- Email: [email protected]
Crystal structure, quantum chemical and Hirshfeld surface analysis of substituted imidazo-thiadiazole-5-carbaldehyde
Accepted Manuscript
Crystal structure, quantum chemical and Hirshfeld surface analysis substituted imidazo- thiadiazole-5-carbaldehyde A. Sowmya , G. N. Anil Kumar , Sujeet Kumar , Subhas S. Karki PII: DOI: Reference:
S2405-8300(18)30213-1 https://doi.org/10.1016/j.cdc.2018.11.002 CDC 160
To appear in:
Chemical Data Collections
Received date: Revised date: Accepted date:
24 September 2018 30 October 2018 5 November 2018
Please cite this article as: A. Sowmya , G. N. Anil Kumar , Sujeet Kumar , Subhas S. Karki , Crystal structure, quantum chemical and Hirshfeld surface analysis substituted imidazo- thiadiazole-5carbaldehyde, Chemical Data Collections (2018), doi: https://doi.org/10.1016/j.cdc.2018.11.002
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
ACCEPTED MANUSCRIPT
Crystal structure, quantum chemical and Hirshfeld surface analysis substituted imidazothiadiazole-5-carbaldehyde Sowmya A.a, G. N. Anil Kumar *a, Sujeet Kumar b, Subhas S. Karkib a b
Department of Physics, Ramaiah Institute of Technology, Bangalore 560054, India.
Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India.
Abstract
CR IP T
Contact email: [email protected]
In the present study, we have reported crystal stucture of 6-(4-methoxyphenyl)-2-(naphthalen-1ylmethyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde
via
single
crystal
X-ray
̅ space group. The crystal structure shows
AN US
diffraction. The compound crystallizes in the Triclinic,
(C23H17N3O2S)
intermolecular C – H…O, N – H…N, and π…π interactions. Quantum Theory of Atoms in Molecules (QTAIM) analysis confirmed presence of these interactions with acceptable topological parameters. The PIXEL Coulomb London Pauli (CLP) module was employed to characterize energetics associated with all interactions. Hirshfeld 2D fingerprint plots helped in evaluating intermoleular interactions
M
quantitatively. The molecular electrostatic potential (MEP) was plotted to identify the reaction sites of the molecule. Interestingly, the centrosymmetric molecule exhibits non-linear optical (NLO) properties
ED
calculated using Density Functional Theory (DFT). The mean and hyperpolarizability values are found to be 42.6314x10-24 and 11.4248x10-30 esu respectively indicating that the compound would be a potential
CE
PT
candidate for the NLO applications.
AC
Keywords Crystal structure, Thiadiazoles, Hirshfeld analysis, Hydrogen bond, NLO studies
ACCEPTED MANUSCRIPT Specifications Table
Data accessibility
1
CR IP T
Data category Data acquisition format Data type Procedure
Organic Chemistry, Computational Chemistry, Crystallography 6-(4-methoxyphenyl)-2-(naphthalen-1-ylmethyl)imidazo[2,1b][1,3,4]thiadiazole-5-carbaldehyde X-ray crystallography, computational CIF for Crystallography Analyzed The good quality single crystals suitable for x-ray diffraction were grown at room temperature from ethanol and Dimethyl formamide mixtures in the ratio (2:1) in volume. Single crystal data for compound were collected on Bruker SMART CCD area detector diffractometer with fine focus sealed tube Graphite monochromatic Mo-Kα radiation. Data collection was controlled by APEX2, cell refinement and data reduction was done using SAINT Software. The structure was determined and molecular interactions studied through Hirshfeld Surface analysis CCDC-1830258 https://www.ccdc.cam.ac.uk/structures-summary-form
AN US
Subject area Compounds
Rationale
Understanding the nature of interactions in crystals is an important aspect of crystal engineering to
M
design new solids.[1] The role of intermolecular interactions in both chemistry and biology[2] is found to be significant [3] hence attracted immense attention. The weak hydrogen bonds such as C-H···X (X =
ED
O, N, S, halogens and π-electrons) also important in understanding 3D structure of molecules in solidstate. Unconventional non-covalent interactions such as halogen bonds [4] Chalcogen bonds, and
PT
pnicogen bonds and also the π-hole interactions have gained attention in the fields of chemistry and biology[5,6]. In this study we have reporting crystal of 6-(4-methoxyphenyl)-2-(naphthalen-1-
CE
ylmethyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (TDZ), which exhibits cytotoxic activity against different human and murine cancer cell lines[7]. In general Imidazo[2,1-b][1,3,4]thiadiazoles exhibit a
AC
wide range of biological activities[8]. These include antitumor, anti-tubercular, antimicrobial, antifungal, anticonvulsant, analgesic, anti-inflammatory, anesthetic, and cytotoxic activities[9]. Structural studies of some of Imidazo[2,1-b][1,3,4]thiadiazoles reported shows presence of non covalent interactions[10,11]. In view of these, it is of interest to quantitatively explore the geometry and intermolecular interactions using computational tools such as PIXEL and Crystal Explorer for quantitative investigation intermolecular interactions present in the crystal structures of the molecule TDZ reported.
ACCEPTED MANUSCRIPT
2
Procedure
2.1
Synthesis crystallization
CR IP T
Chemical scheme of molecule TDZ
AN US
The compound (TDZ) was prepared using reported procedure [7]. The Vilsmeier reagent was prepared at 273 K by adding phosphorous oxychloride (2.3 g, 15 mmol) dropwise into a solution of DMF (10 ml). The 6-(4-methoxyphenyl)-2-(naphthalen-1-ylmethyl) imidazo[2,1-b] [1,3,4] thiadiazole (4 mmol) was added slowly to the Vilsmeier reagent by cooling for 2 hours. Further stirring was continued for 6 h at 363 K.
M
The reaction mixture was poured into 100 ml of water. The precipitate obtained was filtered, and neutralized with a cold aqueous solution of sodium carbonate forming the compound (TDZ). The solid
ED
obtained was washed with water, filtered and dried. Single crystals were obtained after two week by
Single crystal X-ray diffraction
CE
2.2
PT
slow evaporation using solution of ethanol/DMF (2:1 v:v).
AC
Single crystal data for compound were collected on Bruker SMART CCD area detector diffractometer with fine focus sealed tube Graphite monochromatic Mo-Kα radiation (λ = 0.71073 Å). Data collection was controlled by APEX2, cell refinement and data reduction was done using SAINT Software [12]. Multiscan Absorption correction was done using SADABS. The structures were solved by direct methods with SHELXS and refined by full matrix least squares on F2 Least-squares matrix using SHELXL-2014/7 program [13]. All the non-hydrogen atoms were refined anisotropically and all hydrogen atoms bound to carbon were placed in the calculated positions, and refined isotropically with Ueq =1.2—1.5 Ueq(C). Molecular diagrams plotted using Ortep3 and mercury 3.5.1 software [14,15]. Geometrical calculations using
ACCEPTED MANUSCRIPT PARST [16] and PLATON [17] software present in the program suite WinGX. The crystal data and refinement details are presented in Table 1.
2.3
Computational Details
Quantum chemical abinitio calculations are carried out for molecule (TDZ) at the crystallographical geometry using Gaussian 09 software[18]. Lattice energy and intermolecular interaction energies evaluated using the PIXEL-CLP module[19]. The Total lattice energy is partioned into columbic, fingerprint plots were
CR IP T
polarization, dispersion and repulsion Components. Hirshfeld surfaces and
generated using Crystal Explorer 17.5 [20]. Molecular electrostatic potential (MEP) maps are useful in understanding sites for electrophilic and nucleophilic reaction as well as hydrogen bonding interaction.. MEP is calculated at DFT/B3LYP/6-31(d,p)level of theory and plotted using Molecoolqt[21]. Topological , local potential energy (Vb) and Kinetic potential
AN US
properties such as electron density (ρ), Laplacian (
energy (Gb) at noncritical points were calculated for all non-covalent contacts using AIMALL based on Bader’s theory of Atoms in Molecules at B3LYP/6-31(d,p) level [22, 23].
Data, value and validation
3.1
Conformation, lattice energy and ESP maps
ED
M
3
PT
The compound TDZ (C23H17N3O2S) crystallized in Triclinic crystal system, space group P̅ with Z = 2. The molecule is non-planar and the dihedral angle between naphthalene ring and imidazo thiadiazole
CE
moiety is 83.48(3)°. The methoxy phenyl moiety shows slight deviation from planarity as it orientated at 6.16(5)° with respect to heterocyclic moiety which is also evident from the N3—C16—C17—
AC
C18*174.6(5):+ and C14—C16—C17—C18 [-5.6 (3):+ torsion angles. The imidazo thiadiazole moiety is almost planar indicating π-conjugation in both rings. This is confirmed deviation in C – S and C – N bond distances. The bond lengths S1—C13 [1.7221(16)Å] S1—C12 [1.7507(18)Å] from normal value(CS=1.82Å) indicating delocalization of sulphur. Amongst the C – N bond lengths the C12 – N1 [1.298(5)Å] is the shortest when compared with C16 – N3 [1.376(2)Å],C13 – N2 [1.341(1)Å] and C13 – N3 [1.313(2)Å]and C14 – N2[1.403(2)Å] which indicates a higher double bond character associated with the C – N bond in the thiadiazole ring than in the imidazole ring. There was a significant variation in the
ACCEPTED MANUSCRIPT bond angles around carbon in sp3 and sp2 hybridization states such as C15 – C14 – C16 angle of 137.99(4): is the one which exhibits most significant deviation of 17.99: from sp3 angle of 120: probably to keep the inter electronic repulsions to minimum extent. The angle S1 – C13 – N1 is observed as 137.35(4): which is due to reduce the repulsion between N – S atoms located at 1, 3 positions. The C18 – C17 – C22 angle of 117.27(3): is another example of deviation from normal value. The total lattice energy is divided into columbic, polarization, dispersion, and repulsive energy. The
CR IP T
lattice energy of the compound TDZ calculated using PIXEL method is fond to be -196.1 kJ/mol. From Table 2 it is clear that the dispersion energy contributes more towards total lattice energy of molecule. Further, Fig 3 energy frameworks corresponding to the different energy components electrostatic, dispersion and the total interaction energy also indicates larger contribution from dispersion energy
3.2
AN US
component.
Crystal packing and energetics
The molecular structure of TDZ is stabilized by various intra and inter molecular interactions. The different molecular pairs extracted from the crystal structure and their interaction bonding strengths
M
calculated using PIXEL and DFT methods (Table 2). As shown in the Table 2, the interaction energies of calculated by these two methods are comparable. Fig. 2 shows various intermolecular interactions exist
ED
in different molecular pairs identified from the crystal structure. The crystal structure is stabilized by intra molecular C18 – H18…O1 hydrogen bond * H…A=2.137 Å, D…A=3.000 Å and D—H…A= 152°+ and
PT
C22—H22…N3 interaction *H…A=2.37Å, D…A=2.754Å and D—H…A= 104°+ by locking conformational
CE
flexibility of phenyl ring.
The most stabilized molecular dimer motif A is formed by intermolecular C-H…O hydrogen bond [d H…O:
AC
2.756Å] with π…π interaction [d Cg2..Cg2: 3.851Å] (Cg2 involves centroid of the phenyl ring C4-C9) along b axis, together contribute energy of -60 KJ/mol. Motif B has interaction energy -43.6KJ/mol .Here along with dispersion component of energy repulsive component also plays significant role in contributing total energy. The H…N interaction of energy -30.9kJ/mol [d
H…N:
2.71Å] present in this motif C. Next
comes once again highly dispersive C-H...O interaction *d H…O: 2.736Å+ with energy of -30.9 KJ/mol. Motif D Consist of Cg…Cg interaction *d Cg1…Cg1=3.685Å] (Cg1 involves N2, N3, C13, C14, C16) with energy
ACCEPTED MANUSCRIPT being -27.8 kJ/mol. The motif E least stabilized molecular pair consists of a C-H…S interaction, *d
H…S:
2.985Å] the interaction energy being -16 kJ/mol which is highly dispersive in nature. 3.3 Hirshfeld surface analysis
The structure of compound TDZ was optimized by density functional theory (DFT) calculations using B3LYP/6-31(d,p) level basis set. The experimental parameters were compared with calculated values
optimized and experimental coordinates of molecule.
CR IP T
and found to complement each other with good correlation. The Fig 2 overlay diagram shows the
Fig. 4 shows the Hirshfeld surface of TDZ molecule mapped over d norm based on van der Waals radii. In the Hirshfeld surface, the dark blue colour shows the positive dnorm values indicating the contacts, which
AN US
are longer than the van der Waals radii, whereas the dark red colour represents the negative dnorm values, which are shorter than the sum of van der Waals radii. White colour indicates the dnorm zero values, i.e, the contact distances close to van der Waals contacts. The electronegative potential region is representing red, electropositive region by blue, and zero potential by green colour. Fig. 5 shows the finger print plots of TDZ molecule representing two dimensional descriptions of intermolecular
M
interactions of atom pair in the crystal. The central sharp spike in the bottom of the finger print plot corresponds to the H··· H type of intermolecular interactions, whereas the large spikes on both sides of
ED
the lobes are attributed to the O…H/H…O and H…S/S…H type of interactions. The percentage of contribution of H…H and C…H type interactions in the total Hirshfeld surface is 40.6% and 12.1%
PT
respectively. The C…C, and O…H type of interactions contribute small amount (6.6% and 5.5%) along
CE
with S…H and N…H interactions (4.4% and 3.9%) in the total Hirshfeld surface.
AC
3.4 QTAIM analysis
The Quantum theory of atoms in molecules (QTAIM) proposed by Bader, has been applied to analyse the nature of intermolecular interactions in terms of a quantum mechanical parameter such as electron density at the bond critical points (BCP's). The calculated electron density (ρ), the Laplacian of the electron density ( 2ρ), local potential energy density (V), local gradient kinetic energy density (G) at the bond critical points (BCP’s) for the various dimeric pairs(motifs A-E) of crystal structure are given in Table 4. The presence of (3, -1) bond critical point (BCP) for the proton (H···A) acceptor contact as a
ACCEPTED MANUSCRIPT confirmation of hydrogen bonding interaction. In the current study all the values of BCP and - 2ρ BCP fall within the range of the H-bonds.
3.5 Dipole Moment and Hyperpolarizability: The calculated dipole moment, linear polarizability (αo 10−23 esu) and first-order hyperpolarizability (βo . 10−30 esu) values in gas phase are calculated using B3LYP/6-31+g(d,p) level are shown in table 5. The
CR IP T
third rank tensor of the hyper-polarizability can have described by 3D matrix can be reduced to ten components due to Kleinmann symmetry [24+. The β components are described using coefficient in the Taylor series expansion of the energy in the external electric field. The external electric field depends on energy of unperturbed molecules, dipole moment, polarizability and first order hyper-polarizability of the molecules were calculated by taking the Cartesian coordinate system at center of mass of the
AN US
compound by finite field of approach and it is expressed as
CE
PT
ED
M
√
)
√
)
(
)
(
) ]
AC
√[(
(
In order to have strong second-order NLO properties, the constituting molecules of crystal need to exhibit large molecular hyper-polarizabilities, which are generally characterized by a highly extended piconjugated chain with strong electron donor acceptor pairs at the ends and also the compound must
ACCEPTED MANUSCRIPT crystallize in non-centrosymmetric structure [25, 26]. In our present study, the title compound exhibits NLO property in terms of calculated mean polarizability (αo) and the hyper-polarizability (βo) even though crystal symmetry forbids an experimental Second Harmonic Generation effects due to the presence of inversion symmetry under centro-symmetric space group P̅. The NLO property of the compound may be possible due to the unequal anti-parallel packing of the molecules particularly the piconjugated napthalene rings of the molecule generating pi-pi stacking interactions in crystal packing may leads to residual non-centrosymmetry in P̅ thus giving rise to polarizability [27]. The larger values
CR IP T
of hyperpolarizability are observed along βzxx and βxxy direction indicates major delocalisation of electron cloud along that direction. The π electron cloud movement from donar to acceptor atoms mediating naphthalene ring may be responsible for high value of fist order hyper polarizability.
It is found that the calculated the mean polarizability (αo) and the static hyper-polarizability (βo) values for title molecule are found to be 42.6314x10-24 and 11.4248x10-30 esu respectively which are higher
AN US
than that of urea standard. (Table 5) Thus the molecule can be a potential candidate for NLO application.
Conclusion
M
4
The crystal stucture of 6-(4-methoxyphenyl)-2-(naphthalen-1-ylmethyl) imidazo[2,1-b] [1,3,4] thiadiazole
ED
-5-carbaldehyde was determined. The crystal structure was stabilized by intermolecular C – H…O, N – H…N, and π…π interactions. QTAIM analysis confirmed presence of these interactions with acceptable
PT
topological parameters. Hirshfeld surface analysis and fingerprint plots indicated H…H and C…H type interactions 40.6% and 12.1% respectively. The NLO study indicated the molecule will be a better
AC
CE
candidate for NLO application.
ACCEPTED MANUSCRIPT Acknowledgements The authors are grateful to Professor T. N. Guru Row, Indian Institute of Science and DST India, for the data collection on the CCD facility. GNA thank RIT for computational facility sanctioned under TEQIP-II
AC
CE
PT
ED
M
AN US
CR IP T
Program.
ACCEPTED MANUSCRIPT
References 1 2 3
4 5
G. R. Desiraju, J. J. Vittal and A. Ramanan, Crystal Engineering: A Textbook, World Scientific, Singapore, 2011 G. R. Desiraju, J. Am. Chem. Soc., 2013, 135, 9952. G. R. Desiraju, Angew. Chem. Int. Eds., 2007, 46, 8342. J. S. Murray, P. Lane and P. Politzer, J. Mol. Model. 2009, 15, 723. S. P. Thomas, S. P. K. P. Veccham, L. J. Farrujia and T. N. Guru Row, Cryst. Growth Des. 2015, 15, 2110. A. Priimagi, G. Cavallo, P. Metrangolo and G. Resnati, Acc. Chem. Res. 2013, 46,2686.
7
Kumar, S., Hegde, M., Gopalakrishnan, V., Renuka, V. K.,Ramareddy, S. A., De Clercq, E., Schols, D., Gudibande Narasimhamurthy, A. K., Raghavan, S. C. & Karki, S. S. Eur. J. Med. Chem 2014.84, 687–697. Karki, S. S., Panjamurthy, K., Kumar, S., Nambiar, M., Ramareddy,S. A., Chiruvella, K. K. & Raghavan, S. C. Eur. J. Med.Chem.. 2011 46, 2109–2116. M.N. Noolvi, H.M. Patel, S. Kamboj, A. Kaur, V. Mann 2,6-disubstituted imidazo[2,1-b] [1,3,4]thiadiazoles, Eur. J. Chem., 2012, 56, 56-69. A. Sowmya, G. N. Anil Kumar, Sujeet Kumar and Subhas S. Karki Acta Cryst., 2016,. E72,1460–1462. Anilkumar, M. K. Kokila, Puttaraja, S. S. Karki and M. V. KulkarniActa Cryst. (2006). E62, o2014-o2016 Bruker APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA, 2011 G. M. Sheldrick, Acta Crystallogr.,2008, A64, 112. 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 and P. A. Wood, J. Appl. Cryst., 2008, 41, 466. L. J. Farrugia, J. Appl. Cryst., 2012, 45, 849. (a)Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, Oxford, England. (b)M. Nardelli, J. Appl. Crystallogr., 1995, 28, 659. A. L. Spek, Acta Crystallogr., 2009. D65, 148. 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. M. HasegawaIshida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. 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 and D. J. Fox, Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford, CT, 2009. A. Gavezzotti, New J. Chem., 2011, 35, 1360. M. J. Turner, J. J. McKinnon, S. K. Wolff, D. J. Grimwood, P. R. Spackman, D. Jayatilaka and M. A. Spackman, CrystalExplorer17 (2017). University of Western Australia. http://hirshfeldsurface.net. Christian B. Hübschle, MoleCoolQt a molecule viewer J. Appl. Cryst. (2011). 44 T. A. Keith, TK Gristmill Software, Overland Park KS, USA, 2013. R. F. W. Bader, Atoms in Molecules: A Quantum Theory, Oxford University Press, 1990. L. Szabo, V. Chiş, A. Pirnau, N. Leopold, O. Cozar, S. Orosz, J. Mol. Struct. 24 (2009) 385–392. Venkatram Nalla, Raghavender Medishetty,Yue Wang, Zhaozhi Bai, Handong Sun,Ji. Wei and Jagadese J. Vittal, IUCrJ, 2, (2015) 317–321. Yang-Hui Luo,Chen Chen, Dan-Li Hong, Xiao-Tong He, Jing-Wen Wang, and Bai-Wang Sun J. Phys. Chem. Lett. 2018, 9, 2158−2163.
10 11 12 13 14 15 16
AC
19 20
CE
PT
ED
17 18
AN US
9
M
8
CR IP T
6
21 22 23 24 25 26
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
Fig 1. ORTEP diagram of molecule TDZ with atomic labelling scheme at 50% probability level. Dotted lines indicate hydrogen bond
Fig2. Overlay plot of TDZ molecule in crystal structure and optimized structure in gas phase
ACCEPTED MANUSCRIPT
Table1. Crystal Data of TDZ CCDC Number 1830258 C23H17N3O2S
formula weight Crystal system space group
399.45 Triclinic P̅
Temperature (K) a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z Radiation type
296 7.7270 (5) 9.4244 (6) 13.7212 (8) 80.955 (3) 82.583 (3) 77.219 (4) 957.71 (10) 2 Mo Kα
AN US M
PT
Rint (sin θ/λ)max (Å−1) R[F2 >2ς(F2)], wR(F2), S No. of reflections No. of parameters
9931, 3322, 2587
ED
No. of measured, independent and observed [I > 2ς(I)] reflections
CR IP T
Chemical formula
All H-atom parameters refined
CE
H-atom treatment
0.020 0.595 0.038, 0.108, 1.083 3519 330
Δρmax, Δρmin (e Å−3)
AC
0.18, −0.19
Table 2. Lattice energies of the crystal structure of TDZ partitioned into Columbic, polarization, dispersion and repulsion energy components. All energy values are reported in kJ/mol.
Ecoul -20.6
Epol 35.9
Edisp -200.2
Erep 60.6
Etot -196.1
ACCEPTED MANUSCRIPT
Table 3: List of intermolecular interaction energies (KJ mol−1) present in the crystal structure of TDZ symmetry
centroid distance(A⁰)
Ecol
Epol
Edis
Erep
E tot (KJ/mol)
E tot corrected I.E.
Important Interactions
A
-x+1,-y,-z+1
6.266
19.2
-10
-70.3
39.5
-60
-59
C10-H10…O2 Cg2…Cg2
B
-x,-y,-z+1
7.665
-31.5
-9.3
-28.6
25.5
-43.6
-48.57
C15-H15…N1
C
x-1,-y,z
7.727
-9.8
-5
-31.5
15.4
-30.9
-31.88
C11-H11B…O1
D
-x,-y,-z
12.640
-5
-3
-39.4
19.8
-27.8
-25.2
Cg1…Cg1
E
-x+1,-y,-z
10.62
-4.7
-3.9
-20.3
12.9
-16
-15.2
C7-H7…S1
AN US
CR IP T
motif
Table 4. The topological parameters at the bond critical point for the various intermolecular interactions in TDZ molecule.
CE AC
BPL (Å)
5.508303 5.162261 4.542811 5.684254
ED
C10-H10…O2 C15-H15…N1 C11-H11B…O1 C7-H7….S1
PT
A B C D
Interaction
M
Motif
ρ (e/Å3)
0.003719 0.006344 0.011343 0.006014
ρ (e/Å5) 0.017974 0.0229 0.043428 0.022437
|Vb|/Gb 0.7093 0.7183 0.9190 0.6774
ACCEPTED MANUSCRIPT
Table 5. Static dipole moments µ(0;0), polarizability * α(−ω;ω,0)+ and first order hyper-polarizability [β(−ω;ω,0)+ components of molecule TDZ at B3LYP/6-31+G(d,p) level µo = 7.3059(Debye) -0.9634 µo urea = 4.72 -1.1735 -7.1464 α0 = 42.6314 (x10-24)esu 43.2457 2.7820 34.2017 αo urea = 4.78 5.4920 6.0531 50.4378 βo = 11.4248 (x10-30) esu -4.0561 -3.0211 -1.6085 -1.3499 -2.8634 βo urea=0.31 -2.0355 -1.8218 -3.2438 -2.3141 -1.4960
CR IP T
µx µy µz
AN US
αxx αxy αyy αzx αzy αzz
AC
CE
PT
ED
M
βxxx βxxy βyxy βyyy βxxz βyxz βyyz βzxz βzyz βzzz
ACCEPTED MANUSCRIPT
Table 6. Selected geometric parameters (Å, º)
1.7221 (16)
N2—C13
1.341 (2)
S1—C12
1.7507 (18)
N2—N1
1.3762 (18)
N3—C13
1.313 (2)
N2—C14
1.4016 (19)
N3—C16
1.376 (2)
N1—C12
C13—S1—C12
87.68 (8)
N3—C13—N2
C2—C3—C4
120.92 (17)
N3—C13—S1
C6—C5—C4
119.34 (16)
C22—C17—C18
C6—C5—C11
120.28 (17)
C22—C17—C16
C4—C5—C11
120.38 (15)
C18—C17—C16
C12—C11—C5
112.54 (14)
O2—C20—C19
116.07 (16)
N1—C12—C11
123.78 (16)
O2—C20—C21
124.39 (19)
N1—C12—S1
116.77 (12)
C19—C20—C21
119.54 (17)
C11—C12—S1
119.43 (13)
N3—C16—C17—C22
-4.5 (2)
C14—C16—C17—C18
-5.6 (3)
N3—C16—C17—C18
174.68 (15)
C14—C16—C17—C22
175.17 (17)
CR IP T
S1—C13
1.298 (2)
113.03 (14) 137.35 (14) 117.72 (16) 118.59 (15)
AC
CE
PT
ED
M
AN US
123.69 (16)
Fig 3. Molecular electrostatic surface potentials mapped on the electron density iso-surfaces at 0.0050.15 AU.
AC
CE
PT
ED
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
Fig 4 Hirshfeld surfaces mapped with dnorm shape-index and curvedness properties along with molecular pairs involving C-H…O and C-H…N interactions.
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
Fig 5.: Packing of Molecules and Energy frameworks corresponding to the different energy components electrostatic (red) dispersion (green) and the total interaction energy (Blue) viewed down the b-axis.
CE
PT
ED
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
Fig 6 Packing diagram of TDZ indicating C-H…O, C-H…N and π-π interactions.
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
(a)
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
PT
ED
(b)
H…H
C…C O…H S…H
40.60%
12.10%
6.30% 5.50%4.40% 3.90%
AC
N…H
CE
C…H
(c) Fig 7 (a, b) Two dimensional fingerprint plots from the Hirshfeld Surface analysis (c) Relative contributions of various intermolecular contacts in TDZ
AN US
CR IP T
ACCEPTED MANUSCRIPT
Motif B -43.6 KJ/mol
PT
ED
M
Motif A -60KJ/mol
AC
CE
Motif C -30kJ/mol
Motif D -27.8 KJ/mol
Motif E -16KJ/mol
Fig. 8. Various molecular dimers in the crystal structure of the compound TDZ. Dashed lines indicate the intermolecular interactions in motifs.
AC
CE
PT
ED
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
Fig 9. Molecular graphs of TDZ obtained from topological analysis showing different motifs with possible interactions with (3, -1) bond critical points between the interacting atoms.
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
AN US
CR IP T
GRAPHICAL ABSTRACT
Crystal structure, quantum chemical and Hirshfeld surface analysis substituted imidazo- thiadiazole-5-carbaldehyde A. Sowmya , G. N. Anil Kumar , Sujeet Kumar , Subhas S. Karki PII: DOI: Reference:
S2405-8300(18)30213-1 https://doi.org/10.1016/j.cdc.2018.11.002 CDC 160
To appear in:
Chemical Data Collections
Received date: Revised date: Accepted date:
24 September 2018 30 October 2018 5 November 2018
Please cite this article as: A. Sowmya , G. N. Anil Kumar , Sujeet Kumar , Subhas S. Karki , Crystal structure, quantum chemical and Hirshfeld surface analysis substituted imidazo- thiadiazole-5carbaldehyde, Chemical Data Collections (2018), doi: https://doi.org/10.1016/j.cdc.2018.11.002
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
ACCEPTED MANUSCRIPT
Crystal structure, quantum chemical and Hirshfeld surface analysis substituted imidazothiadiazole-5-carbaldehyde Sowmya A.a, G. N. Anil Kumar *a, Sujeet Kumar b, Subhas S. Karkib a b
Department of Physics, Ramaiah Institute of Technology, Bangalore 560054, India.
Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India.
Abstract
CR IP T
Contact email: [email protected]
In the present study, we have reported crystal stucture of 6-(4-methoxyphenyl)-2-(naphthalen-1ylmethyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde
via
single
crystal
X-ray
̅ space group. The crystal structure shows
AN US
diffraction. The compound crystallizes in the Triclinic,
(C23H17N3O2S)
intermolecular C – H…O, N – H…N, and π…π interactions. Quantum Theory of Atoms in Molecules (QTAIM) analysis confirmed presence of these interactions with acceptable topological parameters. The PIXEL Coulomb London Pauli (CLP) module was employed to characterize energetics associated with all interactions. Hirshfeld 2D fingerprint plots helped in evaluating intermoleular interactions
M
quantitatively. The molecular electrostatic potential (MEP) was plotted to identify the reaction sites of the molecule. Interestingly, the centrosymmetric molecule exhibits non-linear optical (NLO) properties
ED
calculated using Density Functional Theory (DFT). The mean and hyperpolarizability values are found to be 42.6314x10-24 and 11.4248x10-30 esu respectively indicating that the compound would be a potential
CE
PT
candidate for the NLO applications.
AC
Keywords Crystal structure, Thiadiazoles, Hirshfeld analysis, Hydrogen bond, NLO studies
ACCEPTED MANUSCRIPT Specifications Table
Data accessibility
1
CR IP T
Data category Data acquisition format Data type Procedure
Organic Chemistry, Computational Chemistry, Crystallography 6-(4-methoxyphenyl)-2-(naphthalen-1-ylmethyl)imidazo[2,1b][1,3,4]thiadiazole-5-carbaldehyde X-ray crystallography, computational CIF for Crystallography Analyzed The good quality single crystals suitable for x-ray diffraction were grown at room temperature from ethanol and Dimethyl formamide mixtures in the ratio (2:1) in volume. Single crystal data for compound were collected on Bruker SMART CCD area detector diffractometer with fine focus sealed tube Graphite monochromatic Mo-Kα radiation. Data collection was controlled by APEX2, cell refinement and data reduction was done using SAINT Software. The structure was determined and molecular interactions studied through Hirshfeld Surface analysis CCDC-1830258 https://www.ccdc.cam.ac.uk/structures-summary-form
AN US
Subject area Compounds
Rationale
Understanding the nature of interactions in crystals is an important aspect of crystal engineering to
M
design new solids.[1] The role of intermolecular interactions in both chemistry and biology[2] is found to be significant [3] hence attracted immense attention. The weak hydrogen bonds such as C-H···X (X =
ED
O, N, S, halogens and π-electrons) also important in understanding 3D structure of molecules in solidstate. Unconventional non-covalent interactions such as halogen bonds [4] Chalcogen bonds, and
PT
pnicogen bonds and also the π-hole interactions have gained attention in the fields of chemistry and biology[5,6]. In this study we have reporting crystal of 6-(4-methoxyphenyl)-2-(naphthalen-1-
CE
ylmethyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (TDZ), which exhibits cytotoxic activity against different human and murine cancer cell lines[7]. In general Imidazo[2,1-b][1,3,4]thiadiazoles exhibit a
AC
wide range of biological activities[8]. These include antitumor, anti-tubercular, antimicrobial, antifungal, anticonvulsant, analgesic, anti-inflammatory, anesthetic, and cytotoxic activities[9]. Structural studies of some of Imidazo[2,1-b][1,3,4]thiadiazoles reported shows presence of non covalent interactions[10,11]. In view of these, it is of interest to quantitatively explore the geometry and intermolecular interactions using computational tools such as PIXEL and Crystal Explorer for quantitative investigation intermolecular interactions present in the crystal structures of the molecule TDZ reported.
ACCEPTED MANUSCRIPT
2
Procedure
2.1
Synthesis crystallization
CR IP T
Chemical scheme of molecule TDZ
AN US
The compound (TDZ) was prepared using reported procedure [7]. The Vilsmeier reagent was prepared at 273 K by adding phosphorous oxychloride (2.3 g, 15 mmol) dropwise into a solution of DMF (10 ml). The 6-(4-methoxyphenyl)-2-(naphthalen-1-ylmethyl) imidazo[2,1-b] [1,3,4] thiadiazole (4 mmol) was added slowly to the Vilsmeier reagent by cooling for 2 hours. Further stirring was continued for 6 h at 363 K.
M
The reaction mixture was poured into 100 ml of water. The precipitate obtained was filtered, and neutralized with a cold aqueous solution of sodium carbonate forming the compound (TDZ). The solid
ED
obtained was washed with water, filtered and dried. Single crystals were obtained after two week by
Single crystal X-ray diffraction
CE
2.2
PT
slow evaporation using solution of ethanol/DMF (2:1 v:v).
AC
Single crystal data for compound were collected on Bruker SMART CCD area detector diffractometer with fine focus sealed tube Graphite monochromatic Mo-Kα radiation (λ = 0.71073 Å). Data collection was controlled by APEX2, cell refinement and data reduction was done using SAINT Software [12]. Multiscan Absorption correction was done using SADABS. The structures were solved by direct methods with SHELXS and refined by full matrix least squares on F2 Least-squares matrix using SHELXL-2014/7 program [13]. All the non-hydrogen atoms were refined anisotropically and all hydrogen atoms bound to carbon were placed in the calculated positions, and refined isotropically with Ueq =1.2—1.5 Ueq(C). Molecular diagrams plotted using Ortep3 and mercury 3.5.1 software [14,15]. Geometrical calculations using
ACCEPTED MANUSCRIPT PARST [16] and PLATON [17] software present in the program suite WinGX. The crystal data and refinement details are presented in Table 1.
2.3
Computational Details
Quantum chemical abinitio calculations are carried out for molecule (TDZ) at the crystallographical geometry using Gaussian 09 software[18]. Lattice energy and intermolecular interaction energies evaluated using the PIXEL-CLP module[19]. The Total lattice energy is partioned into columbic, fingerprint plots were
CR IP T
polarization, dispersion and repulsion Components. Hirshfeld surfaces and
generated using Crystal Explorer 17.5 [20]. Molecular electrostatic potential (MEP) maps are useful in understanding sites for electrophilic and nucleophilic reaction as well as hydrogen bonding interaction.. MEP is calculated at DFT/B3LYP/6-31(d,p)level of theory and plotted using Molecoolqt[21]. Topological , local potential energy (Vb) and Kinetic potential
AN US
properties such as electron density (ρ), Laplacian (
energy (Gb) at noncritical points were calculated for all non-covalent contacts using AIMALL based on Bader’s theory of Atoms in Molecules at B3LYP/6-31(d,p) level [22, 23].
Data, value and validation
3.1
Conformation, lattice energy and ESP maps
ED
M
3
PT
The compound TDZ (C23H17N3O2S) crystallized in Triclinic crystal system, space group P̅ with Z = 2. The molecule is non-planar and the dihedral angle between naphthalene ring and imidazo thiadiazole
CE
moiety is 83.48(3)°. The methoxy phenyl moiety shows slight deviation from planarity as it orientated at 6.16(5)° with respect to heterocyclic moiety which is also evident from the N3—C16—C17—
AC
C18*174.6(5):+ and C14—C16—C17—C18 [-5.6 (3):+ torsion angles. The imidazo thiadiazole moiety is almost planar indicating π-conjugation in both rings. This is confirmed deviation in C – S and C – N bond distances. The bond lengths S1—C13 [1.7221(16)Å] S1—C12 [1.7507(18)Å] from normal value(CS=1.82Å) indicating delocalization of sulphur. Amongst the C – N bond lengths the C12 – N1 [1.298(5)Å] is the shortest when compared with C16 – N3 [1.376(2)Å],C13 – N2 [1.341(1)Å] and C13 – N3 [1.313(2)Å]and C14 – N2[1.403(2)Å] which indicates a higher double bond character associated with the C – N bond in the thiadiazole ring than in the imidazole ring. There was a significant variation in the
ACCEPTED MANUSCRIPT bond angles around carbon in sp3 and sp2 hybridization states such as C15 – C14 – C16 angle of 137.99(4): is the one which exhibits most significant deviation of 17.99: from sp3 angle of 120: probably to keep the inter electronic repulsions to minimum extent. The angle S1 – C13 – N1 is observed as 137.35(4): which is due to reduce the repulsion between N – S atoms located at 1, 3 positions. The C18 – C17 – C22 angle of 117.27(3): is another example of deviation from normal value. The total lattice energy is divided into columbic, polarization, dispersion, and repulsive energy. The
CR IP T
lattice energy of the compound TDZ calculated using PIXEL method is fond to be -196.1 kJ/mol. From Table 2 it is clear that the dispersion energy contributes more towards total lattice energy of molecule. Further, Fig 3 energy frameworks corresponding to the different energy components electrostatic, dispersion and the total interaction energy also indicates larger contribution from dispersion energy
3.2
AN US
component.
Crystal packing and energetics
The molecular structure of TDZ is stabilized by various intra and inter molecular interactions. The different molecular pairs extracted from the crystal structure and their interaction bonding strengths
M
calculated using PIXEL and DFT methods (Table 2). As shown in the Table 2, the interaction energies of calculated by these two methods are comparable. Fig. 2 shows various intermolecular interactions exist
ED
in different molecular pairs identified from the crystal structure. The crystal structure is stabilized by intra molecular C18 – H18…O1 hydrogen bond * H…A=2.137 Å, D…A=3.000 Å and D—H…A= 152°+ and
PT
C22—H22…N3 interaction *H…A=2.37Å, D…A=2.754Å and D—H…A= 104°+ by locking conformational
CE
flexibility of phenyl ring.
The most stabilized molecular dimer motif A is formed by intermolecular C-H…O hydrogen bond [d H…O:
AC
2.756Å] with π…π interaction [d Cg2..Cg2: 3.851Å] (Cg2 involves centroid of the phenyl ring C4-C9) along b axis, together contribute energy of -60 KJ/mol. Motif B has interaction energy -43.6KJ/mol .Here along with dispersion component of energy repulsive component also plays significant role in contributing total energy. The H…N interaction of energy -30.9kJ/mol [d
H…N:
2.71Å] present in this motif C. Next
comes once again highly dispersive C-H...O interaction *d H…O: 2.736Å+ with energy of -30.9 KJ/mol. Motif D Consist of Cg…Cg interaction *d Cg1…Cg1=3.685Å] (Cg1 involves N2, N3, C13, C14, C16) with energy
ACCEPTED MANUSCRIPT being -27.8 kJ/mol. The motif E least stabilized molecular pair consists of a C-H…S interaction, *d
H…S:
2.985Å] the interaction energy being -16 kJ/mol which is highly dispersive in nature. 3.3 Hirshfeld surface analysis
The structure of compound TDZ was optimized by density functional theory (DFT) calculations using B3LYP/6-31(d,p) level basis set. The experimental parameters were compared with calculated values
optimized and experimental coordinates of molecule.
CR IP T
and found to complement each other with good correlation. The Fig 2 overlay diagram shows the
Fig. 4 shows the Hirshfeld surface of TDZ molecule mapped over d norm based on van der Waals radii. In the Hirshfeld surface, the dark blue colour shows the positive dnorm values indicating the contacts, which
AN US
are longer than the van der Waals radii, whereas the dark red colour represents the negative dnorm values, which are shorter than the sum of van der Waals radii. White colour indicates the dnorm zero values, i.e, the contact distances close to van der Waals contacts. The electronegative potential region is representing red, electropositive region by blue, and zero potential by green colour. Fig. 5 shows the finger print plots of TDZ molecule representing two dimensional descriptions of intermolecular
M
interactions of atom pair in the crystal. The central sharp spike in the bottom of the finger print plot corresponds to the H··· H type of intermolecular interactions, whereas the large spikes on both sides of
ED
the lobes are attributed to the O…H/H…O and H…S/S…H type of interactions. The percentage of contribution of H…H and C…H type interactions in the total Hirshfeld surface is 40.6% and 12.1%
PT
respectively. The C…C, and O…H type of interactions contribute small amount (6.6% and 5.5%) along
CE
with S…H and N…H interactions (4.4% and 3.9%) in the total Hirshfeld surface.
AC
3.4 QTAIM analysis
The Quantum theory of atoms in molecules (QTAIM) proposed by Bader, has been applied to analyse the nature of intermolecular interactions in terms of a quantum mechanical parameter such as electron density at the bond critical points (BCP's). The calculated electron density (ρ), the Laplacian of the electron density ( 2ρ), local potential energy density (V), local gradient kinetic energy density (G) at the bond critical points (BCP’s) for the various dimeric pairs(motifs A-E) of crystal structure are given in Table 4. The presence of (3, -1) bond critical point (BCP) for the proton (H···A) acceptor contact as a
ACCEPTED MANUSCRIPT confirmation of hydrogen bonding interaction. In the current study all the values of BCP and - 2ρ BCP fall within the range of the H-bonds.
3.5 Dipole Moment and Hyperpolarizability: The calculated dipole moment, linear polarizability (αo 10−23 esu) and first-order hyperpolarizability (βo . 10−30 esu) values in gas phase are calculated using B3LYP/6-31+g(d,p) level are shown in table 5. The
CR IP T
third rank tensor of the hyper-polarizability can have described by 3D matrix can be reduced to ten components due to Kleinmann symmetry [24+. The β components are described using coefficient in the Taylor series expansion of the energy in the external electric field. The external electric field depends on energy of unperturbed molecules, dipole moment, polarizability and first order hyper-polarizability of the molecules were calculated by taking the Cartesian coordinate system at center of mass of the
AN US
compound by finite field of approach and it is expressed as
CE
PT
ED
M
√
)
√
)
(
)
(
) ]
AC
√[(
(
In order to have strong second-order NLO properties, the constituting molecules of crystal need to exhibit large molecular hyper-polarizabilities, which are generally characterized by a highly extended piconjugated chain with strong electron donor acceptor pairs at the ends and also the compound must
ACCEPTED MANUSCRIPT crystallize in non-centrosymmetric structure [25, 26]. In our present study, the title compound exhibits NLO property in terms of calculated mean polarizability (αo) and the hyper-polarizability (βo) even though crystal symmetry forbids an experimental Second Harmonic Generation effects due to the presence of inversion symmetry under centro-symmetric space group P̅. The NLO property of the compound may be possible due to the unequal anti-parallel packing of the molecules particularly the piconjugated napthalene rings of the molecule generating pi-pi stacking interactions in crystal packing may leads to residual non-centrosymmetry in P̅ thus giving rise to polarizability [27]. The larger values
CR IP T
of hyperpolarizability are observed along βzxx and βxxy direction indicates major delocalisation of electron cloud along that direction. The π electron cloud movement from donar to acceptor atoms mediating naphthalene ring may be responsible for high value of fist order hyper polarizability.
It is found that the calculated the mean polarizability (αo) and the static hyper-polarizability (βo) values for title molecule are found to be 42.6314x10-24 and 11.4248x10-30 esu respectively which are higher
AN US
than that of urea standard. (Table 5) Thus the molecule can be a potential candidate for NLO application.
Conclusion
M
4
The crystal stucture of 6-(4-methoxyphenyl)-2-(naphthalen-1-ylmethyl) imidazo[2,1-b] [1,3,4] thiadiazole
ED
-5-carbaldehyde was determined. The crystal structure was stabilized by intermolecular C – H…O, N – H…N, and π…π interactions. QTAIM analysis confirmed presence of these interactions with acceptable
PT
topological parameters. Hirshfeld surface analysis and fingerprint plots indicated H…H and C…H type interactions 40.6% and 12.1% respectively. The NLO study indicated the molecule will be a better
AC
CE
candidate for NLO application.
ACCEPTED MANUSCRIPT Acknowledgements The authors are grateful to Professor T. N. Guru Row, Indian Institute of Science and DST India, for the data collection on the CCD facility. GNA thank RIT for computational facility sanctioned under TEQIP-II
AC
CE
PT
ED
M
AN US
CR IP T
Program.
ACCEPTED MANUSCRIPT
References 1 2 3
4 5
G. R. Desiraju, J. J. Vittal and A. Ramanan, Crystal Engineering: A Textbook, World Scientific, Singapore, 2011 G. R. Desiraju, J. Am. Chem. Soc., 2013, 135, 9952. G. R. Desiraju, Angew. Chem. Int. Eds., 2007, 46, 8342. J. S. Murray, P. Lane and P. Politzer, J. Mol. Model. 2009, 15, 723. S. P. Thomas, S. P. K. P. Veccham, L. J. Farrujia and T. N. Guru Row, Cryst. Growth Des. 2015, 15, 2110. A. Priimagi, G. Cavallo, P. Metrangolo and G. Resnati, Acc. Chem. Res. 2013, 46,2686.
7
Kumar, S., Hegde, M., Gopalakrishnan, V., Renuka, V. K.,Ramareddy, S. A., De Clercq, E., Schols, D., Gudibande Narasimhamurthy, A. K., Raghavan, S. C. & Karki, S. S. Eur. J. Med. Chem 2014.84, 687–697. Karki, S. S., Panjamurthy, K., Kumar, S., Nambiar, M., Ramareddy,S. A., Chiruvella, K. K. & Raghavan, S. C. Eur. J. Med.Chem.. 2011 46, 2109–2116. M.N. Noolvi, H.M. Patel, S. Kamboj, A. Kaur, V. Mann 2,6-disubstituted imidazo[2,1-b] [1,3,4]thiadiazoles, Eur. J. Chem., 2012, 56, 56-69. A. Sowmya, G. N. Anil Kumar, Sujeet Kumar and Subhas S. Karki Acta Cryst., 2016,. E72,1460–1462. Anilkumar, M. K. Kokila, Puttaraja, S. S. Karki and M. V. KulkarniActa Cryst. (2006). E62, o2014-o2016 Bruker APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA, 2011 G. M. Sheldrick, Acta Crystallogr.,2008, A64, 112. 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 and P. A. Wood, J. Appl. Cryst., 2008, 41, 466. L. J. Farrugia, J. Appl. Cryst., 2012, 45, 849. (a)Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, Oxford, England. (b)M. Nardelli, J. Appl. Crystallogr., 1995, 28, 659. A. L. Spek, Acta Crystallogr., 2009. D65, 148. 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. M. HasegawaIshida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. 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 and D. J. Fox, Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford, CT, 2009. A. Gavezzotti, New J. Chem., 2011, 35, 1360. M. J. Turner, J. J. McKinnon, S. K. Wolff, D. J. Grimwood, P. R. Spackman, D. Jayatilaka and M. A. Spackman, CrystalExplorer17 (2017). University of Western Australia. http://hirshfeldsurface.net. Christian B. Hübschle, MoleCoolQt a molecule viewer J. Appl. Cryst. (2011). 44 T. A. Keith, TK Gristmill Software, Overland Park KS, USA, 2013. R. F. W. Bader, Atoms in Molecules: A Quantum Theory, Oxford University Press, 1990. L. Szabo, V. Chiş, A. Pirnau, N. Leopold, O. Cozar, S. Orosz, J. Mol. Struct. 24 (2009) 385–392. Venkatram Nalla, Raghavender Medishetty,Yue Wang, Zhaozhi Bai, Handong Sun,Ji. Wei and Jagadese J. Vittal, IUCrJ, 2, (2015) 317–321. Yang-Hui Luo,Chen Chen, Dan-Li Hong, Xiao-Tong He, Jing-Wen Wang, and Bai-Wang Sun J. Phys. Chem. Lett. 2018, 9, 2158−2163.
10 11 12 13 14 15 16
AC
19 20
CE
PT
ED
17 18
AN US
9
M
8
CR IP T
6
21 22 23 24 25 26
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
Fig 1. ORTEP diagram of molecule TDZ with atomic labelling scheme at 50% probability level. Dotted lines indicate hydrogen bond
Fig2. Overlay plot of TDZ molecule in crystal structure and optimized structure in gas phase
ACCEPTED MANUSCRIPT
Table1. Crystal Data of TDZ CCDC Number 1830258 C23H17N3O2S
formula weight Crystal system space group
399.45 Triclinic P̅
Temperature (K) a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z Radiation type
296 7.7270 (5) 9.4244 (6) 13.7212 (8) 80.955 (3) 82.583 (3) 77.219 (4) 957.71 (10) 2 Mo Kα
AN US M
PT
Rint (sin θ/λ)max (Å−1) R[F2 >2ς(F2)], wR(F2), S No. of reflections No. of parameters
9931, 3322, 2587
ED
No. of measured, independent and observed [I > 2ς(I)] reflections
CR IP T
Chemical formula
All H-atom parameters refined
CE
H-atom treatment
0.020 0.595 0.038, 0.108, 1.083 3519 330
Δρmax, Δρmin (e Å−3)
AC
0.18, −0.19
Table 2. Lattice energies of the crystal structure of TDZ partitioned into Columbic, polarization, dispersion and repulsion energy components. All energy values are reported in kJ/mol.
Ecoul -20.6
Epol 35.9
Edisp -200.2
Erep 60.6
Etot -196.1
ACCEPTED MANUSCRIPT
Table 3: List of intermolecular interaction energies (KJ mol−1) present in the crystal structure of TDZ symmetry
centroid distance(A⁰)
Ecol
Epol
Edis
Erep
E tot (KJ/mol)
E tot corrected I.E.
Important Interactions
A
-x+1,-y,-z+1
6.266
19.2
-10
-70.3
39.5
-60
-59
C10-H10…O2 Cg2…Cg2
B
-x,-y,-z+1
7.665
-31.5
-9.3
-28.6
25.5
-43.6
-48.57
C15-H15…N1
C
x-1,-y,z
7.727
-9.8
-5
-31.5
15.4
-30.9
-31.88
C11-H11B…O1
D
-x,-y,-z
12.640
-5
-3
-39.4
19.8
-27.8
-25.2
Cg1…Cg1
E
-x+1,-y,-z
10.62
-4.7
-3.9
-20.3
12.9
-16
-15.2
C7-H7…S1
AN US
CR IP T
motif
Table 4. The topological parameters at the bond critical point for the various intermolecular interactions in TDZ molecule.
CE AC
BPL (Å)
5.508303 5.162261 4.542811 5.684254
ED
C10-H10…O2 C15-H15…N1 C11-H11B…O1 C7-H7….S1
PT
A B C D
Interaction
M
Motif
ρ (e/Å3)
0.003719 0.006344 0.011343 0.006014
ρ (e/Å5) 0.017974 0.0229 0.043428 0.022437
|Vb|/Gb 0.7093 0.7183 0.9190 0.6774
ACCEPTED MANUSCRIPT
Table 5. Static dipole moments µ(0;0), polarizability * α(−ω;ω,0)+ and first order hyper-polarizability [β(−ω;ω,0)+ components of molecule TDZ at B3LYP/6-31+G(d,p) level µo = 7.3059(Debye) -0.9634 µo urea = 4.72 -1.1735 -7.1464 α0 = 42.6314 (x10-24)esu 43.2457 2.7820 34.2017 αo urea = 4.78 5.4920 6.0531 50.4378 βo = 11.4248 (x10-30) esu -4.0561 -3.0211 -1.6085 -1.3499 -2.8634 βo urea=0.31 -2.0355 -1.8218 -3.2438 -2.3141 -1.4960
CR IP T
µx µy µz
AN US
αxx αxy αyy αzx αzy αzz
AC
CE
PT
ED
M
βxxx βxxy βyxy βyyy βxxz βyxz βyyz βzxz βzyz βzzz
ACCEPTED MANUSCRIPT
Table 6. Selected geometric parameters (Å, º)
1.7221 (16)
N2—C13
1.341 (2)
S1—C12
1.7507 (18)
N2—N1
1.3762 (18)
N3—C13
1.313 (2)
N2—C14
1.4016 (19)
N3—C16
1.376 (2)
N1—C12
C13—S1—C12
87.68 (8)
N3—C13—N2
C2—C3—C4
120.92 (17)
N3—C13—S1
C6—C5—C4
119.34 (16)
C22—C17—C18
C6—C5—C11
120.28 (17)
C22—C17—C16
C4—C5—C11
120.38 (15)
C18—C17—C16
C12—C11—C5
112.54 (14)
O2—C20—C19
116.07 (16)
N1—C12—C11
123.78 (16)
O2—C20—C21
124.39 (19)
N1—C12—S1
116.77 (12)
C19—C20—C21
119.54 (17)
C11—C12—S1
119.43 (13)
N3—C16—C17—C22
-4.5 (2)
C14—C16—C17—C18
-5.6 (3)
N3—C16—C17—C18
174.68 (15)
C14—C16—C17—C22
175.17 (17)
CR IP T
S1—C13
1.298 (2)
113.03 (14) 137.35 (14) 117.72 (16) 118.59 (15)
AC
CE
PT
ED
M
AN US
123.69 (16)
Fig 3. Molecular electrostatic surface potentials mapped on the electron density iso-surfaces at 0.0050.15 AU.
AC
CE
PT
ED
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
Fig 4 Hirshfeld surfaces mapped with dnorm shape-index and curvedness properties along with molecular pairs involving C-H…O and C-H…N interactions.
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
Fig 5.: Packing of Molecules and Energy frameworks corresponding to the different energy components electrostatic (red) dispersion (green) and the total interaction energy (Blue) viewed down the b-axis.
CE
PT
ED
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
Fig 6 Packing diagram of TDZ indicating C-H…O, C-H…N and π-π interactions.
AN US
CR IP T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
(a)
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
PT
ED
(b)
H…H
C…C O…H S…H
40.60%
12.10%
6.30% 5.50%4.40% 3.90%
AC
N…H
CE
C…H
(c) Fig 7 (a, b) Two dimensional fingerprint plots from the Hirshfeld Surface analysis (c) Relative contributions of various intermolecular contacts in TDZ
AN US
CR IP T
ACCEPTED MANUSCRIPT
Motif B -43.6 KJ/mol
PT
ED
M
Motif A -60KJ/mol
AC
CE
Motif C -30kJ/mol
Motif D -27.8 KJ/mol
Motif E -16KJ/mol
Fig. 8. Various molecular dimers in the crystal structure of the compound TDZ. Dashed lines indicate the intermolecular interactions in motifs.
AC
CE
PT
ED
M
AN US
CR IP T
ACCEPTED MANUSCRIPT
Fig 9. Molecular graphs of TDZ obtained from topological analysis showing different motifs with possible interactions with (3, -1) bond critical points between the interacting atoms.
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
M
AN US
CR IP T
GRAPHICAL ABSTRACT