Interactions of amino acids, carboxylic acids, and mineral acids with different quinoline derivatives

Article abstract of DOI:10.1016/j.molstruc.2011.01.040

A series of quinoline containing receptors having amide and ester bonds are synthesized and characterised. The relative binding abilities of these receptors with various amino acids, carboxylic acids and mineral acids are determined by monitoring the chan

Full text of DOI:10.1016/j.molstruc.2011.01.040

Journal of Molecular Structure 990 (2011) 183–196
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Interactions of amino acids, carboxylic acids, and mineral acids with different
quinoline derivatives
⇑
Dipjyoti Kalita, Himangshu Deka, Shyam Sundar Samanta, Subrata Guchait, Jubaraj B. Baruah
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781 039 Assam, 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 quinoline containing receptors having amide and ester bonds are synthesized and character-
ised. The relative binding abilities of these receptors with various amino acids, carboxylic acids and min-
eral acids are determined by monitoring the changes in fluorescence intensity. Among the receptors
bis(2-(quinolin-8-yloxy)ethyl) isophthalate shows fluorescence enhancement on addition of amino acids
whereas the other receptors shows fluorescence quenching on addition of amino acids. The receptor N-
(quinolin-8-yl)-2-(quinolin-8-yloxy) propanamide has higher binding affinity for amino acids. However,
the receptor N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide having similar structure do not bind to
amino acids. This is attributed to the concave structure of the former which is favoured due to the pres-
ence of methyl substituent. The receptor bis(2-(quinolin-8-yloxy)ethyl) isophthalate do not bind to
hydroxy carboxylic acids, but is a good receptor for dicarboxylic acids. The crystal structure of bromide
and perchlorate salts of receptor 2-bromo-N-(quinolin-8-yl)-propanamide are determined. In both the
cases the amide groups are not in the plane of quinoline ring. The structure of N-(quinolin-8-yl)-2-(quin-
olin-8-yloxy)acetamide, N-(2-methoxyphenethyl)-2-(quinolin-8-yloxy)acetamide and their salts with
maleic acid as well as fumaric acid are determined. It is observed that the solid state structures are gov-
erned by the double bond geometry of these two acid. Maleic acid forms salt in both the cases, whereas
fumaric acid forms either salt or co-crystals.
Received 8 December 2010
Received in revised form 19 January 2011
Accepted 19 January 2011
Available online 26 January 2011
Keywords:
Amides
Quinoline
Acid recognition
Amino acids
Fluorescence
Crystal structures
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
possibilities to functionalize such derivatives so that they have
number of sites for weak interactions and also able to confer direc-
Quinoline derivatives are used as drugs for different diseases
such as tuberculosis, schizophrenia and malaria [1–7]. Apart from
its medicinal value quinoline derivatives are also studied as a
supramolecular host [8–13]. Several quinoline based receptors
containing urea and amide functionality are known for their bind-
ing abilities with various anions. These receptors are selective to-
wards smaller halide anions in comparison to the larger halide
tional properties while self-assembly formation. We have been
interested in the structural studies and molecular recognition of
various anions by quinoline based receptors [14,15]. Many organic
and inorganic receptors for recognition of amino acids are synthe-
sized and their binding properties are studied. Most of these recep-
tors have structures relatively difficult to synthesize or used in the
form of metal complexes [16–21]. In this study we have focused
our interest to understand the binding properties of different or-
ganic and inorganic acids towards quinoline derived receptors.
For this purpose we have chosen a series of fluorescence active
quinoline functionalised receptors listed in Chart 1.
Here we present a comparative binding abilities of different
acids, namely amino acid, mineral acid and carboxylic acid with
these quinoline based receptors by determining their binding con-
stants and also showed that how such bindings takes place in solid
state structures in their co-crystals and salts.
anions [8]. Various weak interactions such as
p–p interaction, H-
bond interaction govern the main architecture of these hosts
[9,10]. As the quinoline group is a Lewis base, the nitrogen atom
of the ring can be easily protonated to form its salt and such hosts
can be used as cationic receptors for anions. The structural aspects,
properties of salts and inclusion compounds of quinoline deriva-
tives are also studied in details [11]. Quinoline derivatives such
as 8-aminoquinoline and 8-hydroxyquinoline have also been used
as guests with suitable hosts [12,13]. Our interest on study of quin-
oline based receptor is because of their medicinal value, ready
availability of binding site, and the presence of a fluorophore group
that makes solution study handy. Further to this there are different
2. Experimental
All reagents and solvents were purchased commercially and
were used without further purification, unless otherwise stated.
1H NMR data were recorded with a Varian 400 MHz FT-NMR
⇑
Corresponding author. Tel.: +91 361 2582311; fax: +91 361 2690762.
E-mail address: juba@iitg.ernet.in (J.B. Baruah).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.01.040

184
D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
Chart 1. Various receptors used for acid binding studies.
spectrometer. The FT-IR spectra were recorded using a PerkinElmer
spectrum one spectrometer in the KBr pellets in the range 4000–
400 cmÀ1. The UV/Vis spectra were recorded using a PerkinElmer
Lambda 750 spectrometer. The fluorescence spectra were recorded
with a PerkinElmer LS 55 fluorescence spectrophotometer. For the
fluorescence titration, solutions of the compounds in methanol
were prepared at definite concentrations (as described in each fig-
7.72 (d, J = 7.2 Hz, 1H); 6.12 (q, J = 6.4 Hz, 1H); 2.01 (d, J = 6.4 Hz,
3H).
2.2. Synthesis of the salt Ia and Ib
Compound I was dissolved in dilute solution of hydrobromic
acid and perchloric acid and allowed to stand for 3 days to obtain
the crystals of their respective salts (Ia and Ib). Ia: Yield 67%, IR
(KBr, cmÀ1): 3393 (bs), 2924 (m), 2851 (m), 1639 (m), 1558 (w),
1456 (m), 1378 (m), 1319 (m), 1157 (bm), 1052 (m), 1034 (m),
816 (m). Ib: Yield 67%, IR (KBr, cmÀ1): 3433 (bs), 3265 (s), 1686
(s), 1644 (m), 1607 (m), 1566 (m), 1475 (m), 1371 (m), 1143 (s),
1120 (s), 1085 (s), 838 (m), 765 (m), 625 (m).
ure captions) and a constant aliquots (10 lL) of different guest
acids (10À2 M in methanol) were added to the host solution. Fluo-
rescence spectra of the solution were recorded after every addition
of the guest acids. The binding constants were determined from
the fluorescence titration curve as reported earlier for 1:1 host–
guest complex formation [22].
2.1. Synthesis of 2-bromo-N-(quinolin-8-yl)propanamide (I)
2.3. Synthesis of 2-(cyclohexylamino)-N-(quinolin-8-yl)propanamide
(II)
To a solution of 8-aminoquinoline (0.433 g, 3 mmol) in dry
dichloromethane (20 mL) triethylamine (0.31 g, 3 mmol) was
added. The solution was stirred at 0 °C for 15 min and 2-bro-
mopropionylbromide (0.316 g, 3 mmol) was added over a period
of 30 min. The reaction mixture was then stirred overnight at room
temperature. To the reaction mixture 20 ml of water was added
and the organic layer was separated using a separatory funnel.
The solution was then dried over anhydrous sodium sulphate
and the solvent was removed under reduced pressure to obtain a
brown solid. The crude product was then recrystallised from
dichloromethane. Yield: 78%. IR (KBr, cmÀ1): 3375 (b), 3042 (s),
3005 (s), 2949 (m), 2896 (m), 1689 (s), 1611 (w), 1587 (m), 1547
(s), 1494 (m), 1428 (s), 1389 (s), 1363 (s), 1245 (w), 1160 (w),
1038 (m), 834 (m), 777 (m). 1H NMR (CDCl3, 400 MHz): 12.01 (s,
1H); 9.78 (d, J = 5.6 Hz, 1H); 9.19 (d, J = 8.4 Hz, 1H); 8.21 (t,
J = 8.4 Hz, 1H); 7.97 (d, J = 8.4 Hz, 1H); 7.89 (t, J = 7.6 Hz, 1H);
2-bromo-N-(quinolin-8-yl)propanamide (I) (0.834 g, 3 mmol),
cyclohexylamine (0.297 g, 3 mmol) and potassium carbonate
(0.5 g, 3.7 mmol) were taken in dry tetrahydrofuran (20 mL) and
stirred at 70 °C for 9 h (progress of the reaction was monitored at
regular intervals using TLC). After completion of the reaction, the
product was filtered and the solvent was removed under reduced
pressure. The product II was further purified by thin layer chroma-
tography (silica gel; hexane/ethyl acetate 3:2). Yield: 48%. IR (KBr,
cmÀ1): 3329 (b), 2927 (m), 2851 (m), 1672 (s), 1520 (s), 1486 (m),
1448 (w), 1423 (w), 1382 (w), 1322 (m), 1130 (m), 1052 (m), 823
(m), 791 (m). 1H NMR (CDCl3, 400 MHz): 11.62 (s, 1H); 8.86 (d,
J = 6.0 Hz, 1H); 8.82 (d, J = 7.2 Hz, 1H); 8.15 (d, J = 8.0 Hz, 1H);
7.51 (m, 2H); 7.42 (m, 1H); 3.51 (q, J = 6.8 Hz, 1H); 2.50 (d,
J = 3.6 Hz, 1H); 2.03 (bs, 1H); 1.63 (m, 4H); 1.46 (d, J = 6.8 Hz,
3H); 1.13 (m, 6H). 13C NMR (CDCl3): 20.9, 25.2, 25.3, 26.2, 33.9,

D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
185
33.3, 56.5, 57.1, 116.5, 121.7, 127.5, 128.3, 134.8, 136.3, 136.6,
139.4, 148.6, 175.3. LC–MS [M + 1]: 298.20.
kept undisturbed for 3–4 days to obtain either the salts or the
co-crystals.
IVa: Yield: 71%. IR (KBr, cmÀ1): 3409 (bs), 1686 (s), 1545 (s),
1491 (w), 1427 (m), 1318 (s), 1274 (s), 1218 (m), 1011 (m),
825 (m), 645 (s).
2.4. Synthesis of N-(quinolin-8-yl)-2-(quinolin-8-yloxy) propanamide
(III)
IVb: Yield: 74%. IR (KBr, cmÀ1): 3393 (bs), 1684 (m), 1603 (m),
1543 (s), 1490 (s), 1427 (w), 1364 (m), 1353 (m), 1315 (m),
1274 (w), 1191 (w), 1120 (w), 961 (w), 873 (m), 824 (m), 793
(m), 745 (w), 611 (m).
The 2-bromo-N-(quinolin-8-yl)propanamide (1.36 g, 5 mmol)
was dissolved in dry acetone (30 ml). To the reaction mixture
K2CO3 (1.0 g, 7.5 mmol) was added and stirred for 20 min. Then
8-hydroxyquinoline (0.725 g, 5 mmol) was added and the reaction
mixture was refluxed at 70 °C for 10 h. (Progress of the reaction
was monitored at regular intervals using TLC.) After completion
of the reaction, the reaction mixture was filtered to remove the
K2CO3. The solvent from the filtrate was then removed under re-
duced pressure to obtain the crude product which was further
purified by thin layer chromatography (silica gel; hexane/ethyl
acetate 3:2). Yield: 48%. IR (KBr, cmÀ1): 3432 (m), 3257 (s), 2764
(s), 1704 (s), 1637 (w), 1516 (s), 1420 (m), 1384 (m), 1309 (m),
1281 (m), 1218 (s), 1163 (m), 1063 (w), 993 (w), 873 (w), 821
(s),777 (w), 609 (m). 1H NMR (CDCl3, 400 MHz): 11.2 (s, 1H), 9.0
(d, J = 4.0 Hz, 1H), 8.8 (d, J = 7.2 Hz, 1H), 8.6 (d, J = 4.4 Hz, 1H), 8.1
(d, J = 8.4 Hz 1H), 8.0 (d, J = 8.4 Hz, 1H), 7.5–7.4 (m, 5H) 7.3
(m,1H), 7.2 (d, J = 7.2 Hz, 1H), 5.2 (q, J = 6.8 Hz, 1H), 1.9 (d,
J = 6.8 Hz, 3H).
2.7. Synthesis of N-(2-methoxyphenethyl)-2-(quinolin-8-
yloxy)acetamide (V)
2-(2-Methoxyphenyl)ethylamine (0.755 g, 5 mmol) was dis-
solved in dry dichloromethane (20 mL) and triethylamine
(0.505 g, 5 mmol) was added to it. The solution was stirred at
0 °C for 15 min and bromoacetylbromide (0. 1.01 g, 5 mmol) was
added to the stirred solution over a period of 30 min. The reaction
mixture was stirred overnight at room temperature. It was then fil-
tered to remove the hydrobromide salts, and the filtrate was re-
moved under reduced pressure. The corresponding amide
obtained was recrystallised from dichloromethane. In the next
step, the amide obtained (1.08 g, 5 mmol), 8-hydroxyquinoline
(0.725 g, 5 mmol) and potassium carbonate (1.0 g, 7.5 mmol) were
taken in dry acetone (20 mL) and the reaction mixture was stirred
at 60 °C for 9 h (progress of the reaction was monitored at regular
intervals using TLC). After completion of the reaction, the reaction
mixture was filtered and the solvent was removed under reduced
pressure. The product obtained was purified by column chroma-
tography. Yield: 54%. IR (KBr, cmÀ1): 3360 (bs), 3051 (s), 2968
(w), 1642 (s), 1601 (m), 1552 (s), 1504 (s), 1497 (s), 1469 (s),
1433 (m), 1380 (m), 1315 (s), 1264 (m), 1251 (s), 1115 (s), 1034
(m), 826 (m), 757 (s). 1H NMR (CDCl3, 400 MHz): 8.8 (d, J = 4 Hz,
2.5. Synthesis of N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide IV
The compound was synthesized by a reported procedure [23].
2.6. Synthesis of the salt and co-crystals of maleic acid and fumaric
acid (Va, Vb, IVa, and IVb)
The receptors were dissolved in aqueous methanol and the
respective acids were added in 1:1 ratio. The solutions were then
Table 1
Crystallographic parameter for compounds.
Compound no.
Ia
Ib
IV
IVa
IVb
V
Va
Vb
Formulae
CCDC no.
Mol. wt.
C
12H12Br2N2O
C12H12BrClN2O5
781137
379.60
C20H15N3O2
790481
329.35
C26H23N3O9
790482
521.47
C24H20N3O7
790480
462.43
C20H24N2O5
790478
372.41
C24H24N2O7
790479
452.45
C22H21N2O5
790477
393.41
781136
360.06
Crystal system
Space group
Temperature/K
Wavelength/Å
a/Å
Triclinic
P-1
296
Monoclinic
P2(1)/n
296
0.71073
5.0946(2)
28.4639(9)
10.0728(3)
90.00
101.073(2)
90.00
1433.49(8)
4
Triclinic
P-1
296
Triclinic
P-1
296
Monoclinic
P2(1)/n
296
0.71073
6.7151(11)
16.530(3)
19.258(4)
90.00
91.372 (6)
90.00
2136.9(6)
4
Triclinic
P-1
296
Monoclinic
P2(1)/n
296
0.71073
17.862(3)
4.8456(8)
26.550(4)
90.00
101.540(9)
90.00
2251.6(6)
4
Monoclinic
P2(1)/c
296
0.71073
17.792(15)
4.909(4)
25.985(16)
90.00
120.21 (4)
90.00
1961 (3)
4
0.71073
7.5545(5)
9.8698(8)
10.1227(8)
62.797(4)
79.255(4)
80.067(4)
656.21(9)
2
0.71073
8.2758(7)
10.0169(8)
10.2197(9)
85.635(5)
85.319(5)
77.445(5)
822.69(12)
2
0.71073
7.5146(7)
12.2378(12)
13.6349(13)
94.239(7)
97.921(7)
97.873(6)
1224.7(2)
2
0.71073
8.7292(14)
10.675(2)
11.0402(19)
87.703(10)
72.230(8)
80.940(9)
967.4(3)
2
b/Å
c/Å
a
/°
b/°
c
/°
V/Å3
Z
Density/Mg mÀ3
Abs. Coeff./mmÀ1
F(0 0 0)
1.822
6.162
352
1.759
3.076
760
1.330
0.088
344
1.414
0.109
544
1.437
0.108
964
1.278
0.092
396
1.335
0.099
952
1.332
0.095
828
Total no. of reflections
3224
3459
2927
4365
3850
3282
3866
3423
Reflections, I > 2
r(I)
2446
1815
2336
2087
1763
2747
1418
1967
Max. 2h/°
56.84
56.70
50.5
50.5
50.5
50.0
50.5
50.5
Ranges (h, k, l)
À10 ꢀ h ꢀ 10
À13 ꢀ k ꢀ 13
À13 ꢀ l ꢀ 13
97.8
À6 ꢀ h ꢀ 6
À37 ꢀ k ꢀ 30
À11 ꢀ l ꢀ 13
96.7
À9 ꢀ h ꢀ 9
À11 ꢀ k ꢀ 11
À12 ꢀ l ꢀ 12
98.4
À8 ꢀ h ꢀ 8
À14 ꢀ k ꢀ 13
À16 ꢀ l ꢀ 16
98.5
À7 ꢀ h ꢀ 8
À19 ꢀ k ꢀ 19
À22 ꢀ l ꢀ 23
99.6
À10 ꢀ h ꢀ 10
À12 ꢀ k ꢀ 12
À9 ꢀ l ꢀ 13
96.8
À21 ꢀ h ꢀ 21
À5 ꢀ k ꢀ 4
À29 ꢀ l ꢀ 27
94.8
À21 ꢀ h ꢀ 20
À5 ꢀ k ꢀ 5
À30 ꢀ l ꢀ 31
96.5
Complete to 2h (%)
Refinement method
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Full-matrix
least-squares
on F2
Data/Restraints/Parameters
2446/0/159
1.075
1815/0/195
0.951
2927/0/226
1.041
4365/0/357
0.871
3850/4/319
1.059
3282/0/265
0.855
3866/0/311
0.765
3423/0/273
0.679
Goof (F2)
R indices [I > 2
r(I)]
0.0572
0.0508
0.0574
0.0409
0.0998
0.0589
0.0493
0.0529
R indices (all data)
0.0717
0.1024
0.0653
0.0958
0.1612
0.0654
0.1454
0.2053

186
D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
1H); 8.2 (d, J = 8.4 Hz, 1H); 7.4 (m, 2H); 7.0 (d, J = 7.2 Hz, 2H), 6.9 (d,
J = 7.2 Hz, 1H); 6.7 (m, 2H); 4.7 (s, 2H); 3.7 (s, 3H); 3.5 (t, J = 6.8 Hz,
2H); 2.8 (t, J = 7.2 Hz, 2H); 2.2 (bs, 1H). 13C NMR (CDCl3): 30.3, 39.4,
55.3, 69.8, 110.4, 111.7, 120.5, 121.6, 122.1, 127.0, 127.5, 127.8,
129.7, 130.6, 136.5, 140.2, 149.4, 153.9, 157.7, 168.6. LC–MS
[M + 1]: 337.17.
N
H
HN
O
Br
Br
Ia
N
HN
O
HBr
NH2
NH
II
O
N
Et3N
DCM
+
Br
HN
O
Br
N
NH2
I
Br
N
OH
N
HClO4
HN
O
O
N
III
N
H
HN
O
ClO4
Br
Ib
Scheme 1. Synthesis of 2-bromo-N-(quinolin-8-yl)propanamide (I) and its derivatives.
O
O
O
O
O
O
O
O
1. K2CO3, Acetone
N
Cl
Cl
+
Br
COOCH3
O
N
2. NaBH4, THF/Methanol
DCM, Et3N
N
N
OH
HO
VI
Scheme 2. Synthesis of compound VI.
O
H
N
O
H
N
NH2
+
NH2
O
N
NEt3
DCM
O
Br
Br
Br
OH
N
N
Br
O
HN
HN
K2CO3, Acetone
O
O
VII
Scheme 3. Synthesis of compound VII.

D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
187
Va: Yield: 74%. IR (KBr, cmÀ1): 3433 (bs), 33,052 (s), 3056 (w),
3006 (w), 2940 (w), 1673 (s), 1618 (m), 1601 (m), 1495 (s),
1464 (s), 1348 (m), 1305 (m), 1280 (m), 1244 (m), 1111 (m),
1034 (w), 874 (w), 858 (m), 830 (m).
to it. The solution was stirred at room temperature for 15 min and
then methyl bromoacetate (0.76 g, 5 mmol) was added and the
reaction mixture was then refluxed at 70 °C for 12 h (Progress of
the reaction was monitored at regular intervals using TLC). After
completion of the reaction, the reaction mixture was then filtered
and the solvent was then removed under reduced pressure to ob-
tain the ester as a yellow solid. In the next step, the ester was re-
duced to the corresponding alcohol using a reported procedure
[24]. Yield: 77%. IR (KBr, cmÀ1): 3405 (b), 3175 (b), 2923 (m),
2861 (m), 1613 (w), 1505 (m), 1475 (m), 1381 (m), 1322 (m),
1266 (m), 1116 (m), 1075 (s), 904 (w), 823 (m). 1H NMR (CDCl3,
400 MHz): 8.8 (d, J = 4.4 Hz, 2 H), 8.0 (d, J = 8.4, 2H), 7.3 (m, 3H),
7.0 (d, J = 7.6 Hz, 1H), 4.2 (t, J = 4.8 Hz, 2H), 4.1 (t, J = 4.8 Hz, 2H),
3.4 (bs, 1H).
Vb: Yield: 77%. IR (KBr, cmÀ1): 3388 (s), 2941 (w), 1703 (w),
1698 (w), 1672 (s), 1551 (m), 1508 (m), 1494 (m), 1424 (m),
1379 (m), 1296 (s), 1262 (s), 1245 (s), 1165 (m), 1111 (s),
1042 (m), 824 (m), 785 (m), 749 (s).
2.8. Synthesis of 2-(quinolin-8-yloxy) ethanol
8-Hydroxyquinoline (.725 g, 5 mmol) was dissolved in dry ace-
tone (20 ml) and potassium carbonate (1.0 g, 7.5 mmol) was added
Fig. 1. Changes in emission spectra (kex = 310 nm) of I (6.7 Â 10À5 M in methanol); on addition of: (a) DL-alanine, (b)
L lL aliquot).
-alanine (10À2 M in methanol in 10
Fig. 2. Changes in fluorescence spectra (kex = 310 nm) of II (1.26 Â 10À4 M in methanol) on addition of: (a) glycine, (b) hydrochloric acid, (c) acetic acid (all 10À2 M in
methanol, in 10 lL aliquot).
Fig. 3. Changes in fluorescence spectra of III (2.5 Â 10À5 M in methanol) on addition of (a) glycine (10À2 M in methanol), (b) hydrochloric acid (10À2 M in methanol), (c) acetic
acid (10À2 M in methanol, in 10
lL aliquot).

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D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
2.9. Synthesis of bis (2-(quinolin-8-yloxy)ethyl) isophthalate (VI)
layer was separated using a separatory funnel. The solvent was
then removed under reduced pressure to obtain a light yellow col-
our solid. The product was further purified by thin layer chroma-
tography (silica gel; hexane/ethyl acetate 5:3). Yield: 73%. IR
(KBr, cmÀ1): 3422 (b), 2921 (w), 1720 (s), 1608 (w), 1508 (m),
1474 (w), 1451 (w), 1382 (m), 1259 (w), 1119 (m), 822 (w), 790
(w). 1H NMR (DMSO-d6, 400 MHz): 8.8(d, J = 2.8 Hz, 1H), 8.4 (s,
1H), 8.3(d, J = 8 Hz, 2H), 8.1(t, J = 6.4 Hz, 3H), 7.6 (t, J = 7.6 Hz,
2H), 7.5 (m, 5H), 7.3(t, J = 5.2 Hz, 2H), 4.7 (s, 4H), 4.5 (s, 4H). LC–
MS (M + 1): 509.22.
The 2-(quinolin-8-yloxy)ethanol (0.756 g, 4 mmol) was dis-
solved in dry dichloromethane (20 ml) and triethylamine
(0.404 g, 4 mmol) was added to it. The solution was stirred at
0 °C for 15 min and isophthaloyl dichloride (0.404 g, 2 mmol)
was added to the stirred solution. The reaction mixture was then
refluxed at 40 °C for 8 h (progress of the reaction was monitored
at regular intervals using TLC). After completion of the reaction,
30 mL of water was added to the reaction mixture and the organic
2.10. Synthesis of VII
Trans-1,2-diaminocylohexane (0.342 g, 3 mmol) was dissolved
in dry dichloromethane (20 mL) and triethylamine (0.61 g,
6 mmol) was added to it. The solution was stirred at 0 °C for
15 min and bromoacetylbromide (1.212 g, 6 mmol) was added to
the stirred solution over a period of 30 min. The reaction mixture
was then stirred overnight at room temperature. To the reaction
mixture 20 mL of water was added and the organic layer was sep-
arated using a separatory funnel. The solution was then dried over
sodium sulphate and the solvent was removed under reduced
pressure to obtain a brown solid. The crude product was then
recrystallised from dichloromethane. The amide thus obtained
(1.06 g, 3 mmol), 8-hydroxyquinoline (0.870 g, 6 mmol) and potas-
sium carbonate (1.0 g, 7.4 mmol) were taken in dry tetrahydrofu-
ran (20 mL) and the reaction mixture was stirred at 70 °C for 9 h
(progress of the reaction was monitored at regular intervals using
Fig. 4. Changes in fluorescence spectra of V (6.67 Â 10À6 M in methanol) with
maleic acid (10À2 M in methanol, in 10
lL aliquot).
Fig. 5. Changes in fluorescence spectra (kex = 310 nm) of VI (6.7 Â 10À5 M in methanol) on addition of: (a) hydrochloric acid (10À2 M in methanol), (b) glycine (10À2 M in
methanol). (c) Acetic acid (10À2 M in methanol, in 10
lL aliquot).
Table 2
Binding constant of different receptors calculated from fluorescence titration.
Guest
Binding constant (/mole)
II
III
IV
V
VI
VII
a
a
a
a
a
a
Glycine
Methionine
8.058 Â 103
1.639 Â 103
5.844 Â 105
3.967 Â 105
1.394 Â 106
1.22 Â 105
3.825 Â 106
5.224 Â 106
6.074 Â 105
7.932 Â 105
1.582 Â 105
1.388 Â 106
4.487 Â 104
1.464 Â 104
1.854 Â 104
6.478 Â 105
2.847 Â 105
6.022 Â 106
1.400 Â 107
5.160 Â 106
5.68 0 Â 104
1.148 Â 105
Hydrobromic acid
Hydrochloric acid
Perchloric acid
Acetic acid
Fumaric acid
Maleic acid
4.952 Â 105
3.369 Â 105
1.087 Â 106
1.055 Â 105
7.520 Â 104
2.271 Â 106
2.103 Â 106
3.625 Â 106
4.813 Â 107
4.052 Â 106
4.475 Â 107
a
a
5.228 Â 105
9.811 Â 105
1.316 Â 105
1.920 Â 105
9.060 Â 105
2.399 Â 107
2.650 Â 105
1.329 Â 106
4.963 Â 106
2.822 Â 106
a
a
a
L
-Ascorbic acid
-Mandelic acid
3.99 Â 105
3.596 Â 105
3.978 Â 105
2.591 Â 104
1.484 Â 105
1.068 Â 105
2.950 Â 104
2.920 Â 104
7.920 Â 104
4.079 Â 106
6.247 Â 106
1.466 Â 106
a
a
a
a
L
D-Mandelic acid
2.220 Â 105
1.142 Â 105
L-Tartaric acid
a
No changes in fluorescence spectra on addition of guest.

D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
189
TLC). After completion of the reaction, the product was filtered and
the solvent was removed under reduced pressure. The product was
further purified by thin layer chromatography. Yield: 57%. IR (KBr,
cmÀ1): 3465 (b), 2927 (m), 2856 (w), 1660 (s), 1551 (m), 1504 (m),
1474 (w), 1437 (w), 1378 (m), 1318 (m), 1260 (m), 1184 (w), 1112
(m), 785 (m), 751 (m). 1H NMR (CDCl3, 400 MHz): 8.92 (d,
J = 4.4 Hz, 2H); 8.17 (d, J = 8.4 Hz, 2H); 7.50 (m, 2H); 7.42 (t,
J = 8.4 Hz, 2H); 7.34 (t, J = 8.0 Hz, 2H); 6.98(d, J = 7.6 Hz, 2H); 4.64
(d, J = 14.8 Hz, 2H); 4.42 (d, J = 15.2 Hz, 2H); 3.95 (bs, 2H); 2.05
(m, 3H); 1.76 (m, 3H); 1.25 (m, 4H). 13C NMR (CDCl3): 25.0, 32.7,
52.5, 69.1, 102.2, 111.1, 121.4, 122.2, 126.9, 129.8, 136.7, 149.4,
168.6. LC–MS [M + 1]: 485.24.
The synthesis of N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetam-
ide was already reported [23] while the N-(2-methoxyphenethyl)-
2-(quinolin-8-yloxy)acetamide (V) was prepared by an analogous
procedure by reacting 2-(2-methoxyphenyl)ethylamine with
bromoacetlybromide followed by treatment with 8-hydroxyquino-
line. The receptor bis(2-(quinolin-8-yloxy)ethyl)isophthalate (VI)
was synthesized by reacting 8-hydroxyquinoline with bromome-
thylacetate followed by reduction of the ester by sodium borohy-
dride to obtain an alcohol 2-(quinolin-8-yloxy) ethanol as an
intermediate compound [24]. The 2-(quinolin-8-yloxy) ethanol
on further treatment with isophthaloyl dichloride resulted in the
formation of receptor VI (Scheme 2).
The reaction of trans-1,2-diaminocylohexane with bromoacetyl
bromide followed by reaction with 8-hydroxyquinoline resulted in
the formation of compound VII (Scheme 3). All the quinoline deriv-
atives I–VII are characterised by recording their NMR, IR spectra
and mass spectra. The crystal structures are determined wherever
suitable crystals are found.
2.11. Crystal structure determination
The X-ray single crystal diffraction data were collected at 296 K
with Mo K
a radiation (k = 0.71073 Å) using a Bruker Nonius
SMART CCD diffractometer equipped with a graphite monochro-
mator. The SMART software was used for data collection and also
for indexing the reflections and determining the unit cell parame-
ters; the collected data were integrated using SAINT software. The
structures were solved by direct methods and refined by full-
matrix least-squares calculations using SHELXTL software. All the
non-H atoms were refined in the anisotropic approximation
against F2 of all reflections. The H-atoms, except those attached
to oxygen atoms were placed at their calculated positions and
refined in the isotropic approximation; those attached to oxygen
were located in the difference Fourier maps, and refined
with isotropic displacement coefficients. The crystallographic
parameters of the compounds are tabulated in Table 1.
3.2. Fluorescence studies
The fluorescence emission of compound I is observed to be
responsive towards amino acids. For example, it shows enhance-
ment of emission intensity at 391 nm (kex = 310 nm) for addition
of L-alanine or DL-alanine (Fig. 1). We have not observed significant
differences among the two isomers on binding to the ligand I.
The fluorescence spectra of the receptor II are also affected by
mineral acids, amino acids, hydroxy acids, and simple carboxylic
acids (Fig. 2). Here we have observed that the fluorescence inten-
sity of II decreases on gradual addition of both mineral acids and
amino acids. However, the change is very rapid in case of mineral
acids than that of the amino acids. From these fluorescence titra-
tion curves we have calculated the binding constants of the various
acids. The binding constant study clearly shows that receptor II
binds mineral acids with much more affinity than that of the amino
acids. The receptor II is also responsive to hydroxy acids such as
ascorbic acid, mandelic acid, and tartaric acid.
3. Results and discussion
3.1. Synthesis and characterisation of receptors
The compound 2-bromo-N-(quinolin-8-yl)propanamide (I) was
synthesized by reacting 2-bromopropionylbromide with 8-amino-
quinoline in dichlorometane in the presence of triethylamine
(Scheme 1). The compound I was transformed to various deriva-
tives such as 2-(cyclohexylamino)-N-(quinolin-8-yl)propanamide
(II) and N-(quinolin-8-yl)-2-(quinolin-8-yloxy) propanamide (III)
by reacting with cyclohexylamine or 8-hydroxyquinoline respec-
tively. The compound I was further converted to bromide and per-
chlorate salts Ia and Ib by reacting with hydrobromic acid or
perchloric acid respectively.
Binding of receptor II was studied with two enantiomeric acids
namely, D-mandelic acid and L-mandelic acid. However, we could
not distinguish the two acids as in both the cases the fluorescence
intensity of II decreases in the same order on gradual addition of
the acids.
The fluorescence emission spectra of receptor III were studied
in presence of different guests. The receptor III shows a remarkable
decrease in fluorescence intensity at 510 nm on gradual addition of
Fig. 6. (A) Fluorescence spectra (kex = 310 nm) of: (a) VI (6.7 Â 10À5 M in methanol); and after addition of amino acid (b) serin, (c) lysine, (d) methionine, (e) glycine and (f)
alanine (100
(100
l
L of 10À2 M solution in methanol). (B) Fluorescence spectra of (a) III (2.5 Â 10À5 M in methanol), (b) Fluorescence quenching of III after addition of amino acid
l
L of 10À2 M solution in methanol) viz. glycine, metheonine, alanine, serin, and lysine.

190
D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
amino acids (Fig. 3a). However, we have observed a mild enhance-
ment of fluorescence emission intensity on addition of mineral
acids to receptor III (Fig. 3b). The binding property of receptor III
was studied with various hydroxy acids and carboxylic acids. It
has been observed that receptor III is responsive towards both hy-
droxy acids, amino acids, mineral acids and simple carboxylic
acids. With simple carboxylic acid like acetic acid it shows a grad-
ual decrease in fluorescence (Fig. 3c). In case of fumaric acid along
with the decrease in intensity at 510 nm a simultaneous increase
in fluorescence intensity at around 420 nm is observed thereby
forming an isoemissive point (the fluorescence curves are available
in supplementary material).
On the other hand the fluorescence emission of receptor V is
neither responsive to amino acids nor to hydroxy acids, but the
fluorescence significantly changes on addition of dicarboxylic acids
such as maleic acid and fumaric acid. The fluorescence intensity of
V decreases on gradual addition of maleic acid and it passes
through an isoemissive point at 457 nm as shown in Fig. 4.
Fig. 7. Comparisons of binding constant of receptor: (a) II, (b) III, (c) IV, (d) V, (e) VI, (f) VII with different guest acids.

D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
191
The fluorescence emission spectra of receptor VI is studied in
presence of different carboxylic acids, amino acids, and mineral
acids. A significant change in the fluorescence emission spectra
of VI on treatment with mineral acid was observed. A methanol
solution of VI shows fluorescence emission at 390 nm upon excita-
on all the receptors other than receptor III and in each case fluores-
cence quenching is observed. The receptor N-(quinolin-8-yl)-2-
(quinolin-8-yloxy) propanamide III has high affinity to bind to
amino acids in comparison to mineral acids. This makes the recep-
tor III a promising candidate for recognising amino acid. Recently
we have demonstrated that the nature of binding matters on the
optical properties of receptors and based on this the mineral acid
and organic acid can be distinguished by quinoline based receptors
[23]. One of the important observations is the greater binding abil-
ity of amino acids in the case of III over IV. Both have similar struc-
ture other than an extra methyl group in III. So the steric effect of
the methyl group is believed to make a transition state that is more
favourable as illustrated in Fig. 8. Such state will be less favored in
the case of IV as the quinoline part will have equal preferences for
tion at 310 nm. On gradual addition of HBr, HCl and HClO4
a
red-shift from 390 nm to 475 nm (85 nm shift) of fluorescence
emission occurs. The spectral changes pass through an isoemissive
point at 435 nm (Fig. 5a).
In order to differentiate the effect of amino acids over mineral
acids on fluorescence emission, amino acid solutions viz. glycine
or methionine were added gradually to a solution of receptor VI
and the fluorescence spectra were recorded. We have observed
an enhancement of the fluorescence emission intensity on addition
of amino acids and unlike in the case of mineral acids no isoemis-
sive point is observed (Fig. 5b). This difference in fluorescence
spectra suggests different types of supramolecular aggregation of
receptor VI with different guests. Comparing the study with min-
eral acids and with amino acids one can infer that the later case
is not due to the simple protonation of VI.
Further we studied the binding properties of receptor VI with
various acids including simple carboxylic acids (Fig. 5c) and a
few hydroxy acids. At this point we have observed that receptor
VI shows a very negligible affinity towards the hydroxy acids.
However, receptor VI shows good affinity towards simple carbox-
ylic acids. In case of simple carboxylic acids maleic acid behaves
in a similar way to the mineral acids thereby passing through an
isoemissive point whereas fumaric acid shows simple enhance-
ment of fluorescence intensity as in the case of acetic acid. This
may be because maleic acid prefers to form salt whereas fumaric
acid prefers to form hydrogen bonded co-crystal [25]. The com-
pound IV and VII are also fluorescence active and they show
changes in fluorescence emission upon binding with acids. Since
the results are analogous the figures are shown in supplementary
materials and the binding constants are summarised in Table 2.
We have also studied the emission spectra in the presence of
other amino acids such as serine, lysine and alanine. The relative
intensity changes in the fluorescence emission spectra of the
receptor VI is found to vary with different amino acids (Fig. 6A),
whereas the changes in the intensity pattern of the receptor III is
found to be similar with all the amino acids (Fig. 6B). In general
the addition of amino acid leads to enhancement of fluorescence
emission intensity of receptor VI and in case of such addition to
receptor III fluorescence quenching is observed.
O
N
HO
H
N
O
O
H
N
H
N
Fig. 8. H-bond interaction of receptor III with amino acid.
Fig. 9. (a) Emission spectra (kex = 310 nm) of II (6.7 Â 10À5 M in methanol); (b)
emission spectra of II in mixed solvent of water and methanol (1:2); (c) emission
spectra of II in mixed solvent of water and methanol (2:1).
From the relative changes in the fluorescence emission due to
guest host interactions, the binding constants for 1:1 host guest
composition of all the systems are determined and these are listed
in Table 2. The calculation of binding constant is done with the
assumptions that 1:1 host–guest complex are formed and also
being supported in majority of the cases by their crystal structures
of the salts and co-crystals which are discussed in the next
subsection.
Based on these results of binding constants a summary of com-
parative data on relative binding with respect to the hosts II–VII
are shown in Fig. 7. It may be suggested that quinoline derivatives
II–VII binds to various amino acids, mineral acids, carboxylic acids
and hydroxy acids, but the binding abilities varies with structure of
the parent receptor compound. Among all the receptors the recep-
tor VI shows enhancement of fluorescence on interaction with
amino acids and the other receptors show quenching. This receptor
is highly sensitive towards both amino acid and mineral acid, thus
it is less selective in binding. Furthermore this receptor is insensi-
tive to hydroxy carboxylic acids other than tartaric acid. Tartaric
acid being a dicarboxylic acid; the binding behaviour of this acid
should be analogous to other dicarboxylic acids such as maleic acid
which bind to this receptor. The mineral acid has also similar effect
Fig. 10. (a) Emission spectra (kex = 310 nm) of VI (6.7 Â 10À5 M in methanol); (b)
emission spectra of VI in mixed solvent of water and methanol (1:2); (c) emission
spectra of VI in mixed solvent of water and methanol (2:1).

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D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
we studied the fluorescence emission spectra in different propor-
tion of mixed solvents namely methanol and water. It is found that
the compounds other than VI, have general tendencies to undergo
fluorescence quenching on increasing proportion of water. As an
illustrative case the change in fluorescence emission of methanolic
solution of II with increase in water concentration is show in Fig. 9.
This is attributed to hydrogen bonding with water molecules. In
the case of VI, as water concentration increases there is a decrease
in fluorescence emission of methanolic solution of it at 391 nm,
with simultaneous generation of new emission peak at 470 nm
(Fig. 10). This emission peak is similar to the additional emission
peak observed on addition of mineral acid to VI (Fig. 5a) but the
difference is that the amount of water needed for such process is
in large excess in comparison to the amount of acid required for
a similar growth of emission at 470 nm.
3.3. Structural study
The bromide and perchlorate salts of 2-bromo-N-(quinolin-8-
yl) propanamide (I) are crystallized and its structures are shown
in Fig. 11. These structures are of very much interest in under-
standing selective anion binding by amide containing receptors de-
scribed earlier [26–28]. The solid state structure of these two
cations have differences in orientation of the amide group, in the
case of the bromide salt it lies in the plane of the quinoline ring
whereas in the case of the perchlorate salt it is perpendicular to
the quinoline plane. In both the cases the anions are coordinated
with the protonated quinoline nitrogen through intermolecular
hydrogen bonding. In case of the bromide salt (Fig. 11a) the anion
is also coordinated with the amide hydrogen whereas in case of the
perchlorate salt (Fig. 11b) the amide hydrogen is projected away
from the coordinated anion.
Fig. 11. Structure of: (a) bromide salt (Ia); (b) perchlorate salt (Ib) of protonated 2-
bromo-N-(quinolin-8-yl) propanamide (Drawn with 50% thermal ellipsoid).
two oppositely directional orientations. This is also reflected in the
crystal structure which is described in the next section. It is also to
be noted that the receptor VI shows enhancement of fluorescence
whereas in other cases quenching of fluorescence is observed. This
is attributed to the interaction of lone pairs of the isophthalate es-
ter groups in H-bonding to the amino acids making them unavail-
able for contributing to the fluorescence quenching of the
quinoline unit. Such phenomenon is already observed earlier in
crown ethers attached to fluorophores [29].
Since the molecules under consideration have quinoline unit,
which has properties of drugs; study of the properties of these
compounds in aqueous medium is necessary for finding out their
applications. The compounds are generally insoluble in water so
Receptor IV crystallizes in the triclinic space group P-1 and has
a bent structure as shown in Fig. 10b. The two quinoline rings lie
almost perpendicular to each other, the dihedral angle between
Fig. 12. (a) Short range interactions in IV, (b) ORTEP diagram of IV showing the asymmetric unit (drawn with 50% thermal ellipsoid), (c) dihedral angle between two planes
containing the quinoline rings in IV.

D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
193
Table 3
Table 4
Hydrogen bond parameters of IV.
Hydrogen bond parameters of IVa.
D–HÁ Á ÁA
dD–H (Å)
dHÁ Á ÁA (Å)
dDÁ Á ÁA (Å)
<D–HÁ Á ÁA(0)
D–HÁ Á ÁA
dD–H (Å)
dHÁ Á ÁA (Å)
dDÁ Á ÁA (Å)
<D–HÁ Á ÁA(0)
C(10)–H(10A)Á Á ÁO(2) [i]
C(10)–H(10B)Á Á ÁN1
0.97
0.97
2.51
2.63
3.4779(17)
3.327
174
138.6
N(1)–H(1N)Á Á ÁO(9) [i]
N(2)–H(2A)Á Á ÁO(7)
0.887(16) 1.748(16) 2.620(3)
167.2(19)
150
0.86
0.82
2.60
1.77
1.75
3.373(2)
2.5854(18) 172
2.554(2)
O(3)–H(3A)Á Á ÁO(5) [ii]
i = Àx, 1Ày, Àz.
O(8)–H(8A)Á Á ÁO(6) [iii] 0.82
166
O(9)–H(9A)Á Á ÁO(1) [iv] 0.841(17) 2.478(19) 2.983(2)
119(2)
168(2)
172(3)
172
O(9)–H(9A)Á Á ÁO(2) [v]
O(9)–H(9B)Á Á ÁO(6)
0.841(17) 1.867(18) 2.696(3)
0.83(2)
0.93
0.93
1.90(2)
2.52
2.48
2.729(2)
3.445(3)
3.223(3)
the two planes containing the two quinoline ring is found to be
83.15° (Fig. 12c). The self assembly of the bent structure is stabi-
lized by various weak interactions such as C–HÁ Á ÁO interactions
(C10–H10BÁÁÁO2) and C–HÁÁÁN interactions (C10–H10AÁÁÁN1). The
short range interactions in IV are shown in Fig. 12a. The hydrogen
bond parameters are tabulated in Table 3.
C(2)–H(2)Á Á ÁO(8) [vi]
C(4)–H(4)Á Á ÁO(4) [vii]
137
i = 1 À x, Ày, 1 À z; ii = À1 + x, y, z; iii = À1 + x, y, z; iv = 1 À x, Ày, 1 À z; v = 1 À x, Ày,
1 À z; vi = x, À1 + y, z; vii = Àx, Ày, Àz.
Receptor IV was also crystallized with two carboxylic acids viz,
fumaric acid (IVa) and maleic acid (IVb). The molecule IVa crystal-
lizes in the triclinic space group P-1 with one half molecule of fu-
maric acid, one molecule of fumarate anion and one molecule of
water in the asymmetric unit. It is observed that the orientation
of the two quinoline rings changes on inclusion of the guest mole-
cules thereby adopting an almost planar geometry. The dihedral
angle between the planes containing the two quinoline rings
changes to 4.9° as shown in Fig. 13a. Another interesting feature
of the structure is that one fumaric acid molecule remains in the
protonated form whereas the other molecule remains as an anion.
The protonated and the unprotonated fumaric acid molecule forms
a self assembly through intermolecular hydrogen bonding as
shown in Fig. 13b. The fumaric acid molecule lies on an inversion
centre with only half of the molecule contained in the crystallo-
graphic asymmetric unit, whereas in case of the deprotonated fu-
maric acid molecule, the entire molecule lies in the asymmetric
unit (Fig. 13c).
bonding (N1–H1NÁÁÁO9, O9–H9AÁÁÁO2 and O9–H9BÁÁÁO6). Fumaric
acid molecule and the fumarate anion forms a self assembly
through intermolecular hydrogen bonding (O8–H8AÁÁÁO6 and O3–
H3AÁÁÁO5) as shown in Fig. 13d. The hydrogen bond parameters
are tabulated in Table 4. From the Table 4 it can be inferred that
the amide nitrogen (N2) forms a relatively weak intermolecular
hydrogen bond with the oxygen atom (O7) of fumaric acid mole-
cule in comparison with the other hydrogen bonds involved in
the structure.
Unlike fumaric acid, maleic acid crystallises in a 1:1 ratio to
form a salt with receptor IV. The salt of maleic acid (IVb) crystallis-
es in the monoclinic space group P2(1)/n with one maleic acid an-
ion and one water molecule in its asymmetric unit (Fig. 14b). In
this case also it is found that the two quinoline rings lie almost
in the same plane, the dihedral angle between the two plans con-
taining the quinoline ring is found to be 1.9°. The receptor IV is
held together by a number of
p
Á Á Á
p interactions (dC12–C1, 3.358 Å;
dC16–C4, 3.361 Å; dC14–C6, 3.473 Å). The maleic acid anion is further
The water molecule is held between one fumaric acid molecule
and one molecule of receptor IV through intermolecular hydrogen
involved in a C–HÁÁÁO interaction (C3–H3ÁÁÁO7) with the receptor IV
and the water molecule is held by a strong hydrogen bond (N1–
Fig. 13. (a) Dihedral angle between two planes containing the quinoline rings in IVa, (b) the two different types of symmetry non-equivalent fumaric acid molecules, (c)
ORTEP diagram of the asymmetric unit of IVa showing the asymmetric unit (drawn with 50% thermal ellipsoid), (d) short range interactions present in IVa.

194
D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
Fig. 14. (a) Short range interactions in IVb, (b) ORTEP diagram of IVb showing the asymmetric unit (drawn with 50% thermal ellipsoid).
Table 6
Table 5
Hydrogen bond parameters of V.
Hydrogen bond parameters of IVb.
D–HÁ Á ÁA
dD–H (Å)
dHÁ Á ÁA (Å)
dDÁ Á ÁA (Å)
<D–HÁ Á ÁA(0)
D–HÁ Á ÁA
dD–H (Å)
dHÁ Á ÁA (Å)
dDÁ Á ÁA (Å)
<D–HÁ Á ÁA(0)
N(2)–H(2N)Á Á ÁO(5)
O(4)–H(4A)Á Á ÁO(2) [i]
O(4)–H(4B)Á Á ÁO(5)
O(5)–H(5A)Á Á ÁN(1)
O(5)–H(5B)Á Á ÁO(4) [ii]
0.87(3)
0.91(3)
0.82(4)
0.86(3)
0.88(4)
2.09(3)
1.97(3)
1.98(4)
1.91(3)
1.95(4)
2.899(2)
2.874(2)
2.794(2)
2.763(2)
2.813(2)
155.0(19)
170(2)
170(3)
173(3)
165(4)
N(1)–H(1N)Á Á ÁO(3) [i]
N(2)–H(2A)Á Á ÁO(5) [ii]
O(3)–H(3A)Á Á ÁO(5)
0.87(3)
0.86
0.82(2)
0.93
0.97
0.84(7)
1.81(2)
2.45
1.90(2)
2.55
2.43
1.77(7)
2.667(5)
3.242(5)
2.724(7)
3.203(7)
3.030(5)
2.458(8)
170(5)
153
178(7)
128
120
138(6)
C(3)–H(3)Á Á ÁO(7) [iii]
C(10)–H(10A)Á Á ÁO(5) [iv]
O(6)–H(6A)Á Á ÁO(4)
i = À1 + x, y, z; ii = 1 À x, 1 À y, Àz.
iI = 3/2 À x, À1/2 + y, 1/2 À z; ii = 1/2 + x, 1/2 À y, À1/2 + z; iii = 1/2 + x, À1/2 À y,
À1/2 + z; iv = 1/2 + x, 1/2Ày, À1/2 + z.
The crystal structures of two salts of IV with mineral acid
namely, perchloric acid and tetrafluroboric acid are already re-
ported [23]. By comparing with the structures of these salts it
can be inferred that the geometry the receptor IV changes in the
presence of guest.
H1NÁÁÁO3) with the protonated quinoline nitrogen (Fig. 14a). The
hydrogen bond parameters are given in Table 5. In this case also
it is observed that the amide nitrogen (N2) forms a relatively weak
hydrogen bond with the oxygen atom (O5) of the guest acid than
that of the other hydrogen bonds involved in the structure.
The receptor V crystallises in the triclinic space group P-1 with
two molecules of water in its asymmetric unit (Fig. 15b). Four
Fig. 15. (a) Short range interactions in V, (b) ORTEP diagram of V showing the asymmetric unit (drawn with 50% thermal ellipsoid), (c) dihedral angle between two planes
containing the quinoline ring and the phenyl ring in V.

D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
195
Fig. 16. (a) Short range interactions in Va, (b) ORTEP diagram of Va showing the asymmetric unit (drawn with 50% thermal ellipsoid), (c) dihedral angle between two planes
containing the quinoline ring and the phenyl ring in Va.
Table 7
water molecules are held together in between two host molecules
Hydrogen bond parameters of Va.
by hydrogen bonds (O4–H4AÁÁÁO2, N2H2NÁÁÁO5, and O5–H5AÁÁÁN1)
as shown in Fig. 15a. The hydrogen bond parameters are tabulated
in Table 6. It is found that the quinoline ring and the phenyl ring
lies in two different planes having dihedral angle 35.2° as shown
in Fig. 15c.
D–HÁ Á ÁA
dD–H (Å)
dHÁ Á ÁA (Å)
dDÁ Á ÁA (Å)
<D–HÁ Á ÁA(0)
N(1)–H(1N)Á Á ÁO(4) [i]
N(2)–H(2N)Á Á ÁO(4) [ii]
O(6)–H(6A)Á Á ÁO(5)
1.03(3)
0.85(3)
0.84(3)
0.93
0.93
0.97
1.73(3)
2.11(3)
1.63(2)
2.40
2.38
2.59
2.729(4)
2.915(4)
2.461(4)
3.138(4)
3.296(4)
3.258(4)
163(3)
157(2)
169(3)
136
170
126
C(2)–H(2)Á Á ÁO(5) [iii]
C(8)–H(8)Á Á ÁO(2) [iv]
C(10)–H(10B)Á Á ÁO(2) [v]
The receptor V was then crystallised with two isomeric dicar-
boxylic acids namely, maleic acid and fumaric acid. In this case
we have observed a 1:1 salt with maleic acid (Va) and a 1:2 co-
crystal with fumaric acid (Vb).
i = x, 1 + y, z; ii = x, 1 + y, z; iii = x, 1 + y, z; iv = 1 À x, Ày, Àz; v = 1 À x, 1 À y, Àz.
Fig. 17. (a) Hydrogen bonded structure of Vb showing encapsulation of one fumaric acid molecule by two molecules of receptor V, (b) ORTEP diagram of Vb showing the
asymmetric unit (drawn with 50% thermal ellipsoid) (c) dihedral angle between two planes containing the quinoline ring and the phenyl ring in Vb.

196
D. Kalita et al. / Journal of Molecular Structure 990 (2011) 183–196
Table 8
bond of the acids; this is in accordance with earlier studies in re-
lated systems [23].
Hydrogen bond parameters of Vb.
D–HÁ Á ÁA
dD–H (Å)
dHÁ Á ÁA (Å)
dDÁ Á ÁA (Å)
<D–HÁ Á ÁA(0)
Supplementary material
N(2)–H(2A)Á Á ÁO(4) [i]
O(4)–H(4A)Á Á ÁN(1) [ii]
0.86
0.82
2.22
1.84
3.052(6)
2.651(5)
163
171
The CIF of compounds are deposited to Cambridge Crystallo-
graphic Database and has the CCDC Nos. 790477-790482,
781136-781137.
i = x, 3/2 À y, À1/2 + z; ii = x, 3/2 À y, 1/2 + z.
The salt Va crystallises in the monoclinic space group P2(1)/n.
The protonated quinoline nitrogen atom forms a hydrogen bond
with the oxygen atom of maleic acid anion (N1–H1NÁÁÁO4). The
maleic acid anion is further involved in various types of weak
interactions (Fig. 16a) such as C–HÁÁÁO interaction (C2–H2ÁÁÁO5),
and hydrogen bonding interaction (N2–H2NÁÁÁO4). The hydrogen
bond parameters are tabulated in Table 7. In the structure of Va
it is observed that the orientation of the two aromatic rings
changes on inclusion of the guest molecule and the dihedral angle
between the two planes containing the rings is found to be 18.5°
(Fig. 16c). This change in orientation is favoured by the presence
Acknowledgements
The authors thank Department of Science and Technology New-
Delhi, India for financial support. The author D.K. thanks Council of
Scientific and Industrial Research, New Delhi, India for a Senior Re-
search fellowship.
References
[1] J. Mao, H. Yuan, Y. Wang, B. Wan, M. Pieroni, Q. Huang, R.B. van Breemen, A.P.
Kozikowski, S.G. Franzblau, J. Med. Chem. 52 (2009) 6966.
[2] P.R. Verhoest, D.S. Chapin, M. Corman, K. Fonseca, J.F. Harms, X. Hou, E.S. Marr,
F.S. Menniti, F. Nelson, R. O’Connor, J. Pandit, C.P. LaFrance, A.W. Schmidt, C.J.
Schmidt, J.A. Suiciak, S. Liras, J. Med. Chem. 52 (2009) 5188.
[3] G.X. Li, Z.Q. Liu, X.Y. Luo, Eur. J. Med. Chem. 45 (2010) 1821.
[4] H. Zeng, R. Cao, H. Zhang, Chem. Biol. Drug Des. 74 (2009) 596.
[5] E. Milner, W. McCalmont, J. Bhonsle, D. Caridha, D. Carroll, S. Gardner, L.
Gerena, M. Gettayacamin, C. Lanteri, T. Luong, V. Melendez, J. Moon, N. Roncal,
J. Sousa, A. Tungtaeng, P. Wipf, G. Dow, Bioorg. Med. Chem. Lett. 20 (2010)
1347.
[6] I. Deb, P. Paira, A. Hazra, S. Banerjee, P.K. Dutta, N.B. Mondal, S. Das, Bioorg.
Med. Chem. 17 (2009) 5782.
[7] M. Albrecht, Triyanti, S. Schiffers, O. Osetska, G. Raabe, T. Wieland, L. Russo,
Kari Rissanen, Eur. J. Org. Chem. (2007) 2850.
[8] S.F. Alshahateet, R. Bishop, D.C. Craig, F. Kooli, M.L. Scudder, CrystEngComm 10
(2008) 297.
[9] R.F. Semeniuc, T.J. Reamer, M.D. Smith, New J. Chem. 34 (2010) 439.
[10] A. Karmakar, R.J. Sarma, J.B. Baruah, CrystEngComm 9 (2007) 379.
[11] Y. Liu, K. Chen, D.S. Guo, Q. Li, H.B. Song, Cryst. Growth Des. 7 (2007) 2601.
[12] C.R. Bondy, P.A. Gale, S.J. Loeb, J. Am. Chem. Soc. 126 (2004) 5030.
[13] M.H. Filby, J.W. Steed, Coord. Chem. Rev. 250 (2006) 3200.
[14] A. Karmakar, J.B. Baruah, Supramol. Chem. 20 (2008) 667.
[15] A. Karmakar, R.J. Sarma, J.B. Baruah, CrystEngComm 9 (2007) 378.
[16] I. Tabushi, Y. Kuroda, T. Mizutani, J. Am. Chem. Soc. 108 (1986) 4514.
[17] A. Galan, D. Andreu, A.M. Echavarren, P. Prados, J. de Mendoza, J. Am. Chem.
Soc. 114 (1992) 1512.
[18] Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N.
Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 117 (1995) 10950.
[19] A. Metzger, K. Gloe, H. Stephan, F.P. Schmidtchen, J. Org. Chem. 61 (1996)
2051.
[20] G. Arena, A. Casnati, A. Contino, A. Magr, F. Sansone, D. Sciotto, R. Ungaro, Org.
Biomol. Chem. 4 (2006) 243.
[21] I. Nicolas, S. Chevance, P.L. Maux, G. Simonneaux, Tetrahedron Asymmetry 21
(2010) 1788.
[22] J.W. Steed, J.L. Atwood (Eds.), Supramolecular Chemistry, John Wiley, New-
York, 2000.
[23] D. Kalita, J.B. Baruah, CrystEngComm 12 (2010) 1562.
[24] J.C.S. da Costa, K.C. Pais, E.L. Fernandes, P.S.M. de Oliveira, J.S. Mendonça,
M.V.N. de Souza, M.A. Peralta, T.R.A. Vasconcelos, ARKIVOC (2006) 128.
[25] D. Kalita, J.B. Baruah, J. Mol. Struct. 969 (2010) 75.
[26] S.A. de Silva, A. Zavaleta, D.E. Baron, O. Allam, E.V. Isidor, N. Kasbimura, J.M.
Percarpio, Tetrahedron Lett. 38 (1997) 2237.
the ethylene spacer that involved in a C–HÁÁÁ
p interaction with
the maleic acid anion (C12–H12ÁÁÁC22).
The receptor V crystallises with fumaric acid leading to a 1:2 co-
crystal (Vb) where one molecule of fumaric acid is held between
two molecules of receptor V (Fig. 15a). The co-crystal Vb crystallis-
es in monoclinic space group P2(1)/c, the fumaric acid molecule
lies on an inversion centre with only half of the molecule contained
in the crystallographic asymmetric unit (Fig. 17b). The fumaric acid
molecule is held by intermolecular hydrogen bonding with recep-
tor V (O4–H4AÁÁÁN1 and N2–H2NÁÁÁO4) as shown in Fig. 17a. The
hydrogen bond parameters are tabulated in Table 8. From the Table
8 it is observed that the fumaric acid molecule forms a much stron-
ger hydrogen bond with the quinoline nitrogen (N1) in comparison
with the amide nitrogen (N2). In this case also it is found that the
geometry of the two aromatic ring changes with the inclusion of
the guest molecule, the dihedral angle between the two planes
containing the rings is found to be 25.4° (Fig. 17c).
4. Conclusions
The non-planar geometry of the quinoline containing receptors,
facilitates binding to anions; thereby enhances the interactions of
such receptors with acids. The high affinity of N-(quinolin-8-yl)-
2-(quinolin-8-yloxy)propanamide for amino acids is due to such
effect. Poor affinity of N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acet-
amide towards binding with amino acids, is related to the higher
flexibility on the orientation of the quinoline ring. Based on the
results of preferential binding of amino acid over hydroxy acids
by receptor VI it may be stated that the overall preorganised struc-
ture of this receptor to have weak interactions with the corre-
sponding anion of acid plays an important role in recognition of
different acids. The structure of the self assemblies in the cases
of fumaric acid and maleic acid with the amide functionalized
quinoline receptors are guided by the geometry around the double
[27] S.Y. Liu, K.Y. Law, Y.B. Hea, W.H. Chan, Tetrahedron Lett. 47 (2006) 7857.
[28] A. Filippi, F. Gasparrini, M. Pierini, M. Speranza, C. Villani, J. Am. Chem. Soc. 127
(2005) 11912.
[29] S.O. Kang, R.A. Begum, K.B. James, Angew. Chem. Int. Ed. 45 (2006) 7882.