Synthesis, crystal structure analysis, small cluster geometries and energy study of (E)-Ethyl-4-(2-(thiofen-2-ylmethylene)hydrazinyl)benzoate

Article abstract of DOI:10.1007/s10870-013-0455-5

Derivatives hydrazone are attributed interesting pharmacological properties. The compound under study (E)-ethyl 4-(2-(thiofen-2-ylmethylene) hydrazinyl)benzoate (1), crystallized from ethanol as translucent light yellow thin plates. They are monoclinic, space group P2₁/c, with unit cell parameters a = 8.846(6), b = 20.734(14), c = 7.583(5) A, β = 95.743(13), V = 1383.8(16) A³. Three hydrogen bonds and two intermolecular π-interaction perpendiculars to the hydrogen bonds patterns are observed in the crystal structure. A detailed description of these interactions will be presented. Also, semiempirical calculations (PM6) show the formation in the gas phase of a supramolecular chain, emulating the C(8) graph set seen in the crystal structure of the compound. Graphical Abstract: The synthesis and crystal structure of the title compound, C₁₄H ₁₄N₂O₂S, is reported.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-013-0455-5

J Chem Crystallogr
DOI 10.1007/s10870-013-0455-5
ORIGINAL PAPER
Synthesis, Crystal Structure Analysis, Small Cluster Geometries
and Energy Study of (E)-Ethyl-4-(2-(thiofen-2-ylmethylene)
hydrazinyl)benzoate
•
Miguel Morales-Toyo Ysaıas J. Alvarado
•
´
•
•
•
Jelen Restrepo Luis Seijas Reinaldo Atencio
Julia Bruno-Colmenarez
Received: 29 January 2013 / Accepted: 13 July 2013
Ó Springer Science+Business Media New York 2013
Abstract Derivatives hydrazone are attributed interesting
pharmacological properties. The compound under study (E)-
ethyl 4-(2-(thiofen-2-ylmethylene) hydrazinyl)benzoate (1),
crystallized from ethanol as translucent light yellow thin
plates. They are monoclinic, space group P21/c, with unitcell
Keywords Hydrazone ꢀ Crystal structure ꢀ
Hydrogen bonds ꢀ Semiempirical calculations
Introduction
˚
parameters a = 8.846(6), b = 20.734(14), c = 7.583(5) A,
3
˚
b = 95.743(13)°, V = 1383.8(16) A . Three hydrogen
Hydrazones have shown potential medical applications due
to their biological activities as antitumor, anticonvulsants,
antimalarial, analgesic, anti-mycobacterial, vasodilators,
anti-inflammatory, antivirals agents [1–3]. In recent works,
we have studied the interaction of 2,4-dinitro-phenylhy-
drazones of furan and thiophene with biomolecular targets
for cancer treatment such as DNA and tubulin [4, 5].
Additionally, the interaction of these compounds with
water and aprotic solvents was also studied, and related
with their biological activities [6]. According to these
studies the hydrophobic effect, associated with the number
of nitro groups on the phenyl ring, is the major driving
force involved in the binding of drugs to their receptor
targets [4, 5]. The hydrophobic character makes necessary
the use of a co-solvent, currently DMSO, which may cause
DNA damage at concentrations above 1 % (v/v) [7].
In this respect, our group was prompted to modify the
structure of the above mentioned hydrazones with the aim
of decreasing hydrophobicity without loss of biological
activity. One strategy consists in substitute the nitro
groups, responsible for the hydrophobic character, by ester
groups. In this sense, we have reported the synthesis,
spectroscopic, and crystallographic characterization of the
(E)-Ethyl-4(2(thiofen-2-ylmethylene)hydrazinyl)benzoate
(1). Additionally, in order to support the description of the
supramolecular structure of crystals, a theoretical study
through semiempirical quantum mechanical methods with
the second-generation hydrogen-bonding correction (PM6-
DH2) was carried out.
bonds and two intermolecular p-interaction perpendiculars
to the hydrogen bonds patterns are observed in the crystal
structure. A detailed description of these interactions will be
presented. Also, semiempirical calculations (PM6) show the
formation in the gas phase of a supramolecular chain, emu-
lating the C(8) graph set seen in the crystal structure of the
compound.
M. Morales-Toyo ꢀ Y. J. Alvarado ꢀ J. Restrepo
´
Laboratorio de Caracterizacion Molecular y Biomolecular
(LCMB), Departamento de Investigacion en Tecnologıa de los
´
´
Materiales y del Ambiente (DITeMA), Instituto Venezolano de
´
Investigaciones Cientıficas (IVIC), 4001 Maracaibo, Venezuela
L. Seijas
Laboratorio de Procesos Dinamicos en Quımica, Departamento
´
de Quımica, Facultad de Ciencias, Universidad de Los Andes,
´
´
5101 Merida, Venezuela
´
R. Atencio
Laboratorio de materiales para tecnologıas emergentes
´
(LaMTE), Departamento de Investigacion en Tecnologıa de los
Materiales y del Ambiente (DITeMA), Instituto Venezolano de
´
Investigaciones Cientıficas (IVIC), 4001 La Can˜ada de Urdaneta,
Venezuela
´
´
J. Bruno-Colmenarez (&)
´
Unidad de Caracterizacion y Estructura de Materiales, Instituto
Zuliano de Investigaciones Tecnologicas, 4001 La Can˜ada de
´
Urdaneta, Venezuela
e-mail: jbrunoc@inzit.gob.ve
123

J Chem Crystallogr
Experimental
H atoms bound to the N atom were placed in calculated
positions and refined using a riding model with N–H =
˚
0.86 A and Uiso(H) = 1.2 Ueq(N).
General Procedures and Materials
Melting point was determined on a digital IA-9100
ELECTROTHERMAL fusiometer. The IR spectrum was
recorded on a Shimadzu model 8300 FTIR spectropho-
tometer, as KBr pellets.
Semiempirical Calculations
The geometrical features and packing of molecular clusters
are determined in good measure by non-covalent interac-
tions, i.e. van-der-Waals and hydrogen bonds, between the
molecules making up the clusters. As a consequence of this
fact, a detailed and exact theoretical characterization of
molecular clusters as those studied here involves intensive
and demanding calculations and require expensive com-
putational tasks. Nevertheless, in general, modeling these
kind of complex systems is difficult to perform with such
desirable high level of calculations, and frequently,
approximated methods have to be employed. Among them,
the semiempirical methods have been widely used
[10].One of the existing limitations of the semiempirical
methods has been the description of many-body interac-
tions, which are important in accounting for the molecular
polarization and charge delocalization among the cluster
components and play a major role in describing coopera-
tive effects. however, in the last few years, corrections, i. e.
those required for including dispersion effects involved in
non-covalent interactions, have been introduced into a wide
range of semiempirical methods [10]. This fact has
broadened substantially the range of applicability of these
methods, in particular, making feasible their application to
the description of complex systems, such as the supramo-
lecular structures found in the organic crystals of cis-4-
aminocyclohexanecarboxylic acid that involve head-to-tail
interactions. Thus, in this work we have performed semi-
empirical calculations using a version of the PM6 method
[11] that has implemented a second generation correction
for the description of hydrogen bonds (DH2) [12]. This
correction includes the dispersion effect as a pairwise
interatomic force field [12]. Additionally, the energy cor-
rections due to the presence of hydrogen bonds are
Synthesis of (E)-Ethyl-4-(2-(thiofen-2-
ylmethylene)hydrazinyl)benzoate (1)
In a 100 mL round bottom flask, 1.24 g (4.62 mmol) of
ethyl 4-hydrazinylbenzoate hydrochloride was dissolved in
50 mL of distilled water under magnetic stirring. Then,
0.52 lL (5.54 mmol) of thiophene-2-carbaldehyde were
added slowly, stirring for about 20 min after the addition of
the aldehyde. The product was collected by filtration,
washed with 0.1 M HCl and then with 20 % NaHSO3. The
product was recrystallized in EtOH as translucent light-
yellow plates with melting point 186–188 °C (Scheme 1).
Single Crystal X-Ray Data Collection and Structure
Determination
The single crystal X-ray diffraction analysis was carried
out on a KAPPA APEX II DUO Diffractometer with
graphite monochromator Mo-Ka radiation (k = 0.71069
˚
A) operating at 50 kV and 30 mA. A thin plate of (1) of
approximate dimensions 0.08 mm 9 0.14 mm 9 0.56 mm
was used. A total of 2160 frames were collected with u and
x scans’ every 0.30° for 10 s each [8].
The structure was solved and refined using the Bruker
SHELXTL Software Package [9]. The non-hydrogen atoms
were refined anisotropically, while the hydrogen atoms
bound to C atoms were placed geometrically and refined
˚
using a riding model, with C–H = 0.93 A, Uiso(H) = 1.2
˚
Ueq(C) for aryl H; C–H = 0.97 A for methylene H; and
˚
C–H = 0.96 A Uiso(H) = 1.5 Ueq(C) for methyl H.
Scheme 1 Synthesis of (E)-Ethyl-4-(2-(thiofen-2-ylmethylene)hydrazinyl)benzoate (1) from ethyl 4-hydrazinylbenzoate hydrochloride (a) and
thiophene-2-carbaldehyde (b) [22]
123

J Chem Crystallogr
dependent on the steric donor–acceptor arrangement,
defined by six internal coordinates: the HꢀꢀꢀA distance, the
AꢀꢀꢀH–D and R–AꢀꢀꢀH angles, and the three torsional angles
defining the relative position of the hydrogen bond.
In this work, we compute the stabilization energy due to
the formation of the clusters per participating molecule, this
is:
Table 1 Crystal data and refinement for compound (1)
Crystal data
Formula
C14H14N2O2S
Formula weight
Crystal system
Space group
274.34
Monoclinic
P21/c (No. 14)
˚
a, b, c (A)
8.846(6) 20.734(14)
7.583(5)
DE En ꢁ ðnE0Þ
¼
ð1Þ
alpha, beta, gamma (deg)
90
n
n
95.743(13)
Here En is the total energy for the cluster, E0 is the energy
of the optimized monomer, n is their number of monomers
in the cluster. The calculation of DE allows evidencing the
cooperative enhancement in the formation energy of the
clusters [13]. Additionally, this quantity is well suited for
extrapolations toward n ? ?, which is the case of
extended chains [14]. This extrapolation is useful for
obtaining estimates of the stabilization energies of exten-
ded systems, as the ones considered here [15].
90
3
˚
V (A )
1383.8(16)
Z
4
D(calc) (g/cm3)
Mu(MoKa)
F(000)
1.317
0.233
576
Crystal size (mm)
Data collection
Temperature (K)
0.08 9 0.14 9 0.56
296
˚
Radiation (A)
MoKa 0.71070
2.0, 28.9
Theta min–max (Deg)
Dataset
Results and Discussion
–11:9; –27:28; –10:10
21936, 3516, 0.032
2491
Tot., uniq. data, R(int)
Observed data [I [ 2.0 sigma(I)]
Refinement
Spectroscopy IR and Synthesis of (E)-Ethyl-4-(2-
(thiofen-2-ylmethylene)hydrazinyl)benzoate
This compound was synthetized from ethyl 4-hydra-
zinobenzoate hydrochloride (a) and thiophene-2-carbalde-
hyde (b) according to the procedure 2. Yield 82 %, yellow
solid. m.p.186–188 °C. IR (KBr) cm-1: 3273.6 (NH);
1681.8 (N=C), 1600.8 (C=C); 1365.5 (–NO2) 1272.9
(C–S–C).
Nref, Npar
3516, 173
R, wR2, S
0.0421, 0.1256, 1.02
0.00, 0.00
Max. and Av. shift/error
Min. and max. resd. dens. [e/Ang^3]
–0.34, 0.32
˚
Table 2 Selected bond distances (A) and angles (°) for compound (1)
Analysis of the Crystal Structure of (E)-Ethyl-4-(2-
N1–N2
1.365(2)
C8–C9
1.3972
(thiofen-2-ylmethylene)hydrazinyl)benzoate
N1–C5
N2–C6
N2–H1
S1–C1
S1–C4
C1–C2
C2–C3
C3–C4
C6–C7
C6–C11
C7–C8
1.281(2)
1.380(2)
0.8600
1.7167
1.7064
1.3970
1.4240
1.3390
1.4010
1.4037
1.3787
C9–C10
1.3984
The details of crystal data and refinement are given in
Table 1. A search previous in the Cambridge Structural
Database (CSD) [16] no produced any results. Table 2
contain relevant bond lengths and angles for this com-
pound. Figure 1 show the molecular structure with the
atom numbering scheme.
C10–C11
1.3805
N2–N1–C5
N1–N2–C6
C6–N2–H1
N1–N2–H1
N2–C6–C7
N1–C5–C1
N2–C6–C11
N2–C6–C7
116.05(13)
120.99(13)
120.00
119.00
The bond distances (Table 2) within the thiophene ring
and benzoate ring are consistent with aromatic delocal-
ization. The dihedral angle between the thiophene ring and
the adjacent benzoate ring is 7.368(53)°.Table 3 shows the
geometrical parameters of the two intermolecular hydrogen
bonds observed in the crystal structure, N2–H1ꢀꢀꢀO1 (blue
bond) and C5–H6ꢀꢀꢀO1 (purple bond), these interactions are
depicted in Fig. 2 as blue and purple dashed lines,
respectively. The first one correspond to a classical inter-
molecular hydrogen bond, the geometric parameters for
this interactions mach with the mean values observed for
118.96(14
122.04(15)
122.00(14)
118.96(14)
N–HꢀꢀꢀO interactions between similar moieties (CSD).
The interaction C5–H6ꢀꢀꢀO1 corresponds to a non-classi-
cal intermolecular hydrogen bond, this type interaction
has been observed between similar moieties in eight
reports on the CSD, of which may be mentioned,
123

J Chem Crystallogr
Dimethyl 3-(((2,4-dinitrophenyl)hydrazono)methyl)-4-methyl-
5-methylenecyclohex-3-ene-1,1-dicarboxylate, refcode EBU-
VUS [17] and methyl 2-(2-bromo-4,5-dimethoxyphenyl)-4-
((2,4-dinitrophenyl) hydrazonomethyl)-7-methoxy-2,3-dihy-
drobenzofuran-3-carboxylate dichloromethane solvate, refcode
QAVXER [18] and have similar geometrical parameters for
the interaction C–HꢀꢀꢀO observed in the crystal structure of
compound 1. As shown in Fig. 2, the intermolecular inter-
actions N–HꢀꢀꢀO and C–HꢀꢀꢀO are represented by the graph
set symbol C(8) and C(10) respectively and these produce
infinite chains along the a axes. The intramolecular non-
classical hydrogen bond C8–H3ꢀꢀꢀO2 (Table 4), observed in
compound 1 can be described by the graph set symbol S(5).
Compound 1, also present two intermolecular p-interaction
perpendicular to the hydrogen bonds patterns above descri-
˚
bed, this interaction involve atoms C4–H11ꢀꢀꢀCg1 [2.88 A,
˚
139°] and C12–O1ꢀꢀꢀCg2 [3.60 A, 86.24°]. Cg1 and Cg2
correspond to centroid the thiophene ring and benzoate ring
respectively.
The p-interaction C4–H11ꢀꢀꢀCg1 produces as parallel
chains growing along the c axis. Between each chain, we
observed the hydrazone molecules alternating with each
other, and connected by the interaction C12–O1ꢀꢀꢀCg2 this
interaction occurs between the carbonyl oxygen from a
Fig. 1 Molecular structure of (E)-Ethyl-4-(2-(thiofen-2-ylmethyl-
ene)hydrazinyl)benzoate [21]
Table 3 Hydrogen bonds and short contacts for compound (1)
H–Bond
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–H–A
Symmetry
Motif
N2–H1ꢀꢀꢀO1
C5–H6ꢀꢀꢀO1
C8–H3ꢀꢀꢀO2
C4–H11ꢀꢀꢀCg1
0.86
0.93
0.93
0.93
2.16
2.58
2.45
2.88
2.986(3)
3.375(3)
2.758(3)
3.632(3)
162
144
100
139
–1 ? x,y,z
–1 ? x,y,z
C(8)
C(10)
S(5)
x,–1/2–y,1/2 ? z
Short Contacts Y–XꢀꢀꢀCg
Y–X
XꢀꢀꢀCg
YꢀꢀꢀCg
Y–X–Cg
86.24
Symmetry
Motif
C12–O1ꢀꢀꢀCg2
1.3434
3.596
3.7190
1–x,–y,–z
Cg1 is the centroid of the thiophene ring and Cg2 is the centroid of the benzoate ring
Fig. 2 View of the structure of (E)-Ethyl-4-(2-(thiofen-2-ylmethylene)hydrazinyl)benzoate along the b axes
123

J Chem Crystallogr
Small Cluster Geometries and Energy
Table 4 Average value on selected geometrical details of ethyl-4-(2-
(thiofen-2-ylmethylene)hydrazinyl)benzoate clusters
˚
˚
The geometry of the optimized monomer (blue) compared
with the crystal structure (green) is exhibited in Fig. 3. The
largest differences of the optimized monomer are in the
thiophene and ester moieties, these differences are due to a
higher planarity of the molecule in the gas phase. The
calculated value for E0 is –69451.171 kcal/mol. The opti-
mized geometry of the dimer is found starting from opti-
mized monomers at several intermolecular relative
orientations. Once this structure was obtained, a monomer
is randomly placed close to it, and optimization of the
trimer is carried out. This procedure is repeated many times
and the result reported corresponds to the obtained mini-
mum having the smallest energy.
Cluster HꢀꢀꢀO (A) NꢀꢀꢀO (A) N–HꢀꢀꢀO (°) Dihedral angle
between interacting
molecules (°)
2
3
4
5
1.892
1.776
1.861
2.032
2.874
2.823
2.847
2.988
155.9
151.0
156.3
150.5
58.1
46.1
28.3
2.07
molecule and the benzoate ring from a symmetry-related
molecule. Between the thiophene ring and benzoate ring
it’s observed a p–p interaction. All this no-covalent inter-
actions generate a packing arrangement as a parallel layers
in zigzag pattern with a packing index of 67.0 % without
solvent accessible voids in the structure.
˚
In the dimer the NꢀꢀꢀO distance is 2.874 and 0.1 A shorter
respect to distance observed in the crystal (Table 5). The
molecules in the gas phase dimer displays a dihedral angle,
between the two mean molecular planes, of 58.1°, while in
the crystal structure, the molecular planes between two
interacting molecules are almost parallel. In the trimer and
the tetramer the average NꢀꢀꢀO distance are 2.823 and
A single p–p interaction between thiophene ring and
benzoate ring links the molecules into pairs. The reference
molecule is related by inversion to the adjacent molecules
lying across the axes along (–x, –y, 1 – z). The ring cen-
troid separations between the thiophene ring and benzoate
˚
˚
2.847 A respectively, being these about 0.14 A shorter than
in the crystal, the dihedral angles of the molecular planes
betweentwo interacting moleculesare 46.1° and 28.3°. In the
pentamer the NꢀꢀꢀO distance is larger than the others clusters
˚
ring from an adjacent molecule is 3.788(2) A. Propagation
of this interaction by inversion thus generates a dimers of
p-stacked molecules along the [100] direction.
˚
˚
with a value of 2.988 A and only differs on 0.002 A with the
distance observed in the crystal, for this cluster the dihedral
angle between two interacting molecules decreases to 2.07°,
this decrease implies a nearing of the hydrogen atoms. These
HꢀꢀꢀH contacts in the pentamer induce short repulsive inter-
action between molecules [19].
For the fully optimized clusters, the variation of the
stabilization energy per participating molecule (DE) is
displayed in Fig. 4a. From there, it is possible to see that,
due to the creation of a HB, a sharp stabilization accom-
panies the formation of the dimer. Moreover, it is also
observed that the bonding of new monomers increases
gradually the stabilization energy per molecule. From
Fig. 3 Comparison of the crystal structure of (E)-Ethyl-4-(2-(thiofen-
2-ylmethylene)hydrazinyl)benzoate (green) with the structure
obtained from the PM6-DH2 calculations (blue)
Fig. 4 a Variation of the stabilization energy per molecule with the number of monomers in the cluster. b Variation of the stabilization energy
per molecule in function of the inverse of the number of monomers, 1/n in compound 1 clusters
123

J Chem Crystallogr
Ojeda-Andara J, Thomas L, Vera-Villalobos J, Morales-Toyo M
(2011) Thermodynamics of solution, interaction with calf thymus
DNA and anticancer activity of phenylhydrazone derivatives.
J Sol Chem. 40(5):26–39
Fig. 4a we can also conclude that the stabilization rate
decreases with the cluster size, which should lead to an
asymptotic value for the stabilization energy per molecule.
At this point it is convenient to recall that simple electro-
static models predict that the stabilization energy per
molecule should be constant; therefore, the additional sta-
bilization is the result of the presence of cooperative
effects, consequence of the formation of consecutives HB
of the type N–HꢀꢀꢀO between the interacting molecules[20].
If the dependence of DE with the cluster size is considered
in terms of the inverse of n, a nearly perfect linear behavior
is obtained (Fig. 4b). This fact, allows us to perform an
extrapolation to the asymptotic limit of an infinite chain,
n ? ?, which leads to an estimate of –7.30 kcal/mol for
the maximum stabilization energy for the clusters. This
value represents an increment of approximately 44 % in
the stabilization energy respect to that of the dimer.
6. Alvarado Y, Caldera-Luzardo J, Ferrer-Amado G, Mancilla-La-
barca V, Michelena E (2007) Determination of the apparent
molar refraction and partial molar volume at infinite dilution of
thiophene-, pyrrole- and furan-2-carboxaldehyde phenylhydraz-
one derivatives in acetonitrile at 293.15 K. J Sol Chem 36(6):
1–11
´
7. Alvarado Y, Ballestas-Barrientos A, Cubillan N, Morales-Toyo
M, Restrepo J, Ferrer-Amado G (2012) Peferential solvation of
thiophene and furan-2-carboxaldehyde phenylhydrazone deriva-
tives in DMSO-Water and DMSO-n-Octanol mixtures. Spectro-
chim Acta Part A 103:361–367
8. Bruker (1998b) SAINT: SAX Area-detector Integration, Version
5.01, Bruker AXS, Inc., Madison, Wisconsin, USA
9. Sheldrick G (2008) A short history of SHELX. Acta Cryst A 64:
112–122
10. Hobza P (2011) The calculation of intermolecular interaction
energies. Annu Rep Prog Chem Sect C 107:148–168
11. Stewart J (2007) Optimization of Parameters for Semiempirical
Methods V: modification of NDDO Approximations and Appli-
cation to 70 Elements. J Mol Modeling 13:1173–1213
Supplementary material
ˇ´
ˇ ´ˇ
12. Korth M, Pitonak M, Rezac J, Hobza P (2010) A transferable
H-bonding correction for semiempirical quantum-chemical
methods. J Chem Theory Comput 6:344–352
X-ray crystallographic data for this structure has been
deposited at the Cambridge Crystallographic Data Center
under code CCDC 908021.
13. Karpfen A (2002) Cooperative effects in hydrogen bonding. Adv
Chem Phys 123:469–510
ˇ
ˇ
14. Jurecka P, Cerny J, Hobza P, Salahub D (2007) Density func-
tional theory augmented with an empirical dispersion term.
Interaction energies and geometries of 80 noncovalent complexes
compared with ab initio quantum mechanics calculations.
J Comput Chem 28(2):555–569
15. Karpfen A (1997) In: Scheiner S (ed) Molecular interacctions
from.van der Waals to strongly bond molecular complexes.
Wiley, Chichester, p 265
Acknowledgments The authors thank Fondo Nacional de Ciencia,
Tecnolog´ıa e Innovacio´n (FONACIT Proyecto de apoyo a Gru-
pos No. G-2005000403) and grant LOCTI-2007-0003, Instituto
Zuliano de Investigaciones Tecnolo´gicas (INZIT), CONDES-LUZ,
and Petroregional del Lago S. A. (PERLA) for partial financial sup-
port of this work, and to Prof. Graciela Diaz de Delgado for helpful
discussions.
16. Allen F (2002) The Cambridge Structural Database: a quarter of a
million crystal structures and rising. Acta Cryst B 58:380–388
17. Kitamura T, Sato T, Mori M (2001) Unexpected results of enyne
metathesis using a ruthenium complex containing an N-hetero-
cyclic carbene ligand. Chem Commun 14:1258–1259
18. O’Malley SJ, Tan KL, Watzke A, Bergman RG, Ellman JA
(2005) Total synthesis of (?)-Lithospermic acid by asymmetric
intramolecular alkylation via catalytic C-H bond activation.
J Am Chem Soc 127:13496–13497
19. Williams DE, Craycroft DJ (1987) Nonbonded hydrogenꢀꢀꢀhydro-
gen repulsion energy from ab initio SCF calculations of methane,
ammonia, water, and methanol dimmers. J Phys Chem 91:
6365–6373
References
1. Rollas S, Ku¨c¸u¨kgu¨zel G (2007) Biological activities of hydrazone
derivatives. Molecules 12:1910–1939
2. Abdel-Zaher E, Dib H, Al-Awadi N, Elnagdi M (2007) Chemistry
of carbofunctionally substituted hydrazones. Arkivoc II:272–315
3. Belskaya N, Dehaen W, Bakulev V (2010) Synthesis and prop-
erties of hydrazones bearing amide, thioamide and amidine
functions. Arkivoc I:275–332
´
4. Alvarado Y, Alvarez-Mon M, Baricelli J, Caldera-Luzardo J,
´
Cubillan N, Ferrer-Amado G, Hassanhi M, Marrero-Ponce Y,
Mancilla V, Rocafull M, San Antonio-Sanchez M, Ojeda-Andara
´
´
20. Rincon L, Almeida R, Garcıa-Aldea D, Diez y Riega H (2001)
Hydrogen bond cooperativity and electron delocalization in
hydrogen fluoride clusters. J Chem Phys 114:5552–5562
21. Brandenburg K, Putz H (2005) DIAMOND. Crystal Impact GbR,
Bonn
´
J, Thomas L (2010) Solubility of thiophene-, furan- and pyrrole-
2-carboxaldehyde phenylhydrazone derivatives in 2.82 mol L–1
aqueous DMSO at 298.15 K, inhibition of lymphoproliferation
and tubulin polymerization: a study based on the scaled particle
theory. J Sol Chem 39:1099–1112
22. ACD/ChemSketch Freeware (2006) version 10.00, Advanced
Chemistry Development, Inc., Toronto, ON, Canada, www.acd
labs.com
´
5. Alvarado Y, Baricelli J, Caldera-Luzardo J, Cubillan N,
Ferrer-Amado G, Marrero-Ponce Y, Mancilla V, Rocafull M,
123