GSH) and increase in
the concentration of oxidized glutathione (GSSG). In our model
calculated the same way as described in DPPH radical assay.
Mannitol was used as positive control.
system [30], reaction was initiated by adding H2O2 (320
a mixture of GSH (160 M) and organoselenium compounds
(10 M) as catalysts and leaving it for 5 min. The GSH and GSSG
were separated by HPLC on a reverse phase C18 column using
a mobile phase of aqueous solution containing 2% methanol in 0.1%
trifluoroacetic acid (TFA) and detected at 210 nm. The reaction
mixture 40 mL was injected into the column and the reaction was
monitored till 310 min, and the recorded values are an average of 2
injections. By plotting the concentration of GSSG vs. time in mins
mM) to
2.5. X-ray crystallography
m
m
Single crystal X-ray diffraction data for [2-NC5H3(3-CO)SeeSe]
(2), and [2-NC5H3(3-CONHPh)Se]2 (4) were collected at room
temperature (298 ꢄ 2 K) on a Rigaku AFC 7S diffractometer using
graphite monochromated Mo-K
a
(l
¼ 0.71069 Å) radiation so that
qmax ¼ 27.5ꢀ. The unit cell parameters (Table 1) were determined
from 25 reflections measured by a random search routine. The
intensity data were corrected for Lorenz, polarization and absorp-
tion effects with an empirical procedure [34]. The structures were
solved by direct methods using SHELX-97 [35], 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 [36].
t50
determined.
The catalytic activity of organoselenium compounds as GPx
, the time needed to perform 50% of the reaction was
mimics was also evaluated by NMR route employing the method
reported by Iwaoka et al. [21,31]. In this method reduction of
hydrogen peroxide, using DTTred (reduced dithiothreitol) as thiol
cofactor was monitored by 1H NMR spectroscopy. In a typical
experiment DTTred (23.1 mg, 0.15 mmol) and organoselenium
compound (0.015 mmol) as a catalyst were dissolved in CD3OD
(0.5 ml) and the reaction was initiated by addition of freshly stan-
3. Results and discussion
3.1. Synthesis and spectroscopy
dardized H2O2 (47.6%) (9.15 ml, 0.15 mmol). At this point reaction
was considered to be at zero time. The progress of the reaction was
Treatment of 2-chloronicotinic acid with Na2Se2 in THF yields
a greenish yellow diselenide (1). Various other selenides were
prepared using 2-chloro-3-nicotinoyl chloride (Scheme 2). Thus,
the reaction of the latter with Na2Se2 in THF afforded a saffron
coloured cyclic diselenide (2). The reactions of 2-chloro-3-
nicotinoyl chloride with various amines yield the corresponding
amides which when treated with Na2Se2 gave dislenides 3e5.
Oxidation of 4 with halogens in CCl4 gave halo compounds, 2-
NC5H3(3-CONHPh)SeX (X ¼ Br (6) and I (7)). The reactions of dis-
elenides with iodine have been known to yield either selenenyl
iodide (RSeI) [14,37] or iodine adduct of diselenide (R2Se2.I2)
monitored by 1H NMR spectroscopy. The relative concentration of
thiol (DTTred 3.67 ppm for CH protons) and disulfide (DTTox
, d ,
d
3.49 ppm for CH protons) was estimated by integrating the
respective resonances. The time required for 50% oxidation of
DTTred to DTTox was calculated which in turn was a measure of 50%
reduction of H2O2 by the cofactor thiol (DTTred). For control, similar
experiment was performed in the absence of an organoselenium
compound.
2.4. Free radical scavenging ability
2.4.1. DPPH radical assay
Radical scavenging (Hꢂ) activity of organoselenium compounds
against 1,1-diphenyl 2-picryl hydrazyl (DPPH) radical was
measured spectrophotometrically [32]. Accordingly working solu-
tion was prepared in 3 ml HPLC grade methanol with the concen-
Table 1
Crystallographic and structural refinement data for [2-NC5H3(3-CO)SeeSe] (2) and
[2-NC5H3(3-CONHPh)Se]2.dmso (4.dmso).
Compound
[2-NC5H3(3-CO)
SeeSe] (2)
[2-NC5H3(3-CONHPh)
Se]2 (4)
tration ranging from 5, 10, 25, 50
positive control butylated hydroxytoluene (BHT) and that of DPPH
was 100 M 1 ml of test compounds of various concentrations were
mM of test compounds and
Chemical formula
Formula weight
Colour of crystal
Crystal size (mm)
Crystal system
a (Å)
C6H3NOSe2
263.01
Orange
0.30 ꢃ 0.15 ꢃ 0.05 0.30 ꢃ 0.20 ꢃ 0.05
C24H18N4O2Se2.dmso
624.42/check 630
Yellow
m
mixed to 2 mL of DPPH in methanol. The absorbance at 517 nm was
measured after incubating the reaction mixture for 30 min at room
temperature. Inhibition (I) of DPPH radical was calculated using
the equation I (%) ¼ 100 ꢃ (Ao ꢁ As)/Ao, where Ao is the absorbance
of control (having all the regents except test compounds), and As is
the absorbance of the tested compound. Results were compared by
using BHT as positive control.
Monoclinic/P21/c
5.2746 (16)
8.366 (4)
16.000 (6)
95.46 (3)
702.8 (5)
4
Monoclinic/C2/c
21.690 (7)
8.761 (4)
13.834 (8)
102.30 (3)
2568.4 (19)
4
1.615
2.996/1240
ꢁ15 ꢅ h ꢅ 28; 0 ꢅ k ꢅ 11;
ꢁ17 ꢅ l ꢅ 17
b (Å)
c (Å)
b
(ꢀ)
V (Å3)
Z
Dc (g/cm3)
2.486
m
(Mo-K
a
) mmꢁ1/F (000)
10.439/488
ꢁ6 ꢅ h ꢅ 6;
ꢁ6 ꢅ k ꢅ 10;
ꢁ11 ꢅ l ꢅ 20
2.56e27.43
1577
2.4.2. 2-Deoxyribose assay
OHꢂ radical scavenging capacity was studied in non-site
specific deoxyribose assay [33]. Solutions of EDTA (5 mM),
Limiting indices
100
(10 mM), 100
from 5 to 50
m
L, FeCl3 (1 mM), 100
m
L, 2-deoxyribose, 100
L, test compounds, 200 L (concentrations ranging
M), phosphate buffer (50 mM, pH 7.4), 300 L and
L were mixed sequencially and the
resulting mixture was incubated at 37 ꢀC for 1 h. To this incubated
mixture added 250 L 4% (W/V) solution of thiobarbituric acid
(TBA) in 0.05 M NaOH and 250 L of 11.2% (W/V) solution of
mL, H2O2
q
range for data collection
No. of reflections collected
No. of independent reflections 805
Data/Restraints/Parameters 1577/0/91
R indices [I > 2 (I)]
2.52e27.51
2947
1964
2947/0/173
m
m
m
m
ascorbic acid (15 mM), 100
m
s
R1 ¼ 0.0437,
wR2 ¼ 0.0847
R1 ¼ 0.1478,
wR2 ¼ 0. 0.1150
0.000
R1 ¼ 0.0520, wR2 ¼ 0.1320
m
R indices (all data):
R1 ¼ 0.0961, wR2 ¼ 0.1609
m
(
(
D
Dr
/
s
)
0.000
trichloro acetic acid (TCA). The reaction mixture was heated on
water bath at approximately 100 ꢀC for 30 min to develop pink
colour and then cooled in ice. The absorbance was measured at
532 nm. Inhibition of 2-deoxyribose from degradation was
max
)max, (Dr
)
0.792e Åꢁ3
,
1.116e Åꢁ3, ꢁ1.052e Åꢁ3
min
ꢁ0.964e Åꢁ3
Goodness-of-fit on F2
0.970
1.051

46
C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
COOH
Cl
COOH
Na2Se2
H2O
N
N
Se
2
1
Benzene
SOCl2
NH2
O
O
O
O
COCl
Cl
Na2Se2
THF
Na2Se2
H2O
Br2 in CCl4
CH2Cl2
N
N
N
Se
Se
H
H
H
N
N
Se
N
N
Se
N
Cl
2
Br
2
4
6
NH3
NH2
CH2Cl2
N
N
I2 in CCl4
O
O
N
NH2
O
Se
7
N
N
Na2Se2
N
Cl
H
N
H
N
Cl
Na2Se2
N
THF
H2O
I
O
O
N
NH2
2
N
N
H
N
Se
N
Se
2
3
5
Scheme 2.
[38,39] depending on the nature of organic groups attached to
selenium. The selenenyl iodides have been isolated when R is either
a bulky group [37] or a group, which facilitates intra-molecular
secondary Se/N interactions [14].
The electronic spectra of these compounds in methanol dis-
played absorptions in the region 230e407 nm. 2-Chloronicotinic
acid exhibited absorption at lmax 220, 268 nm. The longest wave-
length maximum at w400 nm in 3 and 4, which was not observed
diffraction analysis are shown in Figs. 1 and 2 and the selected inter
atomic parameters are given in Tables 2 and 3. The structure of 2
is an example of
a limited number of cyclic diselenides
which are structurally characterized. The SeeSe distance in 2
(2.3378(13) Å) is similar to those reported in cyclic diselenides, e.g., 6-
methoxy-3-H-[1,2]diselenolo[3,4-b]quinoline (2.354 Å) [43], 4,4-
diphenyl-2,3-diselenabicyclo[3.3.0]oct-7-ene (2.322(2) Å) [44],
trans-1,2-diselenane-4,5-diol (2.3108(9) Å) [45], and 1,8:4,5-
bis(diseleno)naphthalene (2.364(1) Å) [46]. The CeSe distances are
similar to trans-1,2-diselenane-4,5-diol [45] and 1,8:4,5-bis(diseleno)
naphthalene [46] but are shorter than those reported for 4,4-
in the spectra of other compounds, could be due to n / s* tran-
sition as similar absorption has been attributed in dio-
rganoditellurides [40,41]. The IR spectra of these compounds
showed a carbonyl absorption in the region 1767e1626 cmꢁ1
.
diphenyl-2,3-diselenabicyclo[3.3.0]oct-7-ene
(2.121(2)
and
The 1H NMR spectra showed expected resonances and peak
multiplicities. The CH-6 proton resonance of pyridyl group
2.201(13) Å) [44]. The CeSeeSeeC torsion angle (3.51ꢀ) can be
compared with 1,8:4,5-bis(diseleno)naphthalene (4.4ꢀ) [46], but is
significantly different from an acyclic diselenide, trans-1,2-
diselenane-4,5-diol (53.93(19)ꢀ) [45], which adopts a distorted chair
conformation.
appeared in a wide range of
resonance of 4 ( 8.32 ppm) is considerably deshielded on oxidation
to the corresponding halo compounds ( 8.99 ppm in 6 and
8.52 ppm in 7). In contrast the NH proton resonance of 4 (
d 8.17e8.99 ppm. The CH-6 proton
d
d
d
The SeeSe distance in 4 (2.3916(12) Å) is slightly longer
than those reported in various pyridyl diselenides such
as 2,2-dipyridyldiselenide (2.2969(9) Å) [47], 4,4-dimethyl-2,2-
12.14 ppm) is shielded in the halo derivatives (d 11.24 ppm in 6 and
10.60 ppm in 7). The CeSe resonance in the 13C NMR spectra of
diselenides appeared at w129 ppm, which is deshielded for the
bromo compound (6) (133.6 ppm). The carbonyl carbon reso-
nances, except 2, appeared in the range 164.0e169.0 ppm. In the
dipyridyldiselenide
(2.2973(7)
Å)
[48],
6,6-dimethyl-2,2-
case of 2 this resonance is considerably deshielded (d 195.4 ppm).
The Se2 moiety in 2 has two distinct selenium atoms, one bonded to
pyridyl ring while the other is bound to the carbonyl carbon atom.
Accordingly the 77Se NMR spectrum of 2 exihibited two signals at
d
439 and 628 ppm, the former attributed to the selenium bound to
the pyridyl ring. The two selenium atoms in the Se2 moiety of 1,
3e5 are chemically equivalent, accordingly their 77Se NMR spectra
showed single resonances. The 77Se NMR resonances for selenenyl
halides are considerably deshielded (
d
768 ppm for 6 and
d
524 ppm
for 7) with reference to the corresponding diselenide 4 (
d
352 ppm).
The observed shifts are within the range reported for RSeX
compounds in literature [14,42].
3.2. Crystal structures of 2 and 4
Molecular structures of [2-NC5H3(3-CO)SeeSe] (2) and [2-
NC5H3(3-CONHPh)Se]2 (4) determined by single crystal X-ray
Fig. 1. Molecular structure of [2-NC5H3(3-CO)SeeSe] (2) with 50% thermal ellipsoid
probability.

C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
47
Fig. 2. ORTEP drawing with crystallographic numbering scheme of [2-NC5H3(3-CONHPh)Se]2.dmso (4.dmso) with 50% thermal ellipsoid probability. Inset shows weak Se/N and
Se/O interatctions.
dipyridyldiselenide (2.2935(1) Å) [49] and bis(3,5-dimethyl-
2-dipyridyl)diselenide (2.352(2) Å) [50], and also in other derivatives,
e.g. [Me2NC4H2N2Se2] (2.3162(16) Å) [51] and (2-Prn2NCH2C6H4Se)2
(2.346 Å) [13]. The pyridyl nitrogen atoms are in cis, cis position
relative to Se(1)eSe(1)0 group. The CeSe distances (1.93 Å) are well in
agreement with the values reported for organoselenium compounds.
An interesting feature of the structure is intra-molecular Se/X
interactions. The molecule shows intra-molecular secondary
Se10/N1 (2.887 Å) and Se1/O1 (2.608 Å) interactions. The Se/N
and Se/O distances are significantly shorter than the sum of van der
Waals radii of SeeN and SeeO [6]. Each selenium atom in 4 is weakly
coordinated to the oxygen atom of the carbonyl group of the same
pyridyl ring with which it is bonded and also to the nitrogen atom of
the other pyridyl ring. The two intra-molecular Se/N and Se/O
interactions appear to be responsible for the observed large
CeSeeSeeC torsion angle of 180ꢀ. The CeSeeSeeC torsion angle in
several pyridyl disenides is w90ꢀ [40,41,52] while it is 180ꢀ in bis(3,5-
dimethyl-2-pyridyl)diselenide [50]. The latter molecule exhibits
weak Se/N interactions. Compound 4 represents the first example
where two intra-molecular Se/X (X ¼ N or O) secondary interactions
exist in a diselenide.
assay, HPLC based thiol-disulfide conversion assay [12] and 1H NMR
based methods [21]. In the present study, the latter two methods
have been used for evaluation of GPx mimicking activity of 1-7
[21,31]. In the 1H NMR assay, H2O2 induced oxidation of DTTred to
DTTox is followed. As the reaction progresses the resonances at
d
¼ 2.63, 3.67 ppm for DTTred decreases with concomitant increase
of signals at
d
¼ 2.87, 3.03, 3.49 ppm due to DTTox. The catalytic
efficiency of nicotinoyl based organoselenium compounds was
determined by time the required for 50% conversion of DTTred to
DTTox, which is termed as t50. The oxidation of DTTred was 50%
completed within 9 min (t50 ¼ 9 min) when [2-NC5H3(3-COOH)Se]2
(1) (0.015 mmol, 10 mol %) was used as a catalyst. The compound
[2-NC5H3(3-CONH2)Se]2 (3) exhibited the best activity among all
the derivatives. At the concentration of 0.015 mmol (10 mol %) the
reaction at the start of the reaction could not be followed as
complete conversion of DTTred to DTTox was observed instanta-
neously. Therefore it was used at
a lower concentration
(0.003 mmol; 2 mol %), where the t50 was w4 min. A comparison of
GPx mimicking activities of the nicotinoyl based organoselenium
compounds (1e7) is shown in Fig. 3 while the t50 values are given in
Table 4. From these results, GPx mimicking activities are in the
order 3 > 7 > 4 > 6 > 1 > 5 > 2.
The GPx mimicking activity of these compounds has also been
evaluated by HPLC method. Several groups have employed
3.3. GPx mimicking activity
To assess the GPx mimicking activity of organoselenium
compounds a number of methods have been employed. These
include absorption spectroscopy based NADPH-reductase coupled
Table 3
Selected bond lengths (Å), bond angles (ꢀ) and torsion angles (ꢀ) for [2-NC5H3(3-
CONHPh)Se]2 (4).
Se1eC1
Se1eSe2
C6eO1
N2eC7
1.923 (6)
2.3916 (12)
1.226 (7)
1.349 (6)
1.420 (6)
92.83 (14)
121.0 (4)
115.8 (4)
180
N1eC1
N1eC5
Se1/O1
Se10/N1
1.324 (6)
1.350 (7)
2.608
Table 2
Selected bond lengths (Å) and angles (ꢀ) for [2-NC5H3(3-CO)SeeSe] (2).
Se1eSe2
C1eSe1
C6eSe2
C6eO1
N1eC1eSe1
C1eSe1eSe2
Se1eSe2eC6
2.3378 (13)
1.944 (8)
1.959(9)
1.223 (9)
115.6 (6)
90.9 (2)
C1eN1
C5eN1
C1eC2
C2eC6
Se2eC6eO1
Se2eC6eC2
C2eC1eSe1
1.350 (9)
1.366 (10)
1.393 (11)
1.484 (10)
121.3 (6)
114.6 (6)
119.9 (6)
2.887
N2eC7
C1eSe1eSe10
C2eC1eSe1
N1eC1eSe1
C10eSe10eSe1eC
N1eC1eSe1eSe10
N2eC6eO1
C2eC6eO1
C2eC6eO1
C2eC1eSe1eSe10
121.9 (5)
119.3 (4)
118.8 (5)
173.1 (4)
93.7 (3)
ꢁ7.3 (4)

48
C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
240
100
90
80
70
60
50
40
30
20
10
0
220
2
200
5
180
160
4
140
120
100
80
7
6
1
60
40
3
20
0
0
10 20 30 40 50 60 70 80 90 100 110 120
6
5
Ebselen
2
4
1
3
7
Time (min)
Organoselenium compounds
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
Fig. 4. t50 Bar graph showed by catalysts by HPLC method.
conditions: [DTTred
]
0
¼ [H2O2]0 ¼ 0.15 mmol and [selenide] ¼ 0.015 mmol.
3.4. Free radical scavenging assays
3.4.1. DPPH assay
oxidation of thiol to disulfide by hydrogen peroxide [9,53,54]. In the
present study oxidation of GSH (reduced glutathione) to GSSG
(oxidized glutathione) by hydrogen peroxide was monitored by
HPLC using a UV detector. Chromatograms due to absorptions of
both GSH and GSSG were monitored every hour upto 3 h. Presence
of selenium compound increased the rate of conversion of GSH to
GSSG. The t50 value i.e., the time required for 50% conversion of GSH
to GSSG was determined for each derivative (Table 4). As observed
in NMR assay, the profile for the GPx like activity followed the trend
3 > 7 > 4 > 6 > 1 > 5 > 2 > ebselen (Fig. 4). It is evident that the
compound 3 is the most potent catalyst and also exhibits better
activity than the well-known compound ebselen.
The hydrogen atom or electron donating abilities of the
synthesized nicotinamide derivatives were measured by
following the change in the absorbance due to DPPH at 517 nm as
a function of the concentration of the selenium compound as
shown in Fig. 5. The IC50 values, i.e. the concentration of sele-
nium compound required to scavenge 50% of DPPH free radical
were estimated and listed in Table 5. The results indicated that
the free radical scavenging ability was highest for 3 followed by 4
and BHT. Compounds 5e7 did not show 50% of inhibition even at
the highest soluble concentration. The order of radical scavenging
The t50 values measured by 1H NMR spectroscopy and HPLC
method are different (Table 4), although the trend of GPx
mimicking activity for these compounds evaluated by different
methods is the same. The reasons for such discrepancy are mainly
ability of
their highest concentration (50
mM) is
3 > 4 > BHT > 5 > 6 (Fig. 6, Table 5). It was found that
compounds 1 and 2 did not exhibit any significant scavenging
activity even at equimolar concentration ratios of the selenium
compound and DPPH.
due to usage of different thiols. In NMR method, a dithiol (DTTred
)
which being a stronger reducing agent, leads to facile reduction of
diselenide linkage [3,55] while in the HPLC method GSH, a mono-
thiol, is used and reduction of diselenide bond by a monothiol,
would be very slow [3,56].
4
7
5
100
3
BHT
80
60
40
20
0
Table 4
Evaluation of GPx like catalytic activity of organoselenium compounds by HPLC and
1H NMR spectroscopy.
Compounds
t50 by HPLC (min) t50 by NMR (min)
at 10 M catalyst
m
[2-NC5H3(3-COOH)Se]2 (1)
[2-NC5H3(3-CO)SeeSe] (2)
[2-NC5H3(3-CONH2)Se]2 (3)
[2-NC5H3(3-CONHPh)Se]2 (4)
159.45
174.53
35.65
17a
>120a
4c
81.64
73b
[2-NC5H3(3-CONHpyrimidine)Se]2 (5) 162.04
>120a
12a
[2-NC5H3(3-CONHPh)SeBr] (6)
[2-NC5H3(3-CONHPh)SeI] (7)
Ebselen
126.04
66.56
220.5
147
47c
e
Selenocystein
e
0
10
20
30
40
50
Concentration of the catalyst used for NMR method.
a
10 mol%.
2.5 mol%.
2 mol%.
Concentration (µM)
b
c
Fig. 5. Scavenging activity (%) on DPPH radicals by nicotinic acid derivatives.

C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
49
Table 5
Antioxidant properties of nicotine derivatives.
Compounds
DPPH assay
IC50 M)
2-Deoxyribose assay
IC050
M)
76.84
(
m
Inhibition at 50
m
M (%)
(m
Inhibition at 150 mM (%)
[2-NC5H3(3-CONH2)Se]2 (3)
[2-NC5H3(3-CONHPh)Se]2 (4)
[2-NC5H3(3-CONHPh)SeI] (7)
[2-NC5H3(3-CONHpyrimidine)Se]2 (5)
[2-NC5H3(3-CONHPh)SeBr] (6)
[2-NC5H3(3-COOH)Se]2 (1)
18.01
20.61
nf
nf
nf
93.01 ꢄ 2.69
91.21 ꢄ 1.9
19.93 ꢄ 1.63
27.95 ꢄ 1.72
7.82 ꢄ 3.52
ni
84.13 ꢄ 4.78
63.70 ꢄ 2.32
31.00 ꢄ 1.34
4.08 ꢄ 2.96
13.70 ꢄ 3.1
2 ꢄ 1.26
102.35
nfa
nfa
nfa
nf
nf
nfa
[2-NC5H3(3-CO)SeeSe] (2)
ni
nfa
nfa
D
-Mannitol
e
e
49.80
e
71.21 ꢄ 3.52
BHT
26.51
86.00 ꢄ 2.3
e
The values are the average of three determinations (ꢄSD). nf, not found till 50
m
M of test compounds. nfa, not found till 150
mM of test compounds. ni, no inhibition even at 1:1
concentration of test compound and DPPH.
3.4.2. Deoxyribose assay
100
90
80
70
60
50
40
30
20
10
0
Inhibition of the degradation of 2-deoxyribose induced by
Fenton-reagent is often used to estimate the hydroxyl radical (ꢂOH)
scavenging ability of antioxidants and other organic compounds.
The IC50 values, i.e. the concentration of selenium compound
required to inhibit the degradation by 50% was estimated and
compared with standard reference compound, mannitol (positive
control) and listed in Table 4 (Fig. 7). The scavenging potential was
the highest for
values of 49.80, 76.84, 102.35
D
-mannitol followed by 3 and 4 derivatives with IC50
M respectively. The behaviour of
m
other derivatives viz., 5e7 towards radical scavenging is more or
less same as in DPPH assay while compounds 1 and 2 do not show
any pronounce scavenging abilities.
The results imply that 3 has significantly more hydrogen or
electron donating ability which may be due to the presence of free
amine. Furthermore absence of amide linkage in derivatives like 1
and cyclic compound 2 showed no significant scavenging ability,
clearly demonstrates the essential role of amide linkage in free
radical scavenging activities in these screened compounds.
BHT
Organoselenium compounds
6
7
5
3
4
Fig. 6. DPPH radical scavenging ability at highest concentration of 50
acid derivative.
m
M of nicotinic
4. Conclusions
In the present study we synthesized new series of nicotinoyl
based organoselenium compounds and evaluated their biological
activities as GPx mimics and free radical scavenger. Two
compounds, 3 and 4 were of great interest as they exhibited potent
free radical scavenging ability by DPPH and 2-deoxyribose assays. It
is noteworthy that the same were catalytically more efficient than
ebselen by means of GPx like activity. From the study it is apparent
that GPx and antioxidant activities of nicotinamide based organo-
selenium compounds depends on the nature of substituent
attached to nitrogen atom of amide group. Introduction of either
electron donating group like phenyl or electron withdrawing group
like pyrimidine to amide linkage has significantly reduced the GPx
and free radical scavenging activity. Similarly making selenium-
halogen linkage by breaking diselenide bond further decreased
both activities. In summary, considering GPx and free radical
scavenging abilities, compound 3 may be considered as prominsing
candidate.
100
Mannitol
7
3
4
6
5
90
80
70
60
50
40
30
20
10
0
Acknowledgements
We thank Drs. T. Mukherjee, S. K. Sarkar and D. Das for
encouragement of this work. We are thankful to Mr. S.K. Yadav for
his help in performing deoxyribose assay. CPP is grateful to Board of
Research in Nuclear Sciences (BRNS), Department of Atomic Energy
(DAE) for the award of a Senior Research Fellowship. We are also
0
25
50
75
100
125
150
Concentration (µM)
Fig. 7. OHꢂ radical abstraction efficiency of nicotinic acid derivatives by deoxyribose
assay.

50
C. Parashiva Prabhu et al. / Journal of Organometallic Chemistry 713 (2012) 42e50
[24] N. Otte, C. Borelli, H.C. Korting, Int. J. Cosmet. Sci. 27 (2005) 255e261.
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grateful to BRNS for the research grant under the Prospective
Research Fund (PRF) Scheme (Grant No. BRNS/2007/38/5).
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Phadnis, P. Prabhu, A. Wadawale and K.I. Priyadarsini, Preparation of orga-
noselenium compounds, BARC/2009/I/003.
[30] P. Prabhu, P.P. Bag, B.G. Singh, A. Hodage, V.K. Jain, M. Iwaoka, K.I. Priyadarsini,
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Appendix A. Supplementary material
CCDC 853553 [2-NC5H3[3-C(O)SeeSe] (2) and 853554[2-
NC5H3(3-CONHPh)Se]2.dmso (4.dmso) contain the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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