J. Chem Soc. Nigeria, Vol. 44, No.

1, pp 107 -114 [2019]

SYNTHESIS, CHARACTERIZATION AND COMPLEXATION OF Cr(III) ION USING

CHLOROQUINE DIPHOSPHATE DRUG

I. E. Otuokere1*, L. O. Okpara1, K. C. Amadi1, N. Ikpo2, G.U. Okafor3 and F.C. Nwadire1

1
Department of Chemistry, Michael Okpara University of Agriculture, Umudike, Nigeria
2
Department of Chemistry, University of Alberta, Canada
3
Department of Chemistry, Enugu State University of Science and Technology
(*Corresponding author’s: ifeanyiotuokere@gmail.com, +2347065297631)
Received 15 November 2018; accepted 24 December 2018, published online 17 January 2019

Abstract
Chloroquine is a member of the drug class 4-aminoquinoline used for the prevention and treatment
of malaria in areas where malaria is known to be sensitive to its effects. It works against the asexual form
of malaria inside the red blood cell. Cr (III) complex of chloroquine was synthesized by reaction of
chloroquine phosphate with chromium (III) chloride. The chromium complex was characterized based on
UV, IR, Mass and 1H NMR Spectroscopy. The UV spectrum of the ligand showed intra charge transfer
which were assigned to the chromophores present in the ligand, while that of the complex suggested intra
ligand charge transfer (ILCT), ligand to metal charge transfer (LMCT), and d-d transition. The IR spectra
of the complex showed the involvement of amine and imine group in coordination to the metals. This
shows that chloroquine acted as a bidentate ligand. 1H NMR Spectra of the complex further showed the
involvement of the amine group in coordination to the metal complex. The results showed that
chloroquine has the ability to sequestrate Cr ion from solution. We recommend the use of chloroquine in
heavy metal extraction and chelation therapy.

Keywords: Chloroquine, spectra, coordination, chromium

Introduction techniques that may be classified under the

Trace amounts of several metals in the body
are essential in the metabolic activities of the
body. This is due to the fact that many enzymes
depend on these metal ions. Increasing
industrialization and technological expansions
has increased metal pollution in the atmosphere
which has laid down some serious toxic effects.
Removal of unwanted metal ions from the body
can be realized by using appropriate chelating
agents. Chelating agents deactivate either the
carcinogenic metal or the enzymes necessary for
the rapid growth of both healthy and malignant
cells [1-4].The use of metals to restore the
normal healthy physiology of the body either by
direct administration of essential metals, or by
chelating out excess or toxic metals, or using
them as carriers for targeted drug delivery, or for
tagging biomolecules for diagnostics, are all
general heading of metallopharmacology [5-7].
Exposure to heavy metals or metal overload
from various sources may cause metal toxicity in
the body, which can interfere with the functions
of various body organs like the central nervous
system (CNS), liver and kidneys. Chelating
ligands have the effect of mobilizing metals
from tissues and maintaining the chelate moiety
during circulation to the kidneys for excretion in
the urine, and to the liver for excretion in the
bile [8-10]. Using ion specific chelating agents
to take away metal overloads in the body is a
new developing science of bioinorganic
chemistry [11]. Recently, the aim of the
bioinorganic chemists towards heterocyclic
ligands and their metal complexes is to study
their pharmacology as the main target of
research [12].

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Biological activities such as antibacterial,
antifungal, antitumor and antiviral activities are
exhibited by nitrogen-containing organic
compounds and their metal complexes.
Transition metal centers are attractive moieties
for reversible recognition of nucleic acids
because they exhibit well-defined coordination
geometries [13-15]. They also show distinctive
electrochemical properties thereby increasing
the functionality of the binding agents [16-17].
Several efforts have been made to detoxify the
effect of metals once they are administered in
the human body. Chelation is considered the
best method used so far. Medicinal treatment of
acute and chronic metal toxicity is provided by
chelating agents. Chelation is one of the
chemical functions that take place in the bodies
of almost all living organisms. It is a process by
which plants and animals utilize inorganic
metals [18-24].
An ideal chelator should have high solubility
in water, resistance to biotransformation, ability
to reach the sites of metal storage, retain
chelating ability at the pH of body fluids and the
property of forming metal complexes that are
less toxic than the free metal ion [25-30].
Chloroquine is a medication used to prevent
and treat malaria in areas where malaria is
known to be sensitive to its effect. Certain types
of malaria, resistant strains, and complicated
cases typically require different or additional
medication. Chelation therapy is approaching a
turning point that should lead to rapid progress
and regain public confidence. The use of
Chloroquine as a chelating agent is scarcely
reported in literature, so the present study
communicates the complexation behaviour of
chloroquine towards Cr (III) ion.
Materials and methods
All chemicals and reagents used in the
experimental work were of analytical grade.
Pure chloroquine diphosphate drug,
(CrCl3.6H2O) was imported from E. Merck
Company, Germany. Melting point of the
complex was determined using MPA160 melting
point apparatus. Infrared spectra were collected
on Perkin Elmer Paragon 1000 FT-IR
spectrophotometer (spectrum BX) equipped with
cesium iodide window (4000-350 cm-1) in KBr
pellets. The UV-Visible spectra were obtained
on a Perkin Elmer spectrometer (200-800 nm)
using DMSO as solvent. The 1H Nuclear
Magnetic Resonance (NMR) spectra were
obtained using 499.800 MHz MR NMR
spectrometer from Agilent Technologies
Synthesis of sulfathiazole-chromium complex
The complex was prepared following a reported
procedure [31]. Cr (III) salt solutions was
prepared by dissolving 6.336 g (0.04mol)
CrCl3.6H2O in 25 ml ethanol. The solution of the
metal salt was added slowly with stirring in a
separate 20 ml of ethanol solution of 12.79 g of
chloroquine diphosphate (0.04mol) at room
temperature maintaining the pH between 6.0-6.5
by adding 10% methanolic ammonia solution.
On refluxing the mixtures for 2 hours and
cooling, the complex separated out. The
complex was washed well with ethanol,
recrystallized, filtered and finally dried in
vacuum and weighed.
Results and discussion
Physical Properties
The dark green colour of the metal complex
suggests the formation of complex because
transition metal complexes are coloured. The
colour of [Cr(CQ)] complex suggests d-d
transition. The change in melting point from
203oC (chloroquine) to 230oC [Cr(CQ)] also
indicates the formation of a new complex. Melting
points of the complex as compared to chloroquine
suggests that new products were formed. The
melting point of [Cr(CQ)] was higher than that of
chloroquine. Research publications has shown that
complexes have higher melting points than the
corresponding free ligand [34].
Infrared spectra of chloroquine and [Cr(CQ)]
are shown in Figures 1 and 2 respectively.
The infrared spectrum of chloroquine was
compared with that of the metal complexes. In the
spectrum of chloroquine (Fig. 1), the vibrational
frequency at 3260 is assigned N-H
stretching. In the spectrum of the [Cr(CQ)]
complex (Fig. 2), the vibrational frequency shifted
to 3110.29 . This shift suggest that
coordination occurred through the N-H functional
group because increase in electron density will
increase the NH bond length and consequently
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 J. Chem Soc. Nigeria, Vol. 44, No. 1, pp 107 -114 [2019]

slow down the vibrational frequency [32]. In the of the complex shifted to 3.7 ppm (Fig. 6). This
infrared spectrum of chloroquine, the C=N shift suggests the involvement of N-H functional
functionality appeared at 1120 , while in the group in complexation. Also, in the chloroquine
metal complex it shifted to 1066.36 [Cr- spectrum, CH3, CH2, and CH appeared as
CQ]. These shifts suggest that coordination multiplets between 0.83-1.33 ppm. These
occurred through the C=N functional group protons also appeared in the complex at 0.83-
because increase in electron density will increase 1.33, this suggests that there was no
the C-N bond length and consequently slows down coordination through these sites. Again in the
the vibrational frequency [32]. The aromatic C-C, proton NMR of the chloroquine, -
the aromatic C-H, the aliphatic C-H, the C-Cl CHCH2CH2CH2-, -CH3-NCH2CH2-, -CH3CH-
vibrational frequencies of the [Cr(CQ)] remained ,aromatic protons appeared at 1.66 ppm (triplet),
unchanged which suggests that these 2.33-2.67 ppm (multiplets), 3.66 ppm (quartet)
functionalities did not participate in coordination. and 6.4-8.43 ppm (multiplets). These chemical
The UV/Vis absorption bands of chloroquine shifts remained unchanged in the proton NMR
and [Cr(CQ)] complex have been shown in of the metal complex. This suggests that
Figures 3 and 4 respectively. The ultraviolet coordination did not occur through these
spectrum of chloroquine in neutral methanol functionalities.
solution in the region of 200-400 nm exhibits Based on the UV, IR and 1H NMR spectra, the
maxima at 218, 253 and 328 nm [33] (Fig. 3). structures (Fig. 7) of the metal complex have been
These transition have been assigned intra ligand successfully proposed.
charge transfer (ILCT). The chromophores that
may exhibit these transitions are C=N and C=C.
In [Cr(CQ)] complex, the absorption band seen
between 220-280 nm (Fig. 4) have been
assigned intra ligand charge transfer (ILCT).
The bands at 300-360 nm have been assigned
ligand to metal charge transfer (LMCT) while
the band at 640 nm have been assigned d-d
transition. The ligand to metal charge transfer
(LMCT) and the d-d transitions suggest that
complexation occurred.
The 1H-NMR spectra of chloroquine and
[Cr(CQ)] complex have been presented in
Figures 5 and 6 respectively. The proton NMR
of chloroquine was compared with the proton
NMR of [Cr(CQ)] complex. In the proton NMR
of chloroquine (Fig. 5), the N-H proton appeared
as a doublet at 5.64 ppm, while the N-H proton

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J. Chem Soc. Nigeria, Vol. 44, No. 1, pp 107 -114 [2019]

Fig. 1: Infrared spectrum of chloroquine in KBr disc [33]

Fig.2: FT-IR spectrum of [Cr(CQ)]

Fig. 3: UV spectrum of chloroquine, Source [33]

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J. Chem Soc. Nigeria, Vol. 44, No. 1, pp 107 -114 [2019]

Fig. 4: UV/Vis spectrum of [Cr(CQ)] complex

Fig. 5: 1H NMR spectrum of chloroquine, Source [33]

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Fig. 6: 1H NMR spectrum of [Cr(CQ)] complex

H3C Acknowledgement
CH3 The authors wishes to appreciate the support
of the Department of Chemistry, University of
H3C N Alberta, Canada
NH

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