DFT, Quantum Chemical Study and Biological
Effects of a Heterocyclic Molecular
Research Article
Journal of Biotechnology & Bioresearch
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Zineb Tribak
1
*, Mohammed Khalid Skalli
1
, Amal Haoudi
1
, Youssef Kandri Rodi
1
and Omar Senhaji
2
1
Laboratory of Applied Organic Chemistry, Faculty of Sciences and Technology, B.P. 2202, Sidi Mohamed Ben Abdellah University, Fez Morocco
2
Biomolecular and Macromolecular Chemistry Team, Faculty of Sciences B.P. 11201, Moulay Ismail University, Meknes Morocco
*Corresponding author: Zineb Tribak, Laboratory of Applied Organic Chemistry, Faculty of Sciences and Technology, B.P. 2202, Sidi Mohamed Ben
Abdellah University, Fez Morocco, Email: tribak.zineb@gmail.com, Tel: +212 659899497
Submission: January 10, 2019; Published: February 21, 2019
Introduction
5-Chloroisatin derivatives [1] are well known for their versatile
therapeutic agents in medicine, exhibiting antimicrobial [2], anti-
inflammatory [3], antioxidant [4,5], anticancer [6], antibiotic [7],
anti-HIV [8], anticonvulsant [9], antitubercular [10] activities and
relaxant effects [11]. Density functional theory (DFT) studies have
evolved to a powerful and very reliable tool, being routinely used
for the determination of various molecular properties [11]. In view
of these observations, the aim of the present investigation was to
design 5-chloro-1-(prop-2-yn-1-yl)indoline-2,3-dione (TZ
P
) in
the search for high expected antibacterial interest against gram
positive bacteria Bacillus subtilis, Staphylococcus aureus and
Gram-negative bacteria Escherichia coli. Then, a description of the
molecular geometry, frontier molecular orbital (HOMO and LUMO),
global and local reactivity descriptors and MEP features of the title
compound using density functional theory using (DFT/B3LYP)
method with the 6-31G (d, p) basis set [12].
Experimental
General
All melting points are uncorrected.
1
H-NMR (300MHz) and
13
C-NMR (75MHz) spectra were obtained on Bruker equipment
using CDCl
3
as solvent. Chemical shifts are given in ppm with TMS
as an internal reference. J values are given in Hertz. Signals are
abbreviated as singlet, s; doublet, d; double-doubles, dd; triplet, t;
multiplet, m. Chromatography was performed with silica (mesh)
and reactions were monitored by thin layer chromatography (TLC)
with silica plates coated with silica gel.
General procedure
5-chloro-1H-indole-2,3-dione (0,4g, 2,20mmol) was dissolved
in 15mL of N, N-di methyl formamide (DMF) and 0,5g (3,3mmol)
of K
2
CO
3
, BTBA (0,1g, 0,3mmol) and 1.2 equivalent of propargyl
bromide were added, and the mixture was stirred for 48 hours
at room temperature. The reaction progress was monitored by
TLC. The solvent was removed in vacuo and co-evaporated with
methylene Chloride (CH
2
Cl
2
) several times, to remove the remaining
traces of DMF. This yielded the product as a red to orange solid. No
purification was necessary.
Compound
TZ
P
: 5-chloro-1-(prop-2-yn-1-yl)indoline-2, 3-dione: yield:
88% ; M.P: 166-170 °C; R
f
= 0.78 ;
1
H NMR (CDCl
3
) δppm 7.57-7.62
(m, 2H, H
Ar
); 7.12 (d, H, H
Ar
,
3
J
H-H
=6Hz); 4.54 (s, 2H, CH
2
); 2.34 (t, H,
4
J
H-H
=3Hz);
13
C NMR (CDCl
3
) δppm: 181.55 (C=O); 156.60 (N-C=O);
147.87, 130.07, 118.50 (CQ); 137.80, 125.24, 112.75 (CH
Ar
) ;73.72
(C≡C) ;71.21 (CH); 29.59 (CH
2
)
Antibacterial activity
Antibacterial screening of compound 5-chloro-1-(prop-2-yn-
1-yl) indoline-2,3-dione (TZ
P
) was determined by a disc diffusion
method, against two bacteria Gram
-
: Pseudomonas aeruginosa,
Escherichia coli, and two others Gram
+
: Bacillus cereus and
Staphylococcus aureus using LB medium. Antibacterial activity
was carried out according to the method reported by [13] by the
determinations of Minimum inhibitory concentration (MIC) and
Minimum bactericidal concentration (MBC) [14]. The diameter of
the inhibition zone around each disc was measured (Table 1).
Abstract
In this paper, the title compound 5-chloro-1-(prop-2-yn-1-yl)indoline-2,3-dione (TZ
P
) has been prepared by N-alkylation method with a good
yield. The structure of the compound was further confirmed from the 1H NMR and 13C NMR Spectral data and It has been screened for its antibacterial
activity. The results revealed that the compound exhibited good to moderate antibacterial activity. Through computational study based on density
functional theory (DFT/B3LYP) using basis set 6-31G (d,p) a number of chemical Quantum descriptors were computed to predict the reactivity and
the reactive sites on the molecules. The molecular geometry and the electronic properties such as frontier molecular orbital were investigated to get a
better insight of the molecular properties. The Molecular electrostatic potential (MEP) for the compound was determined to check their electrophilic
or nucleophilic reactivity.
Keywords: 5-Chlorosatin; N-alkylation; Antibacterial effects; DFT; HOMO; LUMO; MEP