Journal : Solubility of Paracetamol in Pure Solvents

ROGER, C. A. (1999). Solubility of Paracetamol in Pure Solvents. Journal of Chemical Engineering

Data,44, 1391-1395. doi:10.1021

In this journal, solubility of Paracetamol (PA) is being explained thoroughly through a well
conducted experiment to test the solubility of PA in the pure solvents also in the organic solvents. Pure
solvents are the solvent that a solute can be dissolved in it completely while organic solvents are carbon-
based solvents which contains carbon atom in their molecule structure. Water is one of the examples of
a pure solvents, as for organic solvents, the examples are ethanol, methanol, propanol and butanol.
Paracetamol structure which contain few functional groups which are the methyl group, alcohol group,
amide group as well as the most important structure, the benzene ring give out different solubility effect
and reactions towards different solvents depending on the properties of each functional groups on PA
structure.

Paracetamol is being dissolved in a total of 25 solvents consists of both pure solvents and
organic solvents. In this aspect, properties of paracetamol is being figured out in the solubility aspect
while related to organic chemistry as PA itself is an organic compound which few functional groups
which have an organic compound properties.

The journal content indicates that solubility of paracetamol increasing in the increasing
temperature ranges from 5 to 30 °C. Paracetamol has a very low stability in nonpolar hydrocarbons and
chlorinated hydrocarbons. It is also proven that solubility of paracetamol in n-alcohol decreases
monotically with a decrease in polarity of the solvents. Moreover, the solubility also decreases as the
length of carbon chains of ketone increases. Solubility in water is much lower than in polar solvents
such as alcohols. Paracetamol is not very comfortable in water environment. Alcohol group and the
amide group is the polar part of the PA molecular structure which may likely form hydrogen bonds with
the water molecules but the aromatic benzene ring and the methyl group of PA affects the surrounding
water molecules to the extent of net result of a low solubility in water.

Therefore, one of the properties of fever medication, paracetamol is most likely has a lower
solubility in pure solvent (water) compared to the organic solvents. In human body, as PA is being
consumed, it is being absorbed by gastrointestinal tract (GI) and being metabolised by the liver through
glucuronidation, sulfation and N-hydroxylation and dehydration, then glutathione conjugation. It shows
that PA is consumable and able to dissolve in the body as a safe organic compound.
Journal : . Investigation of quantum-chemical properties of Paracetamol

Syrovaya, A. 0., Levashova, O. L., & Andreeva, S. V. (2015). Journal of Chemical and Pharmaceutical
Research. Investigation of quantum-chemical properties of Paracetamol, 7, 0975-7384 , 307-311.
Retrieved June 9 , 2017.

Commonly known, as a chemical compound, molecular activity is very crucial as the first thing
to be observed to determine what reaction that happens throughout the chemical compound so does
Paracetamol. In this journal, quantum – chemical properties of PA is being studied thoroughly which is
very important in understanding the mechanism of activity at the molecular level. Thus, geometric
optimization of PA molecules is performed by PM3 method, Polak-Ribiere algorithm. Every molecular
activity of paracetamol is studied and finally findings on the journals are the distance between the atoms,
total charge density and the molecular orbital of paracetamol molecules.

Based on the journal, the regions with high electron density are on the oxygen atoms at the
phenyl and oxogroups also the nitrogen atom. In contrast, electron are much fewer at the carbon atoms
of the phenol ring that directly bonded to the oxygen and nitrogen atoms while on the hydrogen atoms
reside all the positive charges. These charges determined the net charge of paracetamol molecules that
later affect any reactions of the paracetamol.

Defining the activity of the chemical reaction of a chemical compound, dipole moment of the
molecule must be determined. It is observed that paracetamol dipole moment is 2,624 D which is a low
value of a dipole moment. The lower the dipole moment value, the lower the solubility of a chemical
compound. Thus, having a low value of the dipole moment, paracetamol is then rectified as a compound
with a lower solubility.

Observing the electron density or the electron clouds of paracetamol, electron density of
paracetamol is higher at oxygen, nitrogen atom and the C2, C4 and C11 atoms of paracetamol molecule.
Paracetamol are able to form hydrogen bonds with electro neutral atom of other molecules as hydrogen
atoms of paracetamol are directly bonded to oxygen and nitrogen atoms.

Reactivity of paracetamol molecules is determined by the localization of HOMO (ionization

energy) LUMO (electron affinity) and paracetamol is concluded as a soft reagent as it react actively
with soft reagent due to cysteine residues in protein and glutathione. With all these facts, paracetamol
is a mild and safe medicine to be consumed while referring to all the chemical compound characteristics
of paracetamol. It would not cause any harm if it is consumed at a right amount unless overdosed would
cause hepatic problem.