Complementary hydrogen bonding of a carboxylato-barbiturate with urea and acetamide: Experimental and theoretical approach

Article abstract of DOI:10.1016/j.saa.2011.08.079

A barbiturate derivative, 4-(2,4,6-trioxo-tetrahydro-pyrimidine-5- ylidenemethyl)-benzoic acid (L1) possessing functional complementarity to amides has been synthesized and characterized. Its binding separately with urea and acetamide was monitored using UV-vis, fluorescence and ¹H-NMR spectroscopic titrations. Experiments suggested stronger binding of L1 with urea as compared to acetamide. The solid adducts of L1 prepared separately with urea and acetamide were also characterized using IR, ¹H-NMR spectral and PXRD techniques. Theoretical studies on hydrogen bonded complexes of L1-urea and L1-acetamide in the gas phase, aqueous, and DMSO medium were carried out using density functional theory (DFT) at the B3LYP/6-31G** level. The theoretical calculations agreed to the experimental results.

Full text of DOI:10.1016/j.saa.2011.08.079

Spectrochimica Acta Part A 83 (2011) 532–539
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Complementary hydrogen bonding of a carboxylato-barbiturate with urea and
acetamide: Experimental and theoretical approach
Md. Amin Hasana, A. Seshadityaa, Stanislav Zálisˇ b, Lallan Mishraa,∗
a Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India
b J. Heyrovsky´ Institute of Physical Chemistry, Academy of Sciences of the Czech, Republic, Dolejsˇkova 3, CZ-18223 Prague, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
A barbiturate derivative, 4-(2,4,6-trioxo-tetrahydro-pyrimidine-5-ylidenemethyl)-benzoic acid (L1) pos-
sessing functional complementarity to amides has been synthesized and characterized. Its binding
separately with urea and acetamide was monitored using UV–vis, fluorescence and 1H-NMR spectro-
scopic titrations. Experiments suggested stronger binding of L1 with urea as compared to acetamide. The
solid adducts of L1 prepared separately with urea and acetamide were also characterized using IR, 1H-
NMR spectral and PXRD techniques. Theoretical studies on hydrogen bonded complexes of L1–urea and
L1–acetamide in the gas phase, aqueous, and DMSO medium were carried out using density functional
theory (DFT) at the B3LYP/6-31G** level. The theoretical calculations agreed to the experimental results.
© 2011 Elsevier B.V. All rights reserved.
Received 1 August 2011
Received in revised form 26 August 2011
Accepted 31 August 2011
Keywords:
Barbiturate derivative
Binding study
1H-NMR titration
PXRD
DFT calculation
1. Introduction
elsewhere [51–58] in the recent study of hydrogen bonding sys-
tems. We therefore set up a task of developing an adjustable probe
The design and synthesis of molecular and supramolecular
receptors for the recognition of anionic [1–19], cationic [20] and
neutral molecules [20–22] is a subject of contemporary research.
However, development of thermodynamically stable and selective
receptors of wider applications is still demanding more research in
this area. In this construction, bringing of a substrate in contact with
receptor through non-covalent interactions is more interesting as
such interactions may tune the receptor in different conformations
with little manipulations of external stimuli like light, heat as well
as the polarity of the solvent [19].
In this context, urea being toxic [23–26] and chief constituent
of metabolic product of nitrogenous compounds and a well-known
protein denaturant even at micro molar concentration, caught
our attention recently. Neutral hosts like pyrrole, urea or other
amide groups [27–33] that bind guests exclusively through hydro-
gen bonding have recently been developed. Hamilton and Still
have reported isophthalamide or urea derivatives as receptors for
nucleotide bases, barbiturates, dicarboxylic acids, dicarboxylates,
and peptides [34–42].
molecule that forms complexes with amide analogues and would
produce a differentiated UV–vis absorption band depending on the
hydrogen-bonding sequence.
It was thought to investigate the donor–acceptor properties
of
a new barbiturate derivative, 4-(2,4,6-trioxo-tetrahydro-
pyrimidine-5-ylidenemethyl) benzoic acid (L1) (Fig. 1) for the
recognition of urea and acetamide using UV–vis, fluorescence and
1H-NMR spectral titrations. The formation of stable supramolecular
complexes of (L1) separately with urea and acetamide has also been
isolated in solid state and characterized using their IR spectra and
powder X-ray diffraction data. The complexes are also character-
ized in solution using their 1H-NMR spectra in DMSO-d6 solution.
The formation of supramolecular composition of L1 separately with
urea and acetamide is also investigated theoretically using den-
sity functional theory (DFT) calculations in gas phase, aqueous and
DMSO medium. The selectivity of compound L1 as a receptor candi-
date is made owing to its easy preparation, stability towards air and
moisture and bearing multiple binding sites being complementary
to both urea and acetamide.
In this context, density functional theory (DFT) [43–45] which
has emerged as a reliable and versatile computational method has
been successfully used to study physical and chemical properties
of molecules [46–50]. Moreover, its utility has been pointed out
2. Experimental
2.1. Materials and methods
Urea and acetamide were purchased from Sigma–Aldrich Chem.
Co. and were used as received without further purification. The sol-
vents were purchased from E. Merck and were freshly distilled prior
∗
Corresponding author. Tel.: +91 542 6702449; fax: +91 542 2368174.
E-mail address: lmishrabhu@yahoo.co.in (L. Mishra).
1386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2011.08.079

Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
533
2.3.2. Emission titration
Fluorescence spectra were recorded using a Perkin-Elmer LS-45
luminescence spectrometer. Luminescence titrations were per-
formed by maintaining the concentration of L1 constant at 10−4 M
in DMSO while the concentrations of the urea and acetamide were
varied within (0–325) × 10−6 M and the fluorescence spectra were
measured after incremental additions until fluorescence intensity
reached minimum. The linear fit of the fluorescence intensity data
at a particular wavelength for 1:3 complexation was obtained using
[36] Eq. (2).
ꢀ
ꢁꢀ
ꢁ
IF0
IF − IF0
a
1
=
(2)
b − a
(KS[M]) + 1
where, IF0 and IF are the fluorescence intensities of the free L1 and
L1–guest (urea/acetamide) complex respectively; [M] is the con-
centration of the guest added for complexation. The KS is obtained
as intercept/slope ratio from the plot of IF0/IF − IF0 against [M]−1.The
change in the absorption spectral data at a particular wavelength
fitted in the above equation gives the value of KS.
Fig. 1. Chemical structure of L1 showing H-donor and acceptor sites.
to their use. Elemental analyses (C, H and N) were carried out on
a Perkin-Elmer CE-440 analyzer. IR spectra were recorded using
KBr pellets on a Varian 3100 FT-IR in the 4000–400 cm−1 region.
UV–vis spectra were recorded on a JASCO V-630 spectrometer in
DMSO at room temperature. 1H-NMR spectra were measured on a
JEOL AL 300 FT-NMR spectrometer at room temperature. Fluores-
cence spectra were recorded on a Perkin Elmer LS45 Luminescence
spectrometer.
2.3.3. Structural characterization of composite solids
The samples were mechanically grinded and subjected to struc-
tural characterization using powder X-ray diffraction (XRD) Philips
˚
PW 1710 diffractometer with CuK␣ radiation ꢁ = 1.5418 A. The rat-
ing of X-ray generator (30 KV, 20 mA) and other diffractometer
parameters such as scanning speed, were kept constant for all
diffraction experiments performed on different samples.
2.2. Preparation of
4-(2,4,6-trioxo-tetrahydro-pyrimidine-5-ylidenemethyl)-benzoic
acid (L1)
2.4. DFT calculations
The compound (L1) was synthesized using reported method
[59] by addition of a hot aqueous solution of barbituric acid
(1.28 g, 10 mmol) to a solution of 4-carboxy-benzaldehyde (1.50 g,
10 mmol) in methanol. After stirring under reflux for 2.5 h, the
reaction mixture was cooled at room temperature and filtered.
The solid product thus obtained was washed with ethanol sev-
eral times and dried in vacuo. Yield: 95%, M.P. > 250 ◦C, IR (KBr):
ꢀmax/cm−1 3448 (N–H, O–H), 1746, 1683, 1590 (>C O, >COO), 1328
(C–O), 836 (C–H), 1H-NMR (DMSO-d6, ı ppm): 13.18 (s, 1H, COOH),
11.44 (s, 1H, NH), 11.27 (s, 1H, NH), 8.29 (s, 1H, CH), 7.99 (d, 2H,
J = 6.6 MHz, Ar–H), 7.95 (d, 2H, J = 9 MHz, Ar–H). 13C-NMR: ıC (ppm)
193.0 (>C O, carboxy), 166.6 and 166.5 (>C O), 163.4 (C2), 15.3
(C14), 150.5 (C13), 149.5 (C11), 149.1 (C12), 129.2 (C10), 128.02
(C9), 125.5 (C8), 120.8 (C7), 116.4 (C6), 85.18 (C15), 53.28 (C4) and
33.6 (C5). ESI-MS, m/z 260 [M]+.
Molecular geometries of all systems were optimized using den-
sity functional theory (DFT) methods at B3LYP/6-31G(d,p) level of
calculations using Gaussian09 (G09) program package. The calcu-
lations were performed in gas phase and in solution phases where
solvents, water and DMSO, were modeled using polarizable contin-
uum model (PCM) method. Geometries of L1 hydrogen bonded with
one urea molecule in different positions were optimized and it was
found that in the most stable optimized structure urea is hydrogen
bonded to the carboxyl group of the L1. An inspection of the struc-
tures of these complexes indicates that more urea molecules may
be complexed with L1. Therefore, the geometries of the hydrogen
bonded complexes of L1 with two, three and four urea molecules
were also optimized in gas and solution phases using same level of
calculations. The complexes of L1 hydrogen bonded with one, two,
and three acetamide molecules were also optimized at the same
level of theory in gas and solution phases. The calculations for four
acetamide molecules were also tried but it did not satisfy energy
convergence criteria. In order to compare urea and acetamide bond-
ing with possible L1 dimerization, hydrogen bonded dimer L1–L1
was also examined. The analyses of vibrational frequencies were
performed at the B3LYP/6-31G(d,p) level of theory to ensure that
total energy minimum had real vibrational frequencies and obtain
zero-point energy (ZPE) corrections to total energies and corre-
sponding thermal energy corrections giving enthalpies at 298.15 K.
In vacuo bonding energies were calculated with basis set superpo-
sition error (BSSE) correction.
2.3. Binding studies
2.3.1. UV–vis absorption titration
The absorption titrations of L1 separately with urea and
acetamide were performed by monitoring the changes in the
absorption spectrum of L1 (10−4 M) in DMSO by incremental addi-
tion of urea and acetamide within (0–325) × 10−6 M concentrations
in DMSO. The absorption of free urea and acetamide was eliminated
initially by keeping their equal quantities separately in host (L1) and
reference solution. From the absorption data, the intrinsic associa-
tion constant Ka was determined from a plot of [guest]/(εa − εf) vs
[guest] using Eq. (1).
[guest]
(εa − εf)
[guest]
(εb − εf) + [Ka(εb − εf)]−1
3. Results and discussion
=
(1)
Barbiturate derivative (Fig. 1) was prepared using reported pro-
cedure [59] and has been characterized using its elemental analysis,
IR, NMR, UV–vis, mass spectra, and powder X-ray diffraction data.
Its emission property is also studied. To evaluate its receptor prop-
erty in solution, a titration was performed by the incremental
addition of a solution of urea to a solution of L1 both in DMSO at
where [guest] represents the concentration of urea or acetamide.
The apparent absorption coefficients εa, εf, and εb correspond to
Aobsd/[L1], the extinction coefficient of the free L1 and extinction
coefficient of L1 in fully bound form, respectively [27–30]. The
magnitude of Ka is given by the ratio of slope to the intercept.

534
Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
Fig. 2. (a) Absorption spectra of L1 = 10−4 M in the absence and in the presence of increasing concentrations of urea (0–325) × 10−6 M. Inset: absorbance changes upon
increasing urea concentrations. (b) Absorption spectra of L1 = 10−4 M in the absence and in the presence of increasing concentrations of acetamide (0–325) × 10−6 M. Inset:
absorbance changes upon increasing acetamide concentrations.
regular (∼3 min.) interval of time. The spectroscopic (UV–vis and
fluorescence) variations were recorded. The choice of the solvent
was restricted owing to the solubility of L1 in it. A decrease in
the absorbance (Fig. 2a) was observed upon increasing the con-
centrations of urea till 1:3 (L1: urea) stoichiometry was reached.
Beyond this stoichiometry, no further significant change occurred
in this peak position. An isobestic point is observed at ꢁmax 272 nm
(Fig. 2a). Similar addition of acetamide to a solution of L1 showed
isobestic point at ꢁmax 283 nm (Fig. 2b). Thus, this experiment sup-
ported the formation of L1–urea and L1–acetamide complexes in
1:3 molar ratio. Since no further enhancement in the intensity of the
UV–vis absorption peak was observed beyond this stoichiometry, it
indicates that complex formation is completed at this molar ratio.
The corresponding Job plots (S1) provided additional support to
the stoichiometric ratio, where the changes in absorbance (Ao − A)
of L1 at ꢁmax 320 nm on incremental addition of urea/acetamide
were plotted against molar fractions of L1. As a result, max-
ima were observed at molar fraction of [L1]/([L1] + [urea]) and
[L1]/([L1] + [acetamide]) 0.25. It is in consistence with the earlier
report [60].
H-bonded network using complementary groups present in the
skeleton of both urea and acetamide. To investigate the host–guest
display of L1 separately with urea and acetamide, 1H-NMR spectro-
scopic titrations (Fig. 4) were carried out again with the incremental
addition of urea and acetamide separately to a fixed concentra-
tion of L1 in DMSO-d6. The corresponding changes were measured
after complete (1:3) addition of urea or acetamide in the solu-
tion of L1. Being aware of the controversy [31] that exists on the
signaling of amide, urea, thiourea or pyrrole-type receptors in
organic solvents by barbiturate moieties, i.e. whether an actually
hydrogen-bonded complex was formed or whether –OH deproto-
nates the ligand, the response of compound L1 upon addition of
urea or acetamide was investigated. In a typical experiment, the
concentration of L1 was kept constant at 10−2 M in DMSO-d6 and
aliquots of 4 × 10−1 M concentration of corresponding components
(urea/acetamide) were added to it. The characteristic shifts of the
–NH protons of both urea and acetamide together with barbiturate
group were observed. Two additional peaks observed at ı 10.27
and 10.08 ppm were assigned to the formation of two new H-bonds
The values of association constants (Ka = 2.24 × 107 M−1 for urea
and Ka = 2.07 × 107M−1 for acetamide) suggest that compound L1
has more binding affinity with urea than for acetamide. This exper-
iment also showed that binding of urea with L1 is ∼8 times stronger
than its binding with the receptor reported recently by us [61]. This
could be considered owing to the presence of a carboxylic group
appended in the structural frame of barbituric acid. Thus, L1 was
found as a better receptor of urea than earlier reported barbitu-
rate ligand. The presence of carboxyl group attached to phenyl ring
enhanced the H-bond formation capability of L1 which is supported
by the observation of substantial changes observed in the position
of carboxyl proton in the 1H-NMR spectral titration. The formation
of extensive H-bonding of L1 separately with urea and acetamide is
also expected to quench the fluorescence from free L1 as H-bonding
provides a path for electron/energy travel. Thus, attempt was made
to investigate the emission from L1. It emitted at ꢁemiss 438 nm
when it was excited at ꢁex 350 nm. But the emission from L1 grad-
ually decreases upon incremental addition of either urea (Fig. 3a)
or acetamide (Fig. 3b).
of types
. However, other two peaks observed at
ı 6.87 and 7.28 ppm were assigned to (U) N–H· · ·O C (B) or (U)
C
O· · ·H–N (B), (U) and (B) represents urea and barbiturate group
respectively. The peak observed at ı 5.66 ppm in the spectrum
of L1 upon addition of urea is attributed to the –NH protons of
free urea. Similarly, with addition of increasing concentration of
acetamide to a fixed concentration of L1, new peaks lying closer at
ı 10.17 ppm, were assigned to H-bonds of types
. The peaks observed at ı 7.28, 6.67 and 1.75 ppm were tentatively
assigned to H-bonds of types (A) N–H· · ·O (B) or (B) C O· · ·H–N (A,
acetamide) and –CH3 protons of acetamide respectively. However,
description of such complex spectra calls for deeper investigation
using higher resolution NMR spectrometer. Since crystals of these
H-bonded complexes could not be isolated, attempts were made
to look into the spectral behaviour of the solid obtained after fine
mechanical mixing of L1 separately with urea and acetamide in 1:3
stoichiometry. Corresponding composites were characterized by IR
spectral data followed by PXRD studies and 1H-NMR spectral data.
The decrease in the emission intensity is continued until
addition of 3.0 equiv. of urea/acetamide was completed. Further
addition of urea/acetamide did not change the spectrum sig-
nificantly. The emission experiment supported the formation of

Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
535
Fig. 3. (a) Emission spectra of L1 = 10−4 M in the absence and in the presence of increasing concentrations of urea (0–325) × 10−6 M. Inset: emission intensity changes upon
increasing urea concentrations. (b) Emission spectra of L1 = 10−4 M in the absence and in the presence of increasing concentrations of acetamide (0–325) × 10−6 M. Inset:
emission intensity changes upon increasing acetamide concentrations.
IR spectra of free L1, urea, acetamide, L1·urea and L1·acetamide
adducts (S2) showed that ꢀ(N–H) vibrations of free L1 (3192 cm−1),
urea (3445 cm−1, 3360 cm−1) and acetamide (3392 cm−1) shifted
to 3198 cm−1, 3448 cm−1 and 3365 cm−1 as well as 3201 cm−1 and
3421 cm−1 respectively. Thus, shift in (N–H) vibrations of free com-
ponents in their respective adducts supported that components
interact with their complementary partners through correspond-
ing NH groups. These adducts were further characterized by their
1H-NMR spectral studies. Stronger binding of urea with L1 was
again supported by the appearance of new peaks in the spectrum
of L1·urea adduct apart from the original peaks of L1 and urea (S3).
The PXRD patterns of all components and their adducts were
also recorded (S4). The grain size and the lattice strain of the
samples can be calculated from the integral width of the physical
broadening profile. Therefore, grain size has been calculated using
Scherrer equation (3).
kꢁ
D =
(3)
ˇc cos Â
where D is grain size, K is shape factor, ꢁ is X-ray wavelength, ˇ is
HwHm (Half width at Half maximum) and  is Bragg’s angle. Crys-
tallite sizes calculated using this equation was found to be 36.0 nm
for urea, 9.2 nm for acetamide, 12.5 nm for L1, 15.2 nm for L1·urea
adduct and 17.5 nm for L1·acetamide adduct.
The ZPE-corrected binding energies (ꢂE), and the correspond-
ing enthalpy changes (ꢂH) at 298.15 K (kcal mol−1) in gas phase,
aqueous and DMSO media of free urea, acetamide, L1 and the
all examined complexes are listed in Table 1. Depicts examined
Fig. 4. 1H-NMR spectra of L1 in DMSO-d6 upon addition of different equivalents of (a) urea and (b) acetamide.

536
Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
Table 1
Summary of data of DFT calculation.
Structures
Energy (ZEP cor.) (atomic units)
Enthalpies (atomic units)
Change in energies (ꢂE) (kcal mol−1
)
Change in enthalpies (ꢂH) (kcal mol−1
)
Urea
Gas
−225.209785
−225.22304
−225.223238
−225.204469
−225.217639
−225.217833
DMSO
Water
Acetamide
Gas
DMSO
Water
L1
–
–
−209.150156
−209.165659
−209.160219
−209.145358
−209.159604
−209.154636
–
–
–
–
Gas
DMSO
Water
−947.60658
−947.623517
−947.623742
−947.590171
−947.606991
−947.607217
L1–one urea (conf. a in Fig. 5)
Gas (BSSE cor.) −1172.846323
−1172.824215
−1172.847774
−1172.848112
−14.925
−14.545
−14.762
−14.671
−14.523
−14.472
DMSO
Water
−1172.870159
−1172.870505
L1–one urea (conf. b in Fig. 5)
Gas (BSSE cor.) −1172.833614
−1172.811243
−1172.841401
−1172.841774
−10.824
−10.904
−10.879
−10.419
−10.524
−10.498
DMSO
Water
−1172.863934
−1172.864317
L1–one urea (conf. c in Fig. 5)
Gas (BSSE cor.) −1172.833479
−1172.81111
−1172.841084
−1172.841451
−10.739
−10.775
−10.743
−10.335
−10.325
−10.292
DMSO
Water
−1172.863728
−1172.86410
L1–one urea (conf. d in Fig. 5)
Gas (BSSE cor.) −1172.833249
−1172.810873
−1172.841414
−1172.841791
−10.595
−10.954
−10.928
−10.186
−10.532
−10.505
DMSO
Water
−1172.864013
−1172.864395
L1–one urea (conf. e in Fig. 5)
Gas (BSSE cor.) −1172.832314
−1172.809895
−1172.841414
−1172.841269
−10.008
−10.836
−10.572
−9.573
−10.442
−10.178
DMSO
Water
−1172.863826
−1172.863827
L1–two urea (Fig. 8a)
Gas (BSSE cor.) −1398.066858
−1398.038771
−1398.082087
−1398.082571
−25.545
−25.673
−25.597
−24.888
−24.986
−24.905
DMSO
Water
−1398.110510
−1398.111009
L1–three urea (Fig. 9a)
Gas (BSSE cor.) −1623.292159
−1623.25808
−1623.315802
−1623.316468
−35.281
−35.714
−36.145
−34.201
−34.567
−34.985
DMSO
Water
−1623.35037
−1623.351056
L1–four urea (Fig. 10)
Gas (BSSE cor.) −1848.512222
−1848.471739
−1848.542298
−1848.541535
−41.731
−41.249
−41.389
−39.967
−40.003
−40.153
DMSO
Water
−1848.582429
−1848.581635
L1–one acetamide (conf. aa)
Gas (BSSE cor.) −1156.779677
−1156.757028
−1156.784201
−1156.785421
−14.396
−14.088
−13.915
−13.491
−13.547
−13.496
DMSO
Water
−1156.806136
−1156.806412
L1–one acetamide (conf. ab)
Gas (BSSE cor.) −1156.772864
−1156.749901
−1156.777272
−1156.777601
−10.120
−14.466
−13.442
−9.019
−9.817
−9.789
DMSO
Water
−1156.800269
−1156.800601
L1–two acetamide (Fig. 8b)
Gas (BSSE cor.) −1365.946141
−1365.916963
−1365.953425
−1365.953804
−24.629
−24.442
−24.365
−22.638
−23.320
−23.230
DMSO
Water
−1365.982616
−1365.983008
L1–three acetamide (Fig. 9b)
Gas (BSSE cor.) −1575.111371
−1575.075559
−1575.12308
−1575.123493
−34.088
−34.153
−34.346
−30.945
−32.324
−32.583
DMSO
−1575.158825
−1575.159138
Water
L1–L1 (Fig. 7)
Gas (BSSE cor.) −1895.232481
−1895.198846
−1895.232574
−1895.232574
−12.124
−12.054
−12.027
−11.611
−11.383
−11.667
DMSO
Water
−1895.266244
−1895.266651
a
Acetamide is attached in place of urea.
configurations of L1 hydrogen bonded with one urea molecule
(Fig. 5).
optimized structures of the most stable forms of complexes with
one urea and acetamide are presented in Fig. 6. Each of the com-
plexes of L1 involving one urea and one acetamide molecules
is stabilized by two hydrogen bonds each, out of which one
hydrogen bond is stronger than the other. The two hydrogen
bonding distances in the complexes involving one urea molecule
It is evident from the B3LYP/6-31G(d,p) level calculation both
in vacuo and employing polarizable-continuum model (PCM) that
acid functional group is more reactive than the remaining part
of (L1) ligand. As seen in Table 1 the conformation A is about
4.0 kcal mol−1 more stable than remaining conformations. The
˚
lie in the range 1.555–1.912 A, while those in the complexes

Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
537
Fig. 5. Conformations of the complex of L1 with one urea optimized at the B3LYP/6-31G(d,p) level of theory.
Fig. 6. Optimized structures of L1 with one urea (a) and acetamide (b). The enthalpy changes (ꢂH) at 298.15 K (kcal mol−1) of the complexes obtained at the B3LYP/6-31G(d,p)
level of theory in gas phase, aqueous and DMSO media are given. Hydrogen bond lengths [Å] in gas phase, aqueous and DMSO media are given from top to bottom, respectively.
˚
molecules reveal that the magnitudes of ꢂE and ꢂH values
increased in going from one urea to three urea molecules. The
ꢂH of the complex of L1 with three urea molecules is found to
be 34.20, 34.98 and 34.57 kcal mol−1 in gas phase, aqueous and
DMSO medium respectively. The ꢂE of the complex of L1 with two
urea molecules is found to be 24.89, 24.91 and 24.99 kcal mol−1
in gas phase, aqueous and DMSO medium (Table 1), respectively.
The experimental values of binding constant were also found
to increase from 1:1, 1:2, and 1:3 binding of L1 with urea and
acetamide. The theoretical calculations agree to the experimental
results. It appears that the binding of L1 with three urea molecules
is favorable over the binding of L1 with one or two urea molecules.
Similar observations were made theoretically for the binding of
L1 with two and three acetamide molecules. A comparison of ꢂE
and ꢂH values of the complexes of L1 with urea and those of
the complexes of L1 with acetamide shows that the binding of
involving one acetamide molecule lie in the range 1.533–2.916 A
respectively.
The ꢂH values for L1–L1 dimer (Fig. 7) listed in Table 1, indi-
cate the lower stability of dimer than corresponding aggregates of
L1 with one urea and one acetamide. The binding energies (ꢂE)
and the corresponding enthalpy changes (ꢂH) of the all complexes
showed stable structures in gas phase as well as in aqueous and
DMSO medium.
The optimized structures and ꢂH values of the complexes of
L1 with two urea molecules and those of L1 with two acetamide
molecules are presented in Fig. 8.
Similarly, the optimized structures and ꢂH values of the com-
plexes of L1 with three urea molecules and those of L1 with three
acetamide molecules are presented in Fig. 9.
Further, the binding energies and the corresponding enthalpy
changes of the complexes of L1 with one, two, and three urea
Fig. 7. Optimized structure of L1–L1 dimer. The enthalpy changes (ꢂH) at 298.15 K (kcal mol−1) of the complexes obtained at the B3LYP/6-31G(d,p) level of theory in gas
phase, aqueous and DMSO media are given.

538
Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
Fig. 8. Optimized structures of L1 with two urea (a) and acetamide (b). The enthalpy changes (ꢂH) at 298.15 K (kcal mol−1) of the complexes obtained at the B3LYP/6-31G(d,p)
level of theory in gas phase, aqueous and DMSO media are given. Hydrogen bond lengths [Å] in aqueous media are given.
Fig. 9. Optimized structures of L1 with three urea (a) and acetamide (b). The enthalpy changes (ꢂH) at 298.15 K (kcal mol−1) of the complexes obtained at the B3LYP/6-31G(d,p)
level of theory in gas phase, aqueous and DMSO media are given. Hydrogen bond lengths [Å] in aqueous media are given.
L1 with urea is stronger than that of L1 with acetamide. As the
experiments were performed in DMSO medium, the ꢂE and ꢂH
values of the complexes of L1 with three urea (Fig. 9a) and three
acetamide (Fig. 9b) were also calculated in the DMSO medium at the
B3LYP/6-31G(d,p) level using the polarizable-continuum model.
The ꢂE and ꢂH values of the complexes were found to be similar
in both the aqueous and DMSO medium. Thus, theoretical calcula-
tions strongly support our experimental findings that binding of
L1 with urea molecules in DMSO medium is favorable over the
binding with acetamide molecules. Although experimentally no
significant change in the UV–vis spectrum was observed beyond
1:3 stoichiometry of L1 with urea, yet theoretically it was tried.
As given in Table 1, data show that fourth bonding of urea to L1
(Fig. 10) is weaker since change of enthalpy is about 5.0 kcal mol−1
as compared to that obtained in 1:3 ratio in which enthalpy change
is about 10.0 kcal mol−1 as compared to 1:2 ratio of L1 to urea. How-
ever, in case of in 1:4 ratio of L1 with acetamide, no convergence
was obtained.
4. Conclusion
The designed barbiturate derivative L1 possessing H (D–A–D)
binding sites is found very simple and interesting receptor for both
urea and acetamide. The receptor molecule (L1) binds separately
with three molecules of urea and acetamide in micro molar con-
centration range as monitored by their absorption, emission and
1H-NMR spectroscopic measurements. The composite supramolec-
ular adducts of L1 with urea and acetamide are prepared separately
by grinding the components together. Theoretical calculations car-
ried out at B3LYP/6-31G(d,p) level using the polarizable-continuum
model in gas phase, aqueous, and DMSO medium support the
experimental results. Thus, construction of a carboxyl group on the
skeleton of a barbituric acid provides simple and novel receptor for
urea and acetamide.
Acknowledgements
Fig. 10. Optimized structures of L1 with four urea at the B3LYP/6-31G(d,p) level of
theory in gas phase, aqueous and DMSO media are given. Hydrogen bond lengths
[Å] in aqueous media are given.
Financial support was received from UGC (grant no. F.No.34-
468/2008 to L.M.), New Delhi, India is gratefully acknowledged.

Md.A. Hasan et al. / Spectrochimica Acta Part A 83 (2011) 532–539
539
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