Quantitative evaluation of C-H...O and C-H...π intermolecular interactions in ethyl-3-benzyl-1-methyl-2-oxoindoline-3-carboxylate and 3-Methyl-but-2-en-1-yl-1,3-dimethyl-2-oxoindoline-3-carboxylate: Insights from PIXEL and hirshfeld analysis

Article abstract of DOI:10.1007/s10870-014-0492-8

The X-ray crystallographic structures of two biologically active molecules, namely (±)-ethyl-3-benzyl-1-methyl-2-oxoindoline-3-carboxylate (I) and (±)-3-methyl-but-2-en-1-yl-1,3-dimethyl-2-oxoindoline-3-carboxylate (II) have been investigated based on the

Full text of DOI:10.1007/s10870-014-0492-8

J Chem Crystallogr (2014) 44:131–142
DOI 10.1007/s10870-014-0492-8
ORIGINAL PAPER
Quantitative Evaluation of C–HÁÁÁO and C–HÁÁÁp Intermolecular
Interactions in Ethyl-3-benzyl-1-methyl-2-oxoindoline-3-
carboxylate and 3-Methyl-but-2-en-1-yl-1,3-dimethyl-2-
oxoindoline-3-carboxylate: Insights from PIXEL and Hirshfeld
Analysis
•
Dhananjay Dey Santanu Ghosh Deepak Chopra
•
Received: 29 August 2013 / Accepted: 8 January 2014 / Published online: 6 February 2014
ꢀ Springer Science+Business Media New York 2014
Abstract The X-ray crystallographic structures of two
biologically active molecules, namely ( )-ethyl-3-benzyl-1-
methyl-2-oxoindoline-3-carboxylate (I) and ( )-3-methyl-
but-2-en-1-yl-1,3-dimethyl-2-oxoindoline-3-carboxylate (II)
have been investigated based on the molecular conformation
and supramolecular packing of the molecules in the solid
state. These two structures assemble via C–HÁÁÁO=C and C–
HÁÁÁp intermolecular interactions which contribute towards
the stability of the crystal packing. In order to gain quantita-
tive insights into the nature of non-covalent interaction
between different molecules the interaction energy of the
molecular pairs obtained after analysis of the crystal struc-
tures for both the molecules has been performed by using the
PIXEL approach along with high level DFT?Disp calcula-
tions. Hirshfeld surface analysis and the associated fingerprint
plots provide rapid quantitative insight into the intermolecular
interactions in molecular solids. This article provides support
to the fact that every molecule can be explored in detail for an
understanding of its solid state structure via experimental and
computational tools in crystal engineering.
[3], anti-inflammatory [4, 5], antihypertensive [6] and anticon-
vulsant activities [7]. Oxindole’s derivatives are used to inhibit
the replication of HIV and combat the infections that are caused
by drug-resistance, drug-sensitive, and mutant strains of HIV
[8]. Because of such important applications of this class of
compounds in synthetic organic chemistry and medicinal
chemistry, we have analyzed the crystal structure of these title
compounds by single crystal X-ray diffraction and also subse-
quently explored their crystal packing and molecular confor-
mation in both the solid state and compared with the geometry in
the gas phase. PIXEL calculations were performed in order to
estimate the nature and energies associated with the intermo-
lecular interactions in the crystal lattice. The total lattice energy
is divided into the corresponding coulombic, polarization, dis-
persion and repulsion energies [9]. All the molecular pairs
involved in the crystal packing, were extracted and their ener-
gies were determined from PIXEL and finally compared with
the values obtained from high level DFT?Disp calculations at
the crystal geometry with BSSE [10] corrections. Hirshfeld
surfaces [11] mapped with dnorm using a red-white-blue color
scheme, where red is used to indicate the shorter contacts, white
is used for contacts around the vdW separation, and blue is for
longer contacts along with the fingerprint plots [12] have been
studied to evaluate the contribution of the individual types of
interaction within the crystal structures. Hirshfeld surface and
fingerprint plots of the title compounds also provide the essential
similarities and differences between the two compounds.
Keywords Indoline carboxylates Á Hydrogen bonds Á
PIXEL Á Hirshfeld analysis
Introduction
Oxindole [1] has a wide range of applications and exhibits
biological activities consisting of antibacterial [2], anticancer
Experimental
D. Dey Á S. Ghosh Á D. Chopra (&)
Synthesis and crystallization
Department of Chemistry, Indian Institute of Science Education
and Research (IISER) Bhopal, ITI (Gas Rahat) Building,
Bhopal 462 023, MP, India
The detailed synthetic procedure for these two compounds
has already been reported in the literature [13]. Scheme 1
e-mail: dchopra@iiserbhopal.ac.in
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J Chem Crystallogr (2014) 44:131–142
Scheme 1 Synthetic route for
the preparation of the target
compounds
O
O
O
Table 1 Data collection and structure refinement in I and II
outlines the final step necessary for the synthesis of the two
compounds of interest. Single crystals of these compounds
were grown by the slow evaporation method from
EtOAc?hexane solvent system at low temperature.
Data
I
II
Formula
C19H19NO3
309.35
C16H19NO3
273.32
Formula weight
˚
Wavelength (A)
0.71073
0.71073
X-Ray Crystallography
Solvent system
CCDC no.
Ethylacetate ? hexane Ethylacetate ? hexane
941352
941353
X-ray diffraction datasets were collected on a three circle
Bruker APEX-II diffractometer equipped with a CCD area
Crystal system
Space group
Monoclinic
P21/n
Orthorhombic
Pn21a
˚
detector using Mo-Ka radiation (k = 0.71073 A) in u and
˚
a (A)
13.4007 (3)
8.7952 (2)
15.5729 (4)
17.8207 (10)
18.3624 (8)
9.1595 (5)
x scan modes. The crystal structures were solved by direct
methods using SIR92 [14] and refined by the full matrix
least squares method using SHELXL97 [15] present in the
program suit WinGX [16]. Empirical absorption correction
was applied using SADABS [17]. The non-hydrogen atoms
are refined anisotropically and the hydrogen atoms bonded
to C atoms were positioned geometrically and refined using
a riding model with Uiso (H) = 1.2Ueq(C) for aromatic
hydrogen and the hydrogen atoms connected to double
bond and Uiso (H) = 1.5Ueq(C) for hydrogen atoms of the
methyl and ethyl group. The molecular connectivity was
drawn using ORTEP32 [18] and the crystal packing dia-
grams were generated using Mercury (CCDC) program
[19]. Geometrical calculations were done using PARST
[20] and PLATON [21]. The geometrical restrictions
placed on the intermolecular H-bonds are the sum of the
˚
b (A)
˚
c (A)
a, b, c (ꢁ)
90, 114.1170 (10), 90 90, 90, 90
3
˚
V(A )
1675.24 (7)
4
2997.3 (3)
8
Z
Density (g cm-3
)
1.227
1.211
l (mm-1
)
0.083
0.084
F (000)
656
1168
h (min, max)
2.60, 27.47
Fixed
2.22, 27.60
Fixed
Treatment of
Hydrogens
hmin, max, kmin, max
lmin, max
,
(-17, 17), (-11, 11), (-23, 20), (-23, 23),
(-20, 19) (-11, 6)
14,290 13,693
3,823, 2,889
No. of ref.
No. unique ref./
obs. ref.
5,808, 3,335
˚
van der Waals radii ?0.4 A and the directionality is greater
No. of parameters 208
384
than 110ꢁ [22]. The details of the crystal data, data col-
lection and structure refinements are shown in Table 1.
Hirshfeld surfaces and the associated 2D-fingerprint plots
were generated using Crystal Explorer 3.0 [23].
R_all, R_obs
0.0579, 0.0435
0.1182, 0.0641
0.1882, 0.1595
-0.165, 0.200
1.004
wR2_all, wR2_obs 0.1274, 0.1171
-3
˚
Dqmin, max(eA
)
-0.167, 0.128
G. o. F.
1.056
Crystallographic Modeling of Disorder
The crystal structure of compound II (containing two mol-
ecules in the asymmetric unit) at room temperature (298 K)
exhibits a short C28(sp3)–C29(sp2) bond (of distance 1.29
modelled using the PART instruction by splitting the atom
into two independent positions, namely C28A & C28B and
C29A & C29B (‘A’ contains the higher occupancy for that
˚
˚
A). The ideal value is 1.52 A (default) [24]. This shortening
of the bond distance is mainly due to the positional disorder
of an atom over two sites. The dynamic disorder has been
˚
atom). The final bond distance value refines to 1.503(7) A.
The anisotropic displacement parameter for these two sites
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J Chem Crystallogr (2014) 44:131–142
133
is fixed using EADP. For equivalent bond distances, the
restraints SADI and DFIX have been used. Similar treat-
ment has been performed for the atoms C31 and C32. These
have also been split up into C31A & C31B and C32A &
C32B respectively. The bond distances C30–C31A and
conformation of both the molecules (IIA and IIB) sepa-
rately as is present in the asymmetric unit of II. Overlay
diagram between molecules IIA and IIB shows that
although these two molecules are chemically same, but
their configurations are different and of an opposite nature.
The molecule IIB exhibits dynamic disorder in the crystal.
Before modeling the disorder, the bond distance C28–C29
˚
C30–C32A are 1.461(9) and 1.456(10) A respectively.
˚
was 1.291(8) A and after the crystallographic treatment for
Theoretical Calculations
disorder, the bond distance C28A–C29A and C28B–C29B
˚
refined to a value of 1.507(8) and 1.483(14) A, these values
All theoretical calculations have been performed taking the
major conformer for the second molecule (subsequently
referred as B), out of the two molecules in the asymmetric
unit, the first molecule (referred to as A) exhibiting no
positional disorder. The geometrical optimization of the
molecule was performed at the B3LYP/6-31G** level of
calculation at the crystal geometry using TURBOMOLE
[25]. The atomic coordinates of the optimized geometry
were visualized with Mercury software. The selected tor-
sion angles of compound I and II obtained from theoretical
calculations (following geometrical optimization) were
then compared with the experimentally obtained values.
DFT?Disp calculations were done with the functional
B97-D using a higher basis set aug-cc-pVTZ in TURBO-
MOLE. The lattice energies of these crystal structures have
been calculated by PIXEL using the Coulomb-London-
Pauli (CLP) model of intermolecular coulombic, polariza-
tion, dispersion and repulsion energies. Furthermore, high
level DFT?Disp quantum mechanical calculations for
comparison with the pairing energies obtained from PIXEL
method have been performed.
are closely related to those obtained from the geometrical
optimization of the molecule. Furthermore, a comparison
of the torsions C27–O6–C28–C29 and O6–C28–C29–C30
obtained from experimental data and a comparison with the
theoretical values reveals changes in magnitude of 37.4ꢁ
and 19.9ꢁrespectively. Table 2 and 3 list some selected
torsion angles and bond angles for the compounds I and II.
Table 4 lists all the geometrically relevant intermolec-
ular hydrogen bonds presented in the title compounds. In
molecule I, O1 and O2 oxygen atoms act as a hydrogen
bond acceptor. The hydrogen atoms present in the N-
methyl group are most acidic (due to electronegativity
difference and resonance effect of the nitrogen lone pair
with the adjacent carbonyl group) followed by those
belonging to the ethyl ester group (due to electron with
drawing inductive effect of the oxygen atom). The oxygen
atom present in the 2-oxindole moiety has a strong capacity
for hydrogen bond formation as is reflected in the forma-
tion of C–HÁÁÁO=C hydrogen bonds (with O1 and aromatic
ring hydrogen H3, H9, H11 and aliphatic hydrogen H13C).
Figure 3a–f represents the different structural motifs which
contribute towards the crystal packing. In compound I, the
maximum stabilization comes from C–HÁÁÁp intermolecular
interactions, involving H2 (ring hydrogen) and H13B (and
aliphatic hydrogen) with Cg2 (centre of gravity of C7–C8–
C9–C10–C11–C12) and Cg1 (centre of gravity of C1–C2–
C3–C4–C5–C6) to generate a dimer across the centre of
symmetry. The energy stabilization is -9.1/-10.3 kcal/
mole (Fig. 4a) obtained using PIXEL/TURBOMOLE. One
C–HÁÁÁO=C hydrogen bond involving O1 with H13C forms
a dimer across the centre of symmetry with an interaction
energy of -6.6/-8.0 kcal/mole (Fig. 4b). Additional
C–HÁÁÁp (involving H18C and H8 with Cg2 and C3) and
C–HÁÁÁO=C (O1 with H3) interaction together generates a
molecular pair, the pairing energy being -5.8/-6.7 kcal/
mole (Fig. 4c). Another molecular pair (Fig. 4d) (involving
the bifurcated acceptor atom, O2 with H12 and H5) having
similar interaction energy (-5.8/-7.5 kcal/mole) also
stabilizes the crystal packing. In additional, a compara-
tively weak C–HÁÁÁp (involving H17B) and C–HÁÁÁO=C
(involving O1 with H11) mutually forms a dimeric
chain along the b axis, the energetic contribution being
Results and Discussion
Compound I (Fig. 1a) crystallizes in a centrosymmetric
monoclinic space group P21/n with one molecule in the
asymmetric unit, thus having Z = 4 whereas II (Fig. 1b
and c) crystallizes in a non-centrosymmetric orthorhombic
space group Pn21a with two molecules in the asymmetric
unit, having Z = 8. The N-methyl 2-oxindole moiety is a
common skeleton for both the molecules which are
chemically and crystallographically different. In compound
I, one benzyl group and ethyl ester group are connected
with the carbon atom, C15, but in case of II, one methyl
group and one dimethylallyl ester group are attached with
C9 & C25 respectively for the molecule A and B
respectively.
To gain insights into conformational differences in these
molecules in the solid state, overlay diagrams are shown in
Fig. 2 wherein the 2-oxindole moiety is superimposed. In
case of compound I, C14–C15–C16–O2 torsion varies by
8ꢁ (Fig. 2a). In Fig. 2b and c, the conformation of molecule
I is compared by overlapping with the molecular
-4.6/-5.3 kcal/mole (Fig. 4e). Finally, there is
a
123

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J Chem Crystallogr (2014) 44:131–142
Fig. 1 a ORTEP of compound I
drawn with 30 % ellipsoidal
probability. b ORTEP of
compound II, without the
treatment of disorder. c ORTEP
of compound II having disorder
along O6–C28=C29–C30 chain
of the molecule B in the
asymmetric unit (containing two
molecules A and B) drawn with
30 % ellipsoidal probability
Fig. 2 Overlay diagrams
between a I (experimental) and I
(theoretical), b I (experimental)
and IIA (experimental), c I
(experimental) and IIB
(experimental), d IIA
(experimental) and IIB
(experimental), e IIB
(experimental) and IIB
(theoretical)
Table 2 Selected torsion angles (ꢁ) for I and II
Torsion (I)
Experimental/theoretical Torsion (IIA)
Experimental/theoretical Torsion (IIB)
Experimental/theoretical
C27–O6–C28–C29 125.0(7) 87.4a
O6–C28–C29–C30
97.0(10) 116.9a
C16–C15–C19–C7 177.3(10) 178.6a
C19–C15–C16–O3 165.5(10) 164.0a
C14–C15–C16–O2 138.3(14) 145.1a
C17–O3–C16–C15 172.1(11) 177.9a
a
C11–O3–C12–C13 161.7(4) 163.3a
O3–C12–C13–C14 117.0(5) 126.8a
C12–O3–C11–C9
O3–C11–C9–C10
179.0(4) 179.3a
163.9(3) 163.2a
C28–O6–C27–C25 175.9(4) 179.0a
C26–C25–C27–O6 163.5(3) 152.18
Italicised values obtained from theoretical B3LYP/6-31G** calculations
C–HÁÁÁO=C interaction (involving O1 with H9), forming a
molecular chain along the crystallographic b-axis, the
energy being -3.4/-3.4 kcal/mole (Fig. 4f; Table 5).
In the solid state, N-methylic hydrogen atoms in com-
pound II do not exhibit more acidic nature compared to I in
the crystal packing. In case of compound II, containing two
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J Chem Crystallogr (2014) 44:131–142
135
Table 3 Selected Bond angles (8) for I and II
Bond angle (I)
Experimental/theoretical
Bond angle (IIA)
Experimental/theoretical
Bond angle (IIB)
Experimental/theoretical
C16–O3–C17
C16–C15–C14
C16–C15–C19
C7–C19–C15
a
117.8(11) 116.8a
109.1(10) 110.7a
110.8(10) 109.0a
113.8(10) 115.2a
C6–C9–C11
C9–C11–O3
C10–C9–C11
110.2(2) 109.8a
110.8(3) 111.3a
110.1(3) 110.0a
C22–C25–C27
C26–C25–C27
C25–C27–O6
110.2(3) 110.0a
110.8(3) 109.5a
111.6(4) 112.3a
Italicised values obtained from theoretical B3LYP/6-31G** calculations
Table 4 List of Intermolecular hydrogen bonds
˚
D–H(A)
˚
˚
I
D–HÁÁÁA
DÁÁÁA(A)
HÁÁÁA(A)
\D–HÁÁÁA(8)
Symmetry code, operation
C12–H12ÁÁÁO2
C5–H5ÁÁÁO2
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
3.592(2)
3.481(2)
3.666(2)
3.405(2)
3.593(2)
3.610(2)
3.859(2)
3.791(2)
3.827(2)
3.772(2)
3.632(2)
2.61
2.69
2.88
2.37
2.62
2.83
2.83
2.85
2.79
2.94
2.86
151
130
130
160
149
129
159
145
161
150
129
\D–H…A(8)
174
156
178
152
155
159
143
148
147
155
127
148
144
154
116
148
-x ? 1/2, y ? 1/2, -z ? 1/2, 21
-x ? 1/2, y ? 1/2, -z ? 1/2, 21
x, y-1, z
C11–H11ÁÁÁO1
C9–H9ÁÁÁO1
-x ? 3/2, y ? 1/2, -z ? 1/2, 21
-x ? 1, -y, -z, i
C13–H13CÁÁÁO1
C3–H3ÁÁÁO1
x-1/2, -y ? 1/2, z-1/2, n-glide
-x ? 1, -y ? 1, -z, i
-x ? 1, -y ? 1, -z, i
x-1/2, -y ? 1/2, z ? 1/2, n-glide
x-1/2, -y ? 1/2, z ? 1/2, n-glide
x, y-1, z
C13–H13BÁÁÁp(C2)
C2–H2ÁÁÁp(C9)
C18–H18CÁÁÁCg2
C8–H8ÁÁÁp(C3)
C17–H17BÁÁÁp(C4)
D–HÁÁÁA
˚
D–H(A)
˚
˚
II
D…A(A)
H…A(A)
Symmetry code, operation
x, y, z ? 1
C20–H20ÁÁÁO4
C26–H26BÁÁÁO2
C4–H4ÁÁÁO1
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
1.08
3.485(5)
3.855(6)
3.449(5)
3.768(8)
3.430(5)
3.551(6)
3.763(5)
3.688(7)
3.906(5)
3.973(5)
3.679(5)
3.868(5)
3.774(7)
3.715(5)
3.813(6)
3.816(6)
2.41
2.84
2.37
2.78
2.42
2.52
2.84
2.73
2.96
2.97
2.93
2.91
2.85
2.71
3.21
2.86
-x ? 2, y ? 1/2, -z ? 1, 21
x, y, z-1
C31–H31AÁÁÁO2
C7–H7BÁÁÁO2
C23–H23CÁÁÁO5
C13–H13ÁÁÁO5
C32–H32CÁÁÁO2
C7–H7CÁÁÁO4
C23–H23BÁÁÁO1
C3–H3ÁÁÁCg2
C19–H19ÁÁÁCg1
C5–H5ÁÁÁCg2
C21–H21ÁÁÁCg1
C10–H10CÁÁÁp(C17)
C32–
x ? 1/2, y, -z ? 3/2, a-glide
x-1/2, y, -z ? 3/2, a-glide
x ? 1/2, y, -z ? 1/2, a-glide
x ? 1/2, y, -z ? 3/2, a-glide
x-1/2, y, -z ? 1/2, a-glide
x, y, z-1
x, y, z-1
x, y, z
x, y, z
x-1/2, y, -z ? 1/2, a-glide
x ? 1/2, y, -z ? 3/2, a-glide
-x ? 2, y ? 1/2, -z ? 1, 21
-x ? 3/2, y ? 1/2, z ? 1/2, n-glide
H32AÁÁÁp(C20)
Cg1=C1–C2–C3–C4–C5–C6 (I, II), Cg2=C7–C8–C9–C10–C11–C12 (I), C17–C18–C19–C20–C21–C22 (II), Cg1=C13–C14 (II), Cg2=C29–
C30 (II)
molecules in the asymmetric unit, there exists three types
of molecular pairs A–A, A–B and B–B held via C–HÁÁÁO,
C–HÁÁÁp and p-p which are the key supramolecular ele-
ments contributing toward the stability of the crystal
packing. Energetically A–B type molecular pairs are more
stable than the A–A type and B–B type. C–HÁÁÁp and p..p
both forms molecular stacks across the centre the
symmetry (involving H2, H3, H18, and H19) with a
high energetic stabilization, the magnitude being
-10.0/-12.5 kcal/mole (Fig. 5a) obtained from PIXEL
and TURBOMOLE. In addition, one C–HÁÁÁO=C (involves
O2 with H32C) and one C–HÁÁÁp (isolated double bond
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J Chem Crystallogr (2014) 44:131–142
Fig. 3 Packing motifs of I a showing different C–HÁÁÁp interactions
down the crystallographic ac plane. b showing C–HÁÁÁO=C hydrogen
bonds with the oxygen atom down the ac plane. c showing bifurcated
C–HÁÁÁO=C hydrogen bond with the acceptor oxygen atom (O1) down
the ab plane. d Packing diagram of II showing the array of molecules
(AÁÁÁA) forming a tetrameric sheet down the ac plane. e and f depicts
an alternate layer of molecules (IIAÁÁÁIIB) viewed down the ab plane
and ac plane respectively
present in the allyl group) intermolecular interaction holds
the molecules along the a axis, having an interaction
energy of -7.6/-8.7 kcal/mole (Fig. 5b). Another molec-
ular pair along the same direction, utilizing the a glide
having energy comparable to the previous one, containing
two different types of C–HÁÁÁO (involving O2 with H31A
and O5 with H13), including one C–HÁÁÁp (H21 with
isolated double bond) with an energy stabilization of
-7.2/-8.1 kcal/mole (Fig. 5c) provides additional stabil-
ity. Acceptor O1 with H23B and O4 with H7C generates a
dimer across the centre of symmetry having interaction
energy of -5.4/-7.0 kcal/mole (Fig. 5d). Molecular pairs
e (A–B), f (A–A), g (B–B) and h (B–B) having energies in
the stabilization range of -2.8 to -1.8 kcal/mole also
contribute towards the stability of the crystal packing.
Table 6 lists the calculated lattice energies which are clo-
sely related to each other.
Thus we observe that the crystal structures of novel
molecules containing complex molecular architectures are
assembled via a judicious interplay of C–HÁÁÁO and C–HÁÁÁp
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J Chem Crystallogr (2014) 44:131–142
137
Fig. 4 Molecular pairs (a–f in Table 5) of compound I in order of decreasing interaction energy obtained from PIXEL. Cg1 = C1–C2–C3–C4–
C5–C6, Cg2 = C7–C8–C9–C10–C11–C12
intermolecular interaction which contribute towards the
stability in the solid state. It is already well known from the
literature that the C–HÁÁÁp hydrogen bond [26, 27] has been
observed in chemical [28] and biological systems [29, 30]. It
has been reported that such an interaction provides an
energetic stabilization of 7 kcal/mole, the donor and
acceptor being both hard in nature. In the current investiga-
tion the energy values are greater signifying their increased
contribution towards the stability in the crystal packing. It
has been observed that the formation of a C–HÁÁÁp intermo-
lecular interaction with an isolated double bond is not a very
common feature in organic crystals. Compound II contains
this type of C–HÁÁÁp hydrogen bonding with the isolated
double bond of dimethyallylester moiety. An investigation
of the Cambridge Structural Database [CSD version 5.34
updates (Feb 2013)] [31–35] related to an investigation of the
above mentioned interaction (Scheme 2) present in com-
pound II, has been performed. Only 11 hits (containing C, H,
N, and O) have been found to bear C–HÁÁÁp interatomic
˚
distance, the distance and angle range being 2.71 to 2.94 A
and 120ꢁ to 160ꢁ respectively.
CSD code
Bond
distance (A)
Angle (ꢁ)
Molecular
formula
˚
Compound II
2.93, 2.91,
2.85, 2.71
127, 148,
144, 154
C16H19NO3
AFEWEN [36]
BETTEZ [37]
DACWIP [38]
FATWAY [39]
GIMQUP [40]
NUBTUA [41]
OLIZEP [42]
2.85
2.86
2.88
2.90
2.83
2.85
2.90
147
142
151
146
142
142
148
C21H25N1O3
C42H54N2O9
C17H24N2O3
C31H52N2O1
C13H12N2O2
C20H27N1O6
C31H39N1O8,
2.2(H2O)
PORJEM [43]
2.89
154
C
23H29N1O4
123

138
J Chem Crystallogr (2014) 44:131–142
shape index, there are some red and blue triangles which
denote the presence of C–HÁÁÁp intermolecular contacts in
both the molecules. The nature of the dnorm (front and back
views) of the molecule II provides the information about
the differences between two molecules present in the
asymmetric unit. Furthermore there exist a relationship of
the red colored region (in the 2-oxindole moiety) between
the dnorm (front) of IIA and dnorm (back) of IIB and vice
versa. The presence of stacking is evident on the Hirsfeld
surfaces, as large flat regions on both sides of the mole-
cules, which is clearly visible on the curvedness surface
(Fig. 7). In the Fig. 8, C–HÁÁÁp intermolecular interaction
for both the molecules present in the asymmetric unit of II,
has been shown by the dnorm and shape index together.
Each fingerprint plot of these two 2-oxyindole deriva-
tives summarizes the contribution of the interaction
present in the two molecules (Fig. 9). In addition to that,
these plots highlight the similarities and differences
between crystal structures in this class of compounds.
There are some distinct spikes (shown by arrows) which
are appearing in the 2D fingerprint plot for both the
structures. These spikes indicate different interactions
motifs in the crystal lattice. The molecule I contains a
total of four spikes whereas II has three spikes. The
middle spike for molecule IIA is a single spike but for IIB
consist of double spikes. Complementary regions are
visible in the fingerprint plots where one molecule acts as
donor (de [ di) and the other as an acceptor (de \ di). In
CSD code
Bond
distance (A)
Angle (ꢁ)
Molecular
formula
˚
SILPAF [44]
2.92
2.86
2.94
136
147
147
C18H17N1O3
C31H30N2O4
C18H27N1O4
VAQQOV [45]
XENBAV [46]
From the CSD search, all the C–HÁÁÁp bond angles are
observed in the range of 142ꢁ to 154ꢁ signifying their
directional role in self assembly processes in the crystal.
For compound II, similar geometrical features (both dis-
tance and directionality) are observed which is in accor-
dance with those obtained from the CSD.
The Hirshfeld surfaces of these two compounds (I, II)
are described in Fig. 6, showing surfaces that have been
˚
mapped over dnorm (-0.5 to 1.5 A). It is clear that the large
circular depressions (deep red) visible on the front view
and back view of the surfaces are indicative of hydrogen-
bonding contacts. Other visible white spots on the surfaces
are because of the head-to-head HÁÁÁH contacts present in
the crystal lattice. The dominant interactions between the
C–H and carbonyl oxygen atoms in both the compounds
can be seen in the Hirshfeld surface as red spots. Hydrogen
bonds coming from the oxygen atom presented in the
2-oxyindole moiety are energetically stronger than those
from the carbonyl oxygen atom presented in the ester
group. This is depicted in the former being associated with
a deeper red color compared to that in the latter case. In the
Table 5 PIXEL interaction energies (in kcal/mol) between molecular pairs related by a symmetry operation in the crystal
No. Symmetry code
Centroid– ECoul EPol
centroid
distance
EDisp
ERep ETot
DFT-Disp/
B97-D
aug-cc-pVTZ
Involved interactions
I (P21/n)
a
b
c
d
e
f
-x ? 1, -y ? 1, -z
7.136
7.485
7.935
-3.7 -1.4 -9.9
-3.0 -0.9 -5.9
-2.0 -0.8 -6.6
-2.6 -1.0 -5.4
-1.2 -0.9 -5.5
-1.9 -0.8 -3.2
6.0
3.1
3.6
3.2
3.0
2.5
-9.1
-6.6
-5.8
-5.8
-4.6
-10.3
-8.0
-6.7
-7.5
-5.3
-3.4
C13–H13BÁÁÁp(C2); C2–H2ÁÁÁp(C9)
C13–H13CÁÁÁO1
C3–H3ÁÁÁO1; C18–H18CÁÁÁCg2; C8–H8ÁÁÁp(C3)
C12–H12ÁÁÁO2; C5–H5ÁÁÁO2
C11–H11ÁÁÁO1; C17–H17BÁÁÁp(C4)
C9–H9ÁÁÁO1
-x ? 1, -y, -z
x-1/2, -y ? 1/2, z ? 1/2
-x ? 1/2, y ? 1/2, -z ? 1/2 7.745
x, y-1, z 8.795
-x ? 3/2, y ? 1/2, -z ? 1/2 9.677
-3.4
II (Pn21a)
a
x, y, z (AÁÁÁB)
5.813
-3.0 -1.4 -13.7 8.1
-10.0 -12.5
Cg2ÁÁÁp(C2); C3–H3ÁÁÁCg2; Cg1ÁÁÁp(C18); C19–
H19ÁÁÁCg1
b
c
d
e
x-1/2, y,-z ? 1/2 (AÁÁÁB)
x ? 1/2, y, -z ? 3/2 (AÁÁÁB)
x, y, z-1 (AÁÁÁB)
-x ? 2, y ? 1/2, -z ? 1
(A…B)
6.793
6.973
7.077
8.582
-2.5 -1.1 -8.2
-3.4 -1.1 -7.9
-2.0 -0.8 -5.4
-0.4 -0.3 -3.3
3.9
4.1
2.7
1.2
-7.6
-7.2
-5.4
-2.8
-8.7
-8.1
-7.0
-3.9
C32–H32CÁÁÁO2; C5–H5ÁÁÁCg2
C31–H31AÁÁÁO2; C13–H13ÁÁÁO5; C21–H21ÁÁÁCg1
C7–H7CÁÁÁO4; C23–H23BÁÁÁO1
C26–H26BÁÁÁO2; C10–H10CÁÁÁCg2
f
x, y, z-1 (AÁÁÁA)
x, y, z ? 1 (BÁÁÁB)
-x ? 3/2, y ? 1/2, z ? 1/2
(BÁÁÁB)
9.160
9.159
10.268
-1.5 -0.7 -1.7
-1.4 -0.7 -1.8
-0.4 -0.2 -2.6
1.6
1.8
1.3
-2.3
-2.0
-1.8
-2.1
-2.2
-2.4
C4–H4ÁÁÁO1
C20–H20ÁÁÁO4
C32–H32AÁÁÁp(C20)
g
h
123

J Chem Crystallogr (2014) 44:131–142
139
Fig. 5 Molecular pairs (a–g in Table 5) of compound II in order of decreasing interaction energy obtained from PIXEL.Cg1 = C1–C2–C3–C4–
C5–C6, Cg1 = C13–C14, Cg2 = C17–C18–C19–C20–C21–C22, Cg2 = C29–C30
compound II, there is a slight difference in the percentage
contribution of CÁÁÁH intermolecular interaction and other
related contributions of different types of interactions are
similar to each other.
Table 6 Lattice energy (CLP, in kcal/mol) of compounds I and II
Comp. code
ECoul
EPol
EDisp
ERep
ETot
I
-11.2
-8.6
-4.3
-3.4
-32.8
-31.5
18.6
15.8
-29.7
-27.8
II
Conclusions
The field of investigation of the crystal and molecular
structures has advanced to an extent wherein it is possible
to decipher the role of molecular conformation and exploit
the role of weak intermolecular interactions which aid
crystal packing. These features have ramifications in both
reactivity and ordering of molecules in the crystalline state.
Studies on complex natural products is rare, the reason
being that the determination of the molecular structure is of
significance and importance to the organic chemist.
Scheme 2 Cambridge Structural Database (CSD) search for the
occurrence of C–HÁÁÁp intermolecular interactions with an isolated
double bond
123

140
J Chem Crystallogr (2014) 44:131–142
Fig. 6 Hirshfeld surfaces mapped with dnorm (front view), dnorm (back view), and Shape index for the title compounds I and II (A & B)
Fig. 7 Curvedness of compound I and II (A and B)
Fig. 8 a dnorm, b shape index and c molecular packing with dnorm and shape index between two crystallographically distinct molecules A and B
in the asymmetric unit of compound II involving C–HÁÁÁp intermolecular interaction
However, it is of interest to re-iterate the fact that forces
beyond covalent bonding also play a significant role in
packing the molecules and an understanding of their nature
is also of interest in structural chemistry.
In this study performed on oxoindoline carboxylates, it has
been found that C–HÁÁÁp intermolecular interaction and p-p
stacking are the most important contributors towards the
crystal stability in addition to the C–HÁÁÁO intermolecular
123

J Chem Crystallogr (2014) 44:131–142
141
Fig. 9 Fingerprint plots a–d for I, e–h for IIA and i–l for IIB: full (left column) and resolved into C–HÁÁÁO (second column), CÁÁÁH (third
column), HÁÁÁH (right) contacts showing the percentages of contacts contributed to the total Hirshfeld surface area for the molecules
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molecules. Hirshfeld surface analysis and fingerprint plots
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bution of individual types of interaction within the crystal
structures. It is of interest to extend such studies in more
complex molecular architectures and also exploit the occur-
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