Synthesis of Cyclic Sulfite Diesters and their Evaluation as Sulfur Dioxide (SO2) Donors

Article abstract of DOI:10.1002/cbic.201900614

Although sulfur dioxide (SO₂) finds widespread use in the food industry as its hydrated sulfite form, a number of aspects of SO₂ biology remain to be completely understood. Of the tools available for intracellular enhancement of SO₂ levels, most suffer from poor cell permeability and a lack of control over SO₂ release. We report 1,2-cyclic sulfite diesters as a new class of reliable SO₂ donors that dissociate in buffer through nucleophilic displacement to produce SO₂ with tunable release profiles. We provide data in support of the suitability of these SO₂ donors to enhance intracellular SO₂ levels more efficiently than sodium bisulfite, the most commonly used SO₂ donor for cellular studies.

Full text of DOI:10.1002/cbic.201900614

Accepted Article
Title: Synthesis and evaluation of cyclic sulfite diesters as sulfur
dioxide (SO2) donors
Authors: Satish Malwal, Kundansingh A Pardeshi, and Harinath
Chakrapani
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemBioChem 10.1002/cbic.201900614
Link to VoR: http://dx.doi.org/10.1002/cbic.201900614
A Journal of
www.chembiochem.org

10.1002/cbic.201900614
ChemBioChem
COMMUNICATION
Synthesis and evaluation of cyclic sulfite diesters as sulfur
dioxide (SO2) donors
Satish R. Malwal†, Kundansingh A. Pardeshi, Harinath Chakrapani*
Abstract: Although sulfur dioxide (SO2) finds widespread use in the
food industry as its hydrated form, sulfite, a number of aspects of SO2
biology remain to be completely understood. Among the tools
available for intracellular enhancement of SO2, most suffer from poor
cell permeability and a lack of control over SO2 release. We report
1,2-cyclic sulfite diesters as a new class of reliable SO2 donors that
dissociate in buffer through a nucleophilic displacement to produce
SO2 with tuneable release profiles. We provide data in support of the
suitability of these SO2 donors to enhance intracellular levels of SO2
at an efficiency superior to sodium bisulfite, the most commonly used
SO2 donor for cellular studies.
studies as targets of SO2 include biologically relevant disulfides
and thiols.[8a, 8b, 9] In a second strategy, a series of benzosultines
as SO2 donors with controlled rate of generation of SO2 under
physiological condition, having heat as a trigger was reported
(Scheme 1).[8c] Although benzosultines are stable as solids, they
are not highly suited for prolonged storage at room temperature
as stock solutions. In third strategy, benzosulfones were reported
as photochemically activated SO2 donors by our group and others
(Scheme 1).[8d] These compounds might have limitations
associated with the inconvenience associated with using a light
source in cellular studies and possibly by intensity of light that was
required for SO2 generation.[10] Xian et al. reported sodium
benzothiazole sulfonate as water-soluble SO2 donor, having
limitation of prolonged half-life (t1/2 = 13 days) at physiological pH
Introduction
12]
7.4.[11]
Recently, SO2 donors, using esterase[8f,
,
nitroreductase[13], thiol[14]and light[15] as a trigger, and click
reaction as a mode of SO2 donation, have been reported by our,
Singh’s group and Wang’s group (Scheme 1). These strategies
rely on the use of cellular enzyme or a bio-orthogonal reaction,
which can result in variable generation of sulfur dioxide depending
on the availability of the stimulus. Therefore, new self-immolative
SO2 donors which are stable at room temperature and permeate
cells to enhance intracellular SO2 could help better understand
cellular responses to this important gaseous molecule.
Sulfur dioxide (SO2) is an environmental pollutant that is also
produced during metabolism of sulfur containing amino acids[1] as
well as hydrogen sulfide (H2S), which is known to mediate a
number of cellular processes.[1d, 2] The known vasodilatory effects
of SO2 in animal models suggest possible signaling roles for this
gas as well.[3] SO2 is also used in the food industry as a
preservative and an anti-bacterial agent.[4] At elevated levels SO2
is known to cause biomacromolecular damage and cell death;[5]
these damaging effects are perhaps responsible for the anti-
bacterial properties of this gas. However, due to the limited
understanding of molecular mechanisms of action of this gas,
reliably producing[6] and detecting SO2 within cells are necessary.
While there are numerous probes for SO2, biological studies have
thus far relied on gaseous SO2 or a complex formulation of
inorganic sulfites.[7] Both methods may not be well suited for
enhancing SO2 within cells and offer no temporal control over SO2
release. Furthermore, they are useful for studying effects of SO2
as a single dose, which is unsuitable for study of prolonged
exposure. Thus, the chemical biology of SO2 remains largely
uncharacterized.15 Our laboratory has developed several
strategies having different triggers for generating SO2 under
physiological conditions using small organic molecules.[8] First,
2,4-dinitrophenylsulfonamides with tunable rates of generation of
SO2 when triggered by biological thiols were reported (Scheme
1). The use of thiol is used as a trigger may complicate biological
Scheme 1. Reported strategies for generation of SO2 under physiological
conditions.
Dr. Satish R. Malwal, Dr. Kundansingh Pardeshi, Dr. Harinath
Chakrapani. Indian Institute of Science Education and Research
Pune, Dr. Homi Bhabha Road, Pashan Pune 411 008,
Maharashtra, India
1,2-Cyclic sulfite diesters were considered as SO2 donors
(Scheme 2). Upon attack by a nucleophile (such as water), a
sulfite monoester would be formed, which could spontaneously
decompose to produce SO2. Modulating substituents "R" or
perhaps the pKa of the leaving group would help tune the rate of
substitution by a nucleophile and possibly SO2 release. Here, we
report results of synthesis and evaluation of a series of 1,2-cyclic
sulfite diesters as SO2 donors.
E-mail: harinath@iiserpune.ac.in
†Present address: Department of Chemistry, University of Illinois at
Urbana-Champaign, Urbana, IL 61801, USA
 Corresponding author. Tel.: +91-20-2590-8090; fax: +91-20-
2589-9790; e-mail: harinath@iiserpune.ac.in
Supporting information and the ORCID identification numbers for
the authors of this article can be found under
https://doi.org/10.1002/ cbic.xxxxxx
This article is protected by copyright. All rights reserved.

10.1002/cbic.201900614
ChemBioChem
COMMUNICATION
Table 1. Synthesis of 1,2-cyclic sulfite diesters.
Scheme 2. Sulfite diesters can decompose in pH 7.4 buffer to
produce SO2.
Yield
(%)
Entry
R1
R2
-H
R3
R4
-H
Diol
1
Prod
12
1
2
-H
-H
78
Results and Discussion
-
-
-CH3
-CH3
2
13
96
90
CH3
CH3
1,2-diols used for synthesis of 1,2-cyclic sulfite diesters were
either commercially available (1 and 2; Figure 1) or prepared by
Upjohn dihydroxylation from corresponding olefin by OsO4
mediated dihydroxylation[16] (diols 3-5 and 11; Figure 1) or by
nucleophilic ring opening of 4-substituted styrene oxide by 10%
aq. K2CO3 solution. The diol 6 and 10 were synthesized from L-
tartaric acid, and NaBH4 mediated reduction[17] of (±)-benzoin
respectively. The diols 7 and 8-9 were prepared by ring opening
of corresponding (±)-phenyloxirane and substituted (±)-
phenyloxirane, in 10% K2CO3 reflux condition respectively.
Various 1,2-cyclic sulfite diesters (12-22) were prepared by the
reaction of 1,2-diols with thionyl chloride, triethylamine and
imidazole in DCM at 0 °C (Table 1).[18] The cis-1,2-diols 3 and 4,
gave an isomeric mixture (depending on sulfoxide orientation) of
-
3
-(CH2)3-
-H
-H
3
14
(CH2)3-
-
4
5
6
-(CH2)4-
-COOEt
-COOEt
-H
-H
-H
-H
-H
-H
4
5
6
15
16
17
69
87
80
(CH2)4-
-H
-
COOEt
7
-Ph
-H
-H
-H
-H
-H
-H
-H
-H
-H
7
18
19
20
21
93
81
75
86
8
4-NO2-Ph-
4-F-Ph-
-Ph
-H
8
9
-H
9
10
-Ph
10
-
11
4-NO2-Ph-
-H
-H
11
22
75
14 (1:0.68), 15 (1:0.64) by H NMR.[19] The diols 5, 6 and 11
1
COOEt
afforded mixture of diastereomers of 16, 17 and 18 in the ratios
(depending on chirality of sulfoxide), 16 (1:0.95), 17 (~1:1) and 22
(1:0.86) by 1H NMR. The racemic 1,2-diols 7-10 afforded mixture
of diastereomers for 18-21.
In the cases of 12-15, nearly similar pKa values for the
alcohols implies that any difference in SO2 yields must be due to
increased steric hinderance at the carbon bearing the sulfite ester.
The diesters 12, 14 and 15 gave SO2 yields > 20% after 30 min,
whereas pinacol derivative 13 gave 2% of SO2. These results
suggest that when leaving group was similar the important
determinant of observed reaction rates was sterics supporting the
proposed mechanism (Scheme 2). These results are also
consistent with previous reports[20] of 1,2-cyclic sulfite diesters
undergoing nucleophilic substitution with various nucleophiles
such as chloride, azide and (CH3OOC)2HC− at one of the
activated carbon atoms (Scheme 2).[20-21] The hydrolysis of cyclic
sulfite esters of normal, or cis or trans diols under acidic (cat.
H2SO4/HClO4) or basic (2 eq. NaOH) reflux condition, results in
sulfur-oxygen bond fission to give corresponding diol without
change in stereo-configuration.[20, 22]
Figure 1. 1,2-diols prepared for synthesis of 1,2-cyclic sulfite diesters.
In order to study the electronic effect on decomposition,
diesters 16 and 17 were incubated in pH 7.4 buffer and 93% and
98% SO2, respectively were recorded (Table 2, entry 5 and 6).
These compounds contain an electron withdrawing substituent as
compared to ethylene glycol diester 12. The electron withdrawing
nature of the ester enhances electrophilicity of the carbon bearing
the sulfite functional group contributing to an increased rate of
displacement.
Next, decomposition of derivatives with phenyl substituent
18-21 was carried out. After 30 min, the phenyl derivative 18 gave
73% of SO2 (Table 2, entry 7). The 4-NO2- phenyl derivative 19
on the other hand produced higher amount of SO2 and a 96%
yield was obtained (Table 2, entry 8). Incubation of the 4-F-phenyl
derivative 20 (Table 2, entry 9) resulted in a nearly similar SO2
yield as that of phenyl derivative 18. The diphenyl derivative 21
The aforementioned derivatives 12-22 were evaluated for SO2
release in pH 7.4 phosphate buffer. First, ethylene glycol
derivative 12 was incubated at 37 °C in pH 7.4 buffer for 30 min.
The reaction was monitored for SO2 generation by ion
chromatography equipped with an ion conductivity detector;[8b]
SO2 was quantified as sulfite, SO32-. After 30 min, 12 gave 45% of
SO2 (Table 2, entry 1). The pinacol derivative 13 produced
negligible amounts of SO2 and a 2% yield was recorded (Table 2,
entry 2). These results suggest that increasing sterics on the
carbon bearing the sulfite functional group reduced the propensity
for decomposition of the compound supporting direct
displacement at the carbon, which involves formation of a sulfite
monoester, which in turn rapidly rearranges to produce SO2 and
an alcohol (Scheme 2)
This article is protected by copyright. All rights reserved.

10.1002/cbic.201900614
ChemBioChem
COMMUNICATION
gave 83% SO2 after 30 min (Table 2, entry 10). These results
suggest that electron withdrawing group on phenyl substituent
increases the rate of decomposition, again consistent with a
nucleophilic displacement mechanism. Hence, it appears that
SO2 generation has little dependence on the nature of the leaving
group and the intermediate formed is quite unstable and collapses
to produce sulfur dioxide (Scheme 2). Steric and electronic factors
around the electrophilic carbon determine yields of sulfur dioxide
while the pKa doesn’t appear to affect the outcome of the reaction.
Scheme 3. Reaction of probe 23 with sulfites
The possibility of
a concerted process, i.e. nucleophilic
displacement along with generation of SO2 cannot be ruled out.
Lastly, consistent with this trend compound 22, which has a strong
electron withdrawing group attached to the core skeleton gave an
excellent yield.
Table 2. Sulfur dioxide yields and calculated pKas of 1,2-diols.
a
Entry
1
Compd
12
% SO2 yield after 30 min
pKa
45
2
14.40
14.23
14.25
14.27
11.91
10.64
13.83
13.48
13.73
13.70
11.53
2
13
3
14
25
21
93
98
73
96
68
83
95
Figure 2. (A) UV-vis spectra of probe (10 μM) in presence of 100 μM of 17 in
pH 7.4 1% DMSO/PB. (B) Fluorescence spectra of probe (10 μM) in presence
of 100 μM of 17 in pH 7.4 1% DMSO/PB.
4
15
5
16
6
17
7
18
8
19
9
20
10
11
21
22
aValues are for the corresponding 1,2-diol (most acidic proton) calculated
using ChemBioDraw Ultra 16.0.
A number of SO2 probes that typically use the distinct
nucleophilic properties of sulfite/bisulfite have been developed by
various groups.[23]. For example, Sun et al. have reported probe
Figure 3. Decomposition of 19 in pH 7.4 1% DMSO/PB was monitored by HPLC,
1:1 ACN/H2O isocratic gradient, wavelength, λ = 254 nm. During 30 min, nearly
complete decomposition of 19 with concomitant formation of 8 was observed.
-
23 for selective detection of SO2 derivatives HSO3 /SO32- in pH 7.4
buffer (Scheme 3).[23c] The probe 23 absorbs at 545 nm and upon
-
reaction with HSO3 /SO32- , a distinct and ratiometric shift to an
absorbance at 410 nm (for 24) was observed (see Supporting
Information, Figures S1 and S2). A similar UV profile was
observed when 23 was reacted with the SO2 donor 17 supporting
the intermediacy of sulfite (Figure 2a). The probe 23 fluoresces in
the red region and upon reaction with SO32-/HSO3- it forms green
fluorescing adduct 24 (Figure 2b). When 23 was treated with
sulfite diester 17, we find a similar shift in emission (Figure 2b).
Together, these data independently confirm the ability of 17 to
generate SO2 in pH 7.4 buffer.
The expected product formed during hydrolysis in buffer is
the diol (Scheme 2). In order to confirm this, we incubated 19 in
pH 7.4 buffer and monitored the decomposition and formation of
1-(4-nitrophenyl)ethane-1,2-diol 8 (Figure 3). We find nearly
complete disappearance of 19 during 30 min with the formation of
8 as the exclusive product (Figure 3) and a nearly quantitative
yield of SO2 (Table 2, entry 8). Thus, the decomposition of the
sulfite monoester was rapid and SO2 is likely to be generated as
soon as the intermediate is produced (Scheme 2).
Having established the suitability of cyclic sulfite esters for
molecular biology studies, cell permeability as well as the
suitability of these compounds for enhancing intracellular levels of
SO2 was examined. The ratiometric probe 23 has been previously
reported to be suitable for detection of intracellular sulfite/bisulfite.
When DLD-1 cells treated with 23 (10 μM), we found a distinct
fluorescence signal only in the red channel but not in the green
channel (Figure 4A-C).[23c]
When cells pre-treated with 23 were exposed to 17 (20 μM),
a decrease in fluorescence signal in the red channel with
concomitant increase in fluorescence increase in green channel
was observed (Figure 4D-F). Under similar conditions, when a
similar experiment was conducted with authentic bisulfite, we
found a similar profile.[23c] However, an increased concentration
of 200 M was necessary to elicit this response whereas with the
donor developed in this study, a significantly lower concentration
could achieve enhancement of intracellular SO2. Above results
This article is protected by copyright. All rights reserved.

10.1002/cbic.201900614
ChemBioChem
COMMUNICATION
suggest the compatibility of cyclic sulfite diesters with cellular
nucleophiles. Lastly, a cell viability assay conducted with human
cervical cancer cells (HeLa) revealed SO2 donors 17 and 13 were
not significant inhibitors of proliferation at 100 μM (see Supporting
Information, Figures S3 and S4). Thus, the SO2 donor 17 might
find convenient use for studying cellular responses to enhanced
reactive sulfur species.
support. SM and KAP acknowledge research fellowships from
Council for Scientific and Industrial Research (CSIR) and
University Grants Commission (UGC), respectively.
Keywords: Sulfur dioxide, Cyclic sulphite ester, Reactive sulfur
species, sulfite
[1]
[2]
a) M. H. Stipanuk, Annu. Rev. Nutr. 1986, 6, 179-209; b) T. P. Singer,
E. B. Kearney, Arch. Biochem. Biophys. 1956, 61, 397-409; c) W.
Wang, B. Wang, Front. Chem. 2018, 6; dP. Bora, P. Chauhan, K. A.
Pardeshi, H. Chakrapani, RSC Adv. 2018, 8, 27359-27374.
a) Y. Zhao, T. D. Biggs, M. Xian, Chem. Commun. 2014, 50, 11788-
11805; b)K. Shatalin, E. Shatalina, A. Mironov, E. Nudler, Science
2011, 334, 986-990.
[3]
[4]
a) Z. Meng, G. Qin, B. Zhang, J. Bai, Mutagenesis 2004, 19, 465-
468; b) W. Dröge, Phys. Rev., 82, 47-95.
a) L. A. Komarnisky, R. J. Christopherson, T. K. Basu, Nutrition 2003,
19, 54-61; b) C. S. Ough, E. A. Crowell, J. Food Sci. 1987, 52, 386-
388.
[5]
a) A. F. Gunnison, Food and Cosmetics Toxicology 1981, 19, 667-
682; b) E. Rencüzoǧullari, H. B. İla, A. Kayraldiz, M. Topaktaş, Mutat.
Res. 2001, 490, 107-112; c) X. Shi, J. Inorg. Biochem. 1994, 56,
155-165.
[6]
[7]
[8]
a) P. Bisseret, N. Blanchard, Org. Biomol. Chem. 2013, 11, 5393-
5398; b) E. J. Emmett, M. C. Willis, Asian J.Org. Chem. 2015, 4,
602-611.
a) H. Niknahad, P. J. O’Brien, Chem. Biol. Interact. 2008, 174, 147-
154; b) Z. Meng, Y. Li, J. Li, Arch. Biochem. Biophys. 2007, 467,
291-296.
a) S. R. Malwal, D. Sriram, P. Yogeeswari, V. B. Konkimalla, H.
Chakrapani, J. Med. Chem. 2012, 55, 553-557; b) S. R. Malwal, D.
Sriram, P. Yogeeswari, H. Chakrapani, Bioorg. Med. Chem. Lett.
2012, 22, 3603-3606; c) S. R. Malwal, M. Gudem, A. Hazra, H.
Chakrapani, Org. Lett. 2013, 15, 1116-1119; d) S. R. Malwal, H.
Chakrapani, Org. Biomol. Chem. 2015, 13, 2399-2406; e) K. A.
Pardeshi, S. R. Malwal, A. Banerjee, S. Lahiri, R. Rangarajan, H.
Chakrapani, Bioorg. Med. Chem. Lett. 2015, 25, 2694-2697; f) K. A.
Pardeshi, G. Ravikumar, H. Chakrapani, Org. Lett. 2018, 20, 4-7.
a) M. J. Pena-Egido, B. Garcia-Alonso, C. Garcia-Moreno, J. Agric.
Food Chem. 2005, 53, 4198-4152; b) B. Garcia-Alonso, M. J. Pena-
Egido, C. Garcia-Moreno, J. Agric. Food Chem. 2001, 49, 423-429;
c) D. Liu, H. Jin, C. Tang, J. Du, Mini Rev. Med. Chem. 2010, 10,
1039-1045.
Figure 4. Live cell imaging carried out with DLD-1 cells (A) cells incubated with
probe 23 (10 μM) from the green channel; (B) imaging of (A) from the red
channel; (C) overlay of (A) and (B); (D) fluorescence imaging of cells incubated
with probe 23 (10 μM) for 30 min, and further incubated with 17 (20 μM) for 30
min from the green channel; (E) fluorescence imaging of (D) from the red
channel; (F) overlap of (D) and (E); (G) fluorescence imaging of cells incubated
with probe 23 (10 μM) for 30 min, and further incubated with NaHSO3 (200 μM)
for 30 min from the green channel; (G) imaging of (F) from the red channel; (I)
overlay of (G) and (H); Scale bar: 100 μm.
[9]
[10]
[11]
R. Kodama, K. Sumaru, K. Morishita, T. Kanamori, K. Hyodo, T.
Kamitanaka, M. Morimoto, S. Yokojima, S. Nakamura, K. Uchida,
Chem. Commun. 2015, 51, 1736-1738.
J. J. Day, Z. Yang, W. Chen, A. Pacheco, M. Xian, ACS Chem. Biol.
2016, 11, 1647-1651.
W. Wang, B. Wang, Chem. Commun. 2017, 53, 10124-10127.
K. A. Pardeshi, T. A. Kumar, G. Ravikumar, M. Shukla, G. Kaul, S.
Chopra, H. Chakrapani, Bioconjugate Chem. 2019, 30, 751-759.
B. Roy, M. Kundu, A. K. Singh, T. Singha, S. Bhattacharya, P. K.
Datta, M. Mandal, N. D. P. Singh, Chem. Commun. 2019, 55,
13140-13143.
Y. Venkatesh, K. S. Kiran, S. S. Shah, A. Chaudhuri, S. Dey, N. D.
P. Singh, Org. Biomol. Chem. 2019, 17, 2640-2645.
G. Fakha, D. Sinou, Molecules 2005, 10, 859-870.
Z. Behzad, B. Tarifeh, Bull. Chem. Soc. Jpn. 2005, 78, 307-315.
a) A. J. Williams, S. Chakthong, D. Gray, R. M. Lawrence, T.
Gallagher, Org. Lett. 2003, 5, 811-814; b) R. Peters, D. F. Fischer,
Org. Lett. 2005, 7, 4137-4140.
D. F. Shellhamer, D. T. Anstine, K. M. Gallego, B. R. Ganesh, A. A.
Hanson, K. A. Hanson, R. D. Henderson, J. M. Prince, V. L. Heasley,
J. Chem. Soc., Perkin Trans. 2 1995, 861-866.
C. A. Bunton, P. B. D. de la Mare, P. M. Greaseley, D. R. Llewellyn,
N. H. Pratt, J. G. Tillett, J. Chem. Soc. 1958, 4751-4754.
aK. Nymann, L. Jensen, J. S. Svendsen, Acta Chem. Scand. 1996,
50, 832-841; bK. Nymann, J. S. Svendsen, Acta Chem. Scand. 1994,
48, 183-186.
H. K. Garner, H. J. Lucas, J. Am. Chem. Soc. 1950, 72, 5497-5501.
a) W. Chen, Q. Fang, D. Yang, H. Zhang, X. Song, J. Foley, Anal.
Chem. 2014, 87, 609-616; b) Y. Sun, D. Zhao, S. Fan, L. Duan, R.
Li, J. Agric. Food Chem. 2014, 62, 3405-3409; c) Y.-Q. Sun, J. Liu,
J. Zhang, T. Yang, W. Guo, Chem. Commun. 2013, 49, 2637-2639;
d) C. Wang, S. Feng, L. Wu, S. Yan, C. Zhong, P. Guo, R. Huang,
X. Weng, X. Zhou, Sensors Actuators B: Chem. 2014, 190, 792-799;
e) M.-Y. Wu, K. Li, C.-Y. Li, J.-T. Hou, X.-Q. Yu, Chem. Commun.
2014, 50, 183-185.
Conclusions
[12]
[13]
In summary, we report a series of 1,2-cyclic sulfite diesters that:
can be easily synthesized; are stable at room temperature; have
tunable SO2 release profiles; and are well suited to study effects
of enhanced intracellular levels of SO2 and duration of exposure
to this reactive species. Together, we present superior
alternatives to inorganic sulfites, the most commonly used SO2
donors. These compounds are easy to prepare and store and
readily dissociate to produce SO2. Due to the fundamental
importance of redox regulation in cellular growth and survival,
perturbation of redox homeostasis has emerged as a possible
mechanism for the development of new therapeutics.[24] Thus,
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
reliably generating reactive oxygen,[25] nitrogen[26] and sulfur
8b, 8e]
species[8a,
may have a range of applications including
developing small molecule-based inhibitors of against bacteria
[22]
[23]
25e]
such as Staphylococcus aureus,[8e,
Mycobacterium
tuberculosis[8a, 8b, 25a, 25b] as well as cancer.[27]
Acknowledgments
The authors thank IISER Pune and the Department of
Biotechnology, Ministry of Science and Technology, India (DBT);
Grant Number: BT/PR6798/MED/29/636/2012 for financial
This article is protected by copyright. All rights reserved.

10.1002/cbic.201900614
ChemBioChem
COMMUNICATION
[24]
a) A. Kumar, A. Farhana, L. Guidry, V. Saini, M. Hondalus, A. J. C.
Steyn, Exp. Rev. Mol. Med. 2011, 13, 1 (e39); b) G. T. Wondrak,
Antioxidants Redox Signal. 2009, 11, 3015-3069.
a) P. Tyagi, A. T. Dharmaraja, A. Bhaskar, H. Chakrapani, A. Singh,
Free Radic. Biol. Medicine 2015, 84, 344-354; b) A. T. Dharmaraja,
M. Alvala, D. Sriram, P. Yogeeswari, H. Chakrapani, Chem.
Commun. 2012, 48, 10325-10327; c) A. T. Dharmaraja, H.
Chakrapani, Org. Lett. 2014, 16, 398-401; d) A. T. Dharmaraja, T.
K. Dash, V. B. Konkimalla, H. Chakrapani, Med. Chem. Comm 2012,
3, 219 - 224; e) V. S. Khodade, M. Sharath Chandra, A. Banerjee,
S. Lahiri, M. Pulipeta, R. Rangarajan, H. Chakrapani, ACS Med.
Chem. Lett. 2014, 5, 777-781.
[26]
[27]
a) K. Sharma, A. Iyer, K. Sengupta, H. Chakrapani, Org. Lett. 2013,
15, 2636-2639; b) K. Sharma, K. Sengupta, H. Chakrapani, Bioorg.
Med. Chem. Lett. 2013, 23, 5964-5967; c) A. T. Dharmaraja, G.
Ravikumar, H. Chakrapani, Org. Lett. 2014, 16, 2610-2613.
S. Li, R. Liu, X. Jiang, Y. Qiu, X. Song, G. Huang, N. Fu, L. Lin, J.
Song, X. Chen, H. Yang, ACS Nano 2019, 13, 2103-2113.
[25]
This article is protected by copyright. All rights reserved.

10.1002/cbic.201900614
ChemBioChem
COMMUNICATION
Entry for the Table of Contents
Synthesis and evaluation of cyclic
sulfite diesters as sulfur dioxide (SO2)
donors*
Satish R. Malwal, Kundansingh A.
Pardeshi, Harinath Chakrapani
Tunable release of sulfur dioxide achieved by cyclic sulfite esters
Page No. – Page No.
This article is protected by copyright. All rights reserved.