Design and synthesis of fluorescent 6-aryl[1,2-c]quinazolines serving as selective and sensitive on-off chemosensor for Hg2+ in aqueous media

Article abstract of DOI:10.1016/j.tetlet.2012.04.128

Three fluorescent quinazolines thiophen-2-yl-5,6-dihydrobenzo-[4,5] imidazo[1,2-c]quinazoline (1), pyridin-3-yl-5,6-dihydrobenzo-[4,5]imidazo-[1,2- c]quinazoline (2) and phenyl-5,5′,6,6′-dihydrobenzo-[4,4′,5, 5′]imidazo-[1.1′,2-c,2′-c]quinazoline (3) have been synthesized. Structures of 1 and 3 have been authenticated crystallographically. Quinazolines 1-3 exhibit highly selective on-off switching for Hg²⁺ ions. The fluorescence intensity displayed a linear relationship with respect to Hg²⁺ concentration (0.1-1.0 μM; R² = 0.99) with detection limit of 2.0 × 10^-7 M.

Full text of DOI:10.1016/j.tetlet.2012.04.128

Tetrahedron Letters 53 (2012) 3550–3555
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Tetrahedron Letters
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Design and synthesis of fluorescent 6-aryl[1,2-c]quinazolines serving as
selective and sensitive ‘on-off’ chemosensor for Hg2+ in aqueous media
⇑
⇑
Rampal Pandey, Mahendra Yadav, Mohammad Shahid, Arvind Misra , Daya Shankar Pandey
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, U.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
Three fluorescent quinazolines thiophen-2-yl-5,6-dihydrobenzo-[4,5]imidazo[1,2-c]quinazoline (1),
pyridin-3-yl-5,6-dihydrobenzo-[4,5]imidazo-[1,2-c]quinazoline (2) and phenyl-5,50,6,60-dihydrobenzo-
[4,40,5,50]imidazo-[1.10,2-c,20-c]quinazoline (3) have been synthesized. Structures of 1 and 3 have been
authenticated crystallographically. Quinazolines 1–3 exhibit highly selective ‘on-off’ switching for Hg2+
ions. The fluorescence intensity displayed a linear relationship with respect to Hg2+ concentration
Received 11 March 2012
Revised 26 April 2012
Accepted 27 April 2012
Available online 2 May 2012
(0.1–1.0
l
M; R2 = 0.99) with detection limit of 2.0 ꢀ 10ꢁ7 M.
Keywords:
Synthesis
Ó 2012 Elsevier Ltd. All rights reserved.
Quinazolines
Crystal structure
UV–vis
Fluorescence
Mercury selective
Quenching
Development of optical methods for the selective detection of
certain transition/post-transition metal ions in environment and
biological systems has attracted considerable current interest.1 In
this context, numerous fluorescent sensors have been synthesized
due to their high sensitivity, selectivity and possible applications in
various areas.2 Mercury is an important metal and its accumulation
in liver, kidney and spleen leads to DNA damage, mitosis impair-
ment and nervous system defects.3 Despite being toxic, Hg and
its salts are used in a number of industrial processes and products.
Therefore, extensive studies have been devoted towards designing
of new fluoroionophores and the development of sophisticated
techniques for the detection and removal of Hg2+ from living sys-
tems.4 Owing to its d10 configuration Hg2+ lacks optical spectro-
scopic signature. Thus its optical detection is achieved by
monitoring changes in the UV–vis or fluorescence resulting from
Hg2+ induced perturbations of a chromophore. Although, numer-
ous Hg2+ selective and sensitive sensors have been reported,5
chemosensors possessing high selectivity towards Hg2+ against a
background of competing analytes in aqueous medium are highly
demanding.6
in the detection of metal ions is well documented, to our
knowledge their application towards Hg2+ sensing has not been
reported.8 The biological importance and unexploited fluorescent
properties of quinazolines motivated us to develop new derivatives
having a suitable recognition site for metal ions. With these points
in mind three new fluorescent quinazolines viz., thiophen-
2-yl-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazo- line 1, pyridin-
3-yl-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazo- line
2
and
phenyl-5,50, 6,60-dihydrobenzo[4,40,5,50]imidazo[1,10,2-c,20-c]qui-
nazoline 3 have been designed and synthesized. With an objective
of developing compounds containing different heterocyclic rings at
6-position of a quinazoline ring, 1–3 have been designed and
synthesized (Scheme 1). Among these, 1 and 2 contain thiophene
‘S’ and pyridyl ‘N’ at the chelating and non-chelating sites, while
3 does not have any heteroatom at chelating position of the qui-
nazoline nitrogen (–NH). Through this contribution we present
the syntheses, characterizations and applications of 1–3 in selec-
tive detection of Hg2+ over a wide range of interfering cations in
aqueous media.
The quinazolines 1–3 and precursor 2-(2-aminophenyl)-1-benz-
imidazole (4) were synthesized by a general procedure outlined in
Scheme 1 (Figs. S1–S4, Supplementary data).9 Condensation of 4
with the corresponding aldehyde in ethanol afforded the aminal
probes thiophen-2-yl-5,6-dihydro-benzo[4,5]-imidazo[1,2-c]qui-
nazoline 1, pyridin-3-yl-5,6-di-hydrobenzo-[4,5]imidazo[1,2-c]-
Quinazoline derivatives find widespread applications as antag-
onists, DNA-biosensors, epidermal growth factor receptor-tyrosine
kinase (EGFR-TK) imaging, activin-like kinase (ALK5) inhibitors
etc., however, their fluorescent properties have not been
thoroughly explored.7 Although, the use of quinazoline derivatives
quinazoline
2
and phenyl-5,50,6,60-dihydrobenzo[4,40,5,50]-imi-
dazo[1.10,2-c,20-c]quinazoline 3.10 Characterization of 1–3 has
⇑
Corresponding authors. Tel.: +91 542 6702480; fax: + 91 542 2368174.
E-mail addresses: dspbhu@bhu.ac.in, dsprewa@yahoo.com (D.S. Pandey).
been achieved by satisfactory elemental analyses, FT-IR, NMR
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.04.128

R. Pandey et al. / Tetrahedron Letters 53 (2012) 3550–3555
3551
N
N
N
O
EtOH/ 60 0C
4-6 hrs
R
C
+
H
N
H
(5)
NH
H2N
R
1, 2 and 4
(1)
(2)
R
=
=
(3)
R
R
=
N
S
85%
,
,
82%
86%
N
N
N
N
N
NH
N
NH
NH
S
HN
N
N
(1)
(2)
N
(3)
Scheme 1. One pot synthesis of probes 1–3.
(1H and 13C), HRMS and electronic absorption and emission studies.
Structures of 1 and 3 have been determined by X-ray single crystal
analyses. It is worth mentioning that 3 possesses two stereogenic
centers therefore may exist in diastereomeric forms. However, both
stereogenic centres are too far apart from each other for the exis-
tence of any diastereoselective relay during the synthesis. 1H NMR
spectral data of 1–3 along with their assignments have been gath-
ered in Supplementary data (pp. S15). 1H NMR spectra of 1 dis-
played singlets associated with –NH and –CH protons at d 7.73
and 7.18 ppm (Fig. S1). Similarly, signals due to –NH/–CH protons
of 2 and 3 appeared at d 7.69/7.13, 2 and 7.53/7.01 ppm 3 (Figs.
S1–S3). It indicated C-N coupling through initially formed Schiff
base (Scheme S2).
Diffraction quality crystals for 1 were obtained from methanolic
solution at RT, while those for 3 by cooling the ethanolic reaction
mixture. Selected crystallographic and refinement data for 1 and
3 are summarized in Table S1 (Supplementary data). Compound
1 crystallizes in monoclinic system with ‘P21/c’ space group, while
3 in triclinic system with ‘P-1’ group. Crystal structure of 1
displayed a disordered thiophene ring which is very typical of 2-
thienyl substituted compounds (Fig. 1a). An artificial lowering of
the bond lengths with disordered atoms and high values of geo-
metrical parameters have been observed by ignoring the disorder.
It is rather simple and can be a suitable example of negating ef-
fect for structural studies. The C(14)-N(6)/C(14)-N(4) bond lengths
are almost equal (1.454/1.453 Å) and strongly suggest bonding of
N(6) and N(4) to carbon C(14) through a single bond. It can be
clearly seen that sulfur (S1/S10) lies perpendicular to N(4) N(6)
nitrogen. The N(6)ꢁH(6)ꢂ ꢂ ꢂ(N5) are involved in intermolecular
hydrogen bonding interactions with N–H and N–N bond distances
of 2.246 and 2.953 Å, respectively. The N–H–N angle between
N(6)–H(6)–(N5) involved in hydrogen bonding interaction is
139.44°. Among these, the core created between thiophene sulfur
(S1/S10) and quinazoline nitrogen (N6) may best be suited for
interaction with cations. The asymmetric unit of 3 contains three
symmetrical trans-oriented molecules, two half units of 3 and
two ethanol molecules with the chemical formula moiety
C34H24N6,0.5(C34H22N6),2(C2H6O) (see CIF; Fig. 1b). The ethanol
Figure 1. Crystal structures of 1 (a) and 3 (b) with atom numbering scheme (H atoms omitted for clarity).

3552
R. Pandey et al. / Tetrahedron Letters 53 (2012) 3550–3555
Figure 2. Absorption (a) and fluorescence [kex = 350 nm, kem = 423 nm; PMT 400 V] (b) spectra of 1–3, in H2O/ EtOH (60: 40, pH ꢃ7.2; c, 10
lM) solution.
molecules are held with molecular units of 3 through intermolec-
ular hydrogen bonding. The crystal structure strongly supported
the formation of 3 with some disorder at N(7), N(8) and N(9)
(see CIF). Compound 3 bears two identical stereogenic centers
wherein one lies above and the other below the molecular plane.
The optical properties (absorption and emission) of 1–3 have
at 350 nm, these strongly emit at 423 (1), 423 (2) and 426 nm (3).
Resulting spectra are shown in Fig. 2b and data collected in Table
S2. The emission band corresponding to 1 blue shifted in non polar
solvents (Fig. S7) and exhibited a red shift of ꢃ10–15 nm in protic
polar solvents. On the other hand, emission spectra of 2 and 3
showed insignificant changes upon varying the solvent polarity
(Fig. S7). The quantum yields for 1–3 (Uf, pyrene) have been deter-
mined to be 0.76, 0.20 and 0.62.13b Based on the absorption and
emission spectral behaviour, 1 has been chosen as the key probe
for further studies.
been investigated in water/ethanol (60:40) using 10
and the resulting data are summarized in Table S2. Electronic
absorption spectrum of exhibited bands at 291, 302 and
352 nm assignable to
p⁄ and n?p⁄ intramolecular charge
lM solution
1
p
?
transfer (ICT) transitions (Fig. 2a).
To understand the affinity of 1–3 towards various metal ions
both absorption and emission spectral studies have been per-
Compounds 2 and 3 followed a similar pattern and exhibited
bands at almost the same position [k, 289, 301 and 355 nm, 2;
291, 302 and 356 nm, 3]. This observation is consistent with anal-
ogous structural features and the extent of conjugation in 1–3. Fur-
ther, to have an idea about influence of the solvent polarity,
formed in the presence of cations like Na+, K+, Ca2+, Mg2+, Mn2+
,
Co2+, Ni2+, Cu2+, Zn2+, Ag+, Cd2+, Pb2+ and Hg2+ (nitrate salts) in
water/ethanol (60: 40, v/v; c, 10 mM). Upon addition of an excess
of tested metal ions (20.0 equiv; c, 10 mM) the absorption spectra
of 1–3 exhibited insignificant changes except for Hg2+ (Fig. 3 and
S12). The band centred at 352 nm in the spectrum of 1 exhibited
a bathochromic shift upon addition of an excess of Hg2+ and
appeared at ꢃ374 nm, while high energy band showed a marginal
absorption and emission spectra of 1–3 (10 lM) were acquired in
various solvents (Table S3). In a polar solvent like DMSO the low
energy band of 1 appeared at 359 nm (red shift). On the other
hand, in benzene (non polar) it exhibited moderate blue shift,
and in dichloromethane (semi-polar) a blue shift of ꢃ5–6 nm
(Fig. S6). The red and blue shifts in the position of absorption band
may be ascribed to the extent of polarization of the probe in vari-
ous solvents.11 As expected, 2 and 3 followed an analogous pattern
(Fig. S6).
red shift (
D
k, ꢃ4 nm). In an analogous manner, lower energy bands
of and
2
3
displayed relatively small bathochromic shifts
(ꢃ360 nm, 2; ꢃ365 nm, 3; Fig. S12).
Metal ion interaction studies for 1–3 were followed by emission
spectral studies (kex, 350 nm) in the presence of tested metal ions
(20.0 equiv, Fig. 3b and S10). The emission band present at 423 nm
in the spectrum of 1 quenches upon addition of Hg2+ (ꢃ83%), while
other metal ions were ineffective in this regard. Similarly, 2 and 3
Planar benzoannulated compounds fluoresce and find wide
application as fluorescent probes.8,12 The compounds under inves-
tigation may also exhibit significant fluorescence. Upon excitation
Figure 3. (a) Absorption spectra of 1 (10
lM) in the presence of metal nitrates (20 equiv, c, 10 mM). (b) Bar diagram showing relative fluorescence intensity for 1–3 (c, 10 lM)
in the presence of various metal ions. Inset showing the interference study for 1+Hg2+ with various metal ions.

R. Pandey et al. / Tetrahedron Letters 53 (2012) 3550–3555
3553
Figure 4. (a) Absorption and (b) emission titration spectra of 1 (c, 10 l .
M) in the presence of various equiv of Hg2+
y = 0.9479x + 1
R2 = 0.9986
6
4
2
0
1
2
3
y = 0.8298x + 1
R2 = 0.9981
Fo / F
y = 0.499x + 1
R2 = 0.9915
0
1
2
3
]
4
5
[ Hg2+
(a)
(b)
Figure 5. (a) Stern-Volmer plots for 1–3 for estimation of quenching constants in the presence of Hg2+. (b) Linear fluorescence intensity (F/F0, R2 = 0.99) of 1 (1.0
lM) upon
addition of Hg2+ (0–1.0
lM).
exhibited fluorescence quenching of ꢃ77 and 86% in the presence
of Hg2+ (Fig. 3b and S10). To follow selectivity of 1 towards Hg2+
The selectivity of 1–3 for Hg2+ was further followed by fluores-
cence titration studies under similar conditions. Addition of Hg2+
(0.0–5.0 equiv) to a solution of 1 leads to a gradual decrease in
fluorescence intensity of the band centred at k, ꢃ423 nm (83%,
ꢃ6.0-fold, Figs. 4b and 6, inset) and decrease in the quantum yield
,
interference studies were performed under analogous conditions
by the addition of an excess of (20 equiv) metal ions including
Cu2+, Cd2+, Pb2+ and Ag+ .to a solution of 1 containing Hg2+. Notably,
fluorescence intensity of the probable 1+Hg2+ complex (Fig. 3b, in-
set) remains more or less the same in the presence of other metal
(DUf = 0.65). Analogous fluorescence quenching has been observed
for 2 (k, 423 nm) and 3 (k, 426 nm) also, in the presence of Hg2+
(Table S2, Fig. S12). Observed bathochromic shifts of both the
low and high energy bands and a decrease in relative fluorescence
intensity may be attributed to the CT process from the receptor site
to quinazoline ring and enhanced photoinduced electron transfer
process (PET).14 To assess the sensitivity, varying concentrations
ions, suggesting higher affinity and selectivity of 1 for Hg2+
.
The biological applications of probes require sensing in a wide pH
range. The effect of pH on absorption and fluorescence response of 1
towards Hg2+ implies that the probe operates well in the pH range of
6.0–7.4 (c, 5
exists at pH ꢃ7.2 and an increase (pH ꢃ8.4;
, 0.1068 Mꢁ1cmꢁ1) diminishes optical
l
M; Fig. S9). It was observed that the actual species
e
, 0.0977 Mꢁ1cmꢁ1) or
of Hg2+ (0.1–1.0
of 1 (Fig. 5b). A plot between fluorescence intensity vs. concentra-
lM) were added to solution containing 1.0 lM
decrease of the pH (pH ꢃ6.0;
e
density of 1 at 351 nm (Fig. S9a). In contrast fluorescence intensity
increases at higher pH (pH ꢃ 8.4) and is quenched at lower pH (pH
ꢃ6.0) in 1 (Fig. S9b).
tion of Hg2+ (0.1–1.0
lM) exhibited a linear relationship
(R2 = 0.99), suggesting the limit of detection (LOD) of 2.0 ꢀ 10ꢁ7
M and that 1 is potentially useful for the detection of Hg2+
.
To get deep insight into sensitivity and binding of 1 with Hg2+
,
Job’s plot analysis revealed that 1 and 2 interact with Hg2+ in
1:1, while 3 in 1:2 (probe/metal) stoichiometries (Fig. S13).
Further, the binding affinity of 1–3 for Hg2+ was estimated from
Benesi-Hildebrand plots.15 The association constants (Ka) for 1–3
based on non-linear fitting of emission titration data using 1:1
and 1:2 binding model have been found to be 1.34 0.004 ꢀ 104
Mꢁ1 (1), 3.40 0.03 ꢀ 103 Mꢁ1 (2) and 3.78 0.03 ꢀ 106 Mꢁ2] (3)
(Fig. S14). 15 Quenching efficiency of 1–3 has been estimated quan-
titatively from Stern-Volmer plots (Fig. 5a) and found to be
Ksv = 9479 (1); 8298 (2) and 9980 Mꢁ1 (3). Binding constant for 3
is much higher relative to 1 and 2 which may be attributed to
absorption titrations were carried out by sequential addition of
Hg(NO3)2 (c, 10 mM; 0.0–5.0 equiv) to a solution of 1 (c, 10 M) in
ethanol/water (60:40, v/v). Upon addition of Hg2+ molar extinction
l
coefficient of the low energy band (k, ꢃ352 nm;
e )
, 21,100 cmꢁ1Mꢁ1
decreases to ꢃ5,000 cmꢁ1Mꢁ1, concomitantly a new band appeared
at k, ꢃ374 nm (Fig. 4a). The appearance of an isosbestic point at
ꢃ369 nm suggested the presence of more than two species in the
medium. Similarly, bands due to high energy
p?
p⁄ transitions
rationalized and red shifted to appear at 297 and 306 nm. The
UV–vis behaviour of 2 and 3 was almost similar to 1 (Fig. S11).

3554
R. Pandey et al. / Tetrahedron Letters 53 (2012) 3550–3555
The results strongly suggested that quinazoline core in 1–3 leads
to Hg2+-selective ‘turn-off’ signalling, not hetero-rings attached at
6-position, though the presence of a hetero atom at suitable chela-
tion site may increase the sensitivity and stability of the ensuing
product. Based on the present study it may be concluded that more
quinazolines possessing appropriate 6-hetero rings that can be de-
signed and prepared following current protocol that can serve as
highly Hg2+-selective ‘on-off’ probes with increased/decreased sen-
sitivity. The fluorescence intensity of 1–3 is very high so the fluo-
rescence studies have been performed at PMT 400 V.
N
N
N
Hg(NO3)2
NH
S
N
N
EDTA
Hg2+
(a)
(b)
OH2
(1)
S
OH2
To establish the interaction site of 1 with Hg2+, 1H NMR titration
experiment was performed in DMSO-d6 (Fig. S16). Upon addition of
Hg(ClO4)2 (0.5 equiv) to a solution of 1, the aromatic ring protons
exhibited deshielding. The H1 proton due to NH ionophore (br. s,
d 7.73 ppm) shifted downfield to appear at d 8.17 ppm (Fig. S1).
Signals due to H3, H10 and H11, H12 protons merged together
and appeared as a multiplet at d 7.43–7.38 ppm. However, merged
resonances due to H2 and H4 separated after addition of Hg2+ and
appeared at d 7.68 and 7.62 ppm, respectively. With an increase in
the concentration of Hg2+ (1.0–2.0 equiv), signals due to –NH and
H2/H4 protons exhibited a downfield shift and appeared at d 8.54
N
N
N
N
NH
NH
(
D
d, 0.81) and d7.86 ppm (
due to H3, H11 and H12 protons merged and resonated in the
range of d 7.48–7.54, while H5 at d 7.32 ppm ( d = 0.12). The H5
Dd, 0.39), respectively. Similarly, signals
Hg2+
OH2
OH2
Hg(NO3)2
D
(–CH) exhibited a smaller downfield shift relative to –NH (H1) pro-
ton. Downfield shift observed for all the protons clearly indicated
interaction of 1 with Hg2+ ion. 1H NMR titration results suggested
the interaction of Hg2+ with 1 probably, through both the quinaz-
oline N and thiophene ‘S’ donor sites. As 1 offers three interaction
sites, the most probable geometry about Hg2+ may be a distorted
trigonal bipyramidal16 (Fig. S20), which has further been supported
by mass spectral studies (vide supra). Further, to investigate the
involvement of ‘N’ atom of benzimidazole unit besides –NH with
OH2
H2O
Hg2+
NH
(c)
HN
N
N
N
N
(3)
Figure 6. (a) Reversible binding mode of 1 with Hg2+ in the presence of excess
Hg2+ 1H NMR titration experiments were performed using sym-
,
EDTA. (b) Fluorescence intensity change in 1–3 in the presence of Hg2+. (c) Plausible
binding mode of 3 with Hg2+
.
metrical probe 3, which lacks thiophene/ pyridine rings
(Fig. S17). The appearance of only a singlet at d 8.31 ppm (–NH)
after complete binding with Hg2+ (see Supplementary data, pp.
S24–25) suggested the involvement of quinazoline (–NH) and
one benzimidazole nitrogen of both the stereogenic sites (Fig. 6c
and S20).
1:2 (3:Hg2+) stoichiometry. Overall data suggested that probes 1–3
act as sensitive and selective chemosensors for Hg2+ through ‘on-
off’ signalling.
The interaction of 1 with Hg2+ was also followed by the addition
of large amounts of a strong chelating agent like EDTA to a solution
of 1+Hg2+, which resulted in the regeneration of the band due to 1
both in the absorption and emission spectra (Fig. S15). It suggested
reversible interaction between 1 and Hg2+ (Fig. 6a). One may think
that the process may involve liberation of Hg2+ from 1+Hg2+ and its
interaction with EDTA to form a more stable EDTA-Hg complex. To
ascertain this, ꢃ20.0 equiv of Hg2+ was added to a solution of 1
leading to fluorescence quenching to a large extent. Further, addi-
tion of an excess of EDTA (200.0 equiv) to this solution led to
regeneration of emission band. In turn, addition of EDTA
(100.0 equiv) to a solution of 1 led to insignificant changes in the
position of emission band, whereas addition of 40.0 equiv of Hg2+
led to fluorescence quenching to some extent (Fig. S15c). The above
observations clearly indicated that EDTA itself does not interfere
with 1, but accepts back the Hg2+ from 1+Hg2+ complex.
Initially, 1 containing a suitable chelating site represented by S
and N is expected to interact with Hg2+ more effectively over other
cations. Expectedly, it exhibited significant change in the absorp-
tion and emission spectra only in the presence of Hg2+. To further
ascertain whether suphur atom of the quinazoline core is respon-
sible for Hg2+-induced ‘turn-off’ signalling, some other quinazoline
derivatives (2 and 3) having 6-substituted hetero- rings with het-
ero atoms at different positions were synthesized. Notably, 3 also
selectively binds with Hg2+ in analogous manner through both
interacting sites and displayed fluorescence quenching (Fig. 6).
Analysis of the HRMS data further supported the formation of
probes 1–3 and the species arising from interaction between 1
and Hg2+. The molecular ion peak [M+1]+ for 1–3 (100%) appeared
at m/z 304.0906 (calc. 304.0830), 299.1294 (calc. 299.1218) and
517.2141 (calc. 517.2062), respectively (Fig. S18). To provide fur-
ther support to 1:1 stoichiometry between 1 and Hg2+, HRMS spec-
trum of a [1+Hg(H2O)2](NO3)2 was acquired. It displayed a peak
assignable to [M]+ at m/z 541.0869 (541.0748), corresponding to
17
[1+Hg(H2O)2]2+ (Fig. S18).
In addition, to have an idea about
the possibility of –NH deprotonation upon interaction with Hg2+
ions, (Figs. S16 and S20) FAB-MS spectra of the compound obtained
by treatment of Hg(NO3)2 with probe 1, was acquired. The spec-
trum exhibited a peak corresponding to [M]+ of 1:1 complex
[1+Hg(H2O)2](NO3)2 at m/z 665 (665) along with other peaks
(Fig. S19). The presence of both nitrates as counter anions strongly
supported that deprotonation of –NH proton is not taking place
during interaction with Hg2+ ions.
Crystal structure of 1 shows that ‘S’ is disposed away from –NH,
that can structurally reorient upon interaction with Hg2+ to facili-
tate the chelation process.18a From crystal structures of 1 and 3
(Fig. 1) it is obvious that 6-substituted hetero ring may undergo
conformational changes in the presence of Hg2+ ion (Fig. 1). The ob-
served fluorescence quenching may be attributed to the formation
of a mercury complex18b–d It may also arise due to proximity of the
metal with unpaired electrons of the ligand which may lead to
spin-orbit coupling and enhanced intersystem crossing.18e The

R. Pandey et al. / Tetrahedron Letters 53 (2012) 3550–3555
3555
‘turn-off’ signalling with LOD 2.0 ꢀ 10ꢁ7 M for Hg2+ suggested the
possible applications of quinazolines for Hg2+ detection. It is worth
mentioning that though 1–3 detect Hg2+ through ‘turn-off’ signal-
ling, their selectivity for this cation is extremely high. Overall, this
approach provides a straightforward pathway to develop quinazo-
line receptors for Hg2+ sensing in aqueous media.
In this work we have designed and synthesized some new quin-
azolines 1–3 in reasonably good yield. Structures of 1 and 3 have
been determined crystallographically. The compounds under study
exhibit strong fluorescence at RT. The Hg2+ detection has been
demonstrated by absorption, fluorescence, 1H NMR, HRMS and
FAB-MS spectral studies. Fluorescence intensity of 1–3 quenches
selectively in the presence of Hg2+ in 1:1 stoichiometry with 1
and 2, while 1:2 (probe/metal) with 3. The interaction site of
probes has been suggested by 1H NMR titration studies. These
three probes 1–3 possess different hetero-aryl rings at 6-position;
nevertheless displayed a ‘turn-off’ switching behaviour selectively
for Hg2+ under aqueous conditions.
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Acknowledgements
Thanks are due to the Department of Science and Technology
(DST), New Delhi, India for providing financial assistance through
the Scheme SR/S1/IC-15/2006. One of the authors (RP) is grateful
to the Council of Scientific and Industrial Research (CSIR), New Del-
hi, India for providing financial assistance through Senior Research
Fellowship (9/13(288)/2010-EMR-I).
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Supplementary data associated with this article can be found, in
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