Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques

Article abstract of DOI:10.1016/j.cplett.2016.05.031

Molecular assemblies of β-cyclodextrin with few of the most important neurotransmitters, viz., dopamine hydrochloride, tyramine hydrochloride and (±)-epinephrine hydrochloride in aqueous medium have been explored by reliable spectroscopic and physicochemical techniques as potential drug delivery systems. Job plots confirm the 1:1 host-guest inclusion complexes, while surface tension and conductivity studies illustrate the inclusion process. The inclusion complexes were characterized by ¹H NMR spectroscopy and association constants have been calculated by using Benesi-Hildebrand method. Thermodynamic parameters for the formation of inclusion complexes have been derived by van't Hoff equation, which demonstrate that the overall inclusion processes are thermodynamically favorable.

Full text of DOI:10.1016/j.cplett.2016.05.031

Chemical Physics Letters 655-656 (2016) 43–50
Contents lists available at ScienceDirect
Chemical Physics Letters
journal homepage: www.elsevier.com/locate/cplett
Research paper
Exploration of inclusion complexes of neurotransmitters
with b-cyclodextrin by physicochemical techniques
⇑
Mahendra Nath Roy , Subhadeep Saha, Mitali Kundu, Binoy Chandra Saha, Siti Barman
Department of Chemistry, University of North Bengal, Darjeeling 734013, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Molecular assemblies of b-cyclodextrin with few of the most important neurotransmitters, viz., dopamine
hydrochloride, tyramine hydrochloride and (±)-epinephrine hydrochloride in aqueous medium have been
explored by reliable spectroscopic and physicochemical techniques as potential drug delivery systems.
Job plots confirm the 1:1 host–guest inclusion complexes, while surface tension and conductivity studies
Received 23 April 2016
Revised 14 May 2016
In final form 15 May 2016
Available online 17 May 2016
1
illustrate the inclusion process. The inclusion complexes were characterized by H NMR spectroscopy and
association constants have been calculated by using Benesi–Hildebrand method. Thermodynamic param-
eters for the formation of inclusion complexes have been derived by van’t Hoff equation, which demon-
strate that the overall inclusion processes are thermodynamically favorable.
Ó 2016 Elsevier B.V. All rights reserved.
Chemical compounds studied in this article:
b-Cyclodextrin (PubChem CID: 444041)
Dopamine hydrochloride (PubChem CID:
6
5340)
Tyramine hydrochloride (PubChem CID:
6449)
±)-Epinephrine hydrochloride (PubChem
6
(
CID: 441411)
Keywords:
Inclusion complex
b-Cyclodextrin
Neurotransmitter
1
. Introduction
[7,8]. If a drug is hydrophilic, the dissolved drug molecule will not
penetrate from the aqueous exterior into
a lipophilic bio-
Molecular recognition is of profound importance in biology and
membrane. The use of b-CD on drug solubility, bioavailability,
safety, stability and as a carrier in drug formulation may be
achieved by formation of inclusion complexes with drug mole-
cules; in fact, the use of b-CD already has a long history in phar-
macy [9–11].
Dopamine is an important neurotransmitter (NT) in the mam-
malian central nervous system and is a member of catecholamines
[12,13]. It is involved in neuropsychiatric disorders such as Perkin-
son’s disease, which is the second most common central nervous
system disorder [14,15]. Tyramine is also a NT and acts as a cate-
cholamine releasing agent, having nonpsychoactive peripheral
sympathomimetic effects [16]. Epinephrine is a hormone and a
NT, serves as chemical mediators for conveying the nerve impulses
to effectors organs [17]. Epinephrine remains a useful medicine for
several emergency indications and is used as a drug to treat cardiac
arrest and other cardiac dysrhythmias [18,19].
therapeutics, the physical chemistry of this phenomenon acknowl-
edges that binding is often associated with loss in configurational
entropy, but the overall thermodynamics is yet to be well under-
stood [1,2]. The cyclodextrins (CDs) are of particular interest in this
regard. Among various approaches CDs have contributed a lot to
this aspect of drug delivery, because of having fairly rigid and
well-defined hydrophobic cavities and hydrophilic outer surfaces,
they can act as molecular receptors (hosts) for a wide variety of
organic and inorganic, as well as biological and pharmaceutical
guest molecules, forming host–guest complexes or supramolecular
assemblies [3,4]. The cavity size of b-cyclodextrin (b-CD) is more
appropriate than other CDs to encapsulate a great variety of mole-
cules [5,6]. The drugs, to be pharmacologically active, must possess
some degree of aqueous solubility, as well as they should be lipo-
philic to permeate the biological membranes via passive diffusion
Few previous workers demonstrated interactions between sim-
ilar guest molecules and CD [20,21]. Pardave et al. demonstrated
electrochemical and spectrophotometric studies of interaction
⇑
Corresponding author.
E-mail address: mahendraroy2002@yahoo.co.in (M.N. Roy).
http://dx.doi.org/10.1016/j.cplett.2016.05.031
009-2614/Ó 2016 Elsevier B.V. All rights reserved.
0

4
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M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
between dopamine and b-CD, whereas, Rajendiran et al. showed
interaction between epinephrine and CD [22–24]. In the present
article formation of inclusion complexes of three NTs, e.g., dopa-
mine hydrochloride (DH), tyramine hydrochloride (TH) and (±)-
epinephrine hydrochloride (EH) with b-CD (Scheme 1) have been
explored by UV–Vis spectroscopy, surface tension, conductivity
fraction of the NTs in the range 0–1 (Tables S1–S3, supporting
information) [26,27]. Absorbance values were measured at respec-
tive kmax for a series of solutions at 298.15 K. The value of R at the
maximum deviation provides the stoichiometry of the inclusion
complex (IC) (e.g., R = 0.5 for 1:1 complexes; R = 0.33 for 1:2 com-
plexes; R = 0.66 for 2:1 complexes, etc.). Here, for each of the three
plots maxima were found at R = 0.5, which clearly indicate 1:1 sto-
ichiometry between the host and the guest (Fig. 1).
1
and H NMR study. Associated thermodynamic parameters have
also been evaluated to communicate a quantitative idea about
encapsulation of the above NTs while complexed with b-CD.
2.2. Surface tension study explains the inclusion as well as
2
. Result and discussion
stoichiometric ratio of the inclusion complexes
2.1. Job plot demonstrates the stoichiometry of the host–guest
Surface tension (c) measurement provides significant indication
assembly
about formation of IC as well as stoichiometry of the host–guest
assembly [28–30]. b-CD, because of having lipophilic outer surface
Job’s method of continuous variation was applied to recognize
the stoichiometry of the host–guest assembly by using UV–visible
spectroscopy [25]. Job plots were generated by plotting
A ꢀ R vs
R, where A is the difference in absorbance of NTs with and
without b-CD and R = [NT]/([NT] + [CD]), through varying the mole
and hydrophilic rims, does not show any change in
c while
dissolved in aqueous medium in considerable range of
a
D
concentration [31,32]. In the present work all the three guest NTs
have a common feature in their structures, i.e., they have a
hydrophobic –CH –CH –Ph [–CH –CH(OH)–Ph for EH] group and
2 2 2
D
Scheme 1. Molecular structure of the three neurotransmitters and b-cyclodextrin.
0.08
0.06
0.04
0.02
0.00
0.03
0.05
0.04
0.03
0.02
0.01
0
.02
.01
0
0.00
0.00
0.00
0.50
1.00
1.50
0.00
0.50
1.00
1.50
0.00
0.50
1.00
1.50
R
R
R
(
a)
(b)
(c)
Fig. 1. Job plot of different neurotransmitter-b-CD systems at 298.15 K. (a) Dopamine hydrochloride at kmax = 278 nm, (b) tyramine hydrochloride at kmax = 275 nm and (c)
±)-epinephrine hydrochloride at kmax = 278 nm. R = [NT]/([NT] + [b-CD]), A = absorbance difference of the NTs without and with b-CD.
(
D

M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
45
a terminal –NH+
them surfactant like activities, thus
of the NTs are found to be lower than that of pure water. Here
[–NH+
– for EH] group (Scheme 1), which make
of aqueous solutions of each
of
3
2
c
c
aqueous NTs has been measured with increasing concentration of
b-CD at 298.15 K (Tables S4–S6). DH, TH and EH showed increasing
trend of
c with increasing concentration of b-CD (Fig. 2) may be
because of removal of the NT molecules (surface active) from the
surface of the solution into the hydrophobic cavity of b-CD forming
host–guest inclusion complexes (Scheme 2).
Each plot also indicates that there is a break point at certain
concentrations after which the slops become less. Finding of break
point in surface tension curve not only indicates formation of IC
but also provides information about its stoichiometry, i.e., appear-
ance of single, double and so on break point in the plot indicates
1
:1, 1:2 and so on stoichiometry of host:guest ICs (Scheme 3) [33].
The values of and corresponding concentrations of b-CD at
c
each break have been listed in Table 1 and the overall variation
have been listed in Tables S4–S6, which clearly point out that the
breaks have been found at certain concentrations of NTs and b-
CD where their concentration ratio in the solution was almost
1
:1. Hence this study proves formation of 1:1 ICs between NTs
and b-CD.
2.3. Conductivity study illustrates inclusion process and their
stoichiometric ratio
Conductivity (
sured to get clue whether ICs have been formed while b-CD being
added to it [34,35]. The studied NTs show considerable because
of having their charged structures. As b-CD was added to the aque-
ous solution of a NT (Tables S7–S9), the was observed to show
j) of aqueous solutions of the NTs has been mea-
j
j
decreasing trend probably because of encapsulation of the NT
molecules inside into the cavity of b-CD (Scheme 2). After a certain
concentration of b-CD a break was found in each of the conductiv-
Scheme 2. Formation of inclusion complexes of (a) dopamine hydrochloride, (b)
tyramine hydrochloride and (c) (±)-epinephrine hydrochloride with b-CD.
ity curves (Fig. 3), indicating the formation of ICs. The values of
j
and corresponding concentrations of b-CD at each break have been
shown in Table 1, which reveal that the ratio of the concentrations
of a NT and b-CD at the break point was found to be approximately
1
2
.4. H NMR study confirms inclusion phenomenon
Insertion of any guest molecule into the hydrophobic cavity of
1
:1, suggesting the host–guest ratio to be 1:1.
b-CD consequences in the chemical shift of the guest and b-CD in
the NMR spectra, which is because of the interaction of the b-CD
with the guest molecule [27].
In case of aromatic guest molecules the spectral changes that
can be observed upon inclusion is the diamagnetic shielding of
the aromatic moiety with the interacting atoms of b-CD [33]. In
the structure of b-CD the H3 and H5 hydrogens are situated inside
The break point is found at certain concentration where maxi-
mum inclusion takes place ever before, i.e., though there is a
dynamic equilibrium between the host and the guest, most of
the guest molecules are encapsulated at the break point (1:1 M
ratio of host & guest), beyond this point concentration of b-CD is
higher than that of NT, thus shifting the equilibrium more toward
the IC.
72
71
70
69
68
67
66
65
64
72
71
70
69
68
67
66
65
64
72
71
70
69
68
67
66
65
64
0
1
2
3
4
5
6
7
0
1
2
3
4
5
6
7
0
1
2
3
4
5
6
7
β-CD (mM)
a)
β-CD (mM)
β-CD (mM)
(
(b)
(c)
Fig. 2. Variation of surface tension of aqueous (a) dopamine hydrochloride solution, (b) tyramine hydrochloride solution and (c) (±)-epinephrine hydrochloride solution
respectively with increasing concentration of b-cyclodextrin at 298.15 K.

4
6
M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
environment of the chromophore of the NTs when it goes from
the polar aqueous environment to the apolar cavity of b-CD [38].
Changes in absorption intensity
AÞ of DH (278 nm), TH
275 nm) and EH (278 nm) were studied as a function of concen-
tration of b-CD to determine the value of K (Tables S11 and
ð
D
(
a
S12). The double reciprocal plots have been drawn on the basis
of reliable Benesi–Hildebrand method for 1:1 host–guest ICs
(
Fig. S1, Eq. (1)) [27,39].
1
1
1
1
½NTꢁ
¼
ꢂ
þ
ð1Þ
D
A
D
e
½NTꢁK
a
½bCDꢁ
D
e
a
The values of K for each of the ICs were evaluated by dividing
the intercept by the slope of the straight line of the double recipro-
cal plot (Table 2) [40].
Scheme 3. Different possibilities of host–guest ratio for inclusion complex.
Various thermodynamic parameters for the formation of ICs can
the conical cavity, particularly, the H3 are placed near the wider
rim while H5 are placed near the narrower rim, the other H1, H2
and H4 hydrogens are located at the exterior of the b-CD molecule
easily be derived basing upon the values of K
method with the help of van’t Hoff equation (Eq. (2)).
a
found by the above
o
o
D
H
DS
R
(
Scheme 4) [36,37]. In the present article the molecular interac-
ln K
a
¼ ꢃ
þ
ð2Þ
1
RT
tions have been studied with the help of H NMR spectra. The sig-
nals of interior H3 and H5 of b-CD as well as that of the interacting
aromatic protons of the NTs showed considerable upfield shift in
There is a linear relationship between lnK and 1/T in the above
a
equation (Fig. S2), on the basis of which the thermodynamic
1
o
o
o
H NMR spectra of 1:1 mixture of b-CD and each NT, confirming
parameters
obtained (Table S13) [41].
However, the above study has been performed in a short range
DH , DS and DG for the formation of ICs may be
the ICs were formed (Figs. 4–6). As found from the chemical shifts,
interaction of the H3 with the aromatic guest was much higher
than that of the H5, proving the guest entered through the wider
rim of b-CD (Scheme 5).
o
o
of temperature in which
DH and DS are considered to be non
variable. Non-linear methods may be used for studies in wide
o
range of temperatures. The magnitude of
DH depends on the equi-
2
.5. Association constants and thermodynamic parameters
librium constant of the inclusion complex at different tempera-
tures and thus may have limitation compared to direct
calorimetric methods [42]. On the other hand, in this study ther-
Association constants (K
a
) have been calculated for various NT-
b-CD ICs by UV–visible spectroscopy as a result of changes in molar
modynamic parameters have been calculated from K
which in turn were determined from of the NTs, which is owing
to the changes in the environment of the chromophore of the NTs
a
values,
extinction coefficient ð
De
Þ of the NTs when complexed with b-CD
De
molecule, which is owing to the changes in the polarity of the
Table 1
Values of surface tension (
c
) and conductivity (j
) at the break point with corresponding concentration of aqueous b-cyclodextrin at 298.15 K.a
Dopamine hydrochloride
Tyramine hydrochloride
(±)-Epinephrine hydrochloride
Surface tension
Conc (mM)
ꢃ1
ꢃ1
ꢃ1
ꢃ1
c
(mN m
)
Conc (mM)
4.89
c
(mN m
)
Conc (mM)
4.96
c
(mN m
)
4
.83
71.37
71.47
71.28
Conductivity
Conc (mM)
ꢃ1
ꢃ1
j
0.426
(mS m
)
Conc (mM)
4.85
j
0.417
(mS m
)
Conc (mM)
4.90
j
0.406
(mS m
)
4
.90
a
ꢃ1
ꢃ1
Standard uncertainties (u): temperature: u(T) = ± 0.01 K, surface tension: u(
c
) = ±0.1 mN m , conductivity: u(
j
) = ± 0.001 mS m
.
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0
1
2
3
4
5
6
7
0
1
2
3
4
5
6
7
0
1
2
3
4
5
6
7
β-CD (mM)
a)
β-CD (mM)
β-CD (mM)
(
(b)
(c)
Fig. 3. Variation of conductivity of aqueous (a) dopamine hydrochloride solution, (b) tyramine hydrochloride solution and (c) (±)-epinephrine hydrochloride solution
respectively with increasing concentration of b-cyclodextrin at 298.15 K.

M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
47
OH
H4
H1
H2
H4
H2
CH 6
2
O
HO
HO
H6
C
O
H1
OH
H5
HO
H3
H5
H6
OH
H3
O
7
Scheme 4. (a) Stereo-chemical configuration of b-cyclodextrin, (b) truncated conical structure of b-cyclodextrin with interior and exterior protons.
Fig. 4. 1H NMR spectra of (a) b-CD, (b) dopamine hydrochloride and (c) 1:1 M ratio of b-CD & dopamine hydrochloride in D
O at 298.15 K.
2
when it goes from the polar aqueous environment to the apolar
formation, but this effect is overcome by higher negative value of
o
o
o
cavity of b-CD. Hence, the
D
H and
D
S values presented here are
D
H , making the overall inclusion process thermodynamically
favorable.
The data shown in Table 2 indicate that order of K
exclusively for the formation of inclusion complex, not for the
other solvent interactions taking place in the medium.
a
for ICs with
DG is EH > DH > TH. This may be explained
o
o
The values of
D
G for the formation of ICs were found negative
b-CD and the order of ꢃ
suggesting that the inclusion process proceeds spontaneously,
on account of the difference in the structures of three NTs, which
have almost similar hydrophobic moiety, but EH can form
H-bonds at both rims of b-CD because of having two phenolic
and one alcoholic –OH groups, thus, it forms strongest IC among
the three. Similarly, the results for DH and TH may be explained
because of having two and one –OH groups in their structures
respectively.
o
o
whereas negative values of
DH and DS indicate that the inclusion
process is exothermic and entropy controlled, but not entropy dri-
ven (Table 2). These consequences may be explained on the basis of
molecular association that was taking place while IC was being
formed between b-CD and each NT, resulting in a drop of entropy,
which is unfavorable for the spontaneity of the inclusion complex

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8
M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
Fig. 5. 1H NMR spectra of (a) b-CD, (b) tyramine hydrochloride and (c) 1:1 M ratio of b-CD & tyramine hydrochloride in D
O at 298.15 K.
2
ꢃ6
ꢃ1
3
. Conclusion
(with a specific conductance of 1 ꢀ 10 S cm ) and observed
that the selected neurotransmitters were freely soluble in all pro-
portion of aqueous b-cyclodextrin. All the stock solutions of the
neurotransmitters were prepared by mass (weighed by Mettler
Toledo AG-285 with uncertainty 0.0003g), and then the working
solutions were obtained by mass dilution at 298.15 K. Sufficient
precautions were made to decrease evaporation losses during
mixing.
Molecular recognition of the three important NTs by b-CD has
been shown, which may find its use as potential drug delivery system
in pharmacological science. The molecular assemblies, i.e., formation
of ICs have been explained qualitatively as well as quantitatively so as
to make it dependable in its field of application. b-CD has long been
used as a carrier for its unique structural features, which is further
explored in the present work, confirming that b-CD forms 1:1 ICs
with DH, TH and EH, established by reliable physicochemical tech-
niques. The association constants are found highest for EH, then DH
and then TH for the ICs with b-CD. Hence, this exclusive study
describes that the ICs in aqueous medium can be used as controlled
delivery systems in the field of modern biomedical sciences.
UV–visible spectra were recorded by JASCO V-530 UV/VIS Spec-
trophotometer, with an uncertainty of wavelength resolution of
±2 nm. The measuring temperature was held constant by an auto-
mated digital thermostat.
Surface tensions of the solutions were determined by platinum
ring detachment technique using a Tensiometer (K9, KR U} SS;
ꢃ1
Germany) at 298.15 K. Accuracy of the study was ±0.1 mN m
.
4
. Experimental section
Temperature of the system was maintained by circulating ther-
mostated water through a double-wall glass vessel holding the
solution.
4.1. Source and purity of samples
Conductivities of the solutions were studied by Mettler Toledo
ꢃ1
Dopamine hydrochloride, Tyramine hydrochloride, (±)-
Seven Multi conductivity meter having uncertainty 1.0
lS m
.
Epinephrine hydrochloride and b-cyclodextrin of puriss grade were
purchased from Sigma–Aldrich, Germany and used as it was. The
mass fraction purity of Dopamine hydrochloride, Tyramine
hydrochloride, (±)-Epinephrine hydrochloride and b-cyclodextrin
were ꢄ1.00, P0.98, ꢄ1.00 and P0.98 respectively.
The study was carried out in a thermostated water bath at
298.15 K with uncertainty ±0.01 K. HPLC grade water was used
ꢃ1
with specific conductance 6.0
l
S m . The conductivity cell was
calibrated using 0.01 M aqueous KCl solution.
1
NMR spectra were recorded in D O unless otherwise stated. H
2
NMR spectra were recorded at 400 MHz and 500 MHz using Bruker
ADVANCE 400 MHz and Bruker ADVANCE 500 MHz instruments
respectively. Signals are quoted as d values in ppm using residual
4.2. Apparatus and procedure
Solubility of b-cyclodextrin and chosen neurotransmitters have
been precisely checked in triply distilled and degassed water
protonated solvent signals as internal standard (D
4.79 ppm). Data are reported as chemical shift.
2
O:
d

M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
49
Fig. 6. 1H NMR spectra of (a) b-CD, (b) (±)-epinephrine hydrochloride and (c) 1:1 M ratio of b-CD & (±)-epinephrine hydrochloride in D
2
O at 298.15 K.
1
4
.3. H NMR data
restricted inclusion
through narrower rim
b-Cyclodextrin: 1H NMR (400 MHz, D
O): d = 3.49–3.54 (6H, t,
2
J = 9.2 Hz), 3.57–3.60 (6H, dd, J = 9.6, 3.2 Hz), 3.79–3.84 (18H, m),
.87–3.92 (6H, t, J = 9.2 Hz), 5.00–5.01 (6H, d, J = 3.6 Hz).
3
1
Dopamine hydrochloride: H NMR (400 MHz, D
2
O): d = 2.15
(
–NH ), 2.78–2.81 (2H, t, J = 7.2 Hz), 3.13–3.16 (2H, t, J = 7.2 Hz),
2
feasible inclusion
through wider rim
6.66–6.69 (1H, dd, J = 8.0, 1.6 Hz), 6.76–6.77 (1H, d, J = 2 Hz),
6.81–6.83 (1H, d, J = 8.4 Hz).
Tyramine hydrochloride: 1H NMR (400 MHz, D
O): d = 2.14
), 2.82–2.86 (2H, t, J = 7.2 Hz), 3.14–3.17 (2H, t, J = 7.2 Hz),
.81–6.83 (2H, dd, J = 6.8, 2.0 Hz), 7.12–7.14 (2H, d, J = 8.8 Hz).
2
(
6
–NH
2
Scheme 5. Feasible and restricted inclusion of the guest into the host molecule.
Table 2
Association constant (K
o
So and
Go of different neurotransmitter-b-cyclodextrin inclusion complexes.
a
) and thermodynamic parameters
D
H ,
D
D
Temp (K)a
K
a
ꢀ 10ꢃ3 (M )b
ꢃ1
D
Ho (kJ mol )b
ꢃ1
D
So (J mol
ꢃ1 ꢃ1b
K
D
Go (298.15 K) (kJ mol )b
ꢃ1
Dopamine hydrochloride + b-CD
Tyramine hydrochloride + b-CD
293.15
1.48
1.31
1.13
ꢃ19.80
ꢃ18.37
ꢃ20.30
ꢃ6.83
ꢃ3.38
ꢃ7.94
ꢃ17.77
ꢃ17.36
ꢃ17.93
2
3
98.15
03.15
293.15
1.24
1.11
0.97
2
3
98.15
03.15
(
±)-Epinephrine hydrochloride + b-CD
293.15
1.59
1.40
1.21
2
3
98.15
03.15
a
Standard uncertainties in temperature u are: u(T) = ±0.01 K.
b
ꢃ3
ꢃ1
o
ꢃ1
So = ±0.01 J mol
ꢃ1 ꢃ1
Go = ± 0.01 kJ molꢃ1
.
Mean errors in K
a
= ±0.02 ꢀ 10
M
;
D
H
= ± 0.01 kJ mol
;
D
K
;
D

5
0
M.N. Roy et al. / Chemical Physics Letters 655-656 (2016) 43–50
1
(
±)-Epinephrine hydrochloride: H NMR (400 MHz, D
NH), 2.68 (3H, s), 3.18–3.20 (2H, d, J = 6.4 Hz), 4.81–4.84 (1H, t,
J = 6.4 Hz), 6.77–6.79 (1H, d, J = 8.4 Hz), 6.85–6.87 (2H, m).
2
O): d = 2.14
[5] J. Szejtli, Chem. Rev. 98 (1998) 1743–1753.
[
6] F.B.D. Sousa, A.C. Lima, A.M.L. Denadai, C.P.A. Anconi, W.B.D. Almeida, W.T.G.
Novato, H.F.D. Santos, C.L. Drum, R. Langer, R.D. Sinisterra, Phys. Chem. Chem.
Phys. 14 (2012) 1934–1944.
(
1
b-CD + DH: H NMR (500 MHz, D
J = 7.2 Hz), 3.01 (–NH ), 3.12–3.15 (2H, t, J = 7.2 Hz), 3.45–3.50
6H, t, J = 9.2 Hz), 3.53–3.56 (6H, dd, J = 9.6, 3.2 Hz), 3.59–3.64
6H, t, J = 9.2 Hz), 3.69–3.77 (18H, m), 4.96–4.97 (6H, d,
J = 3.6 Hz), 6.48–6.51 (1H, dd, J = 8.0, 1.6 Hz), 6.56–6.57 (1H, d,
J = 2 Hz), 6.64–6.66 (1H, d, J = 8.4 Hz).
b-CD + TH: H NMR (400 MHz, D
2H, t, J = 7.2 Hz), 3.13–3.16 (2H, t, J = 7.2 Hz), 3.46–3.51 (6H, t,
J = 9.2 Hz), 3.54–3.57 (6H, dd, J = 9.6, 3.2 Hz), 3.62–3.68 (6H, t,
J = 9.2 Hz), 3.71–3.79 (18H, m), 4.96–4.97 (6H, d, J = 3.6 Hz),
.80–6.82 (2H, dd, J = 6.8, 2.0 Hz), 7.07–7.09 (2H, d, J = 8.8 Hz).
2
O): d = 2.77–2.80 (2H, t,
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[
[
[
(
6
1
b-CD + EH: H NMR (500 MHz, D
.17–3.19 (2H, d, J = 6.4 Hz), 3.44–3.49 (6H, t, J = 9.2 Hz), 3.52–3.56
2
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3
(
(
6H, dd, J = 9.6, 3.2 Hz), 3.57–3.63 (6H, t, J = 9.2 Hz), 3.68–3.76
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J = 3.6 Hz), 6.64–6.66 (1H, d, J = 8.4 Hz), 6.73–6.75 (2H, m).
[
Conflict of interest
[
[
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All the authors are thankful to the SAP, Department of Chem-
istry, NBU under university grants commission (UGC), New Delhi
for economic and instrumental assistance to perform this research
work. Dr. Roy is also grateful to UGC, New Delhi, Govt. of India for
being awarded one time grant under BSR for his active service for
advancement of the research work.
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Supplementary data associated with this article can be found, in
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