Structural and energetics of weak non-covalent interactions in two chemically distinct classes of O/N-heterocycles: X-ray and theoretical exploration

Article abstract of DOI:10.1016/j.molstruc.2020.129694

Two different classes of compounds namely xanthenedione and acridinedione derivatives have been synthesized and crystal structures of these compounds (9-(p-tolyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione, C₂₀H₂₀O₃,

Full text of DOI:10.1016/j.molstruc.2020.129694

Journal Pre-proof
Structural and energetics of weak non-covalent interactions in two
chemically distinct classes of O/N-heterocycles: X-ray and theoretical
exploration
Subbiah Thamotharan , Subramaniyan Prasanna Kumari ,
Subramaniapillai Selva Ganesan , Shankar Madan Kumar ,
M. Judith Percino , Neratur Krishnappagowda Lokanath
PII:
S0022-2860(20)32007-X
DOI:
Reference:
https://doi.org/10.1016/j.molstruc.2020.129694
MOLSTR 129694
To appear in:
Journal of Molecular Structure
Received date:
Revised date:
Accepted date:
18 September 2020
24 November 2020
26 November 2020
Please cite this article as:
Subramaniapillai Selva Ganesan ,
Subbiah Thamotharan ,
Subramaniyan Prasanna Kumari ,
M. Judith Percino ,
Shankar Madan Kumar ,
Neratur Krishnappagowda Lokanath , Structural and energetics of weak non-covalent interactions
in two chemically distinct classes of O/N-heterocycles: X-ray and theoretical exploration, Journal of
Molecular Structure (2020), doi: https://doi.org/10.1016/j.molstruc.2020.129694
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.
© 2020 Elsevier B.V. All rights reserved.

HIGHLIGHTS
 Two chemically distinct classes of compounds synthesized.
 Similar energy frameworks.
 Similar contributions of H···H, H···O and H···C contacts towards crystal packing.
 Closed-shell C–H···O and N–H···O interactions.
 PIXEL intermolecular interaction energies for dimers.

Structural and energetics of weak non-covalent interactions in two chemically
distinct classes of O/N-heterocycles: X-ray and theoretical exploration
Subbiah Thamotharana,*, Subramaniyan Prasanna Kumarib, Subramaniapillai Selva Ganesanb,
Shankar Madan Kumarc, M. Judith Percinod and Neratur Krishnappagowda Lokanathe
a
Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and
Biotechnology, SASTRA Deemed University, Thanjavur – 613 401, India
b
Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University,
Thanjavur – 613 401, India
c IOE, Vijnana Bhavan, University of Mysore, Mysuru 570006, India
d Unidad de Polímeros y Electrónica Orgánica, Instituto de Ciencias, Benemérita Universidad Autónoma
de Puebla, Val3-Ecocampus Valsequillo, Independencia O2 Sur 50, San Pedro Zacachimalpa, Puebla-
C.P.72960, México.
e Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru 570 006, India
________________
Corresponding author.
E-mail address: thamu@scbt.sastra.edu (S. Thamotharan).

Abstract
Two different classes of compounds namely xanthenedione and acridinedione derivatives have
been synthesized and crystal structures of these compounds (9-(p-tolyl)-3,4,5,6,7,9-hexahydro-
1H-xanthene-1,8(2H)-dione, C20H20O3, 1 and 9-(p-tolyl)-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione, C20H21NO2, 2) are reported. The X-ray analysis reveals that the central
heterocyclic ring exhibits boat conformation and the cyclohexene rings have envelope
conformations in both structures. The Hirshfeld surface analysis suggests that the relative
contribution of H···H, H···O and H···C contacts have not changed due to the positional isomers
(ortho and para) of 1. The same is true when NH group replaces the O atom in the central ring as
well. The PIXEL energy analysis suggests that the intermolecular C–H···O and C–H···C()
interactions stabilize the crystal structure of 1. In 2, the intermolecular N–H···O, C–H···O and
C–H···C() interactions existing in different dimers. The isostructurality analysis indicates that
the structure 1 shares 2D isostructurality with one of its closely related structure, whereas
structure 2 shares only 0D isostructurality with its closely related structure. The lattice energy
calculation for 1 and its ortho isomer and compound 2 is reported. The energy frameworks
analysis was performed in order to visualize the topology of the energy frameworks for these
crystals. The topological analysis is presented for intermolecular interactions existing in 1 and 2.
The frontier molecular orbital analysis suggests that the HOMO orbital’s localization shows
distinct features for 1 and 2.
Keywords: Xanthenedione; acridinedione; QTAIM; PIXEL; Hirshfeld surface; closed-shell
interactions

1. Introduction
Oxygen and nitrogen-containing heterocycles have received significant attention due to their
wide applications in different research areas including organic synthesis and medicinal chemistry
and in the pharmaceutical industry [1-4]. Xanthene and acridine represent the oxygen and
nitrogen containing heterocyclic cores. 1,8-dioxo-octahydroxanthene and acridines are one of the
heterocyclic skeleton bestowed with numerous biological activity. Mulakayala et al., reported
that octahydroxanthene derivative (A, Scheme 1) with 2-hydroxy phenyl group showed good
anticancer against human chronic myeloid leukemia cells (K562), human colon carcinoma cells
(Colo-205) and human neuroblastoma cells (IMR32) [5]. Similarly, the xanthene derivative (B,
Scheme 1) with 2-phenoxyacetic acid group displays good antiproliferative activity and DPPH
(2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity [6]. Nisar et al., reported
octahydroxanthene analog (C, Scheme 1) function as leishmanicidal agents [7]. Timpe et al.,
identified that the decahydroacridine derivative (D, Scheme 1) shows good photosensitizer
properties [8]. Acridine derivatives also used as a fluorescent probe to monitor the
polymerization reaction [9]. Recently, Kumaran et al., studied the interaction between
acridinedione dyes with bovine serum albumin in water. These authors found that dye’s red-
shifted fluorescence emission behavior due to hydrogen bonding interaction formed between N–
H group of the dye and the protein [10].
Scheme 1. Chemical structures of some xanthenes and an acridine derivative with their
properties.

In this work, we synthesized two chemically different classes of compounds such as
xanthenedione and acridinedione derivatives. The X-ray structures of these two compounds were
determined at room temperature and reported herein. Udayakumar et al., described the crystal
structure namely 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-
tetrahydro-1H-xanthen-1-one, the energetics of dimers using PIXEL energy analysis and the
nature and strength of weak non-covalent interactions in this structure using topological analysis
of the electron density [11]. Subsequently, Taghartapeh et al., reported the catalyst free synthesis
of a series of xanthene derivatives and these derivatives were further characterized by
spectroscopy and photophysical experiments [12]. The crystal structure was re-determined for
one of the xanthene derivatives namely 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-
3,3,dimethyl2,3,4,9-tetrahydro-1H-xanthen-1-one by these authors. Recently, a xanthene
derivative was characterized by means of Hirshfeld surface analysis and electronic structure
calculation [13]. Saeed et al., explored the supramolecular self-assembly of a coumarine-based
acylthiourea synthons dictated by -stacking interactions and these compounds are somewhat
similar to xanthene derivatives [14]. The Hirshfeld surface analysis of intermolecular interactions
and frontier molecular orbital analysis were reported for an acridinedione derivative. This
derivative was forming a dimer via intermolecular O–H···O interaction [15]. The crystal
structures of heterocyclic ring bearing dimethyl and NH groups were reported [16]. In these
structures, the amine group has involved in an intramolecular N–H···O hydrogen bond and
intermolecular N–H···S interaction.
In this work, we described the effect of X group (see Scheme 2, O in 1 and NH in 2) on the
molecular conformation, intermolecular interactions, lattice energies, topology of the energy
frameworks and electronic structures. Further, a detailed analysis of the isostructurality is
presented for 1 and 2 and their related structures. Further, the evaluation of weak non-covalent
interactions is reported based on the topological parameters derived from the quantum theory of
atoms-in-molecules (QTAIM) approach.
2. Materials and methods
2.1. Synthesis and crystallization

The target compounds were synthesized as described earlier [17] and the synthetic route for these
compounds are shown in Scheme 2.
Reaction condition A
O
H
O
Reaction condition
A or B
O
O
ZnCl2 /H2O
120 oC, 3 h
2
O
Reaction condition B
X
Condition A; X = O (compound 1)
Condition B; X = NH (compound 2)
NH4OAc /ZnCl2
120 oC, 30 min.
Scheme 2. Synthesis route of target compounds 1 and 2.
General procedure for the synthesis of 9-(p-tolyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-
dione (1)
To a stirred homogeneous solution of 1,3-cyclohexandione (112 mg, 1 mmol) in water (3 mL), 4-
methylbenzaldehyde (61 mg, 0.5 mmol) and ZnCl2 (17 mg, 0.125 mmol) were successively
added and stirred at 120 °C for 3 hr. After completion of the reaction, the solid product formed
was isolated by simple filtration, washed with water (1  10 mL) and dried. The crude product
was washed with hexane (1  5 mL) and dried under vacuum. A portion of the sample was
recrystallized from absolute ethanol.
General procedure for the synthesis of 9-(p-tolyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-
dione (2)
To a stirred mixture of 1,3-cyclohexandione (112 mg, 1 mmol), 4-methylbenzaldehyde (61 mg,
0.5 mmol), ammonium acetate (231 mg, 3 mmol) in 3 mL of water, ZnCl2 (17 mg, 0.125 mmol)
was added and heated at 120 °C in an open round bottom flask for 30 min. After completion of
reaction, cold water (5 mL) was added and the mixture stirred for further 10 min. The solid
products were isolated by simple filtration, washed with hexane and dried under reduced
pressure. The crude was recrystallized from absolute ethanol.
2.2. Single crystal X-ray diffraction
The X-ray intensity data were collected for single crystals of 1 and 2 on a Rigaku Saturn70
diffractometer using Mo K radiation ( = 0.71073 Å) at room temperature (296 K). The data
were collected and processed using CrystalClear (CrystalClear SM Expert 2.0 r15, Rigaku, 2011)

and a numerical absorption correction was applied (NUMABS, Rigaku, 1999). The structure was
solved by the SIR-92 program [18] and all non-hydrogen atoms were refined anisotropically
using the SHELXL-2018/3 program [19]. In 1, two carbon atoms (C3 and C4) from one of the
cyclohexene rings (ring A) were disordered over two positions. Constrained refinement of the
site-occupation factors for these atoms led to a value of 0.659 (14) for the major conformation.
Similarity restraints were applied to all 1,2 and 1,3 distances involving disordered atoms, so as to
maintain similar geometry about the chemically equivalent atoms. Although the compound 1 is
achiral, the structure possesses a polar axis. Because of the absence of any significant anomalous
scatterers in the compound, attempts to confirm the absolute structure by refinement of the Flack
x parameter in the presence of 1020 sets of Friedel equivalents led to an inconclusive value of
0.5(7) for this parameter [20]. Therefore, the absolute direction of the polar axis was assigned
arbitrarily and the Friedel pairs were merged before the final refinement. In 2, the position of H
atom bound to N atom was located from a difference Fourier map and refined freely along with
its isotropic displacements parameters. The remaining H atoms were positioned in idealized
geometries (C–H = 0.93-0.98 Å with Uiso(H) = 1.2Ueq(C) or 1.5 Ueq(C)). In the case of methyl H
atoms, they were allowed to rotate freely about the C–C bond. Crystallographic data and
refinement parameters are presented in Table 1. The ORTEP plots were produced using the
program PLATON [21]. Crystal packing and dimeric motifs were drawn using MERCURY
program [22].
Table 1
Crystal data and refinement parameters for 1 and 2.
1
2
Crystal data
Chemical formula
Mr
C20H20O3
308.4
C20H21NO2
307.38
Crystal system, space group
Temperature (K)
Orthorhombic, Pna21
296
Monoclinic, P21/n
296
7.3528 (4), 15.6924 (9),
14.4942 (8)
90, 100.546 (5), 90
1644.14 (16)
4
a, b, c (Å)
17.1990 (8), 5.7939 (3),
15.9738 (9)
90, 90, 90
1591.78 (1)
4
, ,  ()
V (Å3)
Z
Radiation type
Mo Kα (=0.71073)
0.09
1.287
Mo Kα (=0.71073)
0.08
1.242
 (mm-1)

Calc (g cm-3)

Crystal size (mm3)
Data collection
Diffractometer
0.23 × 0.20 × 0.15
0.30 × 0.21 × 0.18
Rigaku Saturn70
diffractometer
Rigaku Saturn70
diffractometer
No. of measured, independent and
observed [I  2 (I)] reflections
Rint
20759, 4631, 3133
18271, 3358, 2592
0.055
0.728
0.048
0.625
(sin θ/λ)max (Å−1)
Refinement
R[F2  2(F2)], wR(F2), S
No. of reflections
0.054, 0.127, 1.06
4631
0.054, 0.145, 1.07
3358
No. of parameters/restraints
H-atom treatment
228/16
213
Riding model
0.17, −0.16
2032467
Riding model
0.26, −0.19
2032466
max, min (e Å-3)
CCDC No.
2.3. Theoretical calculations
The Hirshfeld surface analysis [23], decomposed 2D-fingerprint plots (2D-FP) [24, 25]
and energy frameworks [26] were performed using the program CrystalExplorer17 [27] to study
intermolecular interactions. For energy frameworks calculation, the B3LYP/6-31G(d,p) level of
theory was used as recommended by the CrystalExplorer program.
To identify the existence of supramolecular constructs (0D, 1D, 2D and 3D) in a pair of
molecules, the analysis of similarity and dissimilarity between structures was performed using
the program XPax2.0 [28, 29]. Further, the intermolecular interaction energies for dimers in the
crystal structures of 1 and 2 and lattice energies for these crystals were calculated using the
PIXEL method [30-32]. For the PIXEL energy calculation, the electron density of the molecule
has been obtained at the MP2/6-31G** level of theory using the program Gaussian09 [33].
The gas phase structural optimization and vibrational frequency calculation were carried
out using the program Gaussian09 with the Minnesota functional M06-2X [34] with cc-pVTZ
basis set was used along with the Grimme’s empirical dispersion (D3) correction [35]. The
vibrational frequency calculation showed no imaginary frequency which in turn confirmed true
energy minima on the potential energy surface. Further, the binding energies for various dimers
at their crystal structure geometry were computed using the counterpoise method [36]. The basis
set superposition errors were corrected for these energies. The corrected energies were compared
with the intermolecular interaction energies obtained by the PIXEL method.
Bader’s quantum theory of atoms-in-molecules (QTAIM) approach [37, 38] was used to
study the nature and strength of different intermolecular interactions in 1 and 2. The topological

properties were calculated for these dimers at their crystal structure geometry using the program
AIMALL [39] with M06-2X-D3/cc-pVTZ level of theory. The dissociation energies (De) for
intermolecular interactions were calculated based on EML formula [40]. Koch and Popelier
fourth criterion (KP-4 rule) dealt with the mutual penetration of the H atoms and the acceptors
atoms [41] and the KP-4 rule was used to differentiate hydrogen bonding from van der Waals
interactions as mentioned earlier [42, 43].
3. Results and discussion
3.1. Description of molecular features of 1 and 2
The CSD (Cambridge Structural Database, 2020.1 CSD release April 2020) search was
carried out for structures 1 and 2 after excluding para-methyl group in the respective structure
and the resulting structures form as templates. This search yielded ten structures (csd refcodes:
CONKEY [44], CUQTAJ [45], EROTUB [46], EXUDUY [47], FAQGUB [48], FEZCAP [49],
HATJAQ [50], HATTAA [51], NODXEK [52] and VEDGOD [53]) for 1 as a template, while 3
structures (csd refcodes: NUNCUU [54], ACEYOX [55] and WOVDET [56]) were found for 2
as a template. It is noted that one of the reported structures (CUQTAJ) is an ortho-isomer of
compound 1 (para-isomer).
Compound 1, a xanthene-1,8-dione derivative, was crystallized in the orthorhombic
system with polar space group Pna21. The central heterocyclic ring (B) exhibits boat
conformation and the atoms O3 (0.144 (1) Å) and C7 (0.113 (1) Å) deviate from the mean plane
formed by the ring B atoms. The cyclohexene rings (A and C) adopt distorted envelope
conformation. In ring C, the flap atom C11 is oriented towards the phenyl ring. As mentioned in
the experimental section, two carbon atoms (C3 and C4) disordered over two positions in ring A.
In the major disordered component, the flap atom C3A is orientated away from the phenyl ring.
In contrast, C3B atom is projected towards the phenyl ring. The thermal ellipsoidal plots for
major and minor components of structure 1 is illustrated in Fig. 1(a,b).
The atoms that connect rings AB/BC is used for structural superimposition of 1 and its
related structures to see the conformational variations, especially on the substituted ring D. As
shown in Fig. 2 (a), the orientation of the flap is opposite to ring D in FEZCAP, HATTAA and

VEDGOD and in other structures, the orientation of the flap atom as similar to the major
disordered components. Similarly, the flap atom of ring C in all structures (except major
disordered component of 1) is oriented towards the phenyl ring found in the minor disordered
component of 1. Moreover, phenyl ring (ring D) in all structures shows deviations with respect to
the mean plane of rings A/B/C.
Compound 2, an acridine-1,8-dione derivative, was crystallized in the monoclinic system
with centrosymmetric space group P21/n. The central heterocyclic ring (B) adopts boat
conformation as observed in 1 and the atoms N1 (0.116 (1) Å) and C7 (0.162 (1) Å) deviate from
the mean plane formed by the ring B atoms. The cyclohexene rings (A and C) exhibit distorted
envelope conformations. The flap atoms of these rings are oriented towards the phenyl ring D.
Similar feature has been observed in the related structures of 2 except in WOVDET (flap atom
was disordered over two orientations). The thermal ellipsoidal plot for structure 2 is depicted in
Fig. 1(c). The overlay diagram of 2 and its related structures show a slight rotation is observed
for substituted phenyl rings as observed in 1 and its related structures (Fig. 2). Different
substituents in the phenyl ring could generate these structural variations and thus making
different crystal packing in the solid state.
Fig. 1. Thermal ellipsoidal plots for structures 1 [(a) major disordered component and (b) minor
disordered component] and 2.

Fig. 2. Structural superimposition of (a) 1 and its closely related structures and the enantiomeric
related molecules of FAQGUB, HATJAQ were used (b) 2 and its related structures. In all cases,
C1=C6 and C8=C13 bonds were used for structural superimposition.
3.2. Optimized structures and analysis of frontier molecular orbital (FMO)
The major disordered component of 1 is in good agreement with its corresponding
optimized structures. The structural superimposition of this pair reveals that rings A, B and C are
superimposed very well and a slight rotation of ring D is observed (Fig. S1). A similar
conformational feature is noted for minor disordered component and its corresponding optimized
structures (Fig. S2). This slight rotation of the phenyl ring could be correlated with the crystal
packing effect. Further, the optimized structures suggest that the orientation of the flap atoms of
rings A and C has a minor role in the context of the conformer’s stability and the energy
difference between major and minor disordered components is as low as 0.32 kcal mol-1. As
shown in Fig. S3, the X-ray structure of 2 and its optimized structure show good overlap except
for the phenyl ring.
The FMO analysis suggests some commonalities and distinct features for structures 1 and
2 (Fig. 3). The localization of the lowest unoccupied molecular orbital (LUMO) is very similar in
1 and 2. However, the localization of the highest occupied molecular orbital (HOMO) is different
in these structures. In 1, the HOMO orbital is localized over the phenyl ring, whereas the
corresponding orbitals NH group, C=C bonds and carbonyl oxygens of the acridine core. This

distinct feature suggests that these molecules have different charge transfer mechanisms. The
band gap energy indicates that the xanthene derivative is kinetically more stable than the acridine
derivative. The frontier molecular orbital analysis of 10-benzyl-9-(3-ethoxy4-hydroxyphenyl)-
3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione showed that band gap
energy (HOMO-LUMO) calculated was 3.6 eV, which is a nearly two-fold reduction in the title
compounds. The large differences in the band gap energy could be due to benzyl and ethoxy
groups in the reported compound [15].
Fig. 3. Localization of HOMO and LUMO orbitals in 1 and 2.
3.3. Hirshfeld surface analysis and 2D fingerprints
The short inter-contacts were identified and visualized using the Hirshfeld surface
analysis. The short inter-contact’s strength was estimated qualitatively through the intensity of
the red spots on the HS. Further, the relative contribution of different inter-contacts was
quantified using 2D-fingerprint plots.
In 1, two intense red spots represent the intermolecular C–H···O interactions involving
both carbonyls as acceptors as shown in Fig. 4. In 2, more number of close contacts is observed
compared to 1. A more intense red area is observed for intermolecular N–H···O interaction in 2

and less intense red spots correspond to different close inter-contacts including C–H···O, C–
H···C and H···H interactions.
In 1, the intermolecular H···H interactions significantly contribute to the crystal packing
with a value of 59.4%. The intermolecular H···O interactions contribute 22.4% to the total HS
area and appeared as double spikes with the shortest di+de value of ~2.4 Å. The relative
contribution of H···O contacts was around 10% in 14-(3,4,5-trimethoxyphenyl)-14H-
dibenzo[a,j]xanthene derivative [57] which bearing no C=O ligand. In another related compound
namely 12-(4-bromophenyl)-2-(prop-2-ynyloxy)-9,10-dihydro-8H-benzo[a]xanthen-11(12H)-on
which contains a single C=O moiety [13], the relative contribution of H···O inter-contacts is
slightly increased (~13%) as compared to the compound containing no C=O ligand. The H···O
contacts reduced slightly in a relate structure containing only C=O ligand [11] as compared to 1.
This feature suggested the importance of C=O ligands present in the title compound 1. In the
total HS area, the intermolecular H···C contacts occupy 17.8% in 1. In contrast, the
corresponding contact is increased significantly (26-37%) in the above two xanthene derivatives,
and this significant increase due to additional moieties which are involved in intermolecular C–
H···C interactions.
It should be noted that both major and minor disordered components of 1 have nearly
equal contribution of H···H, H···O and H···C interactions. As shown in Fig. 5, the relative
contributions of these contacts are comparable in the structures of 1 (p-tolyl derivative) and its
ortho isomer [45]. However, the shortest H···O contacts are located around 2.5 Å (di+de) in the
ortho isomer.

Fig. 4. (a) Hirshfeld surface mapped over the normalized contact distances (dnorm) (a) structure of
of 1 (major component) and (b) structure of 2.
As can be seen from Fig. 5, the NH group does not significantly alter the contribution of
H···H, H···O and H···C interactions in 2 compared to 1 and its ortho isomer. However, we could
see some differences in the distribution of these contacts from the fingerprint plots. For instance,
the shortest H···H contacts are located around 2.0 Å (di+de) in 2 and the corresponding contacts
appeared beyond 2.0 Å in 1 and its ortho isomer. Similarly, a pair of sharp spikes appear at 1.9 Å
for the intermolecular H···O interaction and this short distance is due to the presence of N–H···O
interactions in 2. The H···C interactions which represent C–H··· interactions also located at a
shorter distance (~2.6 Å in 2) compared to 1 and its ortho isomer. Overall, this analysis suggests
that differences in the geometrical parameters of the interactions could generate different types
of dimers and thus different crystal packing. However, they do not show many variations in the
relative contributions of different inter-contacts.

Fig. 5. 2D fingerprint plots showing the contribution of different inter-contacts towards total HS
areas in 1 and its ortho isomer and 2.
3.4. Dimeric motifs in the crystal structure of 1
As mentioned in the experimental section, two CH2 groups of ring A are disordered over
two conformations. From the major disordered component of 1, there are four dimers (D1, D2,
D3A and D4A) identified from the PIXEL energy analysis and the intermolecular interaction
energies are ranging from -8.5 to -3.1 kcal mol-1 (Table 2). The binding energies (Ecp)
calculated by the DFT method for these dimers are comparable and maximum overestimation is
found to be 1.1 kcal mol-1 (for dimer D3A). The dimers observed in the major disordered
component are depicted in Fig. 6. The disordered groups have involved as donors and
participated in the intermolecular interactions (dimers D3A and D4A) in the major disordered
component. Similarly, the atoms of minor disordered component have also involved in the
intermolecular interactions (dimers D3B and D4B; Fig. S4). The intermolecular interaction
energies for these dimers in the major and minor disordered components are comparable.

The strong dimer in 1 is stabilized by a pair of C–H···O interactions resulting in a closed
dimeric pair. In this dimer, the carbonyl groups of ring A and C have participated as acceptors.
The electrostatic and dispersion energies contribute 35% and 65%, respectively towards
stabilization of dimer D1. In a closely related cyclohexanone derivative, a similar type of C–
H···O interaction in which C=O ligand acts as an acceptor observed and the net interaction
energy of dimer is also comparable to that of dimer D1 in 1 [58]. It has been reported that the
single C=O function as an acceptor in a closely related xanthene derivative for the intermolecular
C–H···O interactions [11]. However, these interactions are coexisting with the O–H···O
hydrogen bond in the most stable dimer and this additional O–H···O hydrogen bond increases
the stability of the dimer.
Dimer D2 is formed by an intermolecular C–H···O interaction (involving 10B and O1)
and an intermolecular C–H··· interaction (involving H12B and centroid of the phenyl ring).
These two interactions link the adjacent molecules and the resulting dimeric unit extended along
the crystallographic c axis. It should be noted that the dispersion energy contributes about 65%
towards the stabilization of dimer D2.
Dimer D3A stabilizes by an intermolecular C–H··· interaction (involving H32 and the
centroid of the phenyl ring). This weak interaction links the molecules into a chain that runs
parallel to a axis. The intermolecular C–H···O interaction stabilizes the dimer D4A and this
interaction also links the molecules into a zigzag chain that runs parallel to a axis. As expected,
the former dimer has more dispersive than the latter dimer. The dispersion energy contributes
about 70 and 59% towards stabilizing dimer D3A and D4A, respectively.

Table 2
Intermolecular interaction energies (Etot) for dimeric pairs in 1 and 2 calculated by the PIXEL
method. CD: centroid-to-centroid (in Å), Cg1: centroid of the phenyl ring in the respective
structure, Ecp: binding energy (in kcal mol-1) of a dimer calculated by M06-2X-D3/cc-pVTZ
level of theory. Ecoul: Coulombic energy, Epol: Polarization energy, Edisp: Dispersion energy and
Erep: Repulsion energy.
Motif
CD
Symmetry element
Ecoul
Epol
Edisp
Erep
Etot
Intermolecular
interaction
Geometr
(Å,°)a
Ecp
Compound 1 (major disordered component)
D1
D2
5.794
8.498
x, y–1, z
–3.3
–1.9
–9.8
6.5
–8.5
–8.5 C11–H11B···O2
C19–H19···O1
2.43, 13
2.39, 15
2.65, 12
2.78, 13
2.85, 15
2.70, 14
–x+1/2, y–1/2, z+1/2
–3.1
–1.4
–7.7
5.4
–6.8
–7.8 C10–H10B···O1
C12–H12B···Cg1
D3A
D4A
8.693
9.715
x–1/2, –y+3/2, z
x–1/2, –y+5/2, z
–2.0
–1.5
–1.0
–0.7
–7.1
–3.2
4.0
2.0
–6.0
–3.3
–7.1 C3A–H32···Cg1
–3.1 C3A–H31···O2
Compound 1 (minor disordered component)
D3B
D4B
8.689
9.729
x–1/2, –y+3/2, z
x–1/2, –y+5/2, z
–2.8
–1.4
–1.4
–0.5
–7.2
–2.8
6.2
1.6
–5.3
–3.1
–6.5 C3B–H33···Cg1
–3.1 C4B–H43···O2
2.61, 14
2.77, 14
Compound 2
D1
D2
7.044
–x+2, –y, –z
x–1, y, z
–7.8
–2.7
–5.0
–12.1
–7.8
9.5 –13.0 –16.6 C10–H10A···C1
C10–H10A···C6
2.62, 15
2.73, 16
1.91, 16
2.06, 14
2.56, 15
2.61, 14
2.49, 13
2.63, 14
2.69, 15
7.353
–11.9
12.0 –12.6 –13.0 N1–H1···O2
C2–H2B···H7–C7
D3
D4
8.678
7.547
–x+2 , –y+1 , –z
–3.1
–0.9
–1.6
–1.5
–10.0
–5.8
8.3
3.3
–6.4
–4.9
–9.2 C20–H20B···Cg1
–4.6 C11–H11B···O1
C15–H15···O1
x+1/2, –y+1/2, z+1/2
D5
8.744
x–1/2, –y+1/2, z+1/2
–1.2
–1.2
–6.7
4.3
–4.7
–5.4 C4–H4A···O2
C3–H3A···C15()
a Neutron values are given for all D–H···A interactions.

Fig. 6. Dimeric motifs observed in the major components of the crystal structure of 1.
3.5. Dimeric motifs in the crystal structure of 2
Five dimeric motifs were identified from the PIXEL energy analysis and the
intermolecular interaction energies for these dimeric pairs range from -13.0 to -4.7 kcal mol-1
(Table 2). The binding energies calculated by the DFT method for two of the dimers (D1 and
D3) are overestimated as compared to the interaction energies calculated by the PIXEL method.
We note that these two dimers are stabilized by C–H··· interactions. All five dimers observed in
2 are illustrated in Fig. 7.
The most stabilized dimer (D1) formed in 2 by bifurcated intermolecular C–H···C()
interactions (involving H10A and C1/C6 atoms) and atoms C1 and C6 make a double bond in
ring A. The motif D1 acts as a basic pattern in the crystal structure. The contribution of
electrostatic and dispersion energies is 46% and 54% towards this dimer’s stabilization. The next
most stabilized dimer D2 is primarily stabilized by intermolecular N–H···O hydrogen bond
involving amine group and the carbonyl oxygen (O2) of ring C. This hydrogen bond links the
molecules into a chain which runs parallel to the crystallographic a axis. Further, a short H···H

contact (2.06 Å) provides additional stability to the dimer D2. For this dimer stabilization, the
contribution of electrostatic energy (68%) is more than 2-fold of the dispersion energy
component.
The phenyl ring’s para-methyl group has involved in an intermolecular C–H···
interaction with the centroid of the phenyl ring. This dimeric motif, D3, is flanked on both sides
by motif D1 and this supramolecular feature is extended along the crystallographic b axis. One of
the carbonyl oxygens (O1, ring A) acts as an acceptor for two different C–H···O interactions
making a dimer D4 and this dimer also flanked on both sides by the basic motif (D1). The least
stable dimer (D5) in 2 stabilizes by intermolecular C–H···O (involving H4A and O2) and C–
H···C() (involving H3A and C15) interactions. This dimer is connected on both sides by
molecular dimer D3. It should be noted that the contribution of dispersion energy is in the range
of 68-74% towards the stabilization of the latter three dimers D3-D5.
Fig. 7. Dimeric motifs observed in the crystal structure of 2.
3.6. Isostructurality analysis

A comparison of crystal structure 1 and its ten closely related structures was based on
relative geometric conformation and positions of molecules performed to identify the
supramolecular constructs. For this purpose, we used Gelbrich’s XPac program. The analysis
reveals that the structures 1 and CONKEY show a 2D supramolecular construct (layer of
molecules match), as depicted in Fig. 8(a) and the molecules in the layer are interlinked by C–
H···O interactions involving carbonyl groups as acceptors. The other structures do not share any
isostructural features with the structure of 1. Similarly, a comparative analysis of 2 and its three
closely related structures reveals that the structure 2 and WOVDET display 0D supramolecular
construct (dimer match) i.e. the relative orientation of molecules in D1 of 2 is similar to that of
the dimer in WOVDET (Fig. 8(b)). In both of these structures, this dimer stabilizes by
intermolecular C–H···C() interactions.
Fig. 8. (a) 2D supramolecular construct in 1 and CONKEY and (b) 0D supramolecular construct
in 2 and WOVDET.

3.7. Lattice energy and energy frameworks
The lattice energies for compound 1 (both major (1a) and minor (1b) disordered
components) and its ortho isomer (CUQTAJ) and compound 2 were calculated using the PIXEL
method (Table 3). As shown from this table, the lattice energy and its components are
comparable for compound 1 and its ortho isomer. They suggest that the methyl group substituted
at 2 or 4th positions does not change the crystal’s stability. The dispersion energy contributes
nearly 70% towards stabilizing the crystal structures of 1 and its ortho isomer. Further, if NH
group replaces the O atom, then the compound’s stability has improved by ~6 kcal mol-1. In 2,
Coulombic and polarization energy term’s contribution increases nearly twice compared to 1 and
its isomer. For stabilizing the crystal structure of 2, the electrostatic and dispersion energies
contributes 45 and 55%, respectively.
Table 3
Lattice energies (in kcal mol-1) for compounds 1, CUQTAJ and 2.
Compound
ECoul
Epol
Edisp
Erep
Etot
1a
-11.2
-12.0
-11.1
-20.9
-5.0
-37.2
21.5
-32.4
-31.7
-30.6
-38.1
1b
-5.1
-4.8
-37.1
-36.5
-38.3
22.9
21.7
31.9
CUQTAJ
2
-10.7
Furthermore, the energy frameworks have been carried out to visualize the interaction
topology in these crystal structures. In 1, molecules are arranged as layers and these layers run
parallel to both a and c axes and the lattice energy calculation suggests that the packing
predominantly dispersive in nature. The basic energy topology forms as square type cylindrical
tubes (dispersion and net interaction energies) and this basic unit extended along the along both a
and c axes (Fig. 9). The horizontal cylindrical tube represents intermolecular C–H···O
interactions and the vertical tubes correspond to the intermolecular C–H···C() and C–H···O
interactions.
In the ortho isomer of 1 (i.e. CUQTAJ), the basic motif forms as a dimer and this unit
extended along the crystallographic a axis. The topology of the energy frameworks for this
structure described as distorted rectangular structure extended along the b axis with the

variations in the cylindrical tube’s diameters. One of the larger horizontal cylindrical tubes
represents the intermolecular C–H···C() and C–H···O interactions. These larger cylindrical
tubes are arranged alternately along the b axis. The relatively small horizontal tubes correspond
to C–H···O interaction. Similarly, the vertical cylindrical tubes with different dimensions also
arranged alternately and both of these tubes (small and larger) represent weak intermolecular C–
H···C() interactions. Though the lattice energies for compound 1 and its ortho isomer are
comparable, the topology of the energy frameworks for these compounds is somewhat different
and one could expect different mechanical properties.
In 2, the crystal packing is entirely different as compared to 1 and its ortho isomer. In
the solid state, molecules of 2 arranged as alternate dimers of D1 and D3 (see Fig. 9) and run
parallel to the crystallographic b axis. However, the topology of the energy frameworks is similar
(with some distortion in the square box) to that of the structure of 1. Another vital difference
noticed between 1 and 2 is the dimension of the vertical cylindrical tubes. The larger and smaller
vertical tubes are formed alternately in 2 rather than smaller tubes as in 1. The larger vertical
cylinders correspond to dimer D1 stabilizes by intermolecular C–H···C() interactions and dimer
D2 forms by intermolecular N–H···O interaction. Smaller vertical tubes represent the dimer D3
(stabilized by C–H··· interactions). The horizontal cylinders are primarily formed by
intermolecular C–H···O interactions. Due to the similarity in the topology of the energy
frameworks in 1 and 2, one could expect similar mechanical behavior for these two crystals.

Fig. 9. Energy frameworks for crystals (a) 1, (b) ortho isomer of 1 and (c) 2, representing the
dispersion (green) and total interaction energy (blue) components. For energies greater than 15
kJ mol-1 have been omitted for clarity.
3.8. Topological analysis of intermolecular interactions in 1 and 2
The nature and strength of different intermolecular interactions existing in various dimers
of structures 1 and 2 were assessed using the topological parameters. The different topological
parameters for intermolecular interactions at their bond critical points (BCPs) are presented in
Tables 3-4. The pictorial representation of dimeric molecular graphs showing different types of
intermolecular interactions is depicted in Figs. S5-6.
As mentioned above, there are four energetically important dimers observed in 1 and
these dimers are stabilized by two types of intermolecular interactions such as C–H···O and C–
H···C() interactions. The positive values of Laplacian of electron density (2(r) > 0) and total
electron density (V(r) + G (r) = H(r) > 0) and |
| < 0 [59] suggesting that the C–H···O and C–
H···C() interactions are closed-shell interactions in nature. The EML dissociation energies (De)
for C–H···O and C–H···C() interactions are ranging from 1.8 to 0.6 kcal mol-1. The De value

suggests that the C–H···O interactions found in dimer D1 is relatively stronger than other
interactions. In a closely related cyclohexanone derivative, the strength of the C–H···O
interactions is related stronger than the corresponding interactions in 1 [58]. The (r) values for
some of the C–H···O interactions observed in reported xanthene derivative [11] are comparable
to those of importance for C–H···O interactions in 1. As can be seen from Fig. S2, the BCP is
formed between atom H32 and C14–C15 bond rather than atom C14 in the dimer D3A. In the
minor disordered component, the equivalent interaction (dimer D3B) is relatively strong
compared to that exists in the major disordered component. It is also noted that the strength of
C–H···O interactions formed by carbonyl oxygens (O1 and O2) as acceptors is comparable.
Further, the KP-4 rule differentiates between hydrogen bond and van der Waals interaction. This
analysis suggests that all the intermolecular interactions found in different dimers of 1 show
hydrogen bond character except C3A–H32···C14 interaction.
Table 4.
Topological parameters for intermolecular interactions in dimers of 1 [values of V(r), G(r) and
H(r) are expressed in kJ mol-1 bohr-3 and De = –0.5×V(r) in kcal mol-1].
2(r)
Interaction
Rij
(Å)
V(r) G(r)
H(r)
De
(r)
(e/Å3) (e/Å5)
|
|
D1
C19–H19···O1
C11–H11B···O2
D2
2.411
2.453
0.063
0.063
0.923
0.871
-14.7 19.9
-14.2 18.9
5.2
4.8
0.74
0.75
1.8
1.7
C10–H10B···O1
C12–H12B···C16
D3A
C3A–H32···C14
D4A
C3A–H31···O2
D3B
C3B–H33···C16
D4B
2.694
2.930
0.043
0.040
0.545
0.452
-9.2 12.0
2.8
2.5
0.77
0.75
1.1
0.9
-7.4
-5.3
-7.3
9.8
7.2
9.9
3.643
2.717
2.865
2.788
0.030
0.033
0.058
0.028
0.333
0.456
0.688
0.372
1.9
2.6
3.5
2.1
0.74
0.74
0.77
0.74
0.6
0.9
1.4
0.7
-11.8 15.3
-5.9 8.0
C4B–H43···O2
The intermolecular N–H···O, C–H···O, C–H···C() interactions stabilize the dimers
formed in 2 (Fig. S3). Besides, there is a short intermolecular H···H contact that provides
additional stability to the dimer D2. All the above mentioned interactions are closed-shell in
nature according to the positive values of Laplacian of electron density (2(r) > 0) and total

electron density (H(r) > 0) and |
| < 0. The De value is ranging from 6.6 to 1.0 kcal mol-1 for
these interactions. The intermolecular N–H···O interaction is found to be strong interaction
compared to other interactions in this structure. Similarly, the intermolecular C4–H4A···O2 is
weaker, among other interactions. It should be noted that the strength of a short H···H contact
(H-H bonding) is relatively stronger than some of the C–H···O and C–H···C() interactions. The
KP-4 rule suggests that all C–H···O and C–H···C() and N–H···O interaction are displaying
hydrogen bonding character. Overall, we observe that the strength of C–H···O and C–H···C()
interactions in 1 and 2 are comparable.
Table 5.
Topological parameters for intermolecular interactions in dimers of 2 [values of V(r), G(r) and
H(r) are expressed in kJ mol-1 bohr-3 and De = –0.5×V(r) in kcal mol-1].
2(r)
Interaction
Rij
(Å)
V(r)
G(r)
H(r)
De
(r)
(e/Å3) (e/Å5)
|
|
D1
C10–H10A···C1
D2
3.018
0.064
0.691
-12.8
15.8
3.0
0.81
1.5
N1–H1···O2
H2B···H7
D3
1.935
2.089
0.159
0.060
2.407
0.668
-55.2
-12.5
60.4
15.4
5.2
2.8
0.91
0.82
6.6
1.5
C20–H20B···C14 3.147
0.047
0.557
-9.3
12.2
3.0
0.76
1.1
D4
C15–H15···O1
C11–H11B···O1
D5
2.630
2.515
0.043
0.058
0.558
0.761
-9.3
-12.6
12.2
16.7
3.0
4.0
0.76
0.76
1.1
1.5
C3–H3A···C15
C4–H4A···O2
2.742
2.659
0.052
0.041
0.562
0.510
-9.7
-8.6
12.5
11.2
2.8
2.7
0.78
0.76
1.2
1.0
4. Summary
X-ray structures of chemically two different classes of compounds, namely xanthenedione and
acridinedione have been determined. In both cases, the central ring exhibited boat conformation
and the terminal cyclohexene rings adopted envelope conformation. The conformation of crystal
structure and the electronic structure obtained by DFT method was in good agreement. The flap
atoms orientation in the cyclohexene rings had a minor role in the conformer’s stability. Further,
the substituted phenyl ring had some influence on the phenyl ring’s rotation concerning the core
structure. Further, these two compounds showed a distinct charge transfer mechanism due to O

and NH group’s presence in the core. The title xanthenedione derivative shared 2D
isostructurality with one of its closely related structure. However, the acridinedione displayed 0D
isostructurality with its related structure. The xanthenedione derivative stabilized by
intermolecular C–H···O and C–H··· interactions, whereas acridinedione stabilized primarily by
N–H···O in addition to C–H···O and C–H··· interactions. Further assessment of these
interactions using the QTAIM approach indicates that all these interactions were closed-shell in
nature. The strength of C–H···O and C–H··· interactions was comparable in both structures and
N–H···O interaction was found to be strong among other interactions. These two structures net
lattice energies suggest that the acridinedione derivative was more stable in the solid state than
the xanthenedione. However, the topology frameworks looked similar for these structures,
implying that they could have identical mechanical behavior.
CRediT authorship contribution statement
Subbiah Thamotharan: Conceptualization, Supervision, Investigation, Writing – review &
editing. Subramaniyan Prasanna Kumari: Chemical synthesis, Investigation.
Subramaniapillai Selva Ganesan: Chemical synthesis, Investigation. Shankar Madan
Kumar: Data curation, Investigation. M. Judith Percino: Resources, Writing- review & editing.
Neratur Krishnappagowda Lokanath: Data curation, visualization
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
ST and MJP would like to thank Laboratorio Nacional de Supercomputo del Sureste (LNS-
BUAP) for computational resources. SSG thanks DST-SERB (EMR/2016/000317) for financial
support. MKS thanks IOE and DST-PURSE LAB, Vijnana Bhavan, University of Mysore.
References
[1] K. Nagaraju, M. Suresh, B.J. Sreekantha, Design of Carbon-carbon and Carbon-heteroatom Bond
Formation Reactions under Green Conditions, Current Organic Chemistry 23(28) (2019) 3154-3190.

[2] J. Cossy, A. Guérinot, Natural products containing oxygen heterocycles-synthetic advances between
1990 and 2015., Advances in Heterocyclic Chemistry 119 (2016) 107-142.
[3] P. Kaur, R. Arora, N.S. Gill, Review on oxygen heterocycles., Indo am. J. Pharm. Res. 3 (2013) 9067-
9084.
[4] N. Kerru, L. Gummidi, S. Maddila, K.K. Gangu, S.B. Jonnalagadda, A Review on Recent Advances in
Nitrogen-Containing Molecules and Their Biological Applications, Molecules 25(8) (2020).
[5] N. Mulakayala, P.V.N.S. Murthy, D. Rambabu, M. Aeluri, R. Adepu, G.R. Krishna, C.M. Reddy, K.R.S.
Prasad, M. Chaitanya, C.S. Kumar, M.V. Basaveswara Rao, M. Pal, Catalysis by molecular iodine: A rapid
synthesis of 1,8-dioxo-octahydroxanthenes and their evaluation as potential anticancer agents,
Bioorganic & Medicinal Chemistry Letters 22(6) (2012) 2186-2191.
[6] G.S. Suresh Kumar, A. Antony Muthu Prabhu, P.G. Seethalashmi, N. Bhuvanesh, S. Kumaresan, Self-
catalyzed syntheses, structural characterization, DPPH radical scavenging-, cytotoxicity-, and DFT studies
of phenoxyaliphatic acids of 1,8-dioxo-octahydroxanthene derivatives, Journal of Molecular Structure
1059 (2014) 51-60.
[7] M. Nisar, I. Ali, M. Raza Shah, A. Badshah, M. Qayum, H. Khan, I. Khan, S. Ali, Amberlite IR-120H as a
recyclable catalyst for the synthesis of 1,8-dioxo-octahydroxanthene analogs and their evaluation as
potential leishmanicidal agents, RSC Advances 3(44) (2013) 21753-21758.
[8] H.J. Timpe, S. Ulrich, J.P. Fouassier, Photochemistry and use of decahydroacridine-1,8-diones as
photosensitizers for onium salt decomposition, Journal of Photochemistry and Photobiology A:
Chemistry 73(2) (1993) 139-150.
[9] R. Popielarz, S. Hu, D.C. Neckers, Applicability of decahydroacridine-1,8-dione derivatives as
fluorescent probes for monitoring of polymerization processes, Journal of Photochemistry and
Photobiology A: Chemistry 110(1) (1997) 79-83.
[10] R. Kumaran, M. Vanjinathan, P. Ramamurthy, Role of hydrogen-bonding and photoinduced electron
transfer (PET) on the interaction of resorcinol based acridinedione dyes with Bovine Serum Albumin
(BSA) in water, Journal of Luminescence 164 (2015) 146-153.
[11] M. Udayakumar, K. Jagatheeswaran, S.S. Ganesan, N.S. Venkataramanan, S. Madan Kumar, K.
Byrappa, S. Thamotharan, Investigation of 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-
dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one: Crystal structure, AIM and NBO analysis, J. Mol. Struct.
1133 (2017) 510-518.
[12] M.R. Taghartapeh, N. Noroozi Pesyan, H. Rashidnejad, H.R. Khavasi, A. Soltani, Synthesis,
spectroscopic and photophysical studies of xanthene derivatives, Journal of Molecular Structure 1149
(2017) 862-873.
[13] H. Singh, A DFT approach for theoretical and experimental study of structure, electronic, Hirshfeld
surface and spectroscopic properties of 12-(4-bromophenyl)-2-(prop-2-ynyloxy)-9,10-dihydro-8H-
benzo[a]xanthen-11(12H)-on single crystal, Chemical Physics 524 (2019) 1-13.
[14] A. Saeed, S. Ashraf, U. Flörke, Z.Y. Delgado Espinoza, M.F. Erben, H. Pérez, Supramolecular self-
assembly of a coumarine-based acylthiourea synthon directed by π-stacking interactions: Crystal
structure and Hirshfeld surface analysis, Journal of Molecular Structure 1111 (2016) 76-83.
[15] N. Suresh Babu, V. Sughanya, A. Dhandapani, R. Kalaivanan, Crystal structure, Hirshfeld surface and
frontier molecular orbital analysis of 10-benzyl-9-(3-ethoxy-4-hydroxyphenyl)-3,3,6,6-tetramethyl-
3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione, Acta Crystallographica Section E 76(4) (2020) 585-588.
[16] A. Saeed, U. Flörke, A. Fantoni, A. Khurshid, H. Pérez, M.F. Erben, Close insight into the nature of
intermolecular interactions in dihydropyrimidine-2(1H)-thione derivatives, CrystEngComm 19(11) (2017)
1495-1508.
[17] G. Subramaniapillai Selva, K. Jagatheeswaran, G. Asaithampi, Zinc Chloride Catalyzed Collective
Synthesis
of
Arylmethylene
Bis(3-
hydroxy-2-cyclohexene-1-ones)
and
1,8-Dioxo-
octahydroxanthene/acridine Derivatives, Letters in Organic Chemistry 11(9) (2014) 682-687.

[18] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M.C. Burla, G. Polidori, M. Camalli, SIR92 –
a program for automatic solution of crystal structures by direct methods, Journal of Applied
Crystallography 27(3) (1994) 435-435.
[19] G. Sheldrick, Crystal structure refinement with SHELXL, Acta Crystallogr. C71(1) (2015) 3-8.
[20] S. Parsons, H.D. Flack, T. Wagner, Use of intensity quotients and differences in absolute structure
refinement, Acta Crystallographica Section B 69(3) (2013) 249-259.
[21] A. Spek, Structure validation in chemical crystallography, Acta Crystallogr. D65 (2009) 148-155.
[22] C.F. Macrae, I.J. Bruno, J.A. Chisholm, P.R. Edgington, P. McCabe, E. Pidcock, L. Rodriguez-Monge, R.
Taylor, J. van de Streek, P.A. Wood, Mercury CSD 2.0 - new features for the visualization and
investigation of crystal structures, J. Appl. Crystallogr. 41(2) (2008) 466-470.
[23] M.A. Spackman, D. Jayatilaka, Hirshfeld surface analysis, CrystEngComm 11(1) (2009) 19-32.
[24] M.A. Spackman, J.J. McKinnon, Fingerprinting intermolecular interactions in molecular crystals,
CrystEngComm 4(66) (2002) 378-392.
[25] J.J. McKinnon, D. Jayatilaka, M.A. Spackman, Towards quantitative analysis of intermolecular
interactions with Hirshfeld surfaces, Chemical Communications (37) (2007) 3814-3816.
[26] M.J. Turner, S.P. Thomas, M.W. Shi, D. Jayatilaka, M.A. Spackman, Energy frameworks: insights into
interaction anisotropy and the mechanical properties of molecular crystals, Chemical Communications
51(18) (2015) 3735-3738.
[27] M.J. Turner, J.J. McKinnon, S.K. Wolff, D.J. Grimwood, P.R. Spackman, D. Jayatilaka, M.A. Spackman,
CrystalExplorer17, University of Western Australia (2017).
[28] T. Gelbrich, M.B. Hursthouse, A versatile procedure for the identification, description and
quantification of structural similarity in molecular crystals, CrystEngComm 7(53) (2005) 324-336.
[29] T. Gelbrich, T.L. Threlfall, M.B. Hursthouse, XPac dissimilarity parameters as quantitative descriptors
of isostructurality: the case of fourteen 4,5′-substituted benzenesulfonamido-2-pyridines obtained by
substituent interchange involving CF3/I/Br/Cl/F/Me/H, CrystEngComm 14(17) (2012) 5454-5464.
[30] A. Gavezzotti, Calculation of Intermolecular Interaction Energies by Direct Numerical Integration
over Electron Densities. I. Electrostatic and Polarization Energies in Molecular Crystals, The Journal of
Physical Chemistry B 106(16) (2002) 4145-4154.
[31] A. Gavezzotti, Calculation of Intermolecular Interaction Energies by Direct Numerical Integration
over Electron Densities. 2. An Improved Polarization Model and the Evaluation of Dispersion and
Repulsion Energies, J. Phys. Chem. B 107(10) (2003) 2344-2353.
[32] A. Gavezzotti, Efficient computer modeling of organic materials. The atom–atom, Coulomb–
London–Pauli (AA-CLP) model for intermolecular electrostatic-polarization, dispersion and repulsion
energies, New J. Chem. 35(7) (2011) 1360-1368.
[33] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J.
Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M.J.
Bearpark, J. Heyd, E.N. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari,
A.P. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, N.J. Millam, M. Klene, J.E. Knox, J.B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi,
C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J.
Dannenberg, S. Dapprich, A.D. Daniels, Ö. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox,
Gaussian 09, revision D.01, Gaussian, Inc., Wallingford, CT, USA, 2013.
[34] Y. Zhao, D.G. Truhlar, The M06 suite of density functionals for main group thermochemistry,
thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new
functionals and systematic testing of four M06-class functionals and 12 other functionals, Theor. Chem.
Acc. 120(1) (2008) 215-241.

[35] S. Grimme, J. Antony, S. Ehrlich, H. Krieg, A consistent and accurate ab initio parametrization of
density functional dispersion correction (DFT-D) for the 94 elements H-Pu, J. Chem. Phys. 132(15) (2010)
154104.
[36] S.F. Boys, F. Bernardi, The calculation of small molecular interactions by the differences of separate
total energies. Some procedures with reduced errors, Mol. Phys. 19(4) (1970) 553-566.
[37] R.F.W. Bader, A quantum theory of molecular structure and its applications, Chem. Rev. 91(5)
(1991) 893-928.
[38] R. Bader, Atoms in Molecules: A Quantum Theory, Oxford University Press, USA, 1994.
[39] T. Keith, AIMAll 19.02.13, TK Gristmill Software, 2019.
[40] E. Espinosa, E. Molins, C. Lecomte, Hydrogen bond strengths revealed by topological analyses of
experimentally observed electron densities, Chem. Phys. Lett. 285(3) (1998) 170-173.
[41] U. Koch, P.L.A. Popelier, Characterization of C-H-O Hydrogen Bonds on the Basis of the Charge
Density, J. Phy. Chem. B 99(24) (1995) 9747-9754.
[42] A.A. El-Emam, E. Saveeth Kumar, K. Janani, L.H. Al-Wahaibi, O. Blacque, M.I. El-Awady, N.H. Al-
Shaalan, J.M. Percino, S. Thamotharan, Quantitative assessment of the nature of noncovalent
interactions
in
N-substituted-5-(adamantan-1-yl)-1,3,4-thiadiazole-2-amines:
insights
from
crystallographic and QTAIM analysis, RSC Advances 10(17) (2020) 9840-9853.
[43] M. Udayakumar, M. Cerón, P. Ceballos, M.J. Percino, S. Thamotharan, Correlation between
structural and optical properties of π-conjugated acrylonitrile derivatives: Insights from X-ray, energy
frameworks, TD-DFT and charge density analysis, Journal of Molecular Structure 1213 (2020) 128174.
[44] H. Wu, G. Wu, G. Niu, One-pot synthesis of novel xanthene derivatives as anti-prostatic cancer
agents, Latin Am. J. Pharm. 37(2) (2018) 219-223.
[45] M. Brito-Arias, M. Tapia-Albarrán, I. Padilla-Martínez, F. Martínez-Martínez, G. Espinosa, E. Molins,
E. Espinosa, 9-(2-Methylphenyl)-3,4,5,6,9,10-hexa- hydroxanthene-1,8(2H,7H)-dione, Journal of
Chemical Crystallography 29(7) (1999) 759-763.
[46] S.H. Mehdi, R. Hashim, R.M. Ghalib, C.S. Yeap, H.-K. Fun, 9-(3,4-Dimethoxyphenyl)-3,4,5,6,7,9-
hexahydroxanthene-1,8(2H)-dione, Acta Crystallographica Section E 67(6) (2011) o1449.
[47] P. Amreeta, P. Davinder, K.S. Jatin, N. Mahendra, Facile One-Pot Synthesis of Oxo-Xanthenes under
Microwave Irradiation, Current Microwave Chemistry 2(1) (2015) 15-23.
[48] J. Chen, S. Jian, C.-G. Yan, Synthesis of spiro dihydrofurans and 1,8-dioxo-xanthenes via DABCO
catalyzed tandem reaction of aldehyde with cyclohexane-1,3-dione and dimedone, Chem. Res. Chinese
Universities. 27(1) (2011) 49-53.
[49] T.-J. Li, S.-J. Tu, S.-L. Zhu, X.-J. Zhang, Synthesis and crystal structure of 9-(4-methoxylphenyl)-1,8-
dioxo-3,4,5,6,7,9-hexahydroxanthene under microwave irradiation, Chin. J. Struct. Chem. 24 (2005) 25-
28.
[50] R.Y. Agunbiade, J.P. Jasinski, S.P. Millikan, K. Sanusi, Y. Yilmaz, Ü. Ceylan, O.A. Fadare, C.A. Obafemi,
Isolation, characterization, crystal structure, free radical scavenging- and computational studies of 9-[4-
(propan-2-yl)phenyl]-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione from Garcinia kola seeds,
Journal of Molecular Structure 1144 (2017) 396-405.
[51] D. Bhattacharjee, D. Sutradhar, A.K. Chandra, B. Myrboh, l-proline as an efficient asymmetric
induction catalyst in the synthesis of chromeno[2,3-d]pyrimidine-triones, xanthenes in water,
Tetrahedron 73(25) (2017) 3497-3504.
[52] J. Jeyakanthan, D. Velmurugan, The Crystal and Molecular Structure of 1,8-Dioxo-9- (o-nitrophenyl)-
1,2,3,4,5,6,7,8-octahydroxanthene, Crystal Research and Technology 34(10) (1999) 1339-1344.
[53] M.L. da Silva, R.R. Teixeira, L. de Azevedo Santos, F.T. Martins, T.C. Ramalho, Synthesis and special
characterization through X-ray analysis of 1,8-dioxooctahydroxanthenes, Arabian Journal of Chemistry
13(1) (2020) 974-987.