A triphenylene based zinc ensemble as an oxidation inhibitor

Article abstract of DOI:10.1039/c2cc17802h

The zinc complex of a new triphenylene based receptor is evaluated for its anti-oxidant activity which is better in comparison to that of commercially available anti-oxidants.

Full text of DOI:10.1039/c2cc17802h

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A triphenylene based zinc ensemble as an oxidation inhibitorw
Vandana Bhalla,* Harshveer Arora, Abhimanew Dhir and Manoj Kumar
Received 13th December 2011, Accepted 8th February 2012
DOI: 10.1039/c2cc17802h
The zinc complex of a new triphenylene based receptor is evaluated
for its anti-oxidant activity which is better in comparison to that of
commercially available anti-oxidants.
The binding behaviour of compound 3 toward different
metal ions was evaluated with the help of UV-vis and fluores-
cence spectroscopy. The absorption spectrum of compound 3
(10 mM) shows three absorption bands at 246, 296 and 355 nm
in THF : H2O (95 : 5). Among all the metal ions tested
Zinc, an essential nutrient, plays an important role as an
anti-oxidant in the human body.1 Deficiency of zinc increases
the production of reactive oxygen species (ROS),2 which are a
class of radical or non-radical oxygen-containing molecules that
show high reactivity to bio-molecules.3 Excessive ROS generation
is involved in the pathogenesis of many diseases, including
cardiovascular disease, cancer, and neurological disorders.4 Thus,
regulation of generation of these ROS is highly significant.
Our research involves the design, synthesis and evaluation
of artificial receptors for metal ions and anions.5 In continuation of
this work, in the present manuscript, we have synthesized a new
triphenylene based receptor 3 (vide infra) (Scheme 1) which
selectively senses Zn2+ ions.6 Further, the zinc ensemble of 3
(Zn-3) has been evaluated for its anti-oxidizing property and it
was observed that the anti-oxidant activity of Zn-3 is better than
five commercially available anti-oxidants. Earlier, a number of
artificial receptors for Zn2+ ions with bio-mimetic applications
have been reported in the literature7 which includes complexes
for understanding the intrinsic properties of substrate or
inhibitor recognition by Zn2+ ions at the active centers of
enzymes.8 Recently, Reinaud et al. reported the tripodal
bio-mimetic macrocyclic Zn2+ complexes.9 However, the
development of bio-mimetic synthetic zinc complexes showing
anti-oxidant activity has not been explored. Thus, to the best
of our knowledge, this is the first report where a triphenylene
based receptor for Zn2+ ions shows anti-oxidant activity.
Suzuki–Miyaura coupling of 2,3,6,7,10,11-hexabromo-
triphenylene 1a with boronic ester 1b10 yielded hexamine 1c in
70% yield (Scheme 1) (for synthetic details see S3, S9–S11 of ESIw).
Condensation of hexamine 1c with quinoline-2-carboxaldehyde 2
in THF at room temperature furnished compound 3 in 75% yield
(Scheme 1). The structure of compound 3 was confirmed from its
spectroscopic data (for synthetic details see S4, S12–S14 of ESIw)
and its purity was determined from HPLC (see ESIw, S26).
(Zn2+, Fe3+, Fe2+, Cu2+, Hg2+, Ni2+, Cd2+, Pb2+
,
Mn2+, Co2+, Li+, Na+, Mg2+, K+, Ca2+, Ba2+) two new
bands are formed at 290 and 325 nm upon addition of only
Zn2+ ions (200 equiv.) with two isosbestic points at 285 and
335 nm (see ESIw, S6). These changes in the UV-vis spectrum
of 3 upon addition of Zn2+ ions are ascribed to the formation
of a complex between 3 and Zn2+ ions.
Compound
3
showed no fluorescence emission in
THF : H2O (95 : 5) (Fig. 1) when excited at 355 nm, which
may be attributed to photo-induced electron transfer (PET)11
from imino nitrogen to the photo-excited quinoline moiety. Upon
addition of only Zn2+ ions (20 equiv.), an enhancement in the
fluorescence spectrum was observed at 438 nm. The fluorescence
enhancement of receptor 3 in the presence Zn2+ ions is attributed
to the co-ordination of imino and quinolinyl nitrogens of 3 with
Zn2+ leading to the formation of a supramolecular complex, as a
result of which the PET from imino nitrogen to the quinoline
moiety is suppressed. Under the same conditions, the fluorescence
behaviour of 3 was tested with other metal ions (Fe3+, Fe2+
,
Cu2+, Hg2+, Ni2+, Cd2+, Pb2+, Mn2+, Co2+, Li+, Na+,
Mg2+, K+, Ca2+, Ba2+), however no change in emission
spectrum was observed with any other metal ion (see ESIw, S7).
The fluorescence spectra of 3 (5 mM) at various concentrations of
Zn2+ ions are shown in Fig. 1. Fitting the changes in the
fluorescence spectra of compound 3 with Zn2+ ions, using the
nonlinear regression analysis program SPECFIT,12 gave a good
fit and demonstrated that a 1 : 3 stoichiometry (host : guest) was
the most stable species in the solution with a binding constant
log b1,3 = 13.23 (see ESIw, S15 and S16). The complex formation
was further confirmed by mass and IR spectroscopy (for mass
spectrum see ESIw, S25). The IR absorption band at 1616 cmÀ1
due to the imine moiety of 3 shifted to a lower frequency at
1590 cmÀ1 (n = 26 cmÀ1) upon complexation with zinc, which
confirms the coordination of imino nitrogen atoms with Zn2+
ions (see ESIw, S23 and S24). To test the practical applicability
of compound 3 as a Zn2+ selective fluorescence sensor,
competitive experiments were carried out in the presence of
Department of Chemistry, UGC-Centre for Advanced Studies,
Guru Nanak Dev University, Amritsar, Punjab, India.
E-mail: vanmanan@yahoo.co.in; Fax: +91-(183)-2258820;
Tel: +91-(183)-2258802-9 Extn. 3205
w Electronic supplementary information (ESI) available: Experimental
procedure and spectral and analytical data of compounds 1c and 3. See
DOI: 10.1039/c2cc17802h
Zn2+ ions at 20 equiv. mixed with other cations (Fe3+, Fe2+
,
Cu2+, Hg2+, Ni2+, Cd2+, Pb2+, Mn2+, Co2+, Li2+, Na+,
Mg2+, K+, Ca2+, Ba2+) at 200 equiv., no significant variation
was found by comparison with and without the other metal ions
c
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Scheme 1
Fig. 1 Fluorescence emission spectrum of 3 (5 mM) upon addition
of Zn2+ (20 equiv.) ions in THF : H2O (95 : 5). Inset shows the
fluorescence intensity changes upon the addition of Zn2+ ions from
(a) 0 to (b) 20 equiv.
Fig. 2 Fluorescence emission spectra of 4 (3 mM) upon addition of
H2O2 (750 ml) in THF : H2O (95 : 5). Inset shows the (a) ESIPT
phenomenon in b-OH napthaldehyde and (b) its Dakin’s oxidation.
(see ESIw, S7). This means that compound 3 has a high affinity
for Zn2+ ions. The detection limit of 3 as a fluorescent sensor
for the analysis of Zn2+ was found to be 1 Â 10À6 mol lÀ1
,
which is sufficiently low for the detection of submillimolar
concentrations of Zn2+ ions found in many chemical systems.13
The fluorescence quantum yield14 (ff) of compound 3 in the free
and 3ÁZn2+ bound state was found to be 0.001 and 0.65,
respectively (for calculations see ESIw, S4). This substantial
increase in the quantum yield of compound 3 in the presence of
Zn2+ ions showed its credibility as a good Zn2+ sensor.
Further, we evaluated the zinc ensemble of 3 (Zn-3) for its
anti-oxidant activity using fluorescence spectroscopy and
cyclic voltammetric studies (vide infra). For this, we utilized
b-hydroxy naphthaldehyde15 as a template, carried out its Dakin
oxidation16 and observed its fluorescence behaviour in the
presence and absence of Zn-3 as fluorescent probes for detection
of ROS, which has been reported recently.17 However, such an
evaluation of anti-oxidant activity of a metal coordinated ligand
using an organic template is unprecedented.
Scheme 2
emission was observed. This quenching is ascribed to the
oxidative conversion of 4 to species 6 (Scheme 2b). In species
6, the inhibition of ESIPT makes photoinduced electron
transfer (PET) operational (Scheme 2b) and as a result
fluorescence emission gets quenched. Further, to observe the
anti-oxidation effect of Zn-3, we performed the fluorescence
titration with H2O2 under similar conditions in the presence of
250 ml of 100 mM of Zn-3. We observed that in the presence
of Zn-3 the rate of oxidation of 4 decreases and the amount of
H2O2 required to quench the fluorescence is larger (1300 ml)
(see ESIw, S17) than in the absence of Zn-3. This may be
ascribed to the fact that hydroperoxide anions (HOOÀ)
generated during the reaction16 (which are responsible for
the oxidation) show preferential binding to the charged zinc
centre of Zn-3. The rate of oxidation slows down, indicating
that Zn-3 has an anti-oxidant effect.
b-Hydroxy naphthaldehyde 4 (3 mM) shows an emission at
438 nm in THF : H2O (95 : 5) when excited at 318 nm (Fig. 2).
The fluorescence emission of compound 4 is attributed to fast
keto–enol tautomerism (representing the enol form 4 and keto
form 5, Scheme 2a) involving the phenomenon of excited state
intramolecular proton transfer (ESIPT).18 To carry out Dakin
oxidation we added alkaline H2O2/NaOH (pH = 7.4) to the
solution of 4 (3 mM) at 25 1C. Upon addition of H2O2 (225 ml)
the emission band at 438 nm is blue shifted to 383 nm. We
propose that this fluorescence response of compound 4 is due
to the modulation of the existing ESIPT state (5) by the
interaction of HOOÀ ions with the hydroxyl group of 4. Upon
further addition of H2O2 (525 ml) quenching of the fluorescence
We also studied the fluorescence behaviour of Zn-3 toward
other anionsÀ (FÀ, CNÀ, OAcÀ, ClÀ, BrÀ, IÀ, EDTAÀ4
,
HSO4À, NO3 H2PO4À, ClO4À) and observed that no change
in fluorescence emission of Zn-3 was observed with any other
anions (see ESIw, S8). Thus, Zn-3 shows a selective fluores-
cence response towards hydroperoxide anions.
c
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Chem. Commun., 2012, 48, 4722–4724 4723

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at E1/2 = À0.30 (Fig. 4b). Such a dramatic shift in the oxidation
waves of 4 in the presence of Zn-3 is attributed to the slow
oxidation of 4 in the presence of Zn-3. Thus, the electrochemical
studies firmly support the spectroscopic studies and prove the
anti-oxidant behaviour of Zn-3.
To conclude, we synthesized a new triphenylene based
receptor 3 incorporating quinoline moieties which behaves as
a Zn2+ selective chemosensor. The Zn2+ ensemble of 3 shows
anti-oxidant properties and may be used in the real world by
diluting with THF prior to a hydroperoxide assay. This is
proved by different spectral and electrochemical studies using
b-hydroxy naphthaldehyde as an organic template and performing
its Dakin oxidation in the absence and presence of Zn-3.
V.B. is thankful to DST (New Delhi, India) (ref no. SR/S1/
OC-63/2010) and DRDO (Ref. No. ERIP/ER/0703663/M/01/
1105) for financial support.
Fig. 3 Comparison of percentage anti-oxidation activity of Zn-3 with
other commercial anti-oxidants.
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,
[(nBu)4N]ClO4 as supporting electrolyte, using a glassy carbon
working electrode, a (Ag/Ag+) reference electrode, and a Pt wire
counter electrode] exhibits two electrochemical oxidation waves
at E1/2 = À0.175 and E1/2 = À0.70 (Fig. 4). The cyclic
voltammogram of 4+Zn-3 under the same conditions showed
one oxidation wave at E1/2 = À0.13 and a reduction wave
19 European Directive 95/2/EC on food additives, 1995, 1–61.
c
4724 Chem. Commun., 2012, 48, 4722–4724
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