Differential functional theory and molecular docking studies of newly synthesized carbamates

Article abstract of DOI:10.1002/jccs.201800068

Four new carbamates (RZ1–RZ4) were synthesized from different amine moieties through reported methods. The reaction was monitored using thin layer chromatography and characterization was done using m.p., fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) techniques. Density functional theory (DFT) studies were carried out using Gaussian 09 software to compare the theoretical and practical parameters of the synthesized compounds. Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were also drawn to calculate the energy difference between orbitals. In-vitro enzyme inhibition potential against acetylcholine esterase (AChE), butyrylcholine esterase (BChE), and protease was checked through standard protocols that suggested moderate inhibition against selected enzymes. Docking studies were also carried out, which depicted that these compounds have ability to bind on the active site of AChE and BChE.

Full text of DOI:10.1002/jccs.201800068

Received: 21 February 2018
DOI: 10.1002/jccs.201800068
Revised: 10 October 2018
Accepted: 12 October 2018
A R T I C L E
Differential functional theory and molecular docking studies
of newly synthesized carbamates
1
1
1
2
3
Muhammad Danish
| Muhammad A. Raza
| Uzma Anwar | Umer Rashid | Zaheer Ahmed
1
Department of Chemistry, Hafiz Hayat Campus,
University of Gujrat, Gujrat, Pakistan
Four new carbamates (RZ1–RZ4) were synthesized from different amine moieties
through reported methods. The reaction was monitored using thin layer chromatog-
raphy and characterization was done using m.p., fourier-transform infrared spec-
troscopy (FTIR), and X-ray diffraction (XRD) techniques. Density functional
theory (DFT) studies were carried out using Gaussian 09 software to compare the
theoretical and practical parameters of the synthesized compounds. Highest occu-
pied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)
were also drawn to calculate the energy difference between orbitals. In-vitro
enzyme inhibition potential against acetylcholine esterase (AChE), butyrylcholine
esterase (BChE), and protease was checked through standard protocols that
suggested moderate inhibition against selected enzymes. Docking studies were also
carried out, which depicted that these compounds have ability to bind on the active
site of AChE and BChE.
2
Department of Chemistry, COMSATS University
Islamabad, Islamabad, Pakistan
3
RCMS, National University of Science and
Technology, Islamabad, Pakistan
Correspondence
Muhammad Danish, Department of Chemistry,
Hafiz Hayat Campus, University of Gujrat, Gujrat,
Pakistan.
Email: drdanish62@gmail.com
Funding information
Higher Education Commission, Pakistan
KEYWORDS
carbamates, differential functional theory, docking studies, enzyme inhibition
1
| INTRODUCTION
These can be unsaturated as symmetrical/unsymmetrical
and saturated as aliphatic/aromatic/substituted compounds,
[
2–4]
Carbamates (1) called urethanes are the proper esters of car-
bamic acid with acid and ester functionalities linked anatom-
ically with frequent interconversion. They have –O–CO–
NH– linkage with analogous properties to acid and ester
functional groups, neutral but more electrophilic than
amides, and undergo nucleophilic reactions more readily due
for example linezolid (3).
The compounds containing
metallic or nonmetallic inorganic atoms linked to carba-
mate groups are called inorganic carbamates, for example
[
5]
ammonium carbamate (4). Carbamate insecticides were
developed in 1950s as anticholinesterases, they were effec-
tive in killing insects; their different forms vary in their
action routes and in their lethal effects. These are
decomposed simply in the atmosphere within time limits of
weeks or months. Thiocarbamates (5–6) are sulfur-
containing carbamates; exist as O-thiocarbamates (5) and
S-thiocarbamate (6) isomeric forms. Dithiocarbamate (7)
contains two sulfur atoms instead of oxygen acting as an
analog of carbamate. Manganese, zinc complexes with eth-
ylene bisdithiocarbamates are widely used as fungicides in
[
1]
to the presence of good leaving groups. Amino acetates
2) are the organic compounds containing amino and acetate
(
ester functional group moieties.
O
O
R2
N
R1
R2
R1
O
N
R
R3
3
O
1
2
[
6,7]
Organic carbamates are the stable derivatives of car-
bamic acid, which can be obtained by substitution of amino
and acidic groups with various alkyl or aryl combinations.
cultivation field.
sized through one pot synthesis technique and character-
Dithiocarbamate has also been synthe-
[
8]
ized using modern spectroscopy by Nami et al.
©
2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–8.
http://www.jccs.wiley-vch.de
1

2
DANISH ET AL.
O
O
O
O
N
O
N
H
N
O
H N O NH4
2
F
S
3
4
O
S
R
R
R
R
R
R'
N
R
S
N
R
N
S
R"
5
6
7
FIGURE 1 Asymmetric crystal unit of RZ3
Rivastigmine, which acts as anticholinesterase, is an
important carbamate used for the treatment of Alzheimer's
synthesized (Table 1). The appearance of a new peak at
1
,380 cm− due to C–N and disappearance of the C–Cl
1
[
9]
disease. Activities of carbamates and organophosphates
are comparable because both act as inhibitors of cholinester-
ase enzyme. The difference in their action is that the inhibi-
tory effect of carbamates is short-lived and reversal of
influence is so fast that accurate measurement of the cholin-
esterase level in animals is so difficult. Therefore, it is essen-
tial to do analysis rapidly to decrease the reversal process. It
reagent peak further supported that the products were
[
12–15]
synthesized.
The exact structure of RZ3 was confirmed
with single X-ray diffraction (XRD) and we have already
[
16]
reported its structure.
3
| X-RAY CRYSTALLOGRAPHIC
[
10]
causes killing of the central nervous system in insects.
ANALYSIS
Carbamates have been studied for design of prodrugs and
their application in agricultural field is also increasing due to
its diversity in structures. They are also key com-
ponents/intermediates of various industries and being used
The asymmetric unit of RZ3 is shown in Figure 1. The ben-
zene ring A (C1–C6) and group B (C7/C8/C9/N1/N2/N3/
O1) of 4-aminophenzone moiety are planar with
r.m.s. deviation of 0.0037 and 0.0398 Å, respectively. The
carbon C10 and C11 atoms are at a distance of 0.1472
[11]
as protecting agents in synthetic chemistry.
Keeping in
view their importance, four new derivatives of carbamates
were prepared and evaluated biologically.
(
29) and 0.5628 (25) Å, respectively, from the mean square
ꢀ
plane B. The dihedral angle between A/B is 53.636 (50) .
The ethyl formate moiety C (O2/C12/O3/C13/C14) is planar
with r.m.s. deviation of 0.0568 Å. The dihedral angles
2
| RESULTS AND DISCUSSION
ꢀ
ꢀ
between A/C and B/C are 52.264 (87) and 67.725 (79) ,
The targeted compounds were characterized using fourier-
transform infrared spectroscopy (FTIR) spectroscopy and
their spectra were recorded as KBr pellets in the range
respectively. The molecules are dimerized due to N—H…O
2
H–interactions forming an R2 (10) ring motif. The dimers
are interlinked due to C—H…O interactions. In both cases,
O-atoms are of the carbonyl group of 4-aminophenzone.
−1
4
,000–400 cm . According to the Infra red (IR) results,
synthesized products are extensively different from their
corresponding reactants, which indicates the formation of
target compounds. Formation of carbamate derivatives is
confirmed by the appearance of a single peak at 3,150 cm−
of –NH and disappearance of two peaks that is, antisymmet-
ric and symmetric –NH2 stretching vibrations near
4
| DENSITY FUNCTIONAL THEORY
1
The structures of RZ1–RZ2 were optimized with density
functional theory (DFT)/B3LYP/6-31G (d). XRD analysis of
RZ3 was already reported and to confirm the experimental
bond angle and bond length, a DFT study was carried out
that gives a close relation between the experimental and
practical results (Table 1). The structures of RZ1, RZ2, and
RZ4 were elucidated based on FTIR frequencies not only
1
−1
3
,520 cm− and 3,400 cm . Similarly, secondary N–H
−
1
deformation appeared near 1,570 cm . The appearance of
the C O peak at 1,650 cm usually at a lower wave num-
−
1
ber due to resonance, C–O stretching vibration at
1
1
,225 cm− suggested that the targeted compound was
TABLE 1 Fundamental IR vibrations of the products
1
N–H (Def) cm−1
1,515
O (Str) cm−1
C–O (Str) cm−1
1,198
C–N (Str) cm−1
1,380
Code
RZ1
RZ2
RZ3
RZ4
N–H (Str) cm−
C
3,392
1,708
1,685
1,650
1,650
3,280
1,515
1,230
1,335
3,150
1,570
1,225
1,380
3,220
1,576
1,230
1,380

DANISH ET AL.
3
FIGURE 2 Optimized structures of the synthesized compounds through B3LYP/6-31+G
TABLE 2 Bond length and bond angles of RZ3
Bond length (Ao)
N (12)–C (2)
Exp. value
1.4269
1.4645
1.492
Comp. Value
1.42206
1.47885
1.49485
1.40236
1.37244
1.38715
1.47459
1.51833
Bond angles
Exp. value
120.81
116.61
123.19
121.39
109.79
115.20
108.53
123.86
Comp. Value
120.49
114.41
119.08
129.38
115.63
122.79
106.32
126.5
C3–C2–N12
N (16)–C (18)
C (14)–C (22)
C (15)–N (26)
N (26)–C (28)
C (28)–O (30)
O (30)–C (31)
C (31)–C (34)
N12–N16–C18
C18–N16–C14
C15–N26–C28
N20–C28–O30
C28–O30–C31
O30–C31–C34
C2–N12–C13
1.4072
1.348
1.3489
1.456
1.443
TABLE 3 Global chemical reactivity indices of carbamate derivatives
Code
RZ1
RZ2
RZ3
RZ4
Hartree
−669.1282
−0.2125
−0.0067
−0.2058
0.0979
−821.5151
−0.1720
−0.0094
−0.1626
0.0813
−688.5803
−0.1793
−0.0053
−0.1740
0.0870
−840.9668
−0.2034
−0.0392
−0.1642
0.0821
HOMO
LUMO
ΔE(HOMO-LUMO)
μ
η
−0.1046
0.0559
−0.0907
0.05059
−0.200495
−0.263735
2.6146
−0.0923
0.0489
−0.1213
0.0896
ω
Gibbs free energy
Enthalpy
−0.237649
−0.180155
1.8126
−0.219377
−0.280880
2.5175
−0.240525
−0.306911
3.4073
Dipole moment
Repulsion energy
883.9720
1,218.5190
949.51071
1,282.1016
practically but also theoretically. The optimized structures of
RZ1–RZ4 are shown in Figure 2 (Table 2).
RZ3 > RZ1 as shown in Table 3. The frontier molecular
orbitals of the organic molecules take part in the electric
and optical properties (Figures 3–6). They also predict the
The highest occupied molecular orbital (HOMO) and
lowest unoccupied molecular orbital (LUMO) of all the
synthesized molecules were drawn through Gaussian 5.0
and their Hartree-Fock (HF) energy was calculated via
check file, which ranged from −669.1282 to −840.9668.
The order of stability of the compounds is RZ4 > RZ2 >
[
17]
stability and reactivity of the reacting molecules.
The
HOMO–LUMO energy gaps were also calculated. These
energy values are structurally represented in Figures 7 and
8, respectively. Other parameters such as repulsion energy,
dipole moment, enthalpy, Gibbs free energy etc are listed

4
DANISH ET AL.
FIGURE 3 Theoretical and experimental FTIR spectra of RZ1
FIGURE 6 Theoretical and experimental FTIR spectra of RZ4
tested enzymes. Maximum activity was depicted by
2.55 ± 0.6% against BChE followed by AChE and prote-
5
ase 32.24 ± 0.8% and 28.17 ± 0.6%, respectively (Table 4).
Nowadays, carbamate moieties are becoming popular in
medicinal field due to their vast number of biological impor-
tance. They are also involved in the drug design and drug
discovery and being used as potent serine protease, human
immunodeficiency viruses (HIV)-1 protease, β-secretase,
and cysteine protease inhibitors. Our synthesized compounds
are also active against tested enzymes, which is in good
agreement with already reported literature.
FIGURE 4 Theoretical and experimental FTIR spectra of RZ2
(
Table 3) against their respective compounds. All these
parameters suggested that synthesized compounds were
stable as shown in Figure 8.
6
| DOCKING STUDIES
The lower value of the HOMO and LUMO energy gap
was because of the eventual charge transfer interactions
Docking studies were carried out by using MOE software.
The X-ray crystallographic structure of AChE in complex
with donepezil (PDB IDCode 1EVE) was used as the
enzyme structure. However, PDB ID1P0I was selected as
the crystal structure of BChE. As a first step, the ability of
the docking algorithm was validated to reproduce the
cocrystallized pose of donepezil in the 1EVE pocket. The
validation was carried out using the root mean square devia-
tion (RMSD) method. The cocrystallized ligand was red-
ocked and the RMSD between cocrystallized and redocked
conformation was determined. The RMSD value of <2.0 Å
is considered as accurate in predicting binding orientation of
the ligand.
[18]
within the molecules.
The greater the value of the energy
gap of the HOMO–LUMO is, the harder, more stable, and
[19–21]
less reactive the molecule is.
5
| BIOLOGICAL EVALUATION RESULTS
Enzyme inhibition was checked with three enzymes viz pro-
tease, acetylcholine esterase (AChE), and butyrylcholine
esterase (BChE), and it was found from the results that syn-
thesized compounds showed moderate activity against all
The visual inspection of the best-scored docked pose of
compound into the binding site of 1EVE reveals that it forms
interactions with residues of the peripheral anionic site
(PAS) at the entrance of gorge. A π-π stacking interaction
was found between Trp279 and the phenyl ring of the com-
pound. Tyr121 establishes a bifurcated hydrogen bonding
interaction with the oxygen atoms of the pyrazolone ring
and ethyl ester (Figure 9). Another hydrophobic interaction
was established between PAS residue Tyr334 and the
pyrazolone ring. The important anionic site residue, Trp84,
formed a CH-π interaction with the methyl group of ester.
Computed docking score and binding affinity of the
FIGURE 5 Theoretical and experimental FTIR spectra of RZ3

DANISH ET AL.
5
FIGURE 7 HOMO of RZ1 (a), RZ2 (c), RZ3 (e), and RZ4 (g); LUMO of RZ1 (b), RZ2 (d), RZ3 (f), and RZ3 (h)
FIGURE 8 Energy diagram of HOMO and LUMO; RZ1 (a), RZ2 (b), RZ3 (c), and RZ4 (d)

6
DANISH ET AL.
TABLE 4 Enzyme inhibition results of the products
a
a
a
Protease
AChE
% Age
BChE
Code
RZ1
RZ2
RZ3
RZ4
% Age
IC50 μg/mL
Not calculated
211 ± 3
IC50 μg/mL
128 ± 2
% Age
IC50 μg/mL
Not calculated
Not calculated
209 ± 3
20.60 ± 0.9
54.55 ± 0.6
32.27 ± 0.4
34.29 ± 0.8
85.50 ± 1.2
23.55 ± 0.9
32.24 ± 0.8
29.71 ± 0.8
23.81 ± 0.9
26.52 ± 0.9
52.55 ± 0.6
17.07 ± 0.3
Not calculated
Not calculated
Not calculated
Not calculated
Not calculated
Not calculated
a
1
00 μL (5 mg/mL).
FIGURE 9 Depiction of the best ranked docking poses of the compound RZ3. a) A close-up depiction of the ribbon diagram of the docking pose of
compound RZ3 in the binding site of 1EVE; (b) 2D interactions of RZ3
compound is −10.4829 and −6.7448 kcal/mol, respectively.
Alam et al. reported closeness between experimental and
theoretical results of biological testing of some synthesized
separated by filtration and recrystallized by aqueous etha-
nol (Scheme 1).
[
22]
compounds.
7
.2 | characterization
Docking studies were also carried out to correlate the
BChE inhibition activity. BChE from human with PDB
Code 1P0I was selected for this purpose. The binding mode
of compound into the pocket of 1P0I is shown in Figure 10.
Important hydrogen bonding interactions were found
between the carbonyl oxygen of ethyl ester and oxyanion
hole residues Gly116 and Gly117. Glu197 forms a hydrogen
bond with carbamate NH. A π-π stacking interaction was
found between conserved residue Trp82 and the phenyl ring
of the compound. The computed docking score and the bind-
ing affinity of the compound is −9.9104 and
The characterization of the synthesized compounds was
done with FTIR and single crystal XRD analysis.
7.3 | Biological evaluation
Enzyme inhibition activity was determined for proteases,
acetylcholinesterase, and butyrylcholinesterase.
7
.4 | Protease inhibition study
−
6.0296 kcal/mol, respectively.
Protease inhibition activity was determined according to the
reported method of Shahwar et al. with some modifica-
[
23]
tions.
A volume of 100 μL of the sample solution was
7
| EXPERIMENTAL
taken, then 100 μL of the protease enzyme was added in
each test tube, shaken well, and allowed to stand for 5 min.
Afterward, 0.5 mL of the tris buffer solution was added sep-
arately, mixed them, and then 50 μL of the substrate was
added in each test tube. Then, all the solutions were incu-
7
.1 | Synthesis of ethyl carbamates
The target compounds were synthesized through reported
methods by dissolving substituted amine (1.4 mmol) in
dimethyl formamide and followed by addition of anhydrous
potassium carbonate (9.6 mmole) with continuous stirring
ꢀ
bated for 60 min at 37 C and absorbance was measured at
4
00 nm using a ultraviolet (UV)/visible spectrophotometer.
for 30–40 min. Dropwise addition of ethyl chloroacetate
Protease inhibition percentage values were calculated by the
following formula:
ꢀ
(0.23 mL) was carried out within 3 min and heated at 50 C
[
7]
for 3–4 hr. Reaction progress was monitored by thin
layer chromatography using the n-hexane and ethyl acetate
mixture in 3:2 ratios as the mobile phase. On completion,
the reaction mixture was transferred to ice cold water. The
product was formed as solid precipitates that were
Percentage Inhibitionð%Þ
Absorbance of blank−absorbance of sample
=
× 100
Absorbance of blank

DANISH ET AL.
7
FIGURE 10 Depiction of the best ranked docking poses of the compound RZ3. a) A close-up depiction of the ribbon diagram of the docking pose of
compound RZ3 in the binding site of 1P0I; (b) 2D interactions of RZ3
O
HN
O
CH3
RZ4
NH2
O
H3C
O
CH
NH
N
3
O
NH
O
CH
3
N
NH2
Cl
CH3
CH3
OCH3
OCH3
N
O
NH2
N
CH3
O
O
O
RZ1
NH2
CH
RZ3
3
N
H3C
CH3
O
H
C
3
N
NH
O
CH
3
H
C
3
RZ2
SCHEME 1 Synthetic scheme of targeted compounds
7
.5 | AChE/BChE inhibition study
then 100 μL of the enzyme was added in each test tube, shaken
well, and allowed to stand for 5 min. Afterward, 0.5 mL of the
phosphate buffer (NaH PO with pH 7.5) was added sepa-
AChE and BChE inhibition activity was determined according
to the reported method of Abbasi et al with some modifica-
tion. A volume of 100 μL of the sample solution was taken,
2
4
[24]
rately, then shaken, and 50 μL of 5,5'-Dithiobis-(2-

8
DANISH ET AL.
Nitrobenzoic Acid) (DTNB) and 50 μL of the substrate were
ACKNOWLEDGMENT
added in each test tube. Then, all the solutions were incubated
for 1 hr at 37 C and absorbance was measured at 400 nm using
a UV/visible spectrophotometer. Percentage inhibition values
were calculated using the following formula:
Dr Umer Rashid is thankful to Higher Education Commis-
sion, Pakistan for financial support for the purchase of MOE
license under HEC-NRPU project 5291/Federal/NRPU/
R&D/HEC/2016.
ꢀ
Percentage inhibition ð%Þ
absorbance of blank−absorbance of sample
ORCID
=
× 100
Absorbance of blank
Muhammad Danish https://orcid.org/0000-0001-6361-
4
016
Muhammad A. Raza https://orcid.org/0000-0002-6723-
637
7.6 | Docking studies
2
Docking experiments were performed via molecular operating
environment (MOE) docking program version 2016.08. Crystal
structures of AChE and BChE with PDB codes 1EVE and
1P0I, respectively, were selected for these studies. All the water
REFERENCES
molecules were removed from the protein structure, then
hydrogen atoms were added and energy optimization was car-
ried out using default force field. The three-dimensional
[1] O. Kreye, H. Mutlu, M. A. R. Meier, Green Chem. 2013, 15, 1431.
[
[
[
[
2] P. Adams, F. A. Baron, Chem. Rev. 1965, 65, 567.
3] D. P. N. Sutchell, R. S. Satchell, Chem. Soc. Rev. 1975, 4, 231.
4] A. J. Ager, I. Prakash, D. R. Schaad, Chem. Rev. 1996, 96, 835.
5] S. Inoue, Y. Yokoo, Chem. Soc. Jpn. 1972, 45, 3651.
(3D) structures of compounds were modeled through the
builder program implemented in MOE. The geometrical param-
eters for 3D structures of the compounds were optimized, and
partial charges were calculated before docking. The 3D proton-
ation of the downloaded enzymes was done and energy mini-
mization of the retrieved protein molecule was carried out
using default parameters of the MOE energy minimization
algorithm (gradient: 0.05, Force Field: MMFF94X). The
resulting model was subjected to systematic conformational
search at default parameters with a RMS gradient of
[6] M. L. Gullino, Plant Dis. 2010, 94, 1076.
[
[
7] F. E. Adelowo, I. A. Ojo, O. S. Amuda, Adv. Biol. Chem. 2011, 1, 122.
8] S. A. Nami, A. O. Husain, I. Ullah, Spectrochim. Acta Part A 2014,
118, 380.
[9] T. Dantoine, S. Auriacombe, M. Sarazin, H. Becker, J. J. Pere, I. Bourdeix,
Int. J. Clin. Pract. 2006, 60, 110.
10] K. G. Arun, B. Margherita, J. Med. Chem. 2015, 58, 2895.
11] Population Health Branch, Population Health Data and Statistics, Queens-
land Government, Fact Sheet 2002.
12] T. Narasaiah, D. S. Rao, S. Rasheed, G. Madhava, D. Srinivasulu,
B. P. Naidu, C. N. Raju, Pharm. Lett. 2012, 4, 854.
13] T. Ito, T. Uchida, K. Tanabe, H. Yamada, S. Nishimoto, J. Photochem.
Photobiol. 2011, 219, 115.
[
[
[
[
0.01 kcal/mol using Site Finder. For 1EVE, the active site of
the prepared enzyme was defined as the residues within 10 Å
of the reference ligand (donepezil). However, for 1P0I (BChE),
the enzyme was searched for its active site and dummy atoms
were created using alpha spheres as centroids. A key trypto-
phan residue in AChE, Trp84 (TcAChE numbering), is con-
served in BChE (Trp82). The backbone and residues were kept
fixed and the energy minimization was performed. The lowest
energy minimized pose was used for further analysis. Ligand-
interaction module of MOE was used to calculate the 2D
ligand-enzyme interactions. The view of the docking results
and analysis of their surface with graphical representations
were done using MOE and a discovery studio visualizer.
[14] K. F. Ansari, C. Lal, Eur. J. Med. Chem. 2009, 44, 4028.
[
[
15] V. L. R. Sana, V. R. Katla, S. Chennamsetty, A. Shaik, N. R. Chamarthi,
Der Pharm. Sin. 2013, 4, 10.
16] M. Danish, M. N. Tahir, U. Anwar, M. A. Raza, Acta Crystallogr. Sect. E
2015, 71(Pt 4), o267.
[
[
17] M. Sahin, G. Gece, F. Karci, S. Bilgic, J. Appl. Electrochim. 2008, 38, 809.
18] A. A. H. Kadhum, A. A. Al-Amiery, A. Y. Musa, A. Mohamad, Int.
J. Mol. Sci. 2011, 12, 5747.
[19] P. K. Chattaraj, B. Maiti, J. Am. Chem. Soc. 2003, 125, 2705.
[
20] A. A. H. Kadhum, A. A. Al-Amiery, M. Shikara, A. Mohamad, Int.
J. Phys. Sci. 2011, 6, 6692.
[
21] S. Liu, J. Chem. Sci. 2005, 117, 477.
[
22] M. Alam, M. J. Alam, A. A. S. Nami, L. Dong-Ung, A. Mohammad,
S. Ahmad, J. Mol. Struct. 2016, 1108, 411.
[
[
23] D. Shahwar, M. A. Raza, A. Rehman, J. Sci. Food Agric. 2013, 93, 1420.
24] M. A. Abbasi, M. Ilyas, A. Rehmana, A. Sonia, D. Shahwara, M. A. Raza,
K. M. Khan, M. Ashraf, I. Afzal, N. Ambreen, Sci. Iran. 2012, 19, 1580.
25] A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
[
[
7.7 | Computational studies
26] C. Lee, W. Yang, G. R. Parr, Phys. Rev B 1988, 37, 785.
Geometry optimization was carried out for all synthesized
compounds having nitrogen, oxygen, and carbon in their
structure. We used the hybrid Becke 3-parameter exchange
functional together with the Lee-Yang-Parr correlation func-
tional (B3LYP) in density functional theory calculations.
The 6–31g basis set was used for C, H, N, and oxygen
How to cite this article: Danish M, Raza MA,
Anwar U, Rashid U, Ahmed Z. Differential functional
theory and molecular docking studies of newly syn-
thesized carbamates. J Chin Chem Soc. 2019;1–8.
https://doi.org/10.1002/jccs.201800068
[
25,26]
atoms.
The DFT calculations were carried out using
Gaussian 09 software. The initial geometries of RZ3 were
obtained from the crystallographic data.