Structural evaluation of three 2-phenylpyrazolo[4,3-c]quinolin-3-one monohydrates

Article abstract of DOI:10.1016/j.molstruc.2013.08.032

A single crystal X-ray diffraction and theoretical study has been carried out on mono hydrates of three 2H-pyrazolo[4,3-c]quinolin-3(5H)-one derivatives, namely 6-methyl-2-phenylpyrazolo[4,3-c]quinolin-3-one, 3, 6-methyl-2-(4- chlorophenyl)pyrazolo[4,3-c]quinolin-3-one, 4, and 8-methyl-2-(4-nitrophenyl) pyrazolo[4,3-c]quinolin-3-one, 5. The monohydrates were obtained on recrystallization from moist solvents. While there are three tautomeric forms possible for such pyrazolo[4,3-c]quinolin-3-one molecules, the sole form isolated in the solid [(X)×(H₂O)] (X = 3, 4 and 5) compounds was the quinoloid form - the one calculated to be the most stable at the M06-2X/6-311++G(d,p) level of theory. Excellent agreement was found between the calculated and X-ray determined structures. Molecule 5 in [(5)×(H ₂O)] is very near planar while both molecules 3 and 4 in their respective hydrates are much less so as a consequence of angles about 24 between the two aromatic rings. In each hydrate, the pyrazolo[4,3-c]quinolin-3-one molecule is bonded to three water molecules and each water molecule is likewise H-bonded to three pyrazolo[4,3-c]quinolin-3-one molecules. While the water molecules are H-bonded to 3 and 4 via the pyridinyl N and 2x the carbonyl O atoms, in [(5)×(H₂O)] the H-bonds are to pyridinyl N, carbonyl O and a nitro O atoms. Calculations indicated that the found arrangement in [(5)×(H₂O)] is more stable than one using the connections as found in [(3)×(H₂O)] and [(4)×(H₂O)]. While each of the hydrates possess strong N-H?O and O-H?O hydrogen bonds, and weaker C-H?π and π?π interactions, the supramolecular arrays are very different.

Full text of DOI:10.1016/j.molstruc.2013.08.032

Journal of Molecular Structure 1051 (2013) 299–309
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Structural evaluation of three 2-phenylpyrazolo[4,3-c]quinolin-3-one
monohydrates
Vitor F. Ferreira a,b, Katia Z. Leal a,c, Eric B. Lindgren a, Mara R.P. de Oliveira a,b, Maria Celia B.V. de Souza a,b
,
Thatyana R.A. Vasconcelos a,b, James L. Wardell d,e, , Solange M.S.V. Wardell f, Julliane D. Yoneda g
⇑
a Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Batista s/n°, 24020-141 Niterói, RJ, Brazil
b Departamento de Química-Orgânica, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Batista s/n°, 24020-141 Niterói, RJ, Brazil
c Departamento de Físico-Química, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Batista s/n°, 24020-141 Niterói, RJ, Brazil
d Department of Chemistry, University of Aberdeen, Old Aberdeen AB 24 3UE, Scotland, United Kingdom
e Instituto de Tecnología em Fármacos–Farmangunhos, FioCruz – Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil
f CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland, United Kingdom
g Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Fluminense, Rua Des. Ellis Hermydio Figueira 783, 27213-415 Volta Redonda, RJ, Brazil
h i g h l i g h t s
ꢀ
ꢀ
ꢀ
M06-2X/6-311++G(d,p) level calculations on structures and tautomeric stabilities of 2-phenylpyrazolo[4,3-c]quinolin-3-ones.
X-ray crystallographic study of 2-phenylpyrazolo[4,3-c]quinolin-3-one monohydrates.
Supramolecular arrangements of 2-phenylpyrazolo[4,3-c]quinolin-3-one monohydrates.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 May 2013
Received in revised form 14 August 2013
Accepted 15 August 2013
Available online 20 August 2013
A single crystal X-ray diffraction and theoretical study has been carried out on mono hydrates of three
2H-pyrazolo[4,3-c]quinolin-3(5H)-one derivatives, namely 6-methyl-2-phenylpyrazolo[4,3-c]quinolin-
3-one, 3, 6-methyl-2-(4-chlorophenyl)pyrazolo[4,3-c]quinolin-3-one, 4, and 8-methyl-2-(4-nitro-
phenyl)pyrazolo[4,3-c]quinolin-3-one, 5. The monohydrates were obtained on recrystallization from
moist solvents. While there are three tautomeric forms possible for such pyrazolo[4,3-c]quinolin-3-one
molecules, the sole form isolated in the solid [(X)ꢁ(H2O)] (X = 3, 4 and 5) compounds was the quinoloid
form – the one calculated to be the most stable at the M06-2X/6-311++G(d,p) level of theory. Excellent
agreement was found between the calculated and X-ray determined structures. Molecule 5 in [(5)ꢁ(H2O)]
is very near planar while both molecules 3 and 4 in their respective hydrates are much less so as a con-
sequence of angles about 24° between the two aromatic rings. In each hydrate, the pyrazolo[4,3-c]quin-
olin-3-one molecule is bonded to three water molecules and each water molecule is likewise H-bonded
to three pyrazolo[4,3-c]quinolin-3-one molecules. While the water molecules are H-bonded to 3 and 4
via the pyridinyl N and 2x the carbonyl O atoms, in [(5)ꢁ(H2O)] the H-bonds are to pyridinyl N, carbonyl
O and a nitro O atoms. Calculations indicated that the found arrangement in [(5)ꢁ(H2O)] is more stable
than one using the connections as found in [(3)ꢁ(H2O)] and [(4)ꢁ(H2O)]. While each of the hydrates possess
Keywords:
Pyrazolo[4,3-c]quinolin-3-one
Tautomers
X-ray structure determination
Ab initio calculations
strong NAHꢁ ꢁ ꢁO and OAHꢁ ꢁ ꢁO hydrogen bonds, and weaker CAHꢁ ꢁ ꢁ
p
and
pꢁ ꢁ ꢁp interactions, the supra-
molecular arrays are very different.
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
atives have anti-viral [2] and anti-malarial [3] activities, while 2-
phenylpyrazolo[4,3-c]quinolin-3-ones show anti-viral activites
[1,4]: they are also potent antagonists for benzodiazepine recep-
tors [5–7].
The 2-phenylpyrazolo[4,3-c]quinolin-3-ones can exist, theoret-
ically at least, in three tautomeric forms, I, II and III, see Fig. 1, with
each form possessing different donor groups and thus different po-
tential for binding to receptor molecules. The most thermodynam-
ically favoured form is I in aqueous solutions, as calculated by
Karolak-Wojciechowska et al. using the semi-empirical method
Pyrazole derivatives exhibit anti-bacterial, anti-inflammatory,
hypotensive and anti-tumor activities [1]. In particular, pyrazoles
fused with other heterocyclic systems have been found to possess
important biological activities, e.g., pyrazolo[3,4-b]quinoline deriv-
⇑
Corresponding author at: Department of Chemistry, University of Aberdeen, Old
Aberdeen AB 24 3UE, Scotland, United Kingdom. Tel.: +44 1224 312 819.
E-mail address: j.wardell@abdn.ac.uk (J.L. Wardell).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.08.032

300
V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
III
I
II
Fig. 1. Tautomeric forms of 2-phenylpyrazolo[4,3-c]quinolin-3-ones.
AM1 from the MOPAC-93 program [7]. This form is also considered
the effective form by various groups working on benzodiazepine
receptors [8]. A search of the Cambridge Structural Database in
April, 2013 revealed that the structures of only two 2-pyrazol-
o[3,4-b]quinoline derivatives, namely 2-phenyl-2,5-dihydropyraz-
2. Experimental
2.1. General
Melting points were determined on a Fisher-Johns apparatus
and are uncorrected. Infrared spectra were recorded on a Perkin–
Elmer 1420 spectrometer in KBr discs. NMR spectra were recorded
on a Varian Unity Plus 300 spectrometer DMSO-d6 solutions. Reac-
tions were monitored by thin-layer chromatography on silica-gel
pre-coated F254 Merck plates.
olo[4,3-c]-3(3H)-one
(1)
and
2-(4-chlorophenyl)-2,5-
dihydropyrazolo[4,3-c]-3(3H)-one (2), both in tautomeric form I,
had been reported [9].
As 2-phenylpyrazolo[4,3-c]quinolin-3-ones comprise an impor-
tant group of compounds and as we had access to some derivatives
from an earlier anti-viral activity study [4], we have carried out
structure determinations.
2.2. Synthesis
The low solubility of 6-methyl- and 8-methyl-2-(XC6H4)-2H-
pyrazolo[4,3-c]quinolin-3(5H)-ones in organic solvents and the
poor quality of crystals obtained were severely restricting. How-
ever, suitable crystals for single crystal X-ray studies were ob-
tained on recrystallization of: 6-methyl- 2-phenylpyrazolo[4,3-
c]quinolin-3-one, 3, from moist DMSO, 6-methyl-2-(4-chloro-
phenyl)pyrazolo[4,3-c]quinolin-3-one, 4, from moist EtOCH2CH2-
OH, and 8-methyl- 2-(4-nitrophenyl)pyrazolo[4,3-c]quinolin-3-
one, 5, from moist DMSO/EtOAc, see Scheme 1. The crystals ob-
tained in each case were monohydrates, [3ꢁ(H2O)], [4ꢁ(H2O)],
and [5ꢁ(H2O)]. While the intermolecular interactions for the hy-
drates were expected to be much different from those in the
anhydrous compounds, 1 and 2 [9], the influence of the hydrate
molecules on the tautomeric forms and molecular conformations
was unclear. As the activity of these compounds is of paramount
importance in biological media, knowledge of the molecular con-
formations found in the hydrates could be of considerable value.
The crystal structures of these hydrates, as well as theoretical
calculations at the M06-2X/6-311++G(d,p) level, are now
reported.
Following well-reported methods [4,10], the 2-phenylpyrazol-
o[4,3-c]quinolin-3-ones were prepared from successive reactions
of diethyl ethoxymethylenemalonate with a toluidine, thionyl
chloride (20 mL) and an arylhydrazine.
2.2.1. 8-Methyl-2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one, 3
The toluidine and arylhydrazine employed in the synthesis
were 4-toluidine and phenylhydrazine. The crystal used in the
structure determination was grown from moist DMSO/EtOAc as
the monohydrate.
m.p.: 308–309 °C.
1H NMR [300.00 MHz, DMSO-d6] d: 12.75 (1H; s; NH); 8.73 (1H;
0
d; J = 6.3 Hz; H4); 8.37–8.32 (2H; m; H2 ); 8.15 (1H; s; H9); 7.73
0
(1H; d; J = 8.4 Hz; H6); 7.72–7.52 (3H; m; H7 and H3 ); 7.31–7.25
0
(1H; m; H4 ); 2.60 (3H, s; CH3) ppm.
13C NMR [75.0 MHz, DMSO-d6] d: 161.8; 143.1; 140.3; 138.9;
136.4; 133.6; 131.5; 128.8; 124.0; 121.7; 119.5; 118.8; 118.7;
106.0; 21.0 ppm.
IR (cmꢂ1; KBr): mmax 3300–2550 (NH/OH); 1620 (C@O).
Scheme 1. Reagents: (i) R1R2C6H3NH2,
D; (ii) SOCl2, D; (iii) XC6H4NHNH2, D; AcOH, D.

V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
301
Table 1
Crystal data and structure refinement.
[3ꢁ(H2O)]
17H15N3O2
[4ꢁ(H2O)]
C17H14ClN3O2
327.76
[5ꢁ(H2O)]
C17H14N4O4
338.32
Empirical formula
Formula weight
C
293.32
Temperature (K)
120(2)
120(2)
3120(2)
Wavelength (Å)
0.71073
0.6889
0.6889
Crystal system, space group
Orthorhombic, Pbca
Orthorhombic, Pbca
Monoclinic, P21/n
Unit cell dimensions
a (Å)
b (Å)
c (Å)
12.0115(8)
6.9719(4)
32.585(2)
35.11(6)
12.34(2)
6.916(13)
4.706(2)
27.273(13)
11.546(6)
97.449(5)
1469.5(12)
4
b (°)
Volume (Å3)
2728.8(3)
8
1.428
0.096
2996(9)
8
1.453
0.269
Z
Density (calculated) (Mg/m3)
1.529
0.112
Absorption coefficient (mmꢂ1
)
F(000)
1232
1360
704
Crystal size (mmꢂ1
)
0.5 ꢃ 0.06 ꢃ 0.02
3.02–27.49
ꢂ14 6 h 6 15
ꢂ9 6 k 6 8
ꢂ42 6 l 6 37
17,601
0.08 ꢃ 0.04 ꢃ 0.01
1.12–24.27°
ꢂ38 6 h 6 41
ꢂ14 6 k 6 14
ꢂ8 6 l 6 8
22,320
0.06 ꢃ 0.02 ꢃ 0.01
1.87–31.79
ꢂ6 6 h 6 4
ꢂ40 6 k 6 41
ꢂ16 6 l 6 17
19,127
Theta range for data collection (°)
Index ranges
Reflections collected
Independent reflections
3078
2639
4902
[R(int) = 0.1685]
1305
0.99
[R(int) = 0.0612]
2157
0.99
[R(int) = 0.0477]
3815
0.9
Reflections observed (>2sigma)
Data completeness
Absorption correction
Max. and min. transmission
Refinement method
Multi-scans
0.7456 and 0.5653
Full-matrix least-squares on F2
3078/0/209
0.976
Multi-scans
0.860 and 1.000
Full-matrix least-squares on F2
2639/3/215
1.134
Multi-scans
0.882 and 1.000
Full-matrix least-squares on F2
4902/0/236
Data/restraints/parameters
Goodness-of-fit on F2
1.067
Final R indices [I > 2sigma(I)]
R1 = 0.081
wR2 = 0.163
R1 = 0.207
wR2 = 0.218
0.354 and ꢂ0.338
R1 = 0.044
wR2 = 0.107
R1 = 0.059
wR2 = 0.125
0.235 and ꢂ0.291
R1 = 0.062
wR2 = 0.149
R1 = 0.084
wR2 = 0.165
R indices (all data)
Largest diff. peak and hole (eÅꢂ3
)
0.377 and ꢂ0.326
2.2.3. 6-Methyl-2-(4-nitrophenyl)-2H-pyrazolo[4,3-c]quinolin-3(5H)-
one, 5
Table 2
Energies of the tautomeric forms of 2-phenylpyrazolo[4,3-c]quinolin-3-ones calcu-
lated using the Gaussian 09W program, at the M06-2X/6-311++G(d,p) level of theory
[11].
The toluidine and arylhydrazine employed in the synthesis
were 2-toluidine and 4-nitrophenylhydrazine. The crystal used in
the structure determination was grown from moist EtOCH2CH2OH
as the monohydrate.
Compound
I
II
III
(a) Gibbs free energies (kcal molꢂ1
)
m.p.: 278–280 °C.
3
4
5
ꢂ561476.7
ꢂ849888.2
ꢂ689799.1
ꢂ561473.3
ꢂ849884.5
ꢂ689794.9
ꢂ561468.8
ꢂ849880.1
ꢂ689788.9
IR (cmꢂ1; KBr pellets): mmax 3600–2500 (NH/OH); 1650 (C@O).
(b) Relative energies (kcal molꢂ1
D
D
D
)
2.3. Calculations
G (kcal molꢂ1
(I–II)
(I–III)
)
3
4
5
ꢂ3.4
ꢂ3.7
ꢂ4.2
The calculations on the tautomeric forms and aggregates were
performed using the Gaussian 09W program [11]. Molecular geom-
etries of each tautomer and each aggregate were initially based on
the final experimental structures found in the X-ray study. The tau-
tomers were fully optimized using the M06-2X/6-311++G(d,p) le-
vel of theory. Since no imaginary frequency was found, all the
optimized structures were characterized as minima energy struc-
tures. In the case of the aggregates, a single point calculation were
performed using the same level of theory.
ꢂ7.9
ꢂ8.1
ꢂ10.2
2.2.2. 2-(4-Chlorophenyl)-8-methyl-2H-pyrazolo[4,3-c]quinolin-
3(5H)-one, 4
The toluidine and arylhydrazine employed in the synthesis
were 4-toluidine and 4-chlorophenylhydrazine. The crystal used
in the structure determination was grown from moist EtOCH2CH2-
OH as the monohydrate.
m.p.: 272–273 °C.
2.4. Crystallography
1H NMR [300.00 MHz, DMSO-d6] d: 12.95 (1H; s; NH); 8.82 (1H;
0
d; J = 6.6 Hz; H4); 8.38 (2H; d; J = 9.0 Hz; H2 ); 8.14 (1H; s; H9); 7.73
Data for [3ꢁ(H2O)] were obtained at 120(2) K with Mo K
a radia-
0
(1H; d; J = 8.7 Hz; H6); 7.61 (2H; d; J = 9.0 Hz; H3 ); 7.50 (1H; dd;
tion, k = 0.71073 Å, by means of the Bruker–Nonius 95 mm CCD
camera on kappa gonistat diffractometer of the EPSRC crystallo-
graphic service. Data collection was carried out under the control
of the program COLLECT [12] and data reduction and unit cell
refinement were achieved with the COLLECT and DENZO [13] pro-
grams. Data for [4ꢁ(H2O)] and [5ꢁ(H2O)] were obtained at 120(2) K
J = 8.4 and 2.1 Hz; H7); 2.60 (3H, s; CH3) ppm.
13C NMR [75.0 MHz, DMSO-d6] d: 161.8; 143.4; 139.1; 139.0;
136.4; 133.6; 131.6; 128.7; 127.7; 121.7; 120.0; 119.5; 118.6;
105.7; 21.0 ppm.
IR (cmꢂ1; KBr): mmax 3680–2500 (NH/OH); 1620 (C@O).

302
V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
Fig. 2. Atom arrangements and numbering schemes for (a) [3ꢁ(H2O)], (b) [4ꢁ(H2O)] and (c) [5ꢁ(H2O)]. Hydrogen bonds are drawn as dashed lines. Probability ellipsoids are
drawn at the 50% level. Hydrogen atoms are drawn as spheres of arbitrary radius.

V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
303
Table 3
Selected measured and calculated bond angles and lengths, (Å, °).
[3ꢁ(H2O)]
[4ꢁ(H2O)]
[5ꢁ(H2O)]
1 [9]
2 [9]
X-ray
Calculated
X-ray
Calculated
X-ray
Calculated
X-ray
X-ray
N(2)AN(3)
N(3)AC(9)
C(9)AC(3)
C(3)AC(4)
C(4)AN(2)
C(4)AC(4A)
C(4A)AC(8A)
C(8A)AN(1)
N(1)AC(2)
C(2)AC(3)
C(3)AC(4)
O(1)AC(9)
C(13)ACl
1.420(4)
1.376(5)
1.438(5)
1.429(5)
1.316(4)
1.447(5)
1.404(5)
1.399(5)
1.336(4)
1.360(5)
1.429(5)
1.268(4)
1.39
1.40
1.46
1.43
1.29
1.45
1.40
1.40
1.35
1.35
1.43
1.22
1.429(3)
1.384(4)
1.453(4)
1.441(4)
1.317(4)
1.454(4)
1.414(4)
1.409(3)
1.357(3)
1.374(4)
1.441(4)
1.275(3)
1.746(4)
1.39
1.40
1.46
1.43
1.30
1.45
1.40
1.40
1.35
1.35
1.43
1.22
1.74
1.4091(17)
1.4055(18)
1.433(2)
1.4261(19)
1.3156(19)
1.437(2)
1.39
1.40
1.46
1.43
1.30
1.45
1.40
1.40
1.35
1.35
1.43
1.22
1.412(4)
1.375(4)
1.426(4)
1.422(4)
1.312(4)
1.440(4)
1.398(4)
1.403(4)
1.323(4)
1.364(4)
1.422(4)
1.252(3)
1.420(5)
1.382(5)
1.427(6)
1.430(6)
1.303(5)
1.434(5)
1.417(4)
1.404(5)
1.324(5)
1.361(6)
1.430(6)
1.250(5)
1.739(4)
1.407(2)
1.3991(19)
1.3404(19)
1.372(2)
1.4261(19)
1.2410(18)
N(2)AC(4)AC(3)
C(4)AC(3)AC(9)
C(3)AC(9)AN(3)
C(9)AN(3)AN(2)
N(3)AN(2)AC(4)
112.8(4)
105.6(3)
103.8(3)
113.7(3)
103.6(3)
112.5
105.8
102.1
113.7
105.9
112.9(2)
106.0(2)
103.0(2)
114.25(18)
103.78(18)
112.5
105.9
102.0
113.8
105.8
113.28(13)
106.31(13)
102.89(12)
113.55(12)
103.97(11)
112.5
105.9
102.0
113.7
105.8
113.9(2)
106.3(2)
103.3(2)
113.9(2)
103.6(2)
113.0(3)
105.8(4)
103.9(4)
113.05(3)
104.2(3)
with Synchrotron radiation, k = 0.68890 Å, by means of the Rigaku
Saturn724 + (2 ꢃ 2 bin mode) of the EPSRC crystallographic ser-
vice. Data collection, data reduction and unit cell refinement were
achieved with the CrystalClear program [14].
3.3.1. Molecular structures
Fig. 2 shows the atom arrangements and numbering schemes
for [3ꢁ(H2O)], [4ꢁ(H2O)] and [5ꢁ(H2O)]. Selected bond lengths and
angles associated with the pyrazole rings in [3ꢁ(H2O)], [4ꢁ(H2O)]
and [5ꢁ(H2O)] are listed in Table 3, as are the experimental values
for 1 and 2 [9]. The only significant difference between the geomet-
ric parameters for the hydrates and the anhydrous analogues in-
volves the C@O bond lengths, which are longer in the hydrates
due to their involvement in hydrogen bonding to the solvate mol-
ecules. Theoretical values for each lowest energy tautomer, calcu-
lated at the M06-2X/6-311++G(d,p) level of theory, are also listed
with the experimental values. As can be seen the experimental val-
ues for [3ꢁ(H2O)], [4ꢁ(H2O)] and [5ꢁ(H2O)] are close to the calculated
values for 3, 4 and 5.
Molecules of 3–5 in the hydrates exist in the tautomeric form I,
see Fig. 1. Overall, molecule 5 in [5ꢁ(H2O)] is very near planar, with
the angle between the pyrazolo[4,3-c]quinolin-3-one and the
nitrophenyl rings of 7.40 (8)°; furthermore the nitro group is only
3.6 (3)° out of the plane of its attached phenyl ring. Molecules 3
and 4 deviate much more severely from planarity as indicated by
the 23.56(8)° and 24.85(0.12)° angles, respectively, between the
pyrazolo[4,3-c]quinolin-3-one and the phenyl moieties.
Correction for absorption was achieved in each case by a semi-
empirical method based upon the variation of equivalent reflec-
tions with the program SADABS 2007/2 [15] for [3ꢁ(H2O)] and Crys-
talClear program [14] for [4ꢁ(H2O)] and [5ꢁ(H2O)]. The programs
ORTEP-3 for Windows [16] and MERCURY [17] were used in the
preparation of the figures. SHELXL97 [18] and PLATON [19] were
used in the calculation of molecular geometry. The structures were
solved by direct methods using SHELXS-97 [18] and fully refined
by means of the program SHELXL-97 [18]. Difference map peaks
provided positions for the hydrogen atoms of the NH groups and
of water molecules for which the coordinates, along with isotropic
displacement parameters, were fully refined. All other hydrogen
atoms were placed in calculated positions. Crystal data and struc-
ture refinement details are listed in Table 1.
3. Results and discussion
3.1. Synthesis
The PLATON program [19] reveals the presence of
C15AH15ꢁ ꢁ ꢁO1 intramolecular hydrogen bonds in 3–5, with addi-
tionally intramolecular hydrogen bonds, C11AH11ꢁ ꢁ ꢁN2, present
in 4 and 5, see Table 4: in 3, the H11ꢁ ꢁ ꢁN2 separation is just beyond
the cut-off value of 2.50 Å and at best this indicates a very weak
interaction. The chloro and nitro groups in 4 and 5, being electron
withdrawing groups, will render the attached ring hydrogens more
positive and hence more acceptable to involvement in hydrogen
bonding than those in 3. There is a difference in the conformations
of 3 and 4, on one hand, and 5, on the other, as shown by the ori-
entations of the C1A C6 phenyl ring: this is indicated by the
N2AN3AC10AC11 torsion angles of 22.6(5)°, 22.1(3)° and
ꢂ3.3(2)° for 3–5, respectively. The corresponding values for the
anhydrous compounds 1 and 2 were reported to be ꢂ41.2(4)°
and 10.2(5)° [9]. The presence of the methyl group in 3–5 is not
considered to have an influence on these torsion angles.
The synthesis of the 2-phenylpyrazolo[4,3-c]quinolin-3-one
compounds is shown in Scheme 1. The crystals obtained in each
case after recrystallization were monohydrates, [3ꢁ(H2O)], obtained
from moist DMSO [4ꢁ(H2O)], from moist EtOCH2CH2OH and
[5ꢁ(H2O)] recrystallized from moist DMSO/EtOAc.
3.2. Tautomer stability
Calculations on the tautomeric forms were performed using the
Gaussian 09W program, at the M06-2X/6-311++G(d,p) level of the-
ory [11]. As shown in Table 2, for each of 3–5, the most stable form
is I and the least stable form is III. This finding of the most stable
tautomer concurs with that found by Karolak-Wojciechowska
et al. using the semi-empirical method AM1 in the MOPAC-93 pro-
gram [7].
3.3.2. Crystal structures
3.3. Crystallography
Each of the three hydrates possess strong NAHꢁ ꢁ ꢁO and
OAHꢁ ꢁ ꢁO hydrogen bonds, and weaker CAHꢁ ꢁ ꢁ
p
[20] and
pꢁ ꢁ ꢁp
The asymmetric unit consists in each case of a molecule of a sin-
gle molecule of a 2-phenylpyrazolo[4,3-c]quinolin-3-one deriva-
tive and a hydrate molecule.
interactions [21], see Table 4. In addition, there are weak CAHꢁ ꢁ ꢁCl
hydrogen bonds [22] in [4ꢁ(H2O)] and CAHꢁ ꢁ ꢁO hydrogen bonds in
[5ꢁ(H2O)]. Despite most of the strong intermolecular interactions

304
V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
Table 4
Geometric arameters (Å, °) for the intra- and inter-molecular interactions.
Compound
DAHꢁ ꢁ ꢁA
(a) Intramolecular hydrogen bonds
DAH
Hꢁ ꢁ ꢁA
Dꢁ ꢁ ꢁA
DAHꢁ ꢁ ꢁA
[3ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
C(15)AH(15)ꢁ ꢁ ꢁO(1)
0.93
0.93
0.93
0.93
0.93
2.40
2.53
2.42
2.38
2.25
2.958(5)
3.051(6)
2.753(6)
2.731(3)
2.890(3)
118
116
101
102
125
C(15)AH(15)ꢁ ꢁ ꢁO(1)
C(11)AH(11)ꢁ ꢁ ꢁN(2)
C(11)AH(11)ꢁ ꢁ ꢁN(2)
C(15)AH(15)ꢁ ꢁ ꢁO(1)
(b) Intermolecular hydrogen bonds
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
N(1)AH(1)ꢁ ꢁ ꢁOWiv
OWAHW(1)ꢁ ꢁ ꢁO(1)v
OWAHW(2)ꢁ ꢁ ꢁO(1)
N(1)AH(1)ꢁ ꢁ ꢁOW
0.88(4)
0.94(4)
0.88(4)
0.86
0.87(3)
0.88(3)
0.93
0.95(2)
0.90(3)
0.89(3)
0.93
1.83(4)
1.80(4)
1.90(4)
1.89
1.98(3)
1.92(3)
2.75
1.87(2)
1.88(3)
2.07(3)
2.33
2.707(4)
2.735(4)
2.777(4)
2.742(6)
2.841(6)
2.794(6)
3.568(7)
2.777(2)
2.770(2)
2.935(2)
3.215(2)
178(5)
175(4)
175(4)
170
169(3)
172(2)
148
157.9(17)
172(2)
163(2)
158
OWAHW(1)ꢁ ꢁ ꢁO(1)vi
OWAHW(2)ꢁ ꢁ ꢁO(1)vii
C(11)AH(11)ꢁ ꢁ ꢁCl(1)viii
N(1)AH(1)ꢁ ꢁ ꢁOWi
OWAHW(1)ꢁ ꢁ ꢁO(1)
OWAHW(2)ꢁ ꢁ ꢁO(2)ii
C(2)AH(2)ꢁ ꢁ ꢁO(1)iii
Symmetry operations: i = ꢂx, ꢂy, 2 ꢂ z; ii = 2 ꢂ x, ꢂy, 1 ꢂ z; iii = 1 ꢂ x, ꢂy, 2 ꢂ z; iv = ꢂ1/2 + x, 1/2 ꢂ y, ꢂz; v = 1/2 ꢂ x, ꢂ1/2 + y, z; vi = 1 ꢂ x, ꢂ1/2 + y, 1/2 ꢂ z;
vii = 1 ꢂ x, 1 ꢂ y, 1 ꢂ z; viii = 3/2 ꢂ x, ꢂ1/2 + y, z.
Compound
CAHꢁ ꢁ ꢁCga
Hꢁ ꢁ ꢁCg
Hperp
c
CAHꢁ ꢁ ꢁCga
Cꢁ ꢁ ꢁCg
(c) CAHA
[3ꢁ(H2O)]
[4ꢁ(H2O)]
[5ꢁ(H2O)]
p interactions
C(12)AH(12)ꢁ ꢁ ꢁCg(4)ii
C(12)AH(12)ꢁ ꢁ ꢁCg(4)iii
C(16)AH(16B)ꢁ ꢁ ꢁCg(2)i
2.96
2.85
2.72
2.80
2.81
2.68
19.07
9.76
9.98
126
153
129
3.594(4)
3.703(8)
3.412(3)
Compound
(d)
ꢁ ꢁ ꢁ
Cg(I)ꢁ ꢁ ꢁCg(J)a
CgꢁꢁCg
a
b
c
Cg(I)perp
Cg(J)perp
p
p intermolecular contacts
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[3ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[4ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
[5ꢁ(H2O)]
Cg(1)ꢁ ꢁ ꢁCg(3)iii
3.605(2)
3.781(2)
3.631(2)
3.887(2)
3.625(2)
3.887(2)
3.782(2)
3.625(2)
3.605(2)
3.632(2)
3.564(7)
3.732(7)
3.657(7)
3.866(7)
3.598(7)
3.866(7)
3.732(7)
3.598(7)
3.564(7)
3.657(7)
3.517(2)
3.819(2)
3.517(2)
3.517(2)
3.517(2)
3.819(2)
1.55(18)
0
17.35
22.68
18.59
24.62
15.65
25.64
23.79
14.62
18.48
17.56
15.74
22.71
20.14
26.10
16.77
27.18
22.93
16.74
16.87
19.96
21.01
28.50
20.34
14.47
20.74
30.25
18.48
3.4195(14)
3.4603(14)
3.4622(14)
3.5038(14).
3.5075(14)
3.5331(14)
3.4890(14)
3.4904(14)
3.4413(14)
3.4419(14)
3.4106(9)
3.4367(8)
3.4377(8)
3.4388(8)
3.4452(8)
3.4717(9)
3.4423(8)
3.4446(8)
3.4303(8)
3.4338(8)
3.2889(6)
3.2987(6)
3.4053(7)
3.2974(6)
3.2831(6)
3.3559(7)
3.4411(14)
3.4887(14
3.4416(14)
3.5331(14
3.4901(14)
3.5040(14)
3.4606(14)
3.5077(14)
3.4195(14)
3.4625(14)
3.4303(8)
3.4424(8)
3.4338(8)
3.4717(9)
3.4446(8)
3.4388(8)
3.4366(8)
3.4452(8)
3.4106(9)
3.4377(8)
3.2831(6)
3.3560(6)
3.2974(6)
3.4053(7)
3.2889(6)
3.2988(6)
Cg(2)ꢁ ꢁ ꢁCg(2)iii
Cg(2)ꢁ ꢁ ꢁCg(3)iii
Cg(3)ꢁ ꢁ ꢁCg(1)iii
Cg(3)ꢁ ꢁ ꢁCg(2)iii
Cg(1)ꢁ ꢁ ꢁCg(3)iv
Cg(2)ꢁ ꢁ ꢁCg(2)iv
Cg(2)ꢁ ꢁ ꢁCg(3)iv
Cg(3)ꢁ ꢁ ꢁCg(1)iv
Cg(3)ꢁ ꢁ ꢁCg(2)iv
Cg(1)ꢁ ꢁ ꢁCg(3)v
Cg(2)ꢁ ꢁ ꢁCg(2)v
Cg(2)ꢁ ꢁ ꢁCg(3)v
Cg(3)ꢁ ꢁ ꢁCg(1)v
Cg(3)ꢁ ꢁ ꢁCg(2)v
Cg(1)ꢁ ꢁ ꢁCg(3)vi
Cg(2)ꢁ ꢁ ꢁCg(2)vi
Cg(2)ꢁ ꢁ ꢁCg(3)vi
Cg(3)ꢁ ꢁ ꢁCg(1)vi
Cg(3)ꢁ ꢁ ꢁCg(2)vi
Cg(1)ꢁ ꢁ ꢁCg(2)i
Cg(1)ꢁ ꢁ ꢁCg(3)i
Cg(4)ꢁ ꢁ ꢁCg(1)i
Cg(1)ꢁ ꢁ ꢁCg(4)ii
Cg(2)ꢁ ꢁ ꢁCg(1)ii
Cg(3)ꢁ ꢁ ꢁCg(1)ii
23.79
17.56
25.64
14.62
24.62
22.68
15.65
17.35
18.59
16.87
22.93
19.96
27.18
16.74
26.10
22.71
16.77
15.74
20.14
20.74
30.25
14.47
20.34
21.01
28.50
1.06(16)
1.55(18)
1.06(16)
1.55(18)
0
1.06(16)
1.55(18)
1.06(16)
1.20(11)
0
0.27(10)
1.20(11)
0.27(10)
1.20(11)
0
0.27(10)
1.20(11)
0.27(10)
1.10(8)
2.30(8)
6.19(8)
6.19(8)
1.10(8)
2.30(8)
Cg1ACg4 are the centroids of the [N(2), N(3), C(9), C(3), C(4)], [N(1), C(2)AC(4), C(5a), C(8a)], [C(4a), C(11)AC(8), C(8a)] and [C(10)AC(15)] rings, respectively; Alpha is the
dihedral angle between the least squares plannes of the overlapping rings. Beta is the angle between the vectors Cgꢁ ꢁ ꢁCg and Cg(I)perp where Cg(I)perp is the perpendicular
distance of Cg(I) from the plane of ring J. Similarly
c
is the angle between the vectors Cgꢁ ꢁ ꢁCg and Cg(J)perp
.
Symmetry codes: i = 1 + x, y, z; ii = ꢂ1_x, y, z; iii = ꢂ1/2 ꢂ x, ꢂ1/2 + y, z; iv = ꢂ1/2 ꢂ x, 1/2 + y, z; v = x, 1/2 ꢂ y, ꢂ1/2 + z; vi = x, 1/2 ꢂ y, 1/2 + z.
a
Cg(2) and Cg(4) are the centroids of the [N(2), N(3), C(9), C(3), C(4)] and [C(10)AC(15)] rings, respectively;
Symmetry operations: i = ꢂ1 + x, y, z; ii = ꢂx, ꢂ1/2 + y, 1/2 ꢂ z; iii = 3/2 ꢂ x, 1 ꢂ y,ꢂ1/2 + z.
c is the angle at H between the vectors Xꢁ ꢁ ꢁCg and Xperp.:
being common to the three hydrates, significant differences in the
supramolecular arrays are met.
o[4,3-c]quinolin-3-one molecules via one NAHꢁ ꢁ ꢁO and two
OAHꢁ ꢁ ꢁO hydrogen bonds, and each of the phenylpyrazolo[4,3-
c]quinolin-3-one molecules is likewise hydrogen-bonded to three
hydrate molecules, see Fig. 3. The summations of the angles about
the hydrate oxygen atom in [3ꢁ(H2O)], [4ꢁ(H2O)] and [5ꢁ(H2O)] are
358.2°, 356.4° and 347.7°, respectively, indicating a progressive
distortion away from planarity.
To facilitate discussions of the intermolecular interactions, the
interactions are divided into sub-sets. The first sub-set to be con-
sidered involves the strong classical NAHꢁ ꢁ ꢁO and OAHꢁ ꢁ ꢁO hydro-
gen bonds. In each of [3ꢁ(H2O)], [4ꢁ(H2O)] and [5ꢁ(H2O)], the
hydrate molecules are hydrogen bonded to three 2-phenylpyrazol-

V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
305
Fig. 3. Arrangements around the hydrate molecules and the direct interactions of the hydrate molecules with 2-phenylpyrazolo[4,3-c]quinolin-3-ones in (a) [3ꢁ(H2O)], (b)
[4ꢁ(H2O)] and (c) [5ꢁ(H2O)].
There are differences in the arrangements of the three phen-
ylpyrazolo[4,3-c]quinolin-3-one molecules about the hydrate mol-
ecules. In both [3ꢁ(H2O)] and [4ꢁ(H2O] the carbonyl oxygen of the
phenylpyrazolo[4,3-c]quinolin-3-one molecules acts as a double
acceptor in two hydrogen bonds. While in both [3ꢁ(H2O)] and
A more distinct difference is found with [5ꢁ(H2O)]: here the
hydrogen bonds connecting the water molecule to the three phen-
ylpyrazolo[4,3-c]quinolin-3-one molecules are N1AH1ꢁ ꢁ ꢁOW,
OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁO2 hydrogen bonds, where O2
is a nitro group oxygen and O1 is the carbonyl oxygen, see
Fig. 3c. Consequently, there are differences in the intermolecular
arrays produced by [3ꢁ(H2O)], [4ꢁ(H2O)] and [5ꢁ(H2O)]. Table 3 lists
the symmetry operations and geometric parameters of the inter-
molecular interactions.
In [3ꢁ(H2O)], extended combinations of the N1AH1ꢁ ꢁ ꢁOW,
OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁO1 hydrogen bonds generate a
complex array, as partially exemplified in Fig. 4: for reasons of clar-
ity, not all the possible N1AH1ꢁ ꢁ ꢁOW, OWAHW1ꢁ ꢁ ꢁO1 and
{[4]ꢁ(H2O)}
the
hydrate-phenylpyrazolo[4,3-c]quinolin-3-one
N1AH1ꢁ ꢁ ꢁOW, OWAHW1ꢁ ꢁ ꢁO1 and
interactions
involve
OWAHW2ꢁ ꢁ ꢁO1 hydrogen bonds [O1 is the carbonyl oxygen], the
orientations of the molecule, hydrogen-bonded via N1, are differ-
ent, and arise from rotations by 180° about the N1AH1 bond, com-
pare Fig. 3a and b. This rotation of the phenylpyrazolo[4,3-
c]quinolin-3-one molecule within the {[4]3ꢁ(H2O)} moiety is con-
sidered to allow better packing in the crystal.

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V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
Fig. 4. Compound [3ꢁ(H2O)]. A double chain of molecules of 3 and water molecules formed from combinations of N1AH1ꢁ ꢁ ꢁOW, OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁO1
hydrogen bonds. The NAHꢁ ꢁ ꢁO and OAHꢁ ꢁ ꢁO hydrogen bonds are drawn as blue and red green dashed lines respectively. The inset is a view looking down the superimposed
chains. Table 4 lists the symmetry operations, and geometric parameters for the intermolecular interactions. (For interpretation of the references to colour in this figure
legend, the reader is referred to the web version of this article.)
Fig. 5. Compound [4ꢁ(H2O)]. A partial network of molecules of 4 and water generated from N1AH1ꢁ ꢁ ꢁOW, OWAHWꢁ ꢁ ꢁO1, OWAHW2ꢁ ꢁ ꢁO1 and C11AH11ꢁ ꢁ ꢁCl1 hydrogen
bonds. The NAHꢁ ꢁ ꢁO, OAHꢁ ꢁ ꢁO and CAHꢁ ꢁ ꢁCl hydrogen bonds are drawn as blue, red and green dashed lines respectively. Table 4 lists details of the symmetry operations and
geometric parameters for the intermolecular hydrogen bonds. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of
this article.)

V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
307
Fig. 6. [5ꢁ(H2O)]. Alternating centrosymmetric rings, R4ð24Þ and R4ð16Þ, formed between double chains, C2ð14Þ, of alternating hydrate and molecules 5, generated from
4
2
N1AH1ꢁ ꢁ ꢁOW [blue dash lines], OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁ4O2 hydrogen bonds [both red dashed lines]. The short contacts between the double chains, involving
H6AO3, [H6AO3 = 2.61 Å] are shown as black dash lines. Hydrogen atoms not involved in the hydrogen bonds have been omitted for clarity. Table 4 lists the symmetry
operations and geometric parameters. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 7. Compound [5ꢁ(H2O)]. C2AH2ꢁ ꢁ ꢁO1 interactions link strands of different double chains to generate R2ð10Þ rings, which alternate with R6ð10Þ rings, formed from
2
6
combinations of C2AH2ꢁ ꢁ ꢁO1, C1AH1ꢁ ꢁ ꢁOW and OWAHW2ꢁ ꢁ ꢁO2 hydrogen bonds. Molecules in different double chains are drawn in different colours. Table 4 lists the
symmetry operation and geometric parameters.
OWAHW2ꢁ ꢁ ꢁO1 hydrogen bonds have been drawn. However,
N1AH1ꢁ ꢁ ꢁOW and OWAHW1ꢁ ꢁ ꢁO1 hydrogen bonds and the
R44ð24Þ rings from OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁO2 hydrogen
bonds. These double chains, formed by the strong and classical
NAHꢁ ꢁ ꢁO and OAHAO hydrogen bonds, are termed strong double
chains, to differentiate from other double chains discussed below.
Links between these strong double chains are formed by weaker
C2AH2ꢁ ꢁ ꢁO1 hydrogen bonds, thereby producing other double
chains, termed weaker double chains. This involvement of the
CAHꢁ ꢁ ꢁO hydrogen bonds, as shown in Fig. 7, generates an alternat-
ing sequence of centrosymmetric rings [R22ð10Þ], and R66ð30Þ rings
[23]: the latter formed from combinations of C2AH2ꢁ ꢁ ꢁO1,
C1AH1ꢁ ꢁ ꢁOW and OWAHW2ꢁ ꢁ ꢁO2 hydrogen bonds, as shown in
Fig. 7. Additionally there are short contacts between the double
chains involving H6 and O3 [H6AO3 = 2.61 Å; C6ꢁ ꢁ ꢁO3 = 3.530 Å;
C6AH6ꢁ ꢁ ꢁO3 = 172°. However the 2.61 Å distance is outside the
cut-off value for Hꢁ ꢁ ꢁO separations in CAHꢁ ꢁ ꢁO hydrogen bonds
[2.50 Å] and, at best, this indicates a very weak interaction. Table 4
lists details of the symmetry operations and geometric parameters
for these hydrogen bonds.
apparent in Fig.
4
are R44ð16Þ rings [23], generated from
N1AH1ꢁ ꢁ ꢁOW and OWAHW1ꢁ ꢁ ꢁO1 hydrogen bonds, and chains,
C44ð20Þ [23], generated from N1AH1ꢁ ꢁ ꢁOW and OWAHW2ꢁ ꢁ ꢁO1
hydrogen bonds. The inset in Fig. 4 is a view looking through the
R44ð16Þ rings [23].
In [4ꢁ(H2O)], weak C11AH11ꢁ ꢁ ꢁCl1 hydrogen bonds in combina-
tion with the N1AH1ꢁ ꢁ ꢁOW, OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁO1
hydrogen-bonds link {[(H2O)ꢁ4)3]} moieties into a complex net-
work of rings and chains, see Fig. 5. Again for reasons of clarity,
not all the hydrogen bonds have been drawn. Combinations of
N1AH1ꢁ ꢁ ꢁOW, OWAHW1ꢁ ꢁ ꢁO1 and OWAHW2ꢁ ꢁ ꢁO1 hydrogen-
bonds generate R86ð24Þ rings [23], while N1AH1ꢁ ꢁ ꢁOW,
OWAHW1ꢁ ꢁ ꢁO(1), OWAHW2ꢁ ꢁ ꢁO1 and C11AH11ꢁ ꢁ ꢁCl1 hydrogen
bond combinations generate R66ð32Þ rings [23]. In addition, the
C11AH11ꢁ ꢁ ꢁCl1 hydrogen bonds generate C(10) chains[23] of mol-
ecules aligned in the direction of the b axis. Table 4 lists details of
the symmetry operations and geometric parameters for these
hydrogen bonds.
In [5ꢁ(H2O)], strong N1AH1ꢁ ꢁ ꢁOW, OWAHW1ꢁ ꢁ ꢁO1 and
OWAHW2ꢁ ꢁ ꢁO2 hydrogen bonds link the molecules of 5 and water
into double chains of centrosymmetric rings, [R44ð16Þ R44ð24Þ],
C22ð14Þ [23], see Fig. 6. The R44ð16Þ rings are formed from
Other intermolecular interactions present in all three hydrates
are
p
ꢁ ꢁ ꢁ
p
stacking [21] and CAHꢁ ꢁ ꢁ
p [20] interactions, see Table 4
and are illustrated in Fig. 8. The situations for [3ꢁ(H2O)] and
[4ꢁ(H2O)] are similar, but that for [5ꢁ(H2O)] is somewhat different.

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V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
Fig. 8. Stacking and CAHꢁ ꢁ ꢁp interactions in (a) [3ꢁ(H2O)], (b) [4ꢁ(H2O)] and (c) [5ꢁ(H2O)].
In the cases of [3ꢁ(H2O)] and [4ꢁ(H2O)], the stacks of phenylpyraz-
olo[4,3-c]quinolin-3-one molecules are generated from p(1)ꢁ ꢁ ꢁp(3)
(3) interactions, where p(1) (2) and (3) refer
As can be seen in Fig. 8c, the molecules in the stacks are off set
but are all aligned in the same direction.
The combined intermolecular interactions in all three cases
generate three-dimensional arrays.
,
p(2)ꢁ ꢁ ꢁ
p
(2) and p(2)ꢁ ꢁ ꢁ
p
,
p
p
to the diazole, pyridine and phenyl rings of the quinolin-3-one
fragment, respectively. Furthermore in both cases, links between
the
p
ꢁ ꢁ ꢁ
p
stacks are generated from C14AH14ꢁ ꢁ ꢁp(phenyl) interac-
3.4. Calculations
tions. As seen in Fig. 8a and b, the molecules in the stacks alternate
in a head-to-toe manner.
Calculations were also carried out on several sub-structures,
with the initial structures taken as those found in the X-ray study.
Single point calculations were carried out on the {[3]3ꢁ(H2O)},
{[4]3ꢁ(H2O)} and {[5]3ꢁ(H2O)} sub-structures, determined in the X-
ray study and as illustrated in Fig. 3. As the {[X]3ꢁ(H2O)} systems
were not rigid and as the optimization led to deformations from
the initial X-ray derived structures, single point calculations were
adopted, rather than full-geometry optimization as the single point
In [5ꢁ(H2O)], the
3-one molecules are generated from p(1)ꢁ ꢁ ꢁp(2)
(4) interactions, where p(1) (2) and (4) refer to the diazole
pꢁ ꢁ ꢁ
p
stacks of phenylpyrazolo[4,3-c]quinolin-
,
p(1)ꢁ ꢁ ꢁp(3) and
p(1)ꢁ ꢁ ꢁ
p
,
p
p
and pyridine phenyl rings of the quinolin-3-one fragment, and the
nitrophenyl ring, respectively. Unlike in [3ꢁ(H2O)] and [4ꢁ(H2O)],
the CAHꢁ ꢁ ꢁ
p
interactions, specifically C16AH16Bꢁ ꢁ ꢁp(2) interac-
tions, occur within the stacks and not between them, see Fig. 8c.

V.F. Ferreira et al. / Journal of Molecular Structure 1051 (2013) 299–309
309
calculations provided the electronic energy without changing the
initial atom positions. The stabilizations of the {[X]3ꢁ(H2O)}aggre-
gates compared to the three molecules of X and one water mole-
can be obtained free of charge on written application to CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223 336033); on
request by e-mail to deposit@ccdc.cam.ac.uk or by access to
http://www.ccdc.cam.ac.uk. Supplementary data associated with
this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.molstruc.2013.08.032.
cule were calculated to be ꢂ32.0, ꢂ26.3 and ꢂ31.0 kcals molꢂ1
,
respectively for X = 3, 4 and 5.
Another calculation was carried out on {[5]ꢁ(H2O)3} substruc-
tures. As illustrated in Fig. 3c and described above in Section 3.3,
the molecule 5 is bound to three water molecules in a different
fashion compared to both molecules 3 and 4 in their {[X]ꢁ(H2O)3}
sub-structures. Calculations indicated that the sub-structure deter-
mined in the X-ray study for {[5]ꢁ(H2O)3} was more stable, by
ꢂ7.9 kcal molꢂ1, than that obtained with the three water mole-
cules attached to 5 as in {[X]ꢁ(H2O)3} (X = 3 or 4).
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As expected the supramolecular arrangements in [3ꢁ(H2O)],
[4ꢁ(H2O)] and [5ꢁ(H2O)] differ greatly from those in anhydrous 1
and 2 [9]. In 1 and 2, the strongest intermolecular interactions,
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and
p
ꢁ ꢁ ꢁ
p
interactions, directly link molecules. In [3ꢁ(H2O)],
[4ꢁ(H2O)] and [5ꢁ(H2O)], the strongest interactions, NAHꢁ ꢁ ꢁO and
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generated from weaker interactions, such as CAHꢁ ꢁ ꢁ
p
and
p p
ꢁ ꢁ ꢁ
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[5ꢁ(H2O)], on the other, due predominantly to the involvement of
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Full details of the crystal structure determinations in CIF format
have been deposited with the Cambridge Crystallographic Data
Centre with deposition numbers 937219, 937220 and 937221,
respectively for [3ꢁ(H2O)], [4ꢁ(H2O)], and [5ꢁ(H2O)]. Copies of these