Spectroscopic, x-ray diffraction and density functional theory study of intra- and intermolecular hydrogen bonds in ortho-(4-tolylsulfonamido)benzamides

Article abstract of DOI:10.3390/molecules26040926

The conformations of the title compounds were determined in solution (NMR and UVVis spectroscopy) and in the solid state (FT-IR and XRD), complemented with density functional theory (DFT) in the gas phase. The nonequivalence of the amide protons of these compounds due to the hindered rotation of the C(O)–NH₂ single bond resulted in two distinct resonances of different chemical shift values in the aromatic region of their¹H-NMR spectra. Intramolecular hydrogen bonding interactions between the carbonyl oxygen and the sulfonamide hydrogen atom were observed in the solution phase and solid state. XRD confirmed the ability of the amide moiety of this class of compounds to function as a hydrogen bond acceptor to form a six-membered hydrogen bonded ring and a donor simultaneously to form intermolecular hydrogen bonded complexes of the type N–H···O=S. The distorted tetrahedral geometry of the sulfur atom resulted in a deviation of the sulfonamide moiety from co-planarity of the anthranilamide scaffold, and this geometry enabled oxygen atoms to form hydrogen bonds in higher dimensions.

Full text of DOI:10.3390/molecules26040926

molecules
Article
Spectroscopic, X-ray Diffraction and Density Functional Theory
Study of Intra- and Intermolecular Hydrogen Bonds in
Ortho-(4-tolylsulfonamido)benzamides
Malose J. Mphahlele 1,
*
, Eugene E. Onwu 1 and Marole M. Maluleka 2
1
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa,
Private Bag X06, Florida 1710, South Africa; 64061639@mylife.unisa.ac.za
Department of Chemistry, University of Limpopo, Private Bag X1106, Sovenga 0727, South Africa;
2
marole.maluleka@ul.ac.za
*
Correspondence: mphahmj@unisa.ac.za; Tel.: +27-11-670-9301
Abstract: The conformations of the title compounds were determined in solution (NMR and UV-
Vis spectroscopy) and in the solid state (FT-IR and XRD), complemented with density functional
theory (DFT) in the gas phase. The nonequivalence of the amide protons of these compounds
due to the hindered rotation of the C(O)–NH2 single bond resulted in two distinct resonances of
1
different chemical shift values in the aromatic region of their H-NMR spectra. Intramolecular
hydrogen bonding interactions between the carbonyl oxygen and the sulfonamide hydrogen atom
were observed in the solution phase and solid state. XRD confirmed the ability of the amide moiety of
this class of compounds to function as a hydrogen bond acceptor to form a six-membered hydrogen
bonded ring and a donor simultaneously to form intermolecular hydrogen bonded complexes of the
type N–H···O=S. The distorted tetrahedral geometry of the sulfur atom resulted in a deviation of the
sulfonamide moiety from co-planarity of the anthranilamide scaffold, and this geometry enabled
oxygen atoms to form hydrogen bonds in higher dimensions.
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Citation: Mphahlele, M.J.; Onwu,
E.E.; Maluleka, M.M. Spectroscopic,
X-ray Diffraction and Density
Keywords: 2-((4-methylphenyl)sulfonamido)benzamides; intramolecular hydrogen bonding; X-ray;
Hirshfeld analysis; DFT
Functional Theory Study of Intra- and
Intermolecular Hydrogen Bonds in
Ortho-(4-tolylsulfonamido)benzamides.
Molecules 2021, 26, 926. https://
doi.org/10.3390/molecules26040926
1. Introduction
Academic Editor: Nino Russo
Received: 22 December 2020
Accepted: 29 January 2021
Published: 10 February 2021
Sulfonamides are an important class of therapeutic agents, with a broad range of
pharmacological profiles, and many sulfonamide-based compounds are in clinical use
as active pharmaceutical ingredients for the treatment of bacterial and viral infections,
hyperglycemia and hypertension, among others [1,2]. Although predominantly employed
as antibacterial agents, sulfonamide-based compounds also exhibit inhibitory properties
against various enzymes, including carbonic anhydrase, cysteine protease, HIV protease,
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iations.
cyclooxygenase, acetylcholinesterase (AChE) and butyrylcholinestearse (BChE) [
enzyme inhibitory properties result from the propensity of the sulfonamide group to
establish strong electrostatic ( -cation, attractive charge interaction) and hydrogen bond-
2]. Their
π
ing interactions with a wide range of functional groups of protein residues. Interest in
sulfonamides is not only limited to drug development, but also exists in terms of their con-
formations and crystalline structures [
explore hydrogen bonding interactions, control molecular conformations and improve the
physicochemical properties of the drug molecules [ ]. The sulfonamide group generally
adopts tetrahedral geometry, and the oxygen atoms of this group easily form hydrogen
bonds in higher dimensions than amides do. Aromatic sulfonamides have been found
3–5]. This scaffold provides a versatile template to
Copyright:
© 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
6,7
to display conformational chirality emanating from the synclinal conformation [
N-phenylbenzenesulfonamides, for example, exist preferentially in (+)- or ( )-synclinal
conformations with a twist in the same direction of the aromatic rings at both ends. The
6]. The
−
Molecules 2021, 26, 926. https://doi.org/10.3390/molecules26040926
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 926
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hydrogen atom of the sulfonamide group was found to be involved in an intermolecular
hydrogen bonding interaction with the O atom of the sulfonyl group of another, which is
generally stronger than the other intermolecular interactions, such as CH–π, CH–lone pair,
aromatic–aromatic, and other hydrogen bonding interactions. Kikkawa et al. classified
the intermolecular hydrogen-bonding patterns of aromatic sulfonamides into four types,
namely, dimeric, zigzag, helical, and straight patterns, all retaining the synclinal conforma-
tion of the sulfonamide functionality [6]. Integrating intramolecular hydrogen bonding
formation in drug design has become an exciting challenge for medicinal chemistry, as this
noncovalent force results in conformational restriction of small drug molecules, leading to
increased lipophilicity, membrane permeability and pharmacological activity [
model systems with intramolecular and/or intermolecular hydrogen bonded amide groups
are often employed to study these interactions in solution and in the solid state [ ]. Despite
8]. Small
9
the enormous interest in the structural properties of the C-2 N-substituted anthranilamide
derivatives [10], the presence of intramolecular and/or intermolecular hydrogen bonding
in 2-(sulfonylamino)benzamides [11,12] has not been well explored in the literature. This
encouraged us to study the structural properties of 2-(benzenesulfonylamino)benzamides
in solution and solid state by means of spectroscopic (NMR, UV-Vis and IR) and single crys-
tal X-ray diffraction (XRD) techniques, in combination with the density functional theory
(DFT) method in the gas phase. A Hirshfeld surface and a fingerprint plot were generated
to explore the intermolecular interactions in the crystalline structure. The intramolecular
contacts have also been interpreted using Natural Bond Orbital (NBO) analysis.
2. Results and Discussion
2.1. Solution Phase Structural Analysis Using NMR and UV-Vis Spectroscopy
The test compounds were prepared as shown in Scheme 1 and their structures were
determined using a combination of NMR (1H- & 13C-), UV-Vis, IR and mass spectrometric
techniques. The 1H- and 13C-NMR spectra of compounds 2a
,
2b and 2c are enclosed as
Figure S1 of the Supplementary Information (SI). The hydrogen atoms of the amide group
(–C(O)NH2) of the 2-(4-tolylsulfonylamino)benzamides 2a resonated as two distinct
–
c
broad singlets of reduced intensity and different chemical shift values in the aromatic
1
region of their H-NMR spectra. The observed chemical shift nonequivalence of these
amide hydrogen atoms is attributed to the hindered rotation of the H2N–C(O) single bond
in terms of NMR time scale [13]. A singlet for NH of the arylsulfonamido group resonated
significantly downfield around
δ = 12.10 ppm due to the deshielding effect of the S=O
bonds. This downfield shift of the NH signal is also consistent with the participation of this
hydrogen atom in intramolecular hydrogen bond interaction with the carbonyl oxygen.
1a (X = H)
1b (X = Br)
1c (X = I)
2a
2b
2c
Scheme 1. Sulfonylation of anthranilamide derivatives 1a–c.

Molecules 2021, 26, 926
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The absorption spectra of the compounds in
2
(Figure 1) were acquired in DMSO at
room temperature (200–400 nm) and show bands around around
= 275 nm due to π → π* transitions indicative of the presence of benzene chromophore
and sulfonamide moiety.
λ = 250 nm and around
λ
−6
Figure 1. UV-Vis spectra of 2a, 2b and 2c in DMSO (conc. = 1 × 10 mol/L).
2.2. Solid-State Structural Analysis of 3a–c Using IR Spectroscopy and XRD
The FT-IR spectra of the title compounds (refer to Figure S2 in SI) were obtained using
the thin-film method, and the corresponding wavenumbers are listed in Table 1 below.
The assignments are based on the experimental and the simulated IR spectral data of 2a
as a model (refer to Table S1 for the computed IR frequencies for 2a–c). The computed
harmonic vibrational wavenumbers relate to the isolated molecule in a gas phase and are
generally greater than the experimentally observed vibrational wavenumbers for molecules
in the solid state due to negligence of anharmonicity, electron correlation and basis set
deficiencies. The asymmetric and symmetric N–H stretching vibrations of the solid samples
of benzenesulfonamide derivatives are observed in the region,
ν
= 3444–3473 cm−1 and
max
3345–3371 cm−1
the N–H symmetric (
region 3300–3400 cm−1 of their FT-IR spectra, and these correspond to the N–H stretching
,
respectively, due to intermolecular hydrogen bonding [14]. A band for
sym (NH2)) stretching vibration of compounds is observed in the
ν
2
mode of the amide group. The corresponding computed symmetric (νsym (NH2)) stretching
vibrations occur at
The bands in the region
ν
max = 3225 cm−1 for 2a−,1at 3225 cm−1 for 2b and at 3246 cm−1 for 2c
.
ν
2921–2971 cm are attributed to aromatic and aliphatic C–H
max
stretching vibrations. Strong peaks in the regions of 1313–1385 cm−1 and 1149–1161 cm−1
are due to the asymmetric and symmetric S=O stretching vibrations, respectively. The com-
puted S=O asymmetric stretching wavenumber occurred at ν
max = 1318 and 1382 cm−1 for
2a, at 1321 and 1381 cm−1 for 2b, and at 1318 and 1383 cm−1 for 2c. Although sulfonamides
−1
have been found to exhibit S–N stretching vibrations at 924–906 cm
ing frequencies for 2a 2b and 2c are
[14], the correspond-
,
ν
max = 934 cm−1, 939 cm−1, and 961 cm−1, respectively.
The higher stretching vibration values for these compounds presumably reflect the effect
of participation of this scaffold in intramolecular hydrogen bonding interaction.

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Table 1. The experimental IR frequencies (cm−1) for compounds 2a–c.
2a–c
N–H asym/sym str
C–H
C=O
N–H bend
S=O asym/sym str
S–N
2a
2b
2c
3469/3362
3473/3371
3444/3345
2971
2921
2931
1652
1662
1668
1493
1485
1498
1313/1153
1327/1161
1318/1149
935
939
961
After confirming the compound homogeneity and purity by NMR and FT-IR spec-
troscopy, single crystals of compounds 2a were subjected to XRD analysis. The crystal
structures of compounds are represented in Figure 2 and their atom-labelling schemes
differ from systematic numbering. The crystal data and structure refinement of these
compounds are presented in Table S2 (refer to SI). Single crystal XRD analysis of 2a re-
–
c
2
–
c
vealed the presence of intramolecular hydrogen bonding interaction (Table 2) between the
oxygen of the amide (–C(O)NH2) moiety and the NH of the p-tosylsulfonamido group with
bond distance N(2)–H(2)···O(1) of 1.865(18) Å and bond angle 141(2)◦ for 2a (Figure 2a),
1.95(2) and 142(2)◦ for 2b (Figure 2b) and 2.09(2) Å and 138(2)◦ for 2c (Figure 2c). The
hydrogen bonding pattern forms an R1 (6) motif where R, subscript, superscript and the
1
number in parentheses represent the ring, number of donors, acceptors and number of
atoms involved in this hydrogen bonding pattern, respectively. The amide unit of these
compounds also functioned as a hydrogen bond donor to form intermolecular hydro-
gen bonded complexes of the type N–H···O=S, analogous with the literature precedent
for anthranilamide derivatives [15]. The propensity of an amide moiety for hydrogen
bonding plays an important role in the spatial structure of proteins, nucleic acids and
biological membranes, as well as in the interaction of bioactive compounds with recep-
tors [
deviation of the sulfonamide moiety from coplanarity of the anthranilamide scaffold with
the following torsion angle between the two rings: C(8) S(1) N(2) C(2) of
53.07(11)◦
for 2a
C(1)–N(2)–S(1)–C(8) of 64.18(13)◦ for 2b and C(1)–N(2)–S(1)–C(8) of 75.54(17)◦ for
derivative 2c. The packing of molecules of compounds
occurs via N–H···O hydrogen
8]. The distorted tetrahedral geometry of the sulfur atom in each case resulted in
–
–
–
−
,
2
bridges between N(H) atoms of the amide moiety and the oxygen atoms of sulfonyl group
of a nearby molecule. This twisted geometry of the sulfonamide group enabled oxygen
atoms to form hydrogen bonds in higher dimensions. The conformation of the N(2)–C(2)
bond in the C–SO2–NH–C segment of the structure of 2a are gauche and trans with respect
to the S(1)=O(2) and S(1)=O(3) bonds, respectively. Both anti and syn oxygen atoms of the
SO2NH group of 2a are involved in N–H···O interactions with the hydrogen atom of the
amide (NH2CO) moiety of a different molecule to form parallel planes with cyclic motifs
R44(12) (Figure 2a). The N(2)–C(1) bonds in the C–SO2–NH–C segment of the structures of
2b or 2c, on the other hand, are trans and gauche with respect to the S(1)=O(2) and S(1)=O(3)
bonds, respectively. The syn oxygen atom of the SO2NH group of one molecule of 2b forms
a seven-membered cyclic (R21(7)) motif with the benzamide scaffold of another molecule of
this compound through N–H···O=S and C–H···O=S bonding interactions (Figure 2b). The
C–H···O hydrogen bonds play an important role in determining molecular conformation
and crystal packing [16], in molecular recognition processes [17], and in the stabilization of
inclusion complexes [18]. The anti oxygen of this compound is involved in halogen bonding
with the bromine atom (O···Br) to form a chain. A bromine atom contains a region with
positive charge (
characteristics on the drug molecules [19
σ
-hole) responsible for its halogen bonding (XB) formation and stabilizing
20]. Both the syn oxygen atom of the SO2NH
,
moiety and the oxygen atom of the amide group of one molecule of 2c are involved in
N–H···O=S and C=O···H–C interactions of the other molecule, respectively, to form a R22(8)
dimer (Figure 2c). The formation of conventional N–H···O bonds seems to be favored
over halogen bonding interactions for this compound. It has been proposed that planar
molecules show thermochromism, while nonplanar molecules show photochromism [21].
The nonplanar nature of these sulfonamidobenzamides make them suitable candidates for
further studies, as solid-state photochromic materials have potential use as photooptical
memories and switches.

Molecules 2021, 26, 926
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(a)
(b)
Figure 2. Cont.

Molecules 2021, 26, 926
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(c)
Figure 2. The Oak Ridge Thermal Ellipsoid Plot (ORTEP) diagrams and the X-ray crystal structure of
2a (a), 2b (b) and 2c (c) showing intra- and intermolecular hydrogen bonding.
◦
Table 2. Hydrogen bond geometries (Å and ) of compounds 2a, 2b and 2c.
D–H···A
d(D–H)
d(H···A)
d(D···A)
<(DHA)
2a
2b
2c
N(1)–H(1A)···O(2)#1
N(1)–H(1B)···O(3)#2
N(2)–H(2)···O(1)
0.886(19)
0.86(2)
0.873(18)
2.180(19)
2.23(2)
1.865(18)
3.0405(15)
3.0542(15)
2.6045(14)
164(2)
161(2)
141(2)
N(1)–H(1A) . . . O(2)#1
N(1)–H(1B) . . . O(3)#2
N(2)–H(2) . . . O(1)
0.87(2)
0.83(2)
0.77(2)
2.17(2)
2.33(2)
1.95(2)
2.9690(18)
3.1462(19)
2.6022(17)
151(2)
170(2)
142(2)
N(1)–H(1A)···O(2)#1
N(1)–H(1B)···O(1)#2
N(2)–H(2)···O(1)
0.82(3)
0.77(2)
0.80(2)
2.14(3)
2.23(3)
2.09(2)
2.947(2)
2.973(2)
2.7359(19)
172(2)
164(2)
138(2)
2.3. Computational Studies
2.3.1. Hirshfeld Interactions
Sulfonamides are capable of forming highly ordered supramolecular architectures
through hydrogen bonds and stacking interactions [22]. The Hirshfeld surface and 2D
fingerprint studies of 2a were carried out in order to obtain information about intermolecular
π–π
–c
contacts and their quantitative contribution to the supramolecular self-assembly. Strong,
neutral, and weak interactions in the Hirshfeld surface, which are involved in the stabilization
of crystal structure, are depicted as red, white and blue colors, respectively [23]. The Hirshfeld
surfaces and two-dimensional (2D) fingerprint plots of these compounds were obtained
using the corresponding Common Internet File System’s (CIF’s) files. The Hirshfeld surface
and 2D fingerprint plot of 2a (Figure 3) used as a model (refer to Figure S3 for 2b and
S4 for 2c in SI) revealed that multiple C–H···O=S hydrogen bonds and other hydrogen

Molecules 2021, 26, 926
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bonds involving amide and sulfonamide groups played an important role in the assembling
processes. Analyses of the Hirshfeld surfaces revealed that the N–H···O=C hydrogen bond
is the interaction that drives the supramolecular assembly in these compounds, and it is
reinforced by H···H, O···H/H···O, C···H/H···C, C···C and N···H interactions (Figure 3a).
The red spots over the surface indicate the intercontacts involved in hydrogen bonding
interactions and interatomic contacts. These intense red spots appeared as sharp spikes in
the corresponding fingerprint plots (Figure 3b) and are related to the polar O···H hydrogen
bonding interactions. The faded red spots in the dnorm map, and the broad peaks in the
fingerprint plots are due to the hydrophobic C···H and H···H interactions. The percentages
of the contacts that contribute to the total Hirshfeld surface of 2a are as follows: H···
H
(31.6%), O···H/H···O (15.0%), C···H/H···C (15.5%), C···C (4.0%), N···H (2.2%). The major
contributions of the total area of the surface are from H···H (31.6%), C···H/H···C (15.5%)
and O···H/H···O (15.0%) interactions compared to the other intercontacts. The contribution
percentages to the total Hirshfeld surface of 2b (refer to Figure S4 in SI) listed by contact
are H···H (31.4%), O···H/H···O (11.5%), C···H (10.2%) and Br···H (8.6%), C···O (0.9%),
Br···O/O···Br (2.2%) and N···H (1.8%). Those for 2c (refer to Figure S4 in SI) are as follows:
H
···H (36.3%), O···H/H···O (9.5%), C···H (8.3%) and I···H (7.8%), C···O (4.6%) and I···
I
(2.6%). Although there is no halogen bonding interaction for this compound, iodine atoms
are engaged in halogen–halogen interaction.
(a)
(b)
Figure 3. Hirshfeld surface for the crystal structure (a) and 2D fingerprint plot analysis (b) of 2a.

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2.3.2. Optimized Structures of 2a, 2b and 2c from DFT Analyses
The optimized geometries were obtained in the gas phase using a B3LYP/6-311G (d,p)
basis set for 2a and 2b, and a B3LYP/LanL2DZ basis set for 2c. The minimum potential
energy was achieved by solving the self-consisting field interactively (local minimum) to
obtain the corresponding geometries shown in Figure 4. The theoretically calculated values
of the bond angles, dihedral angles and torsion angles of the optimized structures of 2a
,
2b and 2c are given in Table S3 in the Supplementary Information. Selected experimental
and calculated bond lengths, bond angles and torsion angles of compound 2a (used as
a representative model) are represented in Table 3 below. The results revealed a good
agreement between the calculated geometric parameters (bond distances and bond angles)
of compounds 2a, 2b and 2c with those obtained from the CIFs. The differences observed
between the experimental (XRD) and calculated (DFT) parameters is due to the gas phase
and theoretical methods ignoring molecular interactions observed in the solid state. A
short C(7)–N(1) bond length of about 1.33 Å for the test compounds (which is significantly
shorter than the value (1.470 Å) proposed for the C(sp2)–N(sp2) single bond length) [24
]
may be indicative of a double bond character. This, in our view, may be the cause of the
hindered rotation about the C(sp2)–N(sp2) single bond and, therefore, the nonequivalence
1
of the resonances for the amide hydrogen atoms observed in the H-NMR spectra of
these compounds. However, a value of about 1.322 Å observed for the C–N bonds in
some amides has previously also been suggested to be indicative of the single bonded
C(sp2)–N(sp2) [25].
2a
2b
2c
Figure 4. Optimized structures of 2a, 2b and 2c in the gas phase.
The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular
Orbital (LUMO) surfaces of the most stable conformers of 2a 2b and 2c are illustrated in
,
Figure 5. DFT calculations revealed that the HOMO is mainly localized on the anthranil-
amide scaffold and significantly or partially localized on the p-toluenesulfonamide arm
for 2a (Figure 5) and 2b (Figure 5), respectively. The HOMO for 2c (Figure 5) is largely
distributed throughout the sulfonamidobenzamide framework and not on the p-tolyl group.
The LUMO of the three compounds is localized mainly on the sulfonamidobenzamide
framework. The energy gap between the HOMO and LUMO displays the delocalization
of the
transition occurred between the frontier molecular orbitals from HOMO to LUMO, and
the small computed energy gap ( E) values for 2a 0.17954 eV), 2b 0.17089 eV) and
2c (−0.16052 eV) show that these compounds are soft molecules that can be excited using
minimal energy. The strong charge transfer interaction through the -conjugated system
π-electron cloud from the donor to the acceptor unit, respectively. The electronic
∆
(
−
(
−
π
led to substantial ground state donor–acceptor mixing and the appearance of a charge
transfer band in the electron absorption spectrum.

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Table 3. Selected◦XRD and density functional theory (DFT) bond lengths (Å), bond angles (◦) and
dihedral angles ( ) for 2a.
Experimental
DFT
Bond Lengths (Å)
2a: C(7)=O(1), N(2)–S(1)
O(2)–S(1), O(3)–S(1)
C(7)–N(1), C(8)–S(1)
2b: C(7)=O(1), N(2)–S(1)
O(2)–S(1), O(3)–S(1)
C(7)–N(2), C(8)–S(1)
2c: C(7)=O(1), N(2)–S(1)
O(2)–S(1), O(3)–S(1)
C(7)–N(2), S(1)–C(8)
1.2410 (15), 1.6224 (10)
1.4399 (9), 1.4381 (9)
1.3331 (16), 1.7555 (12)
1.2381 (18), 1.6318 (12)
1.4344 (11), 1.4363 (11)
1.333 (2), 1.7585 (15)
1.242 (2), 1.6306 (14)
1.6306(14), 1.4299(12)
1.328 (2), 1.7574 (17)
1.230, 1.689
1.458, 1.455
1.367, 1.798
1.229, 1.692
1.454, 1.458
1.365, 1.797
1.274, 1.624
1.628, 1.628
1.374, 1.784
◦
Bond Angles ( )
2a: N(2)–S(1)–C(8)
O(2)–S(1)–C(8)
O(3)–S(1)–C(8)
C(2)–N(2)–S(1)
2b: N(2)–S(1)–C(8)
O(2)–S(1)–C(8)
O(3)–S(1)–C(8)
C(1)–N(2)–S(1)
2c: N(2)–S(1)–C(8)
O(2)–S(1)–C(8)
O(3)–S(1)–C(8)
C(1)–N(2)–S(1)
107.84 (5)
109.43 (5)
107.47 (5)
126.06 (8)
107.51 (7)
107.71 (7)
108.45 (7)
123.74 (10)
107.08 (8)
108.51 (8)
107.49 (8)
130.22 (12)
107.50
108.20
105.59
125.58
107.51
107.66
108.35
123.74
107.20
108.47
107.28
129.81
◦
Torsion Angles ( )
◦
2a: C(8)–S(1)–N(2)–C(2)
C(3)–C(2)–N(2)–S(1)
C(9)–C(8)–S(1)–N(2)
O(2)–S(1)–N(2)–C(2)
2b: C(1)–N(2)–S(1)–C(8)
C(6)–C(1)–N(2)–S(1)
C(9)–C(8–S(1)–N(2)
C(1)–N(2)–S(1)–O(3)
2c: C(1)–N(2)–S(1)–C(8)
C(6)–C(1)–N(2)–S(1)
C(9)–C(8)–S(1)–N(2)
C(1)–N(2)–S(1)–O(3)
–53.07 (11)
−57.10
−32.38
−66.05
−165.75
64.54
52.26
66.14
179.70
75.54
12.50
110.73
−40.99
−32.18 (16)
−66.54 (11)
−169.35 (10)
◦
64.18 (13)
52.08 (18)
66.41 (14)
179.24 (12)
◦
75.54 (17)
11.00 (3)
−110.21 (15)
−40.99 (18)
A partial double bond character for the C–N bond of primary amides is always invoked
to account for the hindered rotation [24], and is therefore the cause of the nonequivalence
of the resonances for the amide hydrogen atoms observed in their 1H-NMR spectra [13,15].
Although the resonance interaction model provides a convenient explanation for the stabi-
lization of the amino–carbonyl moiety, the changes in electron population and structure
on rotation were previously found not to be in accord with an electron donation from the
amino group to the carbonyl oxygen of formamide [26]. Consequently, the natural bond
orbitals (NBOs) analysis of compounds 2a, 2b and 2c were performed at the B3LYP/6-311G
(d,p) level of theory (2a and 2b) and at the B3LYP/ LanL2DZ (d,p) level of theory (2c) to
further elucidate the delocalization of electron density within these molecules (Table S4
in SI). The interactions between the bonding n1(O3) and antibonding (N2–S1) orbitals of
compounds 2a
with stabilization energy values of 1.43, 1.81 and 2.28 kJ.mol−1, respectively. These com-
pounds exhibit intramolecular hyperconjugation formed by an overlap between n1 (N1)
bonding and * (C7–O1) antibonding orbitals, which is stabilized by the intramolecular
charge transfer (ICT) with stabilization energies of 58.1 (2a), 51.4 (2b) and 61.9 kJ.mol−1
, 2b and 2c show the delocalization of charge in the sulfonamide framework
σ
π

Molecules 2021, 26, 926
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(
2c). There is an increase in electron density (ED) into the C–O and C–N antibonding
orbitals, which elongates the nitrogen–carbon bond. The changes in bond lengths in C=O
and C–N are consistent with the decrease in the double bond character of C=O bond due
to hydrogen bonds, which, in turn, increase the double bond character of C–N bond [27].
Figure 5. HOMO–LUMO distribution of 2a, 2b and 2c, and the energy gap.
3. Materials and Methods
3.1. Chemical Synthesis
3.1.1. Preparation of Substrates
Anthranilamide (1a) was purchased from Sigma-Aldrich (Sigma-Aldrich, Bradford,
UK). 2-Amino-5-bromoanthranilamide (1b) [28] and 2-amino-5-iodoanthranilamide (1b) [29
]
were prepared following methods described in our previous studies. The most convenient
and efficient method for the synthesis of sulfonamides involves the use of alkyl/arylsulfonyl
chlorides and amines as starting materials at room or elevated temperature in the pres-
ence of appropriate solvent and/or amine bases to scavenge the HCl generated from the
reaction [2]. The outcome of this reaction depends on the reaction temperature, time, and
quantities of the sulfonyl chloride and amine base used. High temperature and prolonged
reaction time facilitated the attachment of a second sulfonyl chloride reagent on the aniline

Molecules 2021, 26, 926
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nitrogen atom and/or dehydration of the amide NH2 group into a nitrile group [12,30].
The 2-(p-tolylsulfonamido)benzamides 2a–c were prepared as described below.
3.1.2. Typical Procedure for the Synthesis of the 2-(p-Tolylsulfonamido)benzamides 2a–c
p-Toluenesulfonyl chloride (1.2 equiv.) was added gradually to a stirred solution of
◦
anthranilamide derivative
1
(1 equiv.) in pyridine (2 mL/mmol of
1
) at 0–5 C. The mixture
was allowed to warm to room temperature and, after 0.5 h at this temperature, the mixture
was quenched with an ice-cold water. The precipitate was filtered and recrystallized from
acetonitrile to afford a pure solid product.
2-((4-Methylphenyl)sulfonamido)benzamide (2a), White solid (1.65 g, 92%), mp. 227–230 ◦C
◦
1
(CH3CN) (Lit. [12] 250–251 C); H-NMR (DMSO-d6) 2.30 (3H, s,
−
CH3), 7.03 (1H, t,
J = 7.5 Hz, H-5), 7.29 (2H, dd, J = 2.0 and 8.0 Hz, H-3’,5’), 7.40 (1H, t, J = 8.0 Hz, H-4), 7.49
(1H, d, J = 8.5 Hz, H-3), 7.62 (2H, d, J = 8.5 Hz, H-2’,6’), 7.74 (1H, d, J = 8.0 Hz, H-6), 7.78
(1H, br s,
−
NHCO), 8.27 (1H, br s, –NHCO), 12.16 (1H, s,
−
NHS); 13C-NMR (DMSO-d6)
21.4, 119.2, 119.4, 123.2, 123.3, 127.2, 129.4, 130.1, 130.2, 133.1, 133.2, 136.6, 139.8, 144.0,
171.1; HRMS (ES): m/z [M + H]+ calc 291.0725 for C14H15N2O3S; found 291.0759.
5-Bromo-2-((4-methylphenyl)sulfonamido)benzamide (2b), White solid (1.72 g, 96%), mp. 194–196 ◦C
(CH3CN); 1H-NMR (DMSO-d6) 2.29 (3H, s,
−
CH3), 7.33 (2H, d, J = 7.0 Hz, H-3’,5’), 7.46
(1H, d, J = 8.0 Hz, H-3), 7.63 (3H, d, J = 8.5 Hz, H-4 and H-2’,6’), 7.97 (1H, d, J = 1.5 Hz,
H-6), 7.99 (1H, br s, –NHCO), 8.41 (1H, br s, NHCO), 12.06 (1H, s,
NHS); 13C-NMR
−
−
(DMSO-d6) 21.4, 119.6. 121.4, 121.5, 127.2, 130.4, 131.9, 135.5, 136.1, 138.9, 144.5, 169.7;
HRMS (ES): m/z [M + H]+ calc 368.9830 for C14H14BrN2O3S; found 368.9810.
◦
5-Iodo-2-((4-methylphenyl)sulfonamido)benzamide (2c), White solid (1.45 g, 89%), mp. 186–188 C
(CH3CN); 1H-NMR (DMSO-d6) 2.30 (3H, s,
−
CH3), 7.29 (2H, d, J = 8.5 Hz, H-3’,5’), 7.30
(1H, d, J = 9.0 Hz, H-3), 7.61 (2H, d, J = 8.5 Hz, H-2’,6’), 7.71 (1H, dd, J = 1.5 and 9.0 Hz, H-4),
7.87 (1H, br s, NHCO), 8.07 (1H, d, J = 1.5 Hz, H-6), 8.35 (1H, br s, NHCO), 12.04 (1H, s,
−
−
−
NHS); 13C-NMR (DMSO-d6) 21.5, 87.1, 121.3, 121.4, 127.2, 130.2, 136.3, 137.4, 139.4, 141.5,
144.2, 169.7; HRMS (ES): m/z [M + H]+ calc 416.9692 for C14H14IN2O3S; found 416.9225.
3.2. Instrumentation
The 1H- and 13C-NMR spectra of the title compounds were obtained as DMSO-d6
solutions using an Agilent 500 MHz NMR spectrometer (Agilent Technologies, Oxford, UK)
and the chemical shifts are quoted relative to the tetramethylsilane (TMS) peak. The UV-vis
spectra were recorded on a Cecil CE 9500 (9000 Series) UV-Vis spectrometer (ThermoFisher
Scientific, Waltham, MA, USA). The IR spectra of the test compounds were recorded at room
temperature by using the thin-film method on a Bruker VERTEX 70 FT-IR Spectrometer
(Bruker Optics, Billerica, MA, USA) equipped with a diamond attenuated total reflectance
(ATR) accessory. The high-resolution mass spectra were recorded at an ionization potential
of 70 eV using a Micromass Autospec-TOF (double focusing high resolution) instrument
(Waters Corp., Milford, MA, USA).
3.3. Data Collection and Refinement
Intensity data were determined on a Bruker Venture D8 Photon CMOS diffractometer
with graphite-monochromated MoKa1 (l = 0.71073 Å) radiation at 173 K using an Oxford
Cryostream 600 cooler. Data reduction was carried out using the program SAINT+, version
6.02 [31] and empirical absorption corrections were made using SADABS [31]. Space group
assignments was made using XPREP [31]. The structure was solved in the WinGX [32
]
suite of programs, using intrinsic phasing through SHELXT [32] and refined using full-
matrix least-squares/difference Fourier techniques on F2 using SHELXL-2017 [33]. All C
bound hydrogen atoms were placed at idealized positions and refined as riding atoms with
isotropic parameters 1.2 times those of their parent atoms. O– and N–bound hydrogen
atoms were located in the difference Fourier map and their coordinates and isotropic

Molecules 2021, 26, 926
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displacement parameters refined freely. Diagrams and publication material were generated
using ORTEP-3 [32], and PLATON [34].
3.4. Computational Methods
The structures were fully optimized by density functional theory using the Gaus-
sian 09 program package (Gaussian Inc., revision D.01, Wallingford, CT, USA) [35] in the
gas phase. The DFT computations were carried out using the hybrid functional Becke’s
three-parameter nonlocal exchange functional with the Lee–Yang–Parr correlation func-
tion (B3LYP) [36], together with the 6-311++G(d,p) [37
LanL2DZ ECP basis set for the iodine atom [39,40].
,38] basis set for all atoms and the
3.5. Hirshfeld Surface Analyses
The three-dimensional Hirshfeld (HF) surfaces and two-dimensional (2D) fingerprint
plots of the title compounds were carried out using the Crystal Explorer software [41]. The
normalized contact distance (dnorm) is based on the distance from the point to the nearest
nucleus external to the surface (de) and the distance to the nearest nucleus internal to the
surface (di) [42].
4. Conclusions
The results of this study demonstrate that the conformations of 2-((4-methylphenyl)
sulfonamido)benzamides in solution and in the solid state are controlled by inter- and
1
intramolecular networks of different types of hydrogen bonding. H-NMR spectroscopy
showed that the amide protons resonate in different chemical shift environments, and
their nonequivalence is due to hindered rotation of the C(O)–NH2 single bond. Significant
downfield shift of the resonance for the sulfonamide hydrogen in the 1H-NMR spectra of
these compounds is due to its involvement in intramolecular hydrogen bonding interaction
with the carbonyl oxygen and its proximity to the strongly electron withdrawing -SO2-
group. Use of the XRD method provided unambiguous proof of the existence of a six-
membered intramolecular hydrogen bonded ring (graph set descriptor, R2 (6)) involving
2
hydrogen atom of the sulfonamide group and carbonyl oxygen. Moreover, XRD analyses
confirmed the ability of the amide moiety of these compounds to function as a hydrogen
bond donor and acceptor simultaneously. The distorted tetrahedral geometry of the sulfur
atom caused the sulfonamide group to be twisted out of coplanarity of the intramolecularly
hydrogen bonded anthranilamide scaffold. This twisted geometry enabled the oxygen
atoms of the sulfonamide group to form hydrogen bonds in higher dimensions than the
amide group. Despite conformational similarities, the molecular packing schemes of the
test compounds have been found to differ considerably depending on the intermolecular
interactions present in their crystal lattices. The capability of the sulfonamidobenzamide
scaffold to engage in noncovalent and hydrophobic interactions make the title compounds
suitable candidates for deployment in medicinal chemistry. The small HOMO–LUMO
energy gap of these compounds, on the other hand, make them attractive targets for
future studies of nonlinear optical (NLO) properties. Likewise, the nonplanar nature of
this scaffold make these compounds suitable candidates for further studies as solid-state
photochromic materials with potential applications as photooptical memories and switches.
1
Supplementary Materials: Copies of the H-NMR and 13C-NMR spectra (Figure S1), IR spectra
(
Figure S2), computed IR spectral data (Table S1), crystal data and structure refinement for com-
pounds 2a (Table S2), the Hirshfeld surface and 2D fingerprint plot (Figures S3 and S4), the
calculated geometric parameters (bond lengths and angles) of 2a (Table S3), and second-order
perturbation theory analysis of the Fock matrix in NBO basis for compounds 2a (Table S4) The CIF
–
c
–
c
–
c
files containing complete information on the studied structures were deposited with the Cambridge
Crystallographic Data Center, CCDC 2043901 (2a), CCDC 2049537 (2b) and CCDC 2049356 (2c), and
are freely available upon request from the following website: www.ccdc.cam.ac.uk/datarequest/cif
or by contacting the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: +44-1223-336033; email: deposit@ccdc.cam.ac.uk.

Molecules 2021, 26, 926
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Author Contributions: Conceptualization, literature review, synthesis and analysis, and writing of
the original draft (M.J.M.); IR and UV-Vis specral data (E.E.O.); DFT calculations (M.M.M.), revision
and editing (M.J.M. & M.M.M.). All authors have read and agreed to the published version of
the manuscript.
Funding: This project was funded by the University of South Africa and the National Research
Foundation (NRF) in South Africa (NRF GUN: 118554). The views and opinions expressed herein are
those of the authors and not of the funding bodies.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: No other data were reported.
Acknowledgments: We are grateful to the University of Stellenbosch Central Analytical Facility
(CAF) and the University of the Witwatersrand for mass spectrometric and X-ray data, respectively.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
2.
Lavanya, R. Sulphonamides. A pharmaceutical review. Int. J. Pharm. Sci. Inv. 2017, 6, 2319–6718.
Mondal, S.; Malakar, S. Synthesis of sulfonamide and their synthetic and therapeutic applications: Recent advances. Tetrahedron
2020, 76, 131662. [CrossRef]
3.
4.
de Castro, M.R.C.; Aragão, A.Q.; da Silva, C.C.; Perez, C.N.; Queiroz, D.P.K.; Queiroz Júnior, L.H.K.; Barreto, S.; de Moraes, M.O.;
Martins, F.T. Conformational variability in sulfonamide chalcone hybrids: Crystal structure and cytotoxicity. J. Braz. Chem. Soc.
2016, 27, 884–898. [CrossRef]
Perlovich, G.L.; Ryzhakov, A.M.; Tkachev, V.V.; Hansen, L.K.; Raevsky, O.A. Sulfonamide molecular crystals: Structure, subli-
mation thermodynamic characteristics, molecular packing, hydrogen bonds networks. Cryst. Growth Des. 2013, 13, 4002–4016.
[CrossRef]
5.
6.
Arshad, M.N.; Faidallah, H.M.; Asiri, A.M.; Kosar, N.; Mahmood, T. Structural, spectroscopic and nonlinear optical properties of
sulfonamide derivatives; experimental and theoretical study. J. Mol. Struct. 2020, 1202, 127393. [CrossRef]
Kikkawa, S.; Masu, H.; Katagiri, K.; Okayasu, M.; Yamaguchi, K.; Danjo, H.; Kawahata, M.; Tominaga, M.; Sei, Y.; Hikawa,
H.; et al. Characteristic hydrogen bonding observed in the crystals of aromatic sulfonamides: 1D chain assembly of molecules
and chiral discrimination on crystallization. Cryst. Growth Des. 2019, 19, 2936–2946. [CrossRef]
Adsmond, D.A.; Grant, D.J.W. Hydrogen bonding in sulfonamides. J. Pharm. Sci. 2001, 90, 2058–2077. [CrossRef]
Dado, G.P.; Gellman, S.H. Intramolecular hydrogen bonding in derivatives of beta-alanine and gamma-amino butyric acid; model
studies for the folding of unnatural polypeptide backbones. J. Am. Chem. Soc. 1994, 116, 1054–1062. [CrossRef]
Stenfors, B.A.; Collins, R.C.; Duran, J.R.J.; Staples, R.J.; Birosa, S.M.; Ngassa, F.N. Crystal structure of 4-methyl-N-
propylbenzenesulfonamide. Acta Cryst. E 2020, 76, 1070–1074. [CrossRef]
7.
8.
9.
10. Kuhn, B.; Mohr, P.; Stahl, M. Intramolecular hydrogen bonding in medicinal chemistry. J. Med. Chem. 2018, 53, 2601–2611.
[CrossRef]
11. Sarfraz, M.; Sultana, N.; Tariq, M.I.; Parvez, M. Synthesis, molecular packing and anti-cholinesterase activity of some new C-2
N-substituted anthranilamide derivatives. Z. Kristallogr. Cryst. Mater. 2019, 234, 605–611. [CrossRef]
12. Oloyede, H.O.; Görls, H.; Woods, J.A.O.; Winfried Plass, W.; Eseola, A.O. N-Donor 2-(sulfonamido)benzamide ligands, their
palladium(II) coordination species and C–C coupling catalysis efficiencies. J. Mol. Struct. 2019, 1197, 336–344. [CrossRef]
13. Wang, L.-X.; Hu, B.-Q.; Xiang, J.-F.; Cui, J.; Hao, X.; Liang, T.-L.; Tang, Y.-L. N-Aryl-substituted anthranilamides with intramolecu-
lar hydrogen bonds. Tetrahedron 2014, 70, 8588–8591. [CrossRef]
14. Sanphui, P.; Sarma, B.; Nangia, A. Polymorphism in secondary benzene sulfonamides. Cryst. Growth Des. 2010, 10, 4550–4564.
[CrossRef]
15. Mphahlele, M.J.; Maluleka, M.M.; Rhyman, L.; Ramasami, P.; Mampa, R.M. Spectroscopic, DFT, and XRD studies of hydrogen
bonds in N-unsubstituted 2-aminobenzamides. Molecules 2017, 22, 83. [CrossRef] [PubMed]
16. Steiner, T. Unrolling the hydrogen bond properties of C–H···O interactions. Chem. Commun. 1997, 727–734. [CrossRef]
17. Shimon, L.J.W.; Vaida, M.; Addadi, L.; Lahav, M.; Leiserowitz, L. Molecular recognition at the solid-solution interface: A “relay”
mechanism for the effect of solvent on crystal growth and dissolution. J. Am. Chem. Soc. 1990, 112, 6215–6220. [CrossRef]
18. Houk, K.N.; Menzer, S.; Newton, S.P.; Raymo, F.M.; Stoddart, J.F.; Williams, D.J. [C–H···O] Interactions as a control element in
supramolecular complexes: Experimental and theoretical evaluation of receptor affinities for the binding of bipyridinium-based
guests by catenated hosts. J. Am. Chem. Soc. 1999, 121, 1479–1487. [CrossRef]
19. Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. Halogen bonding– A novel interaction for rational drug
design? J. Med. Chem. 2009, 52, 2854–2862. [CrossRef] [PubMed]

Molecules 2021, 26, 926
14 of 14
20. Rahman, A.; Ali, M.T.; Shawan, M.M.A.K.; Sarwar, M.G.; Khan, M.A.K.; Halim, M.A. Halogen-directed drug design for
Alzheimer’s disease: A combined density functional and molecular docking study. SpringerPlus 2016, 5, 1346–1359. [CrossRef]
[PubMed]
21. Moustakali-Mavridis, I.; Hadjoudis, E.; Mavridis, A. Structure of thermochromic Schiff bases. II. Structures of N-salicylidene-3-
aminopyridine and N-(5-methoxysalicylidene). Acta Cryst. B 1980, 36, 1126–1130. [CrossRef]
22. Daniel, A.B.; Auldhas, D.; Joe, I.H.; Sai, B.S.A. Experimental and computational approach on p-toluenesulfonamide and its
derivatives. J. Mol. Struct. 2020, 1218, 128503. [CrossRef]
23. Steiner, T. The hydrogen bond in the solid state. Angew. Chem. Int. Ed. Engl. 2002, 41, 48–76. [CrossRef]
24. Schnur, D.M.; Yuh, H.Y.; Dalton, D.R. A molecular mechanics study of amide conformation. J. Org. Chem. 1989, 54, 3779–3785.
[CrossRef]
25. Camerm, A. Single bond radius of trigonal nitrogen and the C(sp2)–N(sp2) single bond. Can. J. Chem. 1970, 48, 179–181. [CrossRef]
26. Wiberg, K.B.; Breneman, C.M. Resonance interactions in acyclic systems. 3. formamide internal rotation revisited. Charge and
energy redistribution along the C-N bond rotational pathway. J. Am. Chem. Soc. 1992, 114, 831–840. [CrossRef]
27. Joseph, T.; Varghase, H.T.; Panicker, C.Y.; Viswanathan, K.; Dolezal, M.; Van Alsenoy, C. Spectroscopic (FT-IR, FT-Raman), first
order hyperpolarizability, NBO analysis, HOMO and LUMO analysis of N-[(4-(trifluoromethyl)phenyl]pyrazine-2-carboxamide
by density functional methods. Arabian J. Chem. 2017, 10, S2281–S2294. [CrossRef]
28. Paumo, H.K.; Mphahlele, M.J.; Rhyman, L.; Ramasami, P. Synthesis, photophysical properties and DFT study of novel polycarbo-
substituted quinazolines derived from the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines. Tetrahedron 2016, 72, 123–133. [CrossRef]
29. Mphahlele, M.J.; Paumo, H.K.; Rhyman, L.; Ramasami, P. Synthesis and photophysical Properties of polycarbo-substituted
quinazolines derived from the 2-aryl-4-chloro-6-iodoquinazolines. Molecules 2015, 20, 14656–14683. [CrossRef] [PubMed]
30. Stephens, C.R.; Bianco, E.J.; Pilgrim, F.J. A new reagent for dehydrating primary amides under mild conditions. J. Am. Chem. Soc.
1955, 12, 1701–1702. [CrossRef]
31. Bruker. APEX-3, SAINT+, Version 6.02 (Includes XPREP and SADABS); Bruker AXS Inc.: Madison, WI, USA, 2016.
32. Farrugia, L.J. WinGX and ORTEP for Windows An update. J. Appl. Crystallogr. 2012, 45, 849–854. [CrossRef]
33. Sheldrick, G.M. SHELXT-Integrated space-group and crystal-structure determination. Acta Cryst. 2015, 71, 3–8. [CrossRef]
34. Spek, A.L. Structure validation in chemical crystallography. Acta Cryst. 2009, D65, 148–155. [CrossRef]
35. Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G.A.; et al. Gaussian 09, Revision A.01; Gaussian Inc.: Wallingford, CT, USA, 2009.
36. Becke, A.D. Density-functional thermochemistry III. The role of exact exchange. J. Chem. Phys. 1993, 98, 5648–5652. [CrossRef]
37. Lee, C.; Yang, W.; Parr, R.G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density.
Phys. Rev. B 1988, 37, 785–789. [CrossRef]
38. Krishnan, R.; Binkley, J.S.; Seeger, R.; Pople, J.A. Self-consistent molecular orbital methods. XX. A basis set for correlated wave
functions. J. Chem. Phys. 1980, 72, 650–654. [CrossRef]
39. Hay, P.J.; Wadt, W.R. Ab initio effective core potentials for molecular calculations. Potentials for the main group elements Na to Bi.
J. Chem. Phys. 1985, 82, 284–298.
40. Hay, P.J.; Wadt, W.R. Ab initio effective core potentials for molecular calculations. Potentials for K to Au including the outermost core
orbitals. J. Chem. Phys. 1985, 82, 299–310.
41. Wol, S.K.; Grimwood, D.J.; McKinnon, J.J.; Jayatilaka, D.; Spackman, M.A. Crystal Explorer 3.0; University of Western Australia:
Perth, Australia, 2001.
42. Spackman, M.A.; McKinnon, J.J. Fingerprinting intermolecular interactions in molecular crystals. Cryst. Eng. Comm. 2002
4, 378–392. [CrossRef]
,