Synthesis, crystal structure, DFT calculations, Hirshfeld surfaces, and antibacterial activities of schiff base based on imidazole

Article abstract of DOI:10.1016/j.molstruc.2019.07.071

A new Schiff base 2 was synthesized by condensation of 2-Hydroxy-5-(p-tolyldiazenyl)benzaldehyde and N(-3-aminopropyl)imidazole, and characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy and elemental analysis. Crystal structure of

Full text of DOI:10.1016/j.molstruc.2019.07.071

Accepted Manuscript
Synthesis, crystal structure, DFT calculations, Hirshfeld surfaces, and antibacterial
activities of schiff base based on imidazole
Siham Slassi, Mohammed Aarjane, Khalid Yamni, Amina Amine
PII:
S0022-2860(19)30915-9
DOI:
https://doi.org/10.1016/j.molstruc.2019.07.071
MOLSTR 26824
Reference:
To appear in: Journal of Molecular Structure
Received Date: 3 March 2019
Revised Date: 1 July 2019
Accepted Date: 16 July 2019
Please cite this article as: S. Slassi, M. Aarjane, K. Yamni, A. Amine, Synthesis, crystal structure, DFT
calculations, Hirshfeld surfaces, and antibacterial activities of schiff base based on imidazole, Journal of
Molecular Structure (2019), doi: https://doi.org/10.1016/j.molstruc.2019.07.071.
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

ACCEPTED MANUSCRIPT
Synthesis, Crystal structure, DFT calculations, Hirshfeld surfaces, and Antibacterial
activities of Schiff base based on imidazole
Siham Slassia, Mohammed Aarjanea, Khalid Yamnib, Amina Aminea*
a LCBAE, Equipe Chimie Moléculaire et Molécules Bioactives, Faculté des Sciences
Université Moulay Ismail, BP 11201 Zitoune, Meknès, Morocco.
* Corresponding author: amine_7a@yahoo.fr
b Laboratoire de Chimie des Matériaux et Biotechnologie des Produits Naturels,
E.Ma.Me.P.S., Université Moulay Ismail, Faculté des Sciences, Meknès, Morocco.
Abstract:
A new Schiff base 2 was synthesized by condensation of 2-Hydroxy-5-(p-tolyldiazenyl)benzaldehyde
1
13
and N(-3-aminopropyl)imidazole, and characterized by IR, H NMR, C NMR, mass spectroscopy
and elemental analysis. Crystal structure of 2 has been determined by X-ray diffraction analysis. The
structural parameters and electronic absorption properties of 2 were also studied using Density
Functional Theory (DFT), and Time Dependant Density Functional Theory (TD-DFT). Computations
were performed at DFT/B3LYP/6-31G(d), DFT/CAMB3LYP/6-31G(d) and DFT/MPW1PW91/6-
31G(d) levels of theory. The calculation results of the structural parameters and electronic absorption
properties for compound 2 are presented and compared with the X-ray analysis result and UV-visible
spectrum. Hirshfeld surface analysis was used to show surface contours and two-dimensional
fingerprint plots have been used to analyse intermolecular interactions. The schiff base 2 was assessed
for its in vitro antibacterial activities against four pathogenic strains: Staphylococcus aureus,
Pseudomonas putida, Klebsiella pneumoniae and Escherichia coli.
Keywords: Schiff base, X-ray diffraction, DFT, Electronic absorption, Hirshfeld surfaces,
Antibacterial activity.
1

ACCEPTED MANUSCRIPT
1. Introduction:
Schiff base compounds have been recognized as privileged among organic molecules, owing to their
interesting and important properties. These molecules constitute an important centre of attraction in
many areas like biological, clinical, medicinal, analytical and pharmacological fields [1]. They are
also used in analytical medicinal and polymer chemistry. The azomethine (C=N) linkage in Schiff
bases is significant in determining the mechanism of transamination and resamination reactions in
biological systems [2], and it has been suggested that the azomethine group is responsible of the
biological activities of Schiff bases molecules. In effect, these molecules are well-known as
antibacterial [3,4], antifungal [5,6], anti-inflammatory [7,8], antitumor [9,10], antiviral [11],
antipyretic [12], anti-HIV-1 [13] and antiproliferative [14,15]. Furthermore, the azomethine group is
an important site for coordinating and stabilizing various metals.
Imidazoles, being the core fragment of different natural products and biological or chemical systems,
constitute an important class of heterocycles. The vast therapeutic properties of the imidazole
derivatives drugs have encouraged the researchers in the medicinal field to synthesize a huge number
of novel molecules based on the imidazole unit as antifungal [6], antibacterial [14,15],
antiviral[16,17], anti-inflammatory [18], anticancer [19,20] and antidiabetic agents [21].
In the light of the interesting chemistry of Schiff bases, we herein report the synthesis,
characterization and X-ray diffraction of schiff base (2) based on imidazole, obtained by condensation
of 2-Hydroxy-5-(p-tolyldiazenyl)benzaldehyde and N(3-aminopropyl)imidazole. Using DFT, lowest
unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels
of frontier orbital were determined. UV-visible spectra were investigated experimentally and
theoretically. In addition, Hirshfeld surface analysis was used to analyse intermolecular interactions.
The antibacterial activity of (2) was evaluated against four pathogenic strains: Staphylococcus aureus,
Pseudomonas putida, Klebsiella pneumoniae and Escherichia coli.
2. Results and discussion:
The Schiff base ligand 2 was prepared in excellent yield via the condensation of 2-Hydroxy-5-(o-
1
13
tolyldiazenyl)benzaldehyde and N-(3-aminopropyl)imidazole then characterized by IR, H NMR, C
NMR, mass spectroscopy, elemental analysis and X-ray diffraction. NMR spectra are reported in Fig.
1and Fig. 2.
2.1 Description of the crystal structure:
The synthesized Schiff base with the general formula (C20H21N5O) crystallizes in the monoclinic
space group P2/n. (Table 1) The dihedral angles between the imidazole ring, and the methylphenyl
and the phenol groups are 84.39 (16)° and 81.44 (14)° respectively. An intramolecular O–H···N
2

ACCEPTED MANUSCRIPT
hydrogen bond forms between the –OH substituent of the phenol ring and the adjacent iminomethyl N
atom, enclosing an S6 ring. All the bond lengths are within normal ranges. The N1–N2 and N3–C14
bond lengths, 1.174 (4) and 1.272(4)Å respectively, confirm their double-bond character whereas the
N4–C18 and N4—C19 values are 1.347(3) and 1.370(3)Å, respectively.
The asymmetric unit of Schiff base is reported in Fig. 3.
Figure 3: Building unit of the crystal structure of 2
2.2 Computational Study:
Density functional theory (DFT) computation and time-dependent (TD-DFT) calculations
were performed. The structure of 2 was optimized at the B3LYP/6-31G(d) level. As can be observed
in Tables 2 and 3, the calculated bond distances and angles are in good agreement with the values
obtained from X-ray crystal structure determination. A superposition of the X-ray diffraction and
optimized structures of compound 2 is shown in Fig. 4. The negligible differences between the
experimental and calculated bond lengths and angles are due to the fact that the computations were
performed and calculated in the gas phase, while the X-ray data were obtained in the solid phase.
3

ACCEPTED MANUSCRIPT
Figure 4: Superposition of X-Ray and optimized structures of 2
.
2.3 Theoretical and experimental UV-visible Spectra study:
UV-vis absorption spectrum of
2
was simulated at TD-DFT/B3LYP/6-31G(d), TD-
DFT/CAMB3LYP/6-31G(d) and TD-DFT/MPW1PW91/6-31G(d) levels. The compound was
investigated in chloroform by theoretical calculation. Table 4 shows the calculated oscillator strengths
(f) and wavelengths (λ) (main transitions) along with the experimental wavelengths. The experimental
and theoretical spectra of the compound 2 in chloroform are shown in Fig.5. The obtained results
were closer to the experimental absorption wavelengths. We can say that, MPW1PW91 computations
lead to a better agreement with experiment relatively to B3LYP and CAMB3LYP. As Fig. 5 exhibits,
experimental spectrum of 2 shows three bands at 273, 349 and 437 nm. From the TD–DFT
calculation, the most significant theoretical absorption bands of MPW1PW91 were predicted at
279.57, 362.78 nm in chloroform solution.
4

ACCEPTED MANUSCRIPT
Table 4: Theoretical and experimental electronic absorption spectral values of 2
Compound Excitation
level
λ max (nm)
(f)
Electronic
transition
Major %
Contribution
B3LYP
372.85
288.67
336.20
254.25
362.78
279.57
349
1.0372
HOMO→LUMO
99.5
58.6
95.8
69.7
99.3
50.5
0.4422 HOMO→LUMO+1
1.0876 HOMO→LUMO
0.4336 HOMO-3→LUMO
1.0727 HOMO→LUMO
0.4570 HOMO→LUMO+1
CAMB3LYP
2
MPW1PW91
Exp
273
Figure 5: Experimental and theoretical absorption spectra of Schiff base 2 at B3LYP/6-31G (d),
CAM-B3LYP/6-31G (d) and MPW1PW91/6-31G(d) levels in CHCl3.
2.4 Frontier Molecular Orbitals (FMOs):
The resulting frontier molecular orbitals for azo-schiff base molecule are reported in Fig.6. The
highest occupied molecular orbital HOMO (π donor) is delocalized over the azobenzene moiety
including hydroxyl and methyl substituents and azomethine group, the lowest lying unoccupied
molecular orbital LUMO (π acceptor) is spread over the azobenzene moiety including only the
hydroxyl group. The 279.57 nm transition consists of HOMO → LUMO+1. The 362.78 nm excitation
has mainly HOMO → LUMO character.
5

ACCEPTED MANUSCRIPT
Figure 6: Energy levels and electronic isosurfaces of frontier molecular orbitals.
2.5 Hirshfeld surfaces analysis:
Fig. 7 shows the Hirshfeld surface of the title compound mapped over dnorm (-0.60 to 0.90 A°) and
the shape-index (-1.0 to 1.0 A°). In the dnorm map, the vivid red spots in the Hirshfeld surface are
due to short normalized O—H distances corresponding to O— H···N interactions. Hydrogen-donor
groups constitute the convex blue regions on the shape-index surface and hydrogen-acceptor groups
appear in concave red regions. The two dimensional fingerprint plots quantify the contributions of
each type of non-covalent interaction to the Hirshfeld surface. The major contribution with 48.6% of
the surface is due to H···H contacts, which represent van der waals interactions, followed by C···H,
N···H and O···H interactions, which contribute 28.5, 15.2 and 6.1%, respectively, these contributions
are observed as two sharp peaks in the plot of Fig.8.
6

ACCEPTED MANUSCRIPT
Figure 7: Hirshfeld surfaces for compound (2), mapped with dnorm (top) and shape index (bottom).
Figure 8: Two-dimensional fingerprints of compound (2), showing H···H, C···H, N···H and O···H
close contacts.
Voids in the crystal structure of (2) (Fig. 9) are built on the sum of spherical atomic electron densities
at the appropriate nuclear positions (procrystal electron density). The crystal voids calculation (results
under 0.002 a.u. isovalue) shows the void volume of title compound to be of the order of 226.81 Å3
and surface area in the order of 720.59 Å2. The porosity of the calculated void volume of (2) is
7

ACCEPTED MANUSCRIPT
12.37%. There are no large cavities. We note that the electron-density iso surfaces are not completely
closed around the components, but are open at those locations where interspecies approaches are
found.
Figure 9: Void plot for (2).
2.6 Antibacterial activity:
Firstly, the diffusion agar technique was used to evaluate the antibacterial activity of the Schiff base 2.
Schiff base 2 shows the high zone inhibition diameter against Staphylococcus aureus 20 mm, then K.
pneumoniae with 15mm. For E.coli, the inhibition zone diameter was 13mm and the lower diameter
was observed against P.putida with 9mm.
The Minimum inhibitory concentrations (MIC) results of 2 and the commercially available standard
are presented in table 5, they agree with those of the disc diffusion test. MICs of the Schiff base 2
against the microorganism species were ranged from 28.84 to 92.10 µg.mL-1. The excellent MIC
value was exhibited by 2 against staphylococcus aureus (28.84 µg.mL-1). E.coli (68.18 µg.mL-1) and
K. pneumoniae (42.45µg.mL-1) seem to be less sensible to compound 2. The lower activity was
showed against P.putida with an MIC value of 92.10 µg.mL-1. The obtained antibacterial activities
results of 2 are significant comparing with the activity of the commercialised antibiotic
chloramphenicol. In another hand, compound 2 exhibited encouraging antibacterial activities
comparing to other reported Schiff bases [22-26]. For instance, the imidazole Schiff base ligand
prepared from 1-(3-aminopropyl)imidazole and salicylaldehyde and which was reported first by M.
Kalanithi et al. [27] then by J. McGinley et al. [28]. The authors had found the free ligand and its
Cu(II) and Zn(II) complexes inactive against a number of tested microbes. Interestingly, for our
compound, the functionalization of the salicylate phenyl unit leads to promising antibacterial activities
against the selected pathogenic strains indicating the importance of the azo group in the structure of
compound 2. Hence, Shiff base 2 could be considered as a potent antibacterial compound.
Table 5: Antibacterial activities determined in liquid medium of 2 (MIC in µg.mL-1)
8

ACCEPTED MANUSCRIPT
Bacteria
Produit
2
S.aureus
E.Coli
68.18
22.41
-
K. pneumoniae
P. putida
92.10
37.03
-
28.84
11.65
-
42.45
15.38
-
Chloramphenicol
DMSO
3. Conclusion:
In sum, the Schiff base ligand 2 has been synthesized and characterized. The crystal structure of the
compound was determined by X-Ray diffraction. The geometry and structural parameters of the title
compound 2 was optimized with DFT/B3LYP methods using 6-31G(d) basis set. The electronic
absorption properties of the compound have been studied using TD-DFT computations at
DFT/B3LYP/6-31G(d), DFT/CAMB3LYP/6-31G(d) and DFT/MPW1PW91/6-31G(d) level of
theory, analysed and the theoretical results were similar to the experimental ones. Hirshfeld surface
analysis gave 2D fingerprint plots showing the intermolecular interactions. The Schiff base 2 was
assessed for its in vitro antibacterial activities against pathogenic strains, cocci Staphylococcus
aureus, Pseudomonas putida, Klebsiella pneumoniae and Escherichia coli. The results showed that
the compound exhibited significant activities in particular against S. aureus. Comparison with
analogous reported Schiff bases allows us to conclude about the importance of the azo group in the
structure of compound 2 for its antibacterial properties.
4. Materiel and methods:
4.1 Synthesis of Schiff base: 2
The N-(3-aminopropyl)imidazole (0.5 g, 4 mmol) was added to a methanol solution (30 ml) of 2-
hydroxy-5-(-tolyldiazenyl)benzaldehyde (0.96 g, 4 mmol) prepared earlier [6]. The mixture was
refluxed for 2 h and cooled to room temperature. The solvent was removed on a rotatory evaporator
and the orange product was rinsed and recrystallized with a mixture of methanol and ether. The
product was obtained as orange crystals [29].
9

ACCEPTED MANUSCRIPT
Scheme 1: Synthesis of Schiff base 2
1
Yield 82%, m.p 95 °C. H NMR (300MHz, [D6]DMSO, 25°C, TMS) δ/ppm: 8.63 (s,1H),
7.99 (d,1H , J = 7.2), 7.88(dd, 1H, J = 6.6, J = 2.4), 7.71(d, 2H, J = 8.1), 7.65(s, 1H), 7.32(d,
2H, J = 8.1),7.19 (s, 1H), 6.90-7.00 (m, 2H), 4.04(t, 2H, J= 7.2), 3.55(t, 2H, J= 6.6),
2.34(s,3H), 2.13(qd, 2H, J=6.9). 13C NMR (75 MHz, [D6]DMSO, 25°C, TMS) δ/ppm: 21.49,
31.76, 44.34, 55.74, 117.95, 118.22, 118.73, 122.59, 126.93, 127.06, 129.77, 129.91, 137.12,
141.11, 145.46, 150.69, 163.80, 165.95. MALDI TOF MS calcd: m/z=347.17 Da. Found
m/z= 348.4 [M+1]+. HR-MS(M): for C20H21N5O : 347.1746 found: 347.1745. Selected IR
bands (cm-1) 3105, 2943, 1634, 1580, 1485, 1445, 1377, 1283, 1229, 1107, 999, 959, 905,
851, 756, 689, 662. Anal. Calc. for C20H21N5O: C, 69.14%; H, 6.09%; N, 20.16%. Found: C,
69.23%; H, 6.01%; N, 20.07%.
10

ACCEPTED MANUSCRIPT
Figure 1: 1H NMR spectrum of compound 2
Figure 2: 13C NMR spectrum of compound 2
11

ACCEPTED MANUSCRIPT
4.2 Single crystal X-ray diffraction:
A suitable single crystal was selected for X-ray diffraction analysis. Data of the compound was
collected at room temperature with an Agilent SuperNova diffractometer using graphite
monochromatized CuKα radiation (λ = 1.54184 Å), equipped with a CCD area detector. The phase
problem was solved by direct methods using SHELX97 programs [30]. The structural graphics were
created using DIAMOND program. Experimental data collections details and the crystallographic
features of (2) are reported in Table 1. The atomic coordinates and the basic geometrical data are
reported in Tables 2 and 3.
4.3 DFT details:
The ground state geometry of schiff base 2 was optimized using DFT with Becke-3-Lee-Yang-Parr
(B3LYP) exchange correlation functional with 6-31G(d) basis set for all atoms [31,32]. The
calculation was carried out with Gaussian 09 software package without any symmetry constraint [33].
Then, the optimized geometry was used for energy calculations. Optical absorption spectra were
simulated using the polarisable continuum model (PCM) with TD-DFT at B3LYP/6-31G(d), CAM-
B3LYP/6-31G(d) and MPW1PW91/6-31G(d) levels , based on optimized ground state geometries.
The PCM calculations have been performed in the chloroform solution.
4.4 Hirshfeld surfaces analysis:
Hirshfeld surfaces and fingerprint plots were generated for 2 based on the crystallographic
information file (CIF) using CrystalExplorer [34,35]. Hirshfeld surfaces allow the visualization of
intermolecular interactions. Colors and color intensities are related to the relative strength of the
interaction and the short or long contacts.
4.5 Antibacterial activity:
The Schiff base 2 was tested for its antimicrobial activities against four bacterial strains, one Gram-
positive cocci Staphylococcus aureus and three Gram-negative bacteria Escherichia coli, Klebsiella
pneumoniae and Pseudomonas putida by the agar disc diffusion method using Muller Hinton agar.
The strains were grown in Mueller-Hinton agar at 37 °C for 24 h and the suspension was prepared by
matching a 0.5 McFarland standard. All the compounds were dissolved in dimethyl sulfoxide DMSO
and tested by the procedure of measuring the inhibition zone, as described in literature [36,37]. The
minimum inhibitory concentrations (MIC) of the schiff base 2 were also studied by liquid
microdilutions method, using sterile 96-wells flat-shaped microtitre plates by serial dilution of the
concentrations ranging from 145.16 to 7.42 µg.mL-1. The commercially chloramphenicol was used as
control drug. The analysis of both methods were made in three replicate for each compound.
References
[1] P. Przybylski, A. Huczynski, K. Pyta, B. Brzezinski, F. Bartl, Biological Properties of
12

ACCEPTED MANUSCRIPT
Schiff Bases and Azo Derivatives of Phenols, Curr. Org. Chem. 13(2) (2009) 124–148.
[2] P.P. Dholakiya, M.N. Patel, Synthesis and Reactivity in Inorganic and Metal- Organic
Chemistry Metal Complexesꢀ: Preparation , Magnetic , Spectral , and Biocidal Studies
of Some Mixed Ligand Complexes with Schiff Bases Containing NO and NN
Donor Atoms, (2010) 37–41. doi:10.1081/SIM-120030440.
[3] Z. Parsaee, K. Mohammadi, DFT calculations and antibacterial evaluation of new
macrocyclic Schiff base compounds, J. Mol. Struct. 1137 (2017) 512–523.
doi:10.1016/j.molstruc.2017.02.026.
[4] M. Kumar, K. Gupta, S. Chhibber, Synthesis , characterization and antibacterial
studies of schiff based 1 , 2 , 3-triazole bridged silatranes, J. Organomet. Chem. 871
(2018) 21–27. doi:10.1016/j.jorganchem.2018.06.024.
[5] E. Gungor, S. Celen, D. Azaz, H. Kara, Two tridentate Schiff base ligands and their
mononuclear cobalt (III) complexes: Synthesis, characterization, antibacterial and
antifungal activities, Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 94 (2012)
216–221. doi:10.1016/j.saa.2012.03.034.
[6] S. Slassi, A. Fix-tailler, G. Larcher, A. Amine, A. El-ghayoury, Imidazole and Azo-
Based Schiff Bases Ligands as Highly Active Antifungal and Antioxidant
Components, Heteroatom Chem. 2019 (2019). DOI: 10.1155/2019/6862170.
[7] K.P. Rakesh, H.M. Manukumar, D.C. Gowda, Bioorganic & Medicinal Chemistry
Letters Schiff ’ s bases of quinazolinone derivativesꢀ: Synthesis and SAR studies of a
novel series of potential anti-inflammatory and antioxidants, Bioorg. Med. Chem. Lett.
25 (2015) 1072–1077. doi:10.1016/j.bmcl.2015.01.010.
[8] M. Nath, P. Kumar, A. Kumar, New di- and triorganotin ( IV ) complexes of tripodal
Schiff base ligand containing three imidazole armsꢀ: Synthesis , structural
characterization , anti-inflammatory activity and thermal studies, J. Organomet. Chem.
695 (2010) 1353–1362. doi:10.1016/j.jorganchem.2010.02.009.
[9] K. Zhang, P. Wang, L. Xuan, X. Fu, F. Jing, S. Li, Y. Liu, B. Chen, Bioorganic &
Medicinal Chemistry Letters Synthesis and antitumor activities of novel hybrid
molecules moiety, Bioorg. Med. Chem. Lett. 24 (2014) 5154–5156.
doi:10.1016/j.bmcl.2014.09.086.
[10] M. Shebl, O.M.I. Adly, E.M. Abdelrhman, Binary and ternary copper ( II ) complexes
of a new Schiff base ligand spectral , thermal , antimicrobial and antitumor studies, J.
Mol. Struct. 1145 (2017) 329–338. doi:10.1016/j.molstruc.2017.05.064.
[11] Y. Wang, F. Xu, Y. Zhu, B. Song, D. Luo, G. Yu, Bioorganic & Medicinal Chemistry
Letters Pyrazolo [ 3 , 4- d ] pyrimidine derivatives containing a Schi ff base moiety as
potential antiviral agents, Bioorg. Med. Chem. Lett. 28 (2018) 2979–2984.
doi:10.1016/j.bmcl.2018.06.049.
[12] S. Murtaza, M. Shoaib, F. Kanwal, A. Abbas, S. Ashiq, S. Shamim, Synthesis and
biological evaluation of schiff bases of 4-aminophenazone as an anti-inflammatory ,
analgesic and antipyretic agent, J. Saudi Chem. Soc. 21 (2017) S359–S372.
doi:10.1016/j.jscs.2014.04.003.
13

ACCEPTED MANUSCRIPT
[13] Y. Al-abed, L. Dubrovsky, B. Ruzsicska, Inhibition of HIV-1 Nuclear Import via
Schiff Base Formation with Arylene Bis ( methylketone ) Compounds, 12 (2002)
3117–3119.
[14] W. Song, J. Cheng, D. Jiang, L. Guo, M. Cai, H. Yang, Spectrochimica Acta Part Aꢀ:
Molecular and Biomolecular Spectroscopy Synthesis , interaction with DNA and
antiproliferative activities of two novel Cu ( II ) complexes with Schiff base of
benzimidazole, SAA. 121 (2014) 70–76. doi:10.1016/j.saa.2013.09.142.
[15] B.N. Prasanna, K.N. Mohana, L. Mallesha, Synthesis and antiproliferative activity of
some new fluorinated Schiff bases derived from 1 , 2 , 4-triazoles, J. Fluor. Chem. 156
(2013) 15–20. doi:10.1016/j.jfluchem.2013.08.008.
[16] T.G. Edwards, C. Fisher, Antiviral activity of pyrrole-imidazole polyamides against
SV40 and BK polyomaviruses, Antiviral Res. 152 (2018) 68–75.
doi:10.1016/j.antiviral.2018.02.012.
[17] D. Sharma, B. Narasimhan, P. Kumar, V. Judge, R. Narang, E. De Clercq, J. Balzarini,
European Journal of Medicinal Chemistry Synthesis , antimicrobial and antiviral
evaluation of substituted imidazole derivatives, Eur. J. Med. Chem. 44 (2009) 2347–
2353. doi:10.1016/j.ejmech.2008.08.010.
[18] D. Schemeth, C. Kappacher, M. Rainer, R. Thalinger, G.K. Bonn, Talanta
Comprehensive evaluation of imidazole-based polymers for the enrichment of selected
non-steroidal anti-in fl ammatory drugs, Talanta. 153 (2016) 177–185.
doi:10.1016/j.talanta.2016.03.015.
[19] I. Kr, New derivatives of imidazole as potential anticancer agents, 53 (1998) 342–345.
[20] A. Negi, J. Marin, S.M. Amrutkar, A.T. Baviskar, G. Joshi, S. Singh, U.C. Banerjee,
R. Kumar, Bioorganic & Medicinal Chemistry Imine / amide – imidazole conjugates
derived from 5-amino-4-cyano- N 1-substituted benzyl imidazoleꢀ: Microwave-assisted
synthesis and anticancer activity via selective topoisomerase-II- a inhibition, Bioorg.
Med. Chem. 23 (2015) 5654–5661. doi:10.1016/j.bmc.2015.07.020.
[21] M. Taha, N. Hadiani, S. Imran, H. Rashwan, W. Jamil, S. Ali, S. Muhammad, F.
Rahim, U. Salar, K. Mohammed, Bioorganic Chemistry Synthesis of 6-chloro-2-Aryl-
1H-imidazo [ 4 , 5-b ] pyridine derivativesꢀ: Antidiabetic , antioxidant , b -
glucuronidase inhibiton and their molecular docking studies, Bioorg. Chem. 65 (2016)
48–56. doi:10.1016/j.bioorg.2016.01.007.
[22] K. Mahmood, W. Hashmi, H. Ismail, B. Mirza, B. Twamley, Z. Akhter, I. Rozas, R.J.
Baker, Synthesis, DNA binding and antibacterial activity of metal(II) complexes of a
benzimidazole Schiff base, Polyhedron. 157 (2019) 326–334.
doi:10.1016/j.poly.2018.10.020.
[23] M. Salehi, A. Amoozadeh, A. Salamatmanesh, M. Kubicki, G. Dutkiewicz, S. Samiee,
A. Khaleghian, Synthesis, characterization, crystal structures, computational studies,
and antibacterial activities of two new Schiff bases derived from isophthalaldehyde, J.
Mol. Struct. 1091 (2015) 81–87. doi:10.1016/j.molstruc.2015.02.060.
[24] A. Lapasam, V. Banothu, U. Addepally, M.R. Kollipara, Synthesis, structural and
antimicrobial studies of half-sandwich ruthenium, rhodium and iridium complexes
14

ACCEPTED MANUSCRIPT
containing nitrogen donor Schiff-base ligands, J. Mol. Struct. 1191 (2019) 314–322.
doi:10.1016/j.molstruc.2019.04.116.
[25] M. Mesbah, T. Douadi, F. Sahli, S. Issaadi, S. Boukazoula, S. Chafaa, Synthesis,
characterization, spectroscopic studies and antimicrobial activity of three new Schiff
bases derived from Heterocyclic moiety, J. Mol. Struct. 1151 (2018) 41–48.
doi:10.1016/j.molstruc.2017.08.098.
[26] S. Yousef Ebrahimipour, B. Machura, M. Mohamadi, M. Khaleghi, A novel cationic
cobalt(III) Schiff base complex: Preparation, crystal structure, Hirshfeld surface
analysis, antimicrobial activities and molecular docking, Microb. Pathog. 113 (2017)
160–167. doi:10.1016/j.micpath.2017.10.034.
[27] M. Kalanithi, M. Rajarajan & P. Tharmaraj, Synthesis, spectral, and biological studies
of transition metal chelates of N-[1-(3-aminopropyl)imidazole]salicylaldimine, J.
Coord. Chem. 64 (2011) 842-850. doi: 10.1080/00958972.2011.557432
[27] J. McGinley, M. McCann , K. Ni, T. Tallon, K. Kavanagh, M. Devereux, X. Ma, V.
McKee, Imidazole Schiff base ligands: Synthesis, coordination complexes and
biological activities, Polyhedron, 55 (2013) 169–178.
http://dx.doi.org/10.1016/j.poly.2013.03.023
[29] S. Slassi, O. Stetsiuk, A. Amine, M. Aarjane, H. Zouihri, K. Yamni, data reports 4- [(
E ) - ( 4-methylphenyl ) diazenyl ] phenol, (2019). doi:10.1107/S2414314619000361.
[30] R. Herbst-irmer, G.M. Sheldrick, È.A. Chemie, D.- Go, Re ® nement of Twinned
Structures with SHELXL 97, (1998). doi:10.1107/S0108768197018454.
[31] A.D. Becke, Density-functional thermochemistry . III . The role of exact exchange,
5648 (2001). doi:10.1063/1.464913.
[32] C. Lee, C. Hill, N. Carolina, into a functional of the electron density f f, 37 (1988).
[33] J.R.C. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, H.P. G.
Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li,
K. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M.
Ehara, T. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, K. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M.
Bearpark, J. J. Heyd, E. Brothers, J.C. N. Kudin, V. N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J.B. Burant, S. S. Iyengar, J. Tomasi, M.
Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, A.J. Cross, V. Bakken, C.
Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, V.G.Z. Austin, R.
Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, J.B. G. A. Voth, P.
Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, and D.J.F.
Foresman, J. V. Ortiz, J. Cioslowski, Gaussian09, Revis. A.02, Gaussian, Inc.,
Wallingford CT. (2009).
[34] S. Partitioning, C. Density, Spatial Partitioning of Charge Density, 16 (1977) 198–201.
[35] D.P. Mackinnon, C.M. Lockwood, Multivariate Behavioral Confidence Limits for the
Indirect Effectꢀ: Distribution of the Product and Resampling Methods, (2010) 37–41.
doi:10.1207/s15327906mbr3901.
15

ACCEPTED MANUSCRIPT
[36] A.L. Barry, M.B. Coyle, C. Thornsberry, E.H. Gerlach, R.W. Hawkinsons, B.E.T. Al,
J.C. Microbiol, Methods of Measuring Zones of Inhibition with the Bauer- Kirby Disk
Susceptibility Test, 10 (1979) 885–889.
[37] C.A. Alonso, C. Domínguez, J. Heras, E. Mata, V. Pascual, C. Torres, M. Zarazaga,
Computer Methods and Programs in Biomedicine Antibiogramjꢀ: A tool for analysing
images from disk diffusion tests, Comput. Methods Programs Biomed. 143 (2017)
159–169. doi:10.1016/j.cmpb.2017.03.010.
16

ACCEPTED MANUSCRIPT
Table 1: Crystallographic data, details of data collection and structure refinement parameters for 2.
CCDC number
1889270
Chemical formula
C20H21N5O
347.42
Mr
Crystal system, space group
Monoclinic, P2/n
293
Temperature (K)
a (Å)
12.2410 (4)
5.9386 (2)
25.2112 (9)
90.317 (3)
1832.69 (11)
4
b (Å)
c (Å)
β (°)
V (Å3)
Z
Radiation type
µ (mm-1)
Crystal size (mm)
Cu Kα
0.65
0.35 × 0.22 × 0.13
5548, 3487, 3037
No. of measured, independent and
observed [I > 2σ(I)] reflections
Rint
0.016
(sin θ/λ)max (Å-1)
R[F2 > 2σ(F2)], wR(F2), S
No. of reflections
No. of parameters
ꢁρmax, ꢁρmin (e Å-3)
0.622
0.084, 0.245, 1.08
3487
236
1.02, -0.67
17

ACCEPTED MANUSCRIPT
Table 2: Experimental and theoretical bond distances
Distance
C13—C2
C14—N3
C14—C11
C15—C16
C15—N3
C16—C17
C17—N4
C18—N4
C18—N6
C19—C20
C19—N4
C20—N6
C1—C2
Theoretical
1.5097
1.2747
1.4711
1.535
Experimental
1.501 (5)
1.272 (4)
1.457 (4)
1.500 (4)
1.464 (3)
1.520 (4)
1.465 (3)
1.347 (3)
1.317 (3)
1.354 (4)
1.370 (3)
1.367 (4)
1.372 (5)
1.427 (5)
1.397 (5)
1.333 (6)
1.333 (6)
1.426 (6)
1.537 (5)
1.381 (4)
1.386 (4)
1.399 (5)
1.547 (5)
1.385 (5)
1.401 (4)
1.417 (4)
1.336 (3)
1.174 (4)
1.4529
1.5341
1.4603
1.3687
1.3162
1.3732
1.3821
1.3765
1.4081
1.3868
1.3994
1.3936
1.3997
1.4071
1.4152
1.3969
1.4013
1.4061
1.4124
1.3844
1.4065
1.4164
1.3541
1.263
C1—C6
C2—C3
C3—C4
C4—C5
C5—C6
C5—N1
C7—C8
C7—C11
C8—C9
C8—N2
C9—C10
C10—C12
C11—C12
O1—C12
N1—N2
18

ACCEPTED MANUSCRIPT
Table 3: Experimental and theoretical angles
Angle
Theoretical
104.8159
119.3819
118.1767
125.7455
120.4741
121.3492
120.8914
109.9768
120.4182
119.2652
113.7855
115.7123
125.0225
119.7799
122.796
113.8787
118.7645
116.0647
125.1708
119.691
112.6158
121.3768
105.6623
117.5065
110.7339
117.313
Experimental
103.9 (2)
119.0 (4)
119.3 (4)
121.1 (3)
121.2 (4)
119.4 (4)
123.6 (4)
110.2 (2)
117.8 (4)
123.7 (4)
113.1 (2)
116.4 (4)
119.9 (4)
116.5 (4)
121.6 (3)
111.5 (2)
119.0 (3)
111.1 (3)
129.8 (3)
120.7 (3)
112.8 (2)
120.4 (3)
105.6 (2)
119.4 (3)
111.3 (2)
119.5 (3)
121.1 (3)
119.6 (3)
119.3 (3)
121.5 (2)
106.4 (2)
118.9 (3)
126.2 (2)
108.1 (3)
127.3 (2)
105.2 (3)
C18—N6—C20
C2—C1—C6
C1—C2—C3
N3—C14—C11
C1—C2—C13
C3—C2—C13
C4—C3—C2
N3—C15—C16
C3—C4—C5
C4—C5—C6
C15—C16—C17
C4—C5—N1
C6—C5—N1
C5—C6—C1
C8—C7—C11
N4—C17—C16
C7—C8—C9
C7—C8—N2
C9—C8—N2
C10—C9—C8
N6—C18—N4
C9—C10—C12
C20—C19—N4
C7—C11—C12
C19—C20—N6
C7—C11—C14
C12—C11—C14
O1—C12—C10
C14—N3—C15
O1—C12—C11
C18—N4—C19
C10—C12—C11
C18—N4—C17
N2—N1—C5
C19—N4—C17
N1—N2—C8
125.1804
120.8141
117.2776
119.3208
106.172
119.8651
126.9746
114.8834
126.8219
114.7568
19

ACCEPTED MANUSCRIPT
Highlights
- Synthesis and characterization of Schiff base based on imidazole is reported.
- The structure of Schiff base was confirmed by X-ray crystallography.
- The Schiff base was screened for its potential antibacterial.
- The structure of Schiff base was investigated using DFT and the nature of HOMO and
LUMO, electronic absorption were theoretically studied.