Water mediated self assembly of 5-(2-benzoimidazole-1-yl-ethoxy)-3-methyl- 1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester through CH?O and OH?N interactions

Article abstract of DOI:10.1016/j.molstruc.2011.09.004

Single crystal X-ray structure analysis of 5-(2-benzoimidazole-1-yl-ethoxy) -3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester (2).0.5H ₂O provided experimental proof for H?OC, CH?OH and HO?N interactions. The embedded water molecule

Full text of DOI:10.1016/j.molstruc.2011.09.004

Journal of Molecular Structure 1007 (2012) 20–25
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Water mediated self assembly of 5-(2-benzoimidazole-1-yl-ethoxy)-3-methyl-
1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester through CAHÁ Á ÁO
and OAHÁ Á ÁN interactions
b
b
Priyanka Srivastava a, Ved Prakash Singh a, Ashish Kumar Tewari a, , Carmen Puerta , Pedro Valerga
⇑
a Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India
b Departamento de Ciencia de los, Materiales e Ingenieria Metalurgica, Facultad de Ciencias, Campus Universitario del Rio San Pedro, Puerto Real 11510, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 April 2011
Received in revised form 31 August 2011
Accepted 1 September 2011
Available online 10 September 2011
Single crystal X-ray structure analysis of 5-(2-benzoimidazole-1-yl-ethoxy)-3-methyl-1-phenyl-1H-pyr-
azole-4-carboxylic acid methyl ester (2).0.5H2O provided experimental proof for HÁ Á ÁO@C, CAHÁ Á ÁOAH
and HAOÁ Á ÁN interactions. The embedded water molecule bridges between molecules 2 via non-covalent
interactions. Thus this molecule behaves as a preorganized host molecule for water, presenting a mini-
mum ring-size molecular environment for water binding. Single crystal X-ray structure analysis of
5-(2-benzoimidazole-1-yl-ethoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl esterhemi-
hydrate provided experimental proof for six hydrogen bonds by one molecule of water. The embedded
water molecule bridges six molecules by two types of hydrogen bonding. Theoretical calculations showed
that the conformation of the bicyclic hetero-ring alters only slightly due to the presence of the water mol-
ecule. Thus this organic molecule behaves as a very interesting preorganized host molecule for water,
presenting maximum binding environment for water binding.
Keywords:
Weak interactions
Polymorph
Spectroscopy
DFT
X-ray
NMR
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
water. Interactions of water generally reduce non-polar surface
area of organic molecule exposed to the solvent and reduce the
Weak non-covalent interactions play subtle role in construction
of supramolecular architectures. Among them, CAHÁ Á ÁO, CAHÁ Á Á
and interactions are very important as they are widely active
Á Á Á
amount of structured water providing favorable entropy of associ-
ation. Interactions play key role in the construction of supramolec-
ular architecture [2,3] through supramolecular synthons [4]. The
aggregation of aromatic compounds can also be caused by alterna-
p
p
p
in organic crystals and biological macromolecules. Water is known
to participate actively in molecular recognition processes both in
chemical and especially in biological systems, by mediating the
interactions between binding partners and contribute to either
enthalpic or entropic stabilization. Also, it is known to play an
important role in the recognition and hence stabilization of the
interactions, specifically through CAHÁ Á ÁO networks as observed
in 5-(2-benzoimidazole-1-yl-ethoxy)-3-methyl-1-phenyl-1H-pyr-
azole-4-carboxylic acid methyl ester which is highly stabilized
through CAHÁ Á ÁO and OAHÁ Á ÁN interactions due to the involve-
ment of water. Crystal structures of molecular solids are deter-
mined by large number of weak directional forces responsible for
generating self assembly of molecules. Role of water in the crystal
structures is well documented [1]. Stronger water–water interac-
tions are formed around non-polar organic molecules in order to
compensate weak water–non-polar molecular interactions. The
entropy of dissolution decreases when (2) comes in contact with
tive interactions between
the organization of molecular subunits in the solid state [5].
Among the weak interactions, CAHÁ Á ÁO [6], CAHÁ Á Á [7] and
Á Á Á interactions [8] are important in generating symmetry non-
p systems which are used to manipulate
p
p
p
equivalence in the crystal lattice [9,10]. They are also known to
control drug action [11], and polymorphism [12]. It has been estab-
lished interactions that among these forces, CAHÁ Á ÁO hydrogen
bonds [13] exist as significant secondary interaction and occasion-
ally dominant interaction [14] in molecular solids and therefore
they are widely implicated as important structural determinants
in organic crystals [13] and biological macromolecules [15]. For
example, water molecules at protein–DNA interface contribute to
the complex formation and potentially play important role in
mediating specific interactions [16–18]. The chemistry of pyrazole
derivatives has been the subject of research due to their impor-
tance in various applications and their wide spread of potential
biological and pharmacological activities governed by specific
interactions between host and receptors [19–33]. In the present
study, self assembly of compound (2) mediated through water
molecules is reported which reveals an CAHÁ Á ÁO contact between
⇑
Corresponding author. Tel.: +91 0542 6702476; fax: +91 0542 2368127.
E-mail addresses: tashish2002@yahoo.com (A.K. Tewari), pedro.valerga@uca.es
(P. Valerga).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.09.004

P. Srivastava et al. / Journal of Molecular Structure 1007 (2012) 20–25
21
Table 1
(2) and water molecules in the solid state. The water molecule is
interactions to the -elec-
tron cloud over 5-membered ring of benzimidazole.
Crystallographic data of compound 2.
also hydrogen bonded through OAHÁ Á Á
p
p
Compound
2
Compound name
5-(2-Benzoimidazol-1-yl-ethoxy)-3-methyl-1-
phenyl-1H-pyrazole-4-carboxylic acid methyl ester;
hydrate
2. Experimental procedure
C
21H20N4O3Á0.5H2O
Empirical formula
Formula weight
770.84
100 (2)
2.1. Instrumentation
(g molÀ1
)
All reactions were carried out under simple conditions at room
temperature. Commercially available reagents and solvents were
used without further purification. 1H and 13C NMR spectra were re-
corded on a JEOL AL300 FTNMR spectrometer in CDCl3. TMS is used
as internal reference and chemical shift values are expressed in d,
ppm units. The X-ray diffraction data collected on Bruker SMART
APEX CCD area detector diffractometer. The structure was solved
and refined by using SHELXTL [34] program. Molecular graphics
were designed by using ORTEP-3 version. 1.08. Crystal structure
of compound (2)ÁH2O is shown in ortep diagram with labelling in
Fig. 1.
The crystal data are given in Table 1 and the selected geometri-
cal parameters of inter and intramolecular hydrogen bonds are
summarized in Table 2a and b. In solution growth technique, the
formation of X-ray quality single crystals depends on the choice
of the solvent. In order to select the proper solvent for growing
large-size single crystals, the solubility of (2) was checked in vari-
ous solvents. 3% Ethyl acetate in hexane mixture was found to be
the best solvent for growing single crystals of (2) because of its
good solubility as compared to other solvents. Well-defined single
crystals of good transparency were obtained.
Temperature (K)
Wave length (Å)
Crystal system, space
group
Unit cell dimensions
(Å)
0.71073
Monoclinic, C 2/c
a = 25.990 (3)
b = 10.8447 (12), b = 108.15 (3)
c = 15.950 (2)
2468.83
1.351
1624
Cell volume, V (Å3)
Dcalc. (Mg mÀ3
)
F (000)
Z
8
0.50 Â 0.25 Â 0.23
Crystal size (mm)
Theta range for data
collection (°)
Limiting indices
Reflections collected/
unique
1.86–25.03
À30 6 h 6 27, À12 6 k 6 12, À17 6 l 6 18
3315/3186 [R (int) = 0.0295]
Full-matrix least-squares on F2
Refinement method
Melting point (K)
Final R indices
331–333
R1 = 0.0495, wR2 = 0.0965
R1 = 0.0528, wR2 = 0.0983
[F2 > 2 (F2)]
r
R indices (all data)
1.055
0.23/À0.20
Goodness-of-fit on F2
D
q
max/
D
)
q min
(e ÅÀ3
2.2. Materials
Table 2
(a and b): Geometry of CAHÁ Á Á
To the suspension of benzimidazole (0.17 g, 0.00147 mol) and
anhydrous K2CO3 (0.20 g, 0.0015 mol) in DMF (10 ml) stirred at
r.t. for 30 min was slowly added compound 1 (0.5 g, 0.0015 mol)
with constant stirring (Scheme 1). The reaction mixture was stirred
at room temperature for 24 h. Completion of the reaction was con-
firmed via TLC. DMF was removed under reduced pressure using
rotavap and the product was treated with 1:1 CHCl3–H2O system
(100 ml). The organic layer was collected and the aqueous layer
was washed two times with 100 ml of CHCl3. The organic layers
were combined and washed with water (100 ml) and dried over
anhydrous Na2SO4). Removal of CHCl3 under reduced pressure gave
p
and OAHÁ Á ÁN interactions in compound 2.
S.
Interaction
C/OAHÁ Á Á
p
/N/
C/OAHÁ Á Á
p/N/
No.
C (Å)
C (°)
(a) Intramolecular
1
C(20)AH(20)Á Á Á
p
(benzim-5-
3.16
3.20
153
125
membered ring)
2
C(19)AH(19)Á Á Á
p (benzim-6-
membered ring)
Interaction
S. No.
O/CAH/pÁ Á Áp/N/O (Å)
(b). Intermolecular
1
2
3
4
5
6
p
Á Á Á
p
(2 benzim-5-membered rings)
3.86
C(1)AH(1)Á Á ÁN(4)
C(5)AH(5)Á Á ÁO(4)
C(17)AH(17)Á Á ÁO(3)
2.58 (153°)
2.57 (152°)
2.51 (168°)
3.04 (100°)
2.06 (167°)
C(18)AH(18)Á Á Á
p (pyrazole)
O(4)AH(40)ÁÁÁN(2)
solid residue which was crystallized from 3% ethyl acetate–hexane
solution along with a drop of water to give pure compound 2.
Yield: 0.12 g (22.15%); mp 58–60 °C. 1H NMR (300 MHz, CDCl3,
d ppm): 2.436 (s, 3H, CH3), 3.775 (s, 3H, OCH3), 4.48–4.53 (q, 4H,
CH2 X 2, J = 3.3, 5.1, 4.5 Hz), 7.19–7.83 (m, 9H, Ar-H), 7.83 (s, 1H,
H); 13C NMR (CDCl3, d ppm): 15.18, 44.56, 51.03, 72.67, 99.43,
109.20, 120.33, 122.71, 127.61, 128.88, 133.42, 136.68, 143.10,
143.66, 150.67, 154.09, 163.23.
3. Theoretical calculations
Theoretical molecular models of molecules were calculated by
B3LYP/6-31+G(d,p) level DFT chemical calculations as imple-
mented in Gaussian ’03[35]. An initial model of the 2ÁH2O was ta-
ken from the XRD experiment or rebuilt [36] for the anhydrous (2).
Fig. 1. Ortep diagram of compound (2)ÁH2O with labelling.

22
P. Srivastava et al. / Journal of Molecular Structure 1007 (2012) 20–25
O
O
H3C
H3C
OCH3
OCH3
N
N
(i) K2CO3/ DMF
(ii) 24 h/ R.T.
N
N
N
N
Br
+
O
O
N
N
H
2
1
Scheme 1.
Fig. 2. (a) Single molecule with water; (b)–(d) pictorial representation of water mediated assembly of (2) through OAHÁ Á ÁN, OAHÁ Á Á
p
and CAHÁ Á ÁO interactions.
The force constants matrices of the fully optimized structures were
always positive. The intra and intermolecular interactions were
analyzed with the aid of Mercury [37] and GaussView.
different plane that is highly influenced by interactions of these
rings with embedded water.
The intramolecular stacked structure of compound 2 is stabilized
preferably through edge to face CAHÁ Á Á
p interactions. This gener-
ates a bent structure of molecule 2 with formation of a cavity within
the molecule. The water molecule appears in the cavity which is
developed by six molecules of compound 2. The distance between
6-membered ring centroid of benzimidazole and H(19) of phenyl
4. Results and discussion
Compound 2 possesses intramolecular as well as intermolecular
network of
p
Á Á Á
p
, CAHÁ Á Á , CAHÁ Á ÁN, CAHÁ Á ÁO and OAHÁ Á ÁN inter-
p
ring was found to be 3.20 Å (CAHÁ Á Á
p
). This indicates that the
actions which actively participate in stabilizing the structure lead-
H(19) proton of the phenyl ring is affected by the
p-electron orbitals
ing to self assembly of molecules (Fig. 2a).
located over the 6-membered ring of benzimidazole. Similar inter-
action is observed between the phenyl H(20) and 5-membered ring
Compound 2 is an unsymmetrical molecule in which the pyra-
zole and benzimidazole residues are joined through an ethylene
linker. The molecule is not planar and all aromatic rings are in
of benzaimidazole (CAHÁ Á Á
p
= 3.16 Å CAHÁ Á Á
p angle = 153°).

P. Srivastava et al. / Journal of Molecular Structure 1007 (2012) 20–25
23
Table 3
estingly, a short NÁ Á ÁO contact (2.92 Å) is also observed among the
N2 of pyrazole and O4 of water molecule. The crystal packing
structure also revealed the presence of important parallel dis-
Comparison of selected bond lengths, torsion angles and H-bond dimensions
calculated by theoretical methods (B3LYP/6-31+G(d,p) level) with the experimental
structural model from X-ray diffraction with their e.s.d.’s where applicable (XRD,
distances in Å, angles in u).
placed
p p (3.86 Å) interactions among the benzimidazole 5-
Á Á Á
membered rings of two different molecules of 2, indicating that
the two rings form stacked arrangement. The distance between
centroid of benzimidazole 5-membered ring and N1 (benzimid-
azole 5 membered ring) and that of H5 of benzimidazole 5 mem-
Geometry
1 (anhydrous)
1:H2O
1.398
XRD
C17 C18
C18 C19
C19 C20
1.398
1.396
1.397
1.384(4)
1.387(3)
1.385(3)
1.397
1.397
bered ring (NÁ Á Á
p
and CAHÁ Á Á
p
) of adjacent molecule is 3.59 Å
C9 O1 C10
C14 O2 C21
C1 N1 C7
C1 N1 C8
C7 N1 C8
118.2
115.8
106.0
126.6
127.4
104.6
111.1
119.4
129.5
106.3
114.2
120.6
125.3
105.6
118.2
116.7(2)
115.0(2)
106.5(2)
125.9(2)
127.3(2)
104.2(2)
110.5(2)
118.8(2)
130.6(2)
105.5(2)
114.2(2)
122.9(2)
122.9(2)
and 3.78 Å, respectively. In the second case, (CAHÁ Á Á
p
interaction),
115.9
106.2
126.3
127.4
105.1
111.1
119.3
129.6
106.4
113.8
121.1
125.2
the bond angle is 80.84° which indicated that the H5 is nearly
orthogonally placed over the benzimidazole ring; it means these
two rings create perpendicular planes against each other. Intermo-
lecular CAHÁ Á ÁN interaction among N4 (pyrazole) to H1 (benzimid-
azole) of two adjacent molecules is 2.58 Å (153.24°).
C1 N2 C6
N4 N3 C10
N4 N3 C15
C10 N3 C15
N3 N4 C12
N1 C1 N2
N1 C1 H1
N2 C1 H1
H4O O4 H4O
To study the complex formation between 2 and water in solu-
tion state, 1H NMR titration was performed by incremental addi-
tion of water in a solution of 2 in CDCl3. No shift in any proton
peak was observed indicating that 2 does not form complex with
water in solution which may be due to increased contribution of
hydrophobic effects.
111(3)
C7 N1 C1 N2
C7 N1 C1 H1
C8 N1 C1 N2
C8 N1 C1 H1
C1 N1 C7 C5
C1 N1 C7 C6
C8 N1 C7 C5
C8 N1 C7 C6
C1 N1 C8 H8A
C1 N1 C8 H8B
C1 N1 C8 C9
À0.5
179.7
À176.7
3.4
179.7
0.5
À0.4
179.9
À177.2
3.1
179.5
0.4
À0.3(3)
179.7(2)
À174.2(2)
5.8(4)
178.0(2)
À0.5(2)
À8.2(4)
173.3(2)
À10.1(3)
À127.9(2)
111.0(2)
The structural models of 2ÁH2O, as well as that of water-free 2
were evaluated by quantum chemical calculations. The results of
B3LYP/6-31+G (d,p) level density functional calculations together
with the model obtained from the XRD measurement are summa-
rized in Table 3 and the so-optimized structures are shown in
Fig. 3. The total binding energy for the water to 2 was calculated
to be 76 kJ molÀ1 using BSSE corrected B3LYP/6-31+G (d,p) wave
functions. This value aligns with literature data [38] and naturally
implies not only energy gains due to H-bridges, but also other, albeit
minor, changes in shape and geometry. Only a difference of a few
degrees was found between the torsion angle of the experimental
and calculated structures of 2ÁH2O. There are two types of intramo-
lecular interactions in the calculated model of the 5-(2-Benzoimi-
dazole-1-yl-ethoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid me-thyl ester molecule. The oxygen atom of the ester function
interacts with the suitable H-atom of the methylene group. The
lengths of this H-bond are 2.44 Å, 2.66 Å and 2.46 Å, 2.55 Å in both
calculations respectively. Furthermore, a bicyclic aromatic ring ap-
proaches the water hydrogen at a distance of 1.92 Å. This contact is
replaced in the crystal by an inter-associate contact of a bicyclic aro-
matic ring to water at a distance 2.06 Å. Similar calculated molecu-
lar models were found for both the anhydrous and the hydrate
forms 2 and 2ÁH2O, respectively. Thus, water exerts a moderate
effect on the geometry of the 5-(2-benzoimidazole-1-yl-ethoxy)-
3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester.
À4.1
À3.7
176.7
À26.4
À143.7
94.8
177.2
À25.2
À142.6
95.9
The crystal structure of 2 shows the presence of water mole-
cules in the crystal packing diagram, which play an important role
in the crystal packing as they act as mediator and facilitate the net-
work of weak interactions throughout the crystal packing involv-
ing CAHÁ Á ÁO, and OAHÁ Á ÁN donor–acceptor interactions. The
distance between H40 (water) and N2 of benzimidazole 5-mem-
bered ring (OAHÁ Á ÁN) was 2.06 Å. Packing diagram reveals that
one water molecule is engaged in stabilizing six molecules of 2
as shown in Fig. 2b–d. Incorporation of water generates channel
like regular arrangement of molecules of 2 in which water mole-
cule is trapped in crystal packing through short CAHÁ Á ÁO contacts
of 2.57 Å with an angle of 151.91°. This (2)–water aggregate en-
hances the H-bond acceptor strength of the water oxygen (O4)
by the polarization of the OAH bonds of the water molecule. Inter-
Fig. 3. Near-identical perspective views of 5-(2-benzoimidazole-1-yl-ethoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl esterÁH2O (a) XRD model; (b) of the
calculated anhydrous 1; (c) of calculated 1ÁH2O (all calculated models are at the B3LYP/6-31+G(d,p) level of theory).

24
P. Srivastava et al. / Journal of Molecular Structure 1007 (2012) 20–25
Differences between the experimental 2ÁH2O and the calculated
model were also characterized by means of the root mean square
standard deviation (r.m.s.d.) values of the superposed structures.
Thus comparisons of the anhydrous form geometry of 2 against
those of the calculated one for 2ÁH2O and the one from the crystal
structure of 2Á0.5H2O show only a slight adjustment of the host mol-
ecule upon water binding (Fig. 3).
Theoretical MP2 calculation is also done to study the role of
multipoles in the system because Coulombic interactions can be
expressed as the sum of the attraction terms between charges
and/or permanent multipoles. The orientation of the system is
same as in the DFT calculation, it means, this is the most stable ori-
entation of the system by theoretical calculations. Various coulom-
bic interactions taking part in the molecular system by the
presence of charge, dipole moment, quadrupole moment, octapole
moment and hexadecapole moment in the system. In the case of
purposes. These studies help us to design the molecule having aro-
matic moiety with hydrophilic in nature.
Acknowledgements
Authors gratefully acknowledge Department of Science and
Technology, New Delhi for financial assistance in Young Scientist
scheme. Department of Chemistry, Faculty of Science, Banaras Hin-
du University, Varanasi INDIA is acknowledged for departmental
facilities. VPS also acknowledges to CSIR-New Delhi for senior re-
search fellowship.
Appendix A. Supplementary material
Crystallographic data for the structure 2 reported in this paper
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication No. CCDC – 654472. Supple-
mentary data associated with this article can be found, in the on-
line version, at doi:10.1016/j.molstruc.2011.09.004.
the CH/p interaction, p-base is generally not dipolar. Even if the
CAH group can be a strong dipole when the carbon atom is substi-
tuted with more than one electronegative group or the ring is at-
tached with many groups, the interaction cannot be so strong as
to be observable in polar solvents. Actually CH/
shown to persist even in polar solvent. Thus, the CH/
is clearly different from Coulombic interaction. The aromatic
system has a large quadrupole/or mutipole which can enhance
the CH/ interactions [39]. In the calculation of compound
p
interactions are
References
p
interaction
p
-
[1] M. Hospital, C. Courseille, F. Leroy, B.P. Roques, Biopolymers 18 (1979) 1029.
[2] (a) G.R. Desiraju, Crystal Engineering: The design of organic solids, Elsevier,
Amsterdam, 1989;
p
(b) G.R. Desiraju, The Crystal as a Supramolecular Entity, Wiley, Chichaster,
1995;
(b) J.M. Lehn, Supramolecular Chemistry: Concepts and Perspectives, VCH,
Weinheim, 1995.
(2)ÁH2O by MP2 method there is dipole moment, quadrupole mo-
ment, octapole moment, hexadecapole moment, these multipoles
enhances the CH/p interactions (values are given in the Supple-
[3] (a) C.B. Aakeroy, K.P. Seddon, Chem. Soc. Rev. (1993) 397;
(b) E.A. Archer, H. Gong, M.J. Krische, Tetrahederon 57 (2001) 1139.
[4] G.R. Desiraju, Angew. Chem. Int. Ed. Engl. 34 (1995) 2311.
[5] (a) T. Nishinaga, N. Nodera, Y. Miyata, K. Komatsu, J. Org. Chem. 67 (2002)
6091;
(b) V.R. Vangala, A. Nangia, V.M. Lynch, Chem. Commun. (2002) 1304.
[6] L. Jiang, L. Lai, J. Biol. Chem. 277 (2002) 37732.
[7] M. Nishio, Cryst. Eng. Comm. 6 (2004) 130.
[8] G. Stefan, Angew. Chem. Int. Ed. 47 (2008) 3430.
[9] J.B. Baruah, A. Karmakar, N. Barooah, Cryst. Eng. Comm. 10 (2008) 151.
[10] G.R. Desiraju, Cryst. Eng. Comm. 9 (2007) 91.
[11] (a) L.L. Shen, J. Baranowski, A.G. Pernet, Biochemistry 28 (1989) 3879;
(b) Y. Umezawa, M. Nishio, Biopolymers 79 (2005) 248;
(c) T. Ozawa, K. Okazaki, J. Comput. Chem. 29 (2008) 2656.
[12] (a) G.R. Desiraju, Science 278 (1997) 404;
mentary information).
On the basis of these findings, host 2 may well be considered as
a preorganized compound for water fixation. As expounded by
Cram [40], Lehn [41], Reinhoudt and Dijkstra [42] and Schmidtchen
et al. [43] in many details a preformed molecular scaffold has lots
of advantages in host–guest chemistry from some aspects. Firstly
energy costs of providing a nearly ideal molecular recognition cav-
ity, pocket, cleft or frameworks are already paid off at the covalent
synthesis step of the target host. Thus, creating a supramolecular
assembly will not be prohibitive in energy terms as, e.g. entropy
loss of guest binding may be rewarded by enthalpy gain from
well-placed hydrogen bonding attachment sites. As pointed out
earlier, [41] binding of neutral species such as water may require
more assistance, as neutral guests have much smaller free energies
of complexation. Molecule 2 with its deformed conformation, with
the linked OAHÁ Á ÁN bridge and the juxtaposed PLO functions at
proper distances all qualify for a preorganized minimum-size ring
system. It must be noted that the hydrophobic outer skin of 2 and
the hydrophilic internal region should also promote water binding
by the PLO functions. Thus, an ideal micro-environment is pro-
vided by the molecule 2.
(b) D. Braga, L. Maini, C. Fagnano, P. Taddei, M.R. Chierotti, R. Gobetto, Eur. J.
Chem. 13 (2007) 1222.
[13] (a) G.R. Desiraju, Acc. Chem. Res. 29 (1996) 441;
(b) T. Steiner, Chem. Commun. (1997) 727;
(c) T. Steiner, Angew. Chem. Int. Ed. 41 (2002) 48.
[14] Z. Berkovitch-Yellin, L. Leiserowitz, Acta Crystallogr., Sect. B 40 (1984) 159.
[15] (a) Z.S. Derewenda, L. Lee, U. Derewenda, J. Mol. Biol. 252 (1995) 248;
(b) P. Chakrabarti, S. Chakrabarti, J. Mol. Biol. 284 (1998) 867.
[16] M. Oda, Genes Cells 5 (2000) 319.
[17] J.W. Schwabe, Curr. Opin. Struct. Biol. 7 (1997) 126.
[18] B. Jayaram, T. Jain, Annu. Rev. Biophys. Biomol. Struct. 33 (2004) 343.
[19] J. Elguero, P. Goya, N. Jagerovic, A.M.S. Silva, Ital. Soc. Chem. 6 (2002) 52.
[20] R.N. Mahajan, F.H. Havaldar, S. Fernandes, J. Ind. Chem. Soc. 68 (1991) 245.
[21] P.G. Baraldi, S. Manfridini, R. Romagnoli, L. Stevanato, A.N. Zaid, R. Manserviji,
Nucleos. Nucleot. 17 (1998) 2165.
[22] G.J. Hatheway, C. Hansch, K.H. Kim, S.R. Milstein, C.L. Schimidt, R.N. Smith, F.R.
Quin, J. Med. Chem. 21 (1978) 563.
5. Conclusions
[23] R.V. Reidel, Arzneim Forsch/Drug Res. 31 (1981) 655.
[24] P.D. Mishra, S. Wahidullah, S.Y. Kamat, Ind. J. Chem. B37 (1998) 199.
[25] M. Londershausen, Pestic. Sci. 48 (1996) 269.
The crystal structure of 2Á0.5H2O corroborates the existence of
the proposed OAHÁ Á ÁN interaction. The solid state structure indi-
cates marked activity of the aromatic-CH group in both intra-
[26] S.H. Chen, M. Li, Chem. J. Chin. Univ. (1998) 572.
[27] F. Lepage, B. Hublot, Chem. Abstr. 116 (1992) 128917.
[28] M.R. Harnden, S. Bailey, M.R. Boyd, D.R. Taylor, N.D. Wright, J. Med. Chem. 21
(1978) 82.
[29] A. Elagamey, F.M.A. Taweel, F.A. Amer, H.H. Zoorob, Arch. Pharm. (Weinheim)
320 (1987) 246.
[30] A. Angermann, H. Franke, Chem. Abstr. 131 (2001) 5253.
[31] C.P. Kordik, L. Dax Scott, Chem. Abstr. 135 (2003) 195563.
[32] R.K. Robins, G.R. Revanker, J. Heterocycl. Chem. 22 (1985) 601.
[33] A. Grossurt, H.R. Van, J. Agric. Food Chem. 27 (1979) 406.
[34] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
J.A. Montgomery, Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda,O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox,
and intermolecular CAHÁ Á Á
p hydrogen bridge with aromatic rings.
Due to its high electron density, the five-membered ring of benzo-
imidazole fragment may tightly bind to water molecule. Such a
binding is certainly facilitated by the well-known interactions be-
hind classic intra-associate OAHÁ Á ÁN, OAHÁ Á Á
p and H-bridges as
well as those behind both inter- and intra-associate OAHÁ Á ÁN con-
tacts. Comparisons of the experimental 2Á0.5H2O structure and the
theoretical models for 2 and 2ÁH2O also present 2 as a kind of suit-
able ring of molecule for water binding. Apparently, the hygro-
scopic compound 2 may provide a model for water sensing

P. Srivastava et al. / Journal of Molecular Structure 1007 (2012) 20–25
[36] PCMODEL Version 7, Serena Software, Bloomington, 2000.
25
H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann,
O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K.
Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S.
Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J.
Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L.
Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M.
Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A.
Pople, Gaussian 03, Revision B.05, Gaussian, Inc., Pittsburgh PA, USA, 2003.
[35] G.M. Sheldrick, SHELX-97-2, Program for Crystal Structure Solution and
Refinement. Institute fur anorg chemie, Gottingen, Germany, 2001.
[37] Mercury, Version 1.4.1, Cambridge Structural Database, Cambridge, UK,
2006.
[38] D. Hadzi, Theoretical Treatments of Hydrogen Bonding, J. Wiley & Sons, Wiley
Series in Theoretical Chemistry, New York, 1997.
[39] M. Nishio, M. Hirota, Y. Umezawa, The CH-[pi] Interaction: Evidence, Nature,
and Consequences, Wiley-VCH, 1998.
[40] D.J. Cram, Angew. Chem. Int. Ed. 25 (1986) 1039.
[41] J.M. Lehn, Angew. Chem. 100 (1988) 91.
[42] D.N. Reinhoudt, P.J. Dijkstra, Pure Appl. Chem. (1988) 60477.
[43] F.P. Schmidtchen, A. Gleich, A. Schummer, Pure Appl. Chem. 61 (1989) 1535.