Study on the intermediate ions formed by glutathione peroxidase mimic 2,2'-ditellurobis(2-deoxy-β-cyclodextrin) by electrospray ionization mass spectrometry

Article abstract of DOI:10.1002/rcm.6455

RATIONALE 2,2'-Ditellurobis(2-deoxy-β-cyclodextrin) (2-TeCD) is one of the most well-known glutathione peroxidase (GPx) mimics. However, because the critical reaction intermediates had not previously been isolated or directly detected due to its short lifetime, the catalytic mechanism of 2-TeCD is not very clear and further experiments are needed to characterize each of the intermediates in the catalytic cycle. METHODS Using electrospray ionization mass (and tandem) spectrometry (ESI-MS and ESI-MS/MS) experiments, the decomposition of hydrogen peroxide at the expense of glutathione (GSH) catalyzed by 2-TeCD was monitored on-line. RESULTS The key intermediates were successfully intercepted and structurally characterized for the first time by coupling a microreactor on-line to the ESI ion source, which permitted the fast screening of intermediates directly from solution. CONCLUSIONS The catalytic mechanism of 2-TeCD catalysis has been elaborated based on mass spectrometric data and exerted its peroxidase activity via tellurol, tellurenic acid, and tellurosulfide, in analogy with natural GPX. Copyright

Full text of DOI:10.1002/rcm.6455

Research Article
Received: 28 August 2012
Revised: 18 October 2012
Accepted: 25 October 2012
Published online in Wiley Online Library
Rapid Commun. Mass Spectrom. 2013, 27, 319–324
(wileyonlinelibrary.com) DOI: 10.1002/rcm.6455
Study on the intermediate ions formed by glutathione peroxidase
mimic 2,2’-ditellurobis(2-deoxy-b-cyclodextrin) by electrospray
ionization mass spectrometry
Aiquan Jiao1,2, Na Yang1,2, Xueming Xu1,2 and Zhengyu Jin1,2
*
1The State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China
2School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China
RATIONALE: 2,2’-Ditellurobis(2-deoxy-b-cyclodextrin) (2-TeCD) is one of the most well-known glutathione peroxidase
(GPx) mimics. However, because the critical reaction intermediates had not previously been isolated or directly detected
due to its short lifetime, the catalytic mechanism of 2-TeCD is not very clear and further experiments are needed to
characterize each of the intermediates in the catalytic cycle.
METHODS: Using electrospray ionization mass (and tandem) spectrometry (ESI-MS and ESI-MS/MS) experiments, the
decomposition of hydrogen peroxide at the expense of glutathione (GSH) catalyzed by 2-TeCD was monitored on-line.
RESULTS: The key intermediates were successfully intercepted and structurally characterized for the first time by coupling a
microreactor on-line to the ESI ion source, which permitted the fast screening of intermediates directly from solution.
CONCLUSIONS: The catalytic mechanism of 2-TeCD catalysis has been elaborated based on mass spectrometric data
and exerted its peroxidase activity via tellurol, tellurenic acid, and tellurosulfide, in analogy with natural GPX. Copyright
© 2012 John Wiley & Sons, Ltd.
Glutathione peroxidase (GPx, EC.1.11.1.9),[1,2] one of the most
important antioxidative selenoenzymes, plays a key role in
protecting various organisms from oxidative damage by cata-
lyzing the reduction of harmful hydroperoxides at the
expense of glutathione (GSH) and other thiols.[3] The enzyme
catalytic site contains a selenocysteine residue where sele-
nium undergoes redox cycling (Scheme 1).[4–7] In the catalytic
cycle, enzyme-bound selenol (Enz-SeH) is first oxidized by
hydroperoxide to produce the selenenic acid (Enz-SeOH),
which is further converted into a selenosulfide (Enz-SeSG)
by the nucleophilic attack of GSH. Reaction of selenenyl
sulfide with a second GSH regenerates the active selenol form
of the enzyme. Recently, considerable effort has been spent to
find compounds capable of imitating the properties of GPx,
not only to elucidate the catalytic mechanism, but also for
potential pharmaceutical application.[5,7–9]
In designing small GPX models, previous investigations
have focused on the effect of the substitutes near the reaction
center (such as Se. . .N and Se. . .O) on the catalytic activity of
synthetic selenium compounds.[7–9] However, the effect of the
substrate binding on catalytic efficiency, which generally
plays a vital role in enhancing catalytic activity, has not been
studied using an enzyme model. Cyclodextrins (CDs),
have extensively been exploited as enzyme models and
other biomimetic materials. In the past decade, a series of
cyclodextrin-derived organoselenium and organotellurium
compounds have been developed as GPx mimics.[10–18] Among
these cyclodextrin-derived GPx mimics, 2,2’-ditellurobis(2-
deoxy-b-cyclodextrin) (2-Te-CD) has desirable properties, such
as high substrate specificity and remarkable catalytic efficiency.
2-Te-CD was firstly prepared by attaching a ditelluride group
onto the cyclodextrin second face.[17] The catalytic efficiency
of the 2-TeCD-catalyzed reduction of hydroperoxides by GSH
is higher than that of any other cyclodextrin-derived GPX
mimics and 46-fold more active than the reduction with
ebselen, a well-known GPX mimic.[9] For this reason, 2-TeCD
became an ideal artificial GPX model to help elucidate the cat-
alytic mechanism of the natural GPX. To probe the mechanism
of 2-TeCD promoting the peroxidase reaction, Luo et al. have
carried out detailed steady-state kinetic studies.[15,19] In their
study, the second rate constant kmax/KArSH was found to be
1.05 Â 107 M–1 min–1 and similar to that of natural GPX. The
catalytic mechanism of 2-TeCD catalysis agreed well with a
ping-pong mechanism, in analogy with natural GPx. However,
because the critical reaction intermediates had not previously
been isolated or directly detected due to its short lifetime, the
catalytic mechanism is not very clear and further experiments
are needed to characterize each of the intermediates in the
catalytic cycle.
forming inclusion complexes with
a wide variety of
substrates in aqueous solution, affect the rates of various
chemical reactions with high substrate specificity, so that they
Electrospray ionization mass spectrometry (ESI-MS) is
known for the mild conditions used to form the gaseous ions;
even very labile molecules can be transferred to the gas
phase.[20–22] Then the reactivity and structures of reactive inter-
mediates can be further studied by tandem mass spectrometry
(MS/MS). Thus, ESI-MS (and its tandem version ESI-MS/MS)
* Correspondence to: Z. Y. Jin, The State Key Laboratory of
Food Science and Technology, Jiangnan University, 1800
Lihu Road, Wuxi 214122, China.
E-mail: jinlab2008@yahoo.com
Rapid Commun. Mass Spectrom. 2013, 27, 319–324
Copyright © 2012 John Wiley & Sons, Ltd.

A. Jiao et al.
Figure 1. Microreactor coupled directly to the ESI ion source
employed for on-line monitoring of the catalytic mechanism
of GPX mimic by ESI-MS.
Scheme 1. The catalytic cycle of native GPx.
is rapidly becoming the technique of choice for fast screening of
intermediates directly from solution in chemistry and biochem-
istry.[23–25] In this work, we applied on-line ESI-MS(/MS) to
monitor the decomposition of H2O2 at the expense of GSH cat-
alyzed by 2-TeCD. Since ESI normally releases ions preformed
in solution,[26,27] we expected that transient ionic species should
be detected by ESI-MS from the reacting solution. This work
aims to trap and characterize the transient species which are
involved in the catalytic cycle of 2-TeCD by employing the
on-line ESI-MS technique, and therefore give new insights
about the reaction mechanism catalyzed by 2-TeCD.
were carried out by mass selection of a specific ion in Q1
which was then submitted to collision-induced dissociation
(CID) with helium as collision gas. The product-ion MS analy-
sis was accomplished with the high-resolution orthogonal
time-of-flight (TOF) analyzer.
RESULTS AND DISCUSSION
We initiated our investigation into the reaction via ESI-MS
(/MS) experiments trying to intercept the ion intermediates
that were formed and consumed during the reaction, and
therefore to collect mechanistic information that could
guide the construction of better GPX mimics. Via ESI-MS
operating in the positive ion mode, we monitored the
decomposition of H2O2 at the expense of GSH catalyzed
by 2-TeCD by direct infusion with reaction times around
1 min. However, no ion intermediates were detected in
ESI mass spectra, as depicted in Fig. 2(c), mainly due to
even short-lived reaction intermediates. Thus, the direct
MS screening of the reaction intermediates was discarded
for this catalytic mechanism study.
Microreactors coupled to an ESI-MS spray capillary have
been introduced into catalytic reaction mechanistic studies,
thus allowing the interception of short-lived and transient
compounds. Since ESI-MS is known for its ability to transfer
ions directly from solution to the gas phase with gentleness
and efficiency, even reaction times around 1 s can be screened
through coupling the microreactor depicted in Fig. 1, which
provided therefore proper snapshots of the ion composition
of reaction solutions in short reaction times. Thus, to study
the catalytic reaction we employed a microreactor coupled
to ESI-MS trying to trap and characterize the transient species
that are involved in the catalytic cycle of 2-TeCD.
Figure 2(a) shows the ESI-MS spectrum of the GSH/2-TeCD
mixture in NH4Ac solution. The intense peaks corresponding to
protonated GSH, the (2-Te-CD/NH4) complex and the proto-
nated 1:1 (2-TeCD /GSH) complex are observed at m/z 308,
2510 and 2800, respectively. Also a minor peak corresponding
to the proton-bound GSH dimer, [2GSH + H]+, is observed at
m/z 615. Figure 3(a) shows the ESI-MS/MS spectra for the ion
[2GSH + H]+ of m/z 615. As shown in Fig. 3(a), the abundant sin-
gle fragment peak at m/z 308 corresponds to protonated GSH
and a minor peak at m/z 486 corresponds to the neutral loss
(129 Da), which is a well-documented neutral fragment (the
N-terminal Glu) of GSH, as reported previously.[28–30]
EXPERIMENTAL
General procedures
b-Cyclodextrin (b-CD) and glutathione (g-L-glutamyl-L-
cysteinylglycine, GSH) were purchased from Sigma. Tellur-
ium powder, p-toluenesulfonyl chloride (TsCl) and sodium
borohydride were purchased from Shanghai Chemical
Plant. 2-TeCD[15] was prepared as described previously
and characterized in detail (for details see Supporting
Information). All other chemicals were of the highest purity
commercially available and were used without further
purification.
ESI-MS microreactor monitoring
ESI-MS and ESI-MS/MS experiments in the positive ion
mode were carried out using an API 4000 QTRAP triple
quadrupole mass spectrometer from AB Sciex (Foster City,
CA, USA) equipped with a TurboIonSpray source. The basic
ESI conditions were: curtain gas, 20 arbitrary units; spray
voltage, 4200 V; capillary temperature, 250ꢀC; while the
selected collision energy depended on the dissociation cap-
ability of the precursor ion. The cone and extractor potentials
were set to 15 and 4.5 V, respectively. Samples were directly
infused into the ESI source at flow rates of 5–10 mL min–1
by means of a microsyringe pump via the microreactor.
Solutions of 2-Te-CD and GSH mixtures were prepared with
10 mM ammonium acetate (NH4Ac, pH 7.0) as solvent
(concentration around 0.1 mM). The above solution was
mixed with H2O2 (0.25 mM) using a dual-syringe pump
operating at a flow rate of 5–10 mL min–1 in an effective
micromixer that was coupled directly to the ion source of
the mass spectrometer (Fig. 1), and the solution was fed con-
tinuously into the mass spectrometer. MS/MS experiments
wileyonlinelibrary.com/journal/rcm
Copyright © 2012 John Wiley & Sons, Ltd.
Rapid Commun. Mass Spectrom. 2013, 27, 319–324

Catalytic mechanism of GPX mimic 2-TeCD by ESI-MS
Figure 2. On-line screening of the reaction of GSH with H2O2 catalyzed by 2-TeCD using the microreactor
coupled to ESI-MS: (a) ESI-MS of GSH/2-TeCD mixture in NH4Ac solution; (b) on-line monitoring by
microreactor/ESI-MS of reaction around 5 s; and (c) on-line monitoring by microreactor/ESI-MS of reaction
around 20 s.
Then, we set out to investigate the formation of the intermedi-
ate species in a reaction solution that was prepared by on-line
mixing of GSH/2-Te-CD with H2O2 via the microreactor. The
reaction started by the addition of H2O2 using the microreactor
resulted in a very clean spectrum (Fig. 2(b)) displaying three
cationic species that were easily identified by their absolute
Rapid Commun. Mass Spectrom. 2013, 27, 319–324
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/rcm

A. Jiao et al.
Figure 3. MS/MS spectra of (a) glutathione dimer (2GSH) and (b) the oxidized
glutathione (GSSG). F1 and F2 refer to the fragment ions of GSSG formed by two
consecutive losses of 129 Da.
masses at reaction times of 5 s: [CD-TeH + NH4]+ (m/z 1264),
[CD-TeOH + NH4]+ (m/z 1280), and [CD-TeSG + NH4]+ (m/z 1571).
The overall appearance of the spectrum and relative intensities
of these ions changed drastically from 0.0 to 5 s of reaction in
solution, as indicated by on-line ESI-MS monitoring.
fragment was detected per intermediate with the low colli-
sion energies. For more structural information, the MS/MS
spectra with higher collision energy (55 ev) were observed
(Fig. 4). Figures 4(a)–4(c) show the ESI-MS/MS spectra of
the ions of the m/z 1264 [CD-TeH + NH4]+, m/z 1280
[CD-TeOH + NH4]+ and m/z 1571 [CD-TeSG + NH4]+,
respectively. The same product ions at about m/z 973, 811, 649,
487 and 325 were observed by subsequent loss (162 Da) of the
glucose unit from the precursor ion, showing the exclusive
cleavage of the glycosidic bond.[32] In Fig. 4(c), the most
intense signal from the m/z 1571 ion is a Y (m/z 1442) ion.
The Y ion resulted from the internal loss (129 Da) of a neutral
fragment (the N-terminal Glu) of glutathione.
Scheme 2 presents the proposed reaction mechanism of the
GSH peroxidase reaction of 2-Te-CD based on the ESI(+)-MS
and ESI(+)-MS/MS spectra. This mechanism is based on
previous mechanistic interpretations,[11,15,19] but now shows
three authentic key intermediates, CD-TeH, CD-TeOH
and CD-TeSG, that have been properly detected and charac-
terized by ESI-MS(/MS). The role that tellurium plays in
biochemistry is similar to the role that selenium plays in
the thiol peroxidase reaction of native GPx (Scheme 1). First
of all, 2-TeCD reacts with GSH to give the active tellunol
(CD-TeH) (m/z 1264, [CD-TeH + NH4]+). Then the oxidation
of CD-TeH produces tellurenic acid (CD-TeOH) (m/z 1280,
[CD-TeOH + NH4]+). The CD-TeOH thus produced reacts
with a second GSH to produce tellurosulfide (CD-TeSG)
(m/z 1571, [CD-TeSG+ NH4]+). Finally, a third GSH then
regenerates the active form CD-TeH by attacking the
We also monitored the reaction of GSH with H2O2
catalyzed by 2-TeCD with reaction times around 20 s. The
spectrum as depicted in Fig. 2(c) was observed and no
intermediates were detected. However, an intense signal at
m/z 613 appeared, and the peaks corresponding to the
proton-bound GSH dimer (m/z 615), observed in Fig. 2(a),
were absent. According to the measured molecular mass
data, the m/z 613 ion is formed from the protonated GSH oxi-
dized form (GSSG) which contains a disulfide bond formed
by formal loss of H2 between two thiol groups of two GSH
molecules. Figure 3(b) shows the ESI-MS/MS spectra for the
ion [GSSG + H]+ of m/z 613. The most intense signal from
the m/z 613 ion (Fig. 3(b)) is a F1 (m/z 484) ion formed by a
neutral loss (129 Da). A minor peak (F2) at m/z 355 is also
observed in the MS/MS spectrum of the F1 ion (m/z 484), cor-
responding to the same neutral loss, which is in agreement
with the fact that the GSSG has a symmetrical structure.[31]
This result verifies that 2-TeCD can catalyze GSH oxidization
to GSSG in solution.
All these intermediates, so gently transferred to the gas
phase by ESI in their intact protonated forms, were then indi-
vidually mass-selected by quadrupole Q1 for CID with
helium in quadrupole q2, and were structurally characterized
by MS/MS analysis. However, only one monocharged
wileyonlinelibrary.com/journal/rcm
Copyright © 2012 John Wiley & Sons, Ltd.
Rapid Commun. Mass Spectrom. 2013, 27, 319–324

Catalytic mechanism of GPX mimic 2-TeCD by ESI-MS
Figure 4. CID spectra of species intercepted: (a) m/z 1264, [CD-TeH + NH4]+;
(b) m/z 1280, [CD-TeOH + NH4]+; and (c) m/z 1571, [CD-TeSG + NH4]+.
CDTe-TeCD
GSH
tellurosulfide to form the oxidized glutathione (GSSG). As indi-
cated above, 2-TeCD exerts its peroxidase activity via tellurol,
tellurenic acid and tellurosulfide in the GSH assay system.
H2O2
GSSG
CDTeH
CONCLUSIONS
H2O
CDTeOH
GSH
CDTeSG
The ESI-MS and ESI-MS/MS experiments described herein have
led to new insights into the catalytic mechanism of GPX mimic
2-TeCD by mass spectrometric characterization of its key reaction
intermediates. The species CD-TeH, CD-TeOH and CD-Te-SG
have been transferred to the gas phase, isolated by mass selec-
tion, and for the first time detected and then structurally charac-
terized by MS and MS/MS experiments. The role that tellurium
plays in biochemistry is similar to the role that selenium plays in
GSH
H2O
Scheme 2. Proposed catalytic mechanism of 2-Te-CD.
Rapid Commun. Mass Spectrom. 2013, 27, 319–324
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/rcm

A. Jiao et al.
[15] X. J. Ren, Y. Xue, J. Q. Liu, K. Zhang, J. Zheng, G. Luo,
C. H. Guo, Y. Mu, J. C. Shen. A novel cyclodextrin-derived
tellurium compound with glutathione peroxidase activity.
Chembiochem 2002, 3, 356.
the thiol peroxidase reaction of native GPx. 2-TeCD exerts its
peroxidase activity via tellurol, tellurenic acid and tellurosulfide
in the GSH assay system.
[16] X. J. Ren, L. Q. Yang, J. Q. Liu, D. Su, D. L. You, C. P. Liu,
K. Zhang, G. M. Luo, Y. Mu, G. L. Yan, J. C. Shen. A novel
glutathione peroxidase mimic with antioxidant activity.
Arch. Biochem. Biophys. 2001, 387, 250.
[17] X. J. Ren, Y. Xue, K. Zhang, J. Q. Liu, G. M. Luo, J. Zheng,
Y. Mu, J. C. Shen. A novel dicyclodextrinyl ditelluride com-
pound with antioxidant activity. FEBS Lett. 2001, 507, 377.
[18] X. J. Ren, J. Q. Liu, G. M. Luo, Y. Zhang, Y. M. Luo, G. L. Yan,
J. C. Shen. A novel selenocystine-b-cyclodextrin conjugate
that acts as a glutathione peroxidase mimic. Bioconjugate
Chem. 2000, 11, 682.
[19] Z. Y. Dong, J. Q. Liu, S. Z. Mao, X. Huang, B. Yang, X. J. Ren,
G. M. Luo, J. C. Shen. Aryl thiol substrate 3-carboxy-4-nitro-
benzenethiol strongly stimulating thiol peroxidase activity of
glutathione peroxidase mimic 2,2’-ditellurobis(2-deoxy-beta-
cyclodextrin). J. Am. Chem. Soc. 2004, 126, 16395.
SUPPORTING INFORMATION
Additional supporting information may be found in the
online version of this article.
Acknowledgements
We are grateful to Dr. Kim for providing language help, Drs. Z.
F. Li and C. Y. Ma for their technical assistance, and Miss W.H.
Cui and G.Q. Wang for secretarial assistance. This study was
supported by National ’Twelfth Five-Year’ Plan for Science &
Technology Support of China (Nos. 2012BAD37B02 and
2012BAD37B06) and the Nature Science Foundation of Jiangsu
Province (BY201119).
[20] L. S. Santos, J. O. Metzger. Study of homogeneously catalyzed
Ziegler-Natta polymerization of ethene by ESI-MS. Angew.
Chem. Int. Ed. 2006, 45, 977.
[21] L. S. Santos, J. O. Metzger. On-line monitoring of Brookhart
polymerization by electrospray ionization mass spectrometry.
Rapid Commun. Mass Spectrom. 2008, 22, 898.
[22] L. S. Santos, G. B. Rosso, R. A. Pilli, M. N. Eberlin. The
mechanism of the Stille reaction investigated by electrospray
ionization mass spectrometry. J. Org. Chem. 2007, 72, 5809.
[23] K. J. Koch, F. C. Gozzo, S. C. Nanita, Z. Takats, M. N. Eberlin,
R. G. Cooks. Chiral transmission between amino acids: Chirally
selective amino acid substitution in the serine octamer as a
possible step in homochirogenesis. Angew. Chem. Int. Ed. 2002,
41, 1721.
[24] A. Kamal, N. Markandeya, N. Shankaraiah, C. R. Reddy,
S. Prabhakar, C. S. Reddy, M. N. Eberlin, L. S. Santos. Chemo-
selective aromatic azido reduction with concomitant aliphatic
azide employing Al/Gd triflates/NaI and ESI-MS mechanis-
tic studies. Chem.-Eur. J. 2009, 15, 7215.
REFERENCES
[1] L. Flohe, W. A. Guenzler, H. H. Schock. Glutathione
peroxidase. Selenoenzyme. FEBS Lett. 1973, 32, 132.
[2] J. T. Rotruck, A. L. Pope, H. E. Ganther, A. B. Swanson,
D. G. Hafeman, W. G. Hoekstra. Selenium. Biochemical role as
a component of glutathione peroxidase. Science 1973, 179, 588.
[3] L. Flohé, in Free Radicals in Biology, vol. 5, (Ed: W. A. Pryor).
Academic Press, New York, 1982, pp. 223–253.
[4] L. Flohe, S. Toppo, G. Cozza, F. Ursini. A comparison
of thiol peroxidase mechanisms. Antioxidants & Redox
Signaling 2011, 15, 763.
[5] X. Huang, X. M. Liu, Q. A. Luo, J. Q. Liu, J. C. Shen.
Artificial selenoenzymes: Designed and redesigned. Chem.
Soc. Rev. 2011, 40, 1171.
[6] X. Huang, Y. Z. Yin, J. Q. Liu. Design of artificial selenoen-
zymes based on macromolecular scaffolds. Macromol. Biosci.
2010, 10, 1385.
[7] K. P. Bhabak, G. Mugesh. Functional mimics of glutathione
peroxidase: Bioinspired synthetic antioxidants. Acc. Chem.
Res. 2010, 43, 1408.
[8] G. Mugesh, W. W. du Mont, H. Sies. Chemistry of biologically
important synthetic organoselenium compounds. Chem. Rev.
2001, 101, 2125.
[25] J. Griep-Raming, S. Meyer, T. Bruhn, J. O. Metzger. Investi-
gation of reactive intermediates of chemical reactions in
solution by electrospray ionization mass spectrometry:
radical chain reactions. Angew. Chem. Int. Ed. 2002, 41, 2738.
[26] L. S. Santos. Online mechanistic investigations of catalyzed
reactions by electrospray ionization mass spectrometry: A
tool to intercept transient species in solution. Eur. J. Org.
Chem. 2008, 235.
[27] P. Chen. Electrospray ionization tandem mass spectrometry
in high-throughput screening of homogeneous catalysts.
Angew. Chem. Int. Ed. 2003, 42, 2832.
[28] P. G. Pearson, W. H. Howald, S. D. Nelson. Screening strat-
egy for the detection of derivatized glutathione conjugates
by tandem mass spectrometry. Anal. Chem. 1980, 62, 1827.
[29] D. Stöckigt, S. Haeber. Identification of collision-induced
[9] G. M. Luo, X. J. Ren, J. Q. Liu, Y. Mu, J. C. Shen. Towards more
efficient glutathione peroxidase mimics: Substrate recognition
and catalytic group assembly. Curr. Med. Chem. 2003, 10, 1151.
[10] M. McNaughton, L. Engman, A. Birmingham, G. Powis,
I. A. Cotgreave. Cyclodextrin-derived diorganyl tellurides as
glutathione peroxidase mimics and inhibitors of thioredoxin
reductase and cancer cell growth. J. Med. Chem. 2004, 47, 233.
[11] A. Q. Jiao, N. Yang, J. P. Wang, A. Toure, X. M. Xu, Z. Y. Jin.
Organotellurium-bridged cyclodextrin dimers as artificial
glutathione peroxidase models. J. Incl. Phenom. Macro.
2012, 74, 335.
[12] S. W. Lv, Q. C. Zheng, Y. Mu, X. G. Wang, Y. T. Ji, G. M. Luo,
J. Q. Liu, J. C. Shen. Evaluating substrate specificity of
glutathione peroxidase mimic by molecular dynamics
simulations and kinetics. J. Incl. Phenom. Macro. 2008, 60, 139.
[13] S. W. Lv, X. G. Wang, Y. Mu, T. Z. Zang, Y. T. Ji, J. Q. Liu,
J. C. Shen, G. M. Luo. A novel dicyclodextrinyl diselenide
compound with glutathione peroxidase activity. FEBS J.
2007, 274, 3846.
dissociation fragments from
a protonated glutathione
conjugate by isotope-specific MS3 experiments in an ion
trap. Rapid Commun. Mass Spectrom. 1998, 12, 273.
[30] W. X. Sun, J. Q. Liu, M. Cui, F. R. Song, S. Y. Liu. Cyclodextrin-
catalyzed oxidation of glutathione in solution and in an ion
trap. Rapid Commun. Mass Spectrom. 1999, 13, 950.
[31] P. G. Pearson, E. S. Soderlund, E. Dybing, S. D. Nelson.
Metabolic activation of 1,2-dibromo-3-chloropropane: evi-
dence for the formation of reactive episulfonium ion
intermediates. Biochemistry 1990, 29, 4971
[14] Z. Y. Dong, J. Q. Liu, S. Z. Mao, X. Huang, G. M. Luo,
J. C. Shen. A glutathione peroxidase mimic 6,6’-ditellurobis
(6-deoxy-beta-cyclodextrin) with high substrate specificity.
J. Incl. Phenom. Macro. 2006, 56, 179.
[32] E. C. Huangt, J. D. Henion. Characterization of cyclodex-
trins using ion-evaporation atmospheric-pressure ionization
tandem mass spectrometry. Rapid Commun. Mass Spectrom.
1990, 4, 467.
wileyonlinelibrary.com/journal/rcm
Copyright © 2012 John Wiley & Sons, Ltd.
Rapid Commun. Mass Spectrom. 2013, 27, 319–324