Journal of Physical Chemistry and Functional Materials Volume 3, Issue 1 (2020) 9-13

Journal of Physical Chemistry and Functional Materials

Home Page of Journal: https://dergipark.org.tr/jphcfum

Computational Study on Paracetamol Drug

Lana O. Ahmed a,c and Rebaz A. Omer b,d

a
Department of physics, Faculty of Science & Health, Koya University, Koya KOY45, Kurdistan Region – F.R. Iraq.
b
Department of Chemistry, Faculty of Science & Health, Koya University, Koya KOY45, Kurdistan Region – F.R. Iraq.
c
Firat University, Faculty of Science, Department of Physics, 23169 Elazig, Turkey.
d
Firat University, Faculty of Science, Department of Chemistry, 23169 Elazig, Turkey.

* Corresponding author: E-mail: [email protected]

ABSTRACT ARTICLE INFO

Paracetamol is a drug used to relieve pain and fever. It is also known as Keywords:
acetaminophen and APAP. It's typically used to relieve mild to moderate pain. Paracetamol,
Gaussian software programs 09 conducted a theoretical study to find Paracetamol Density functional theory,
Frontier molecular orbitals,
reactivity. Density Functional Theory (DFT) on the best set 6-31++G using to
Electrostatic potential
determine geometrical structure and energy bandgap. Frontier molecular orbitals
estimated to find the properties of the molecule. Atomic charge distribution has Received: 11-May-2020,
conformed the charge on each atom in the molecular structure. Molecular electrostatic Accepted: 22-May-2020
ISSN: 2651-3080
potential evolution for the paracetamol structure and show that structures with high
electronegativity.

dose of 4 g a day allows a large number of tablets to be taken

1. Introduction
[3]. Paracetamol is a drug which is small in molecular mass
Figure 1. It is a weak acid (pKa 9.7), and is therefore
Two official names of the same chemical compound
essentially unionized at pH values [4]. Paracetamol is
derived from its chemical name are paracetamol (an
marginal to be bound to plasma proteins [5] and with a
international name used in Europe) and acetaminophen (an
delivery capacity of around 50 L following intravenous
international name used in the USA): N-acetyl-para-
dosing. It is assumed that paracetamol is transmitted
aminophenol [1]. Paracetamol (acetaminophen) has one of
without binding to tissues in the body [6]. This lack of
the most commonly used non-prescription medications in
binding means that the concentrations of paracetamol in in
the world, from cradle to grave. It's available and it's cheap.
vitro studies can be directly compared with them in vivo
Paracetamol is tolerated better than non-steroidal anti-
concentrations without tissue absorption or protein binding
inflammatory drugs (NSAIDs), but it may be less effective.
corrections. Chemically, paracetamol is a phenol, which is
A decrease in aspirin use during the 1980's because of its
readily oxidized like other phenols. Usage paracetamol for
connection with Reye's syndrome and allowed used
rheumatic conditions Paracetamol lacks anti-inflammatory
paracetamol for children, to become the antipyretic and
action. It's less toxic than aspirin, moreover, and does not
analgesic [2] and it's also the antipyretic and analgesic
cause anemia and liver harm, often caused by continuous
quality to all age categories. While a safe and effective drug,
use acetanilide and acetphenetidines. Paracetamol is used to
paracetamol doses are uncomfortably high and a maximum
treat fever reduction, muscle and joint recovery & pain
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 Ahmed et al. Journal of Physical Chemistry and Functional Materials
relief, symptoms of cold and flu relief, common headache 3. Result and Discussion
relief [7]. Paracetamol potentiates the effects of 3.1. Energy band gaps
acenocoumarol and warfarin on anticoagulants, with
increased risk of bleeding. The possible processes are The first phase of computational research is to use
inhibition of oral anticoagulant metabolism; however, more Gaussian software 09 to find the optimized molecular
recent data have not confirmed such hypotheses [7, 8]. structure. DFT on the base set 6-31++G was used for
optimized Paracetamol molecular structure with atomic
numbering and orientation of the molecule was determined
in Figure 2. Certain geometrical parameters for the
molecular were shown in a table 1. The bond length for C-
C in a ring equal to 1.3819 Å and for the C=C in the ring
equal to 1.4336 Å, but the bond length for C-C in a chine
equal to 1.5084 Å. Moreover, the bond length for C-H in a
plane equal to 1.0870 Å, and for out of the plane (CH3)
equal to 1.0965 Å but for O-H equal to 0.9770 Å. The bond
length for C-N, C-O and C=O equal to 1.3558, 1.3839 and
Figure 1. N-(4-hydroxyphenyl) acetamide (Paracetamol) 1.2586 Å respectively. The angle between the atoms of
paracetamol structure was very high this is conformed the
2. Computational methods molecule is highly reactive.

All other computations analysis was carried out using

GAUSSIAN 09W [9] and with a personal computer.
Hartree-Fock and Hybrid approach; B3LYP is implemented
using the 6-31++G base set. Becke's three parameter hybrid
model with the Lee-Yang-Parr correlation model (B3LYP)
combined in DFT methods [10, 11]. Becke's three exact
exchange-function parameters (B3) Combined with Lee,
Yang and Parr (LYP) gradient-corrected correlation
functional, predicted the most advantageous effects for
slightly more detailed molecules on molecular dynamics
and vibrational frequencies. The B3LYP (DFT) method at
6-31++G basis set has been chosen for the study Figure 2. Paracetamol structure with energy bandgap
Paracetamol molecule.
Table 1. Some geometrical parameters for paracetamol drug.
Sy. NA NB NC Bond Angle (Å) Dihedral
C1
C2 1 1.381973
C3 2 1 1.433679 121.2945
C4 3 2 1 1.435722 117.9936 -0.23941
C5 4 3 2 1.385728 120.4384 0.199876
C6 1 2 3 1.408956 119.3596 0.123036
H7 1 2 3 1.083558 121.8296 -179.793
H8 2 1 6 1.083924 121.2857 -179.977
H9 4 3 2 1.082444 119.2227 178.6958
H10 5 4 3 1.087071 120.0119 179.6904
O11 6 1 2 1.383965 116.5244 -179.979
N12 3 2 1 1.355847 116.9778 -178.382
C13 12 3 2 1.391021 124.9064 -169.814
C14 13 12 3 1.508425 114.3045 -148.014

3.1. Frontier molecular orbitals and to identify other types of reactions [12]. Reactivity of
the molecule is measured by the energy values of the lowest
Frontier Molecular Orbitals (FMOs) have been used unoccupied molecular orbital (LUMO) and the highest
to determine most reactive site in the conjugated system, occupied molecular orbital (HOMO) and its energy

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 Ahmed et al. Journal of Physical Chemistry and Functional Materials
difference (ΔE) [13]. Figure 3. Show HOMO and LOMO LOMO energy levels for present structure emerged after
were calculated using level B3LYP/6-31++G (d, p) for being fully optimized and finding from MOs which is equal
paracetamol drugs. The energy bandgap (HOMO – LUMO) to -0.02455 eV. The result of energy bandgap shows that
reflects the lowest electronic energy prerequisite for moving paracetamol has lower energy bandgap, it is more reactive
electron from π–π *. For paracetamol molecule the average structures. Chemical hardness, electronegativity, electronic
electronic energy (HOMO) expressed at 39th is measured at chemical potential and electro-philicity index were
-0.24846 eV and lowest electronic energy (LOMO) shown calculated, all data show in a Table 2. and calculated using
at 40th is measured as -0.22348 eV. The energy bandgaps DFT at the basis set 6-31++G.
that were determined by the difference between HOMO and

Figure 3. Frontier surfaces for Pracetmol A) HOMO and B) LUMO computed by B3LYP/6-31++G(d,p) level.

Table 2. Calculated energies, dipole moments (D), frontier orbital energies and description of chemical reactivity of the
compound.

In a Basis Set B3LYP/6- Equations Result of Paracetamol

31++G(d,p)
E Total -514.70464803 -514.70464803
E HOMO -0.24846 -0.24846
E LOMO -0.22348 -0.22348
Energy bandgaps HOMO - LOMO -0.02455
Chemical hardness (η) η = (ELUMO 0.01249
− EHOMO)/2
Electronegativity χ = - (EHOMO 0.23417
(χ) + ELUMO) /2
Chemical potential (μ) μ = (EHOMO -0.23597
+ ELUMO)/2
Electro-philicity index ω = μ2/2η 356.92307
Dipole moment 3.6449 3.6449

3.1. Mulliken charge distribution the atomic charges distribution on the oxygen atoms
indicate that the structural component has potentially
Table 3. demonstrates atomic charges distribution interacted with weak electronic molecules. While nitrogen
which was calculated by Mulliken theory. The calculations atoms have interacted with a more electrophilic species
were carefully developed on the DFT methods and 6- such radicals. Paracetamol contain two oxygen have higher
31++G basis set. In paracetamol molecule these values of negative charge and effected on the neighbor's carbon
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 Ahmed et al. Journal of Physical Chemistry and Functional Materials
atoms, whereas only have one nitrogen atoms. According to
the Mulliken paracetamol is more electrophilic and react
with more nucleophilic species.

Table 3. Mulliken atomic charges distribution

Atom Charge (Coulomb)

C1 0.130781
C2 -0.18917
C3 -0.8307
C4 0.476433
C5 0.088883
C6 -0.46809
H7 0.258555 Figure 4. Electrostatic Potential Map
H8 0.263639
H9 0.269918 4. Conclusion
H10 0.219188
O11 -0.57297 DFT methods at B3LYP/6-31++G basis set was used
N12 -0.02286 for study of paracetamol and to determine the reactivity of
C13 0.365378 the molecule. The geometrical structure for paracetamol is
C14 -0.69745 reactive with higher bond length. The bond angle and bond
O15 -0.44489 length of the structure was show very reactivity of the
H16 0.443492 molecule. Calculating the energy, dipole moments and
H17 0.237654 frontier energy were denoted the molecule's properties
H18 0.253053 including the reactivity. The distribution of atomic charges
and the molecular electrostatic potential (MEP) is
H19 0.219153
determined to look at the areas of higher electron density as
3.2. Molecular Electrostatic Potential (MEP) possible sites of interaction, such as nitrogen and oxygen.
The collectivity data indicated that the paracetamol
Electrostatic potential map surface shows the charge structure was very reactive.
distribution on the atoms in a molecule. The graph diagram
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