Synthesis, Spectral, Chromatographic and Antimicrobial
Studies of Transition Metal Complexes of Chromium (III) and Cobalt (II) Ions with
Alprazolam Drug
Chandra Kant Bhardwaj1*, Naveen Chandra
Talniya2, Abhilasha Mishra3,
Varun Pratap Singh4, Sana Rafi5
1,2Department of Chemistry, Graphic Era Hill
University, Dehradun, Uttarakhand, 248002 India.
3Department of Chemistry, Graphic Era
(Deemed to be University), Dehradun, Uttarakhand, 248002 India.
4Department Mechanical Cluster, School of Advanced
Engineering, UPES, Dehradun,
Uttarakhand, 248007, India.
5Research Scholar, Department of Geography,
Faculty of Natural Sciences,
Jamia Millia Islamia, New Delhi.
*Corresponding Author E-mail:
drckb2012@gmail.com
ABSTRACT:
In this research, Cr(III) and Cobalt (II) complexes
were synthesized by a chemical reaction between metallic nitrate and ligand
alprazolam and metal complexes with the expected formulas ‘‘[(L)M(NO3)3],
[(L) M(NO3)2]’’in this formula M is Cr (III) and Co (II)
accordingly and L is Alprazolam ligand. The characterization of complexes has
been done by elemental analysis, IR studies, and thin-layer chromatography.
Spectral studies of metal complexes of Cr (III) and Cobalt (II) depict the
tridentate and bidentate nature with the drug alprazolam ligand. The present
research showed that the antimicrobial activity of the Co (II) metal complex is
greater than the Cr (III) metal complex. Metal complexes showed higher
antimicrobial activity in comparison to the used ligand (Alprazolam).
KEYWORDS: Antimicrobial studies, Metal complexes, Benzodiazepine
drug, Alprazolam ligand and IR studies.
INTRODUCTION:
In the present study, Alprazolam is used as a ligand.
Alprazolam belongs to the benzodiazepine family and these drugs are used for
anxiety disorders acts on CNS (central nervous system) and showed hypnotic
properties1,2. Benzodiazepine is formed by the fusion of
benzene and diazepine ring and it contains two nitrogen atoms at position one
and four. Metal complexes of benzodiazepine possess anti-cancerous and
biological activity3,4.
In the complex formation of metallic ions,
coordinating sites of metal ions have been fulfilled by ligand molecules, and
the remaining sites are accomplished by the solvent molecule5. In
this research, metal complexes of Cr (III) and Co(II) are being synthesized on
account of elemental analysis, IR studies, chromatographic studiesand
biological activities of the ligand and their complexes. The ligand Alprazolam
acts as a ‘‘Schiff base’’ and it forms complexes with different types of
metallic salts6,7. The Alprazolam drug which is used as ligand in
complex formation showed a specific solute-solvent interaction with alcohols8.
The structure of ligand Alprazolam is shown in figure number 1.
Figure 1: Alprazolam
The Schiff base alprazolam and its metal complexes
were screened for their antimicrobial activity. In this study, the coordination
of Cr (III) and Co(II) with the drug Alprazolam and their metal complexes
showed increased antimicrobial activity. In this research, some bacterial and
fungal species have selected for the antimicrobial studies. The antimicrobial
study explains the application of metal complexes.
MATERIAL AND
METHODS:
Analytical reagents (AR grade) were used
for the experiment as chromium and cobalt metallic nitrates were added to
distilled water to produce molar solutions. Standardization of metal nitrates
has been done by using standard methods. For checking hydrolysis, one or two
drops of concentrated HNO3 were added to the metallic nitrate
solution. Ethyl alcohol was used as a solvent for preparing the ligand
solution. ‘‘Metal and ligand composition has been measured potentiometrically
in complexes by using a standardized solution of NaOH in ethyl alcohol–water
mixture’’. The stoichiometry ratio of complexes of Cr (III) and Co (II) has
been confirmed by Job’s method9. Metal complex is prepared by mixing
a molar solution of metal nitrate and molar solution of alprazolam in a 1:1
ratio, then we get the ppt. of complexes of metal ions, then filtration takes
place and finally washed with the help of hot water which was followed by
ethanol and purity has been checked by TLC10. The precipitate of
these complexes was dried in the oven and stored in desiccators. Retention
factor (Rf) values of complexes are shown in the table 1 and these results
confirm the purity of metal complexes. From the results of thin layer
chromatography it is clear that there is no impurity in the sample.
Table 1: Values of retention factor of
different complexes
|
Solvent used
|
complex of
metal ions
|
Retention
factor value (Rf value)
|
Impurities of
sample
|
|
Ethanol: Benzene
80: 20
|
Chromium (III)-AZ
complexes
|
0.86
|
Invisible
|
|
Cobalt (II) – AZ
complexes
|
0.73
|
Invisible
|
Antimicrobial Study:
Alprazolam and its metal complexes were
tested against some antibacterial and antifungal species by utilizing the
methods of the ‘‘paper disc’’ and ‘‘broth serial dilution’’11. The
complexes of the alprazolam drug were dissolved in sterilized dimethyl formamide
viz. “250 ppm, 500ppm, 750ppm, and 1000ppm’’ concentrations were used. The
graded dilution of the test compound taken in suitable nutrients is incubated
with the organism under examination using an aseptic technique at 37oC
in an incubator under suitable conditions. The antifungal and antibacterial
action of alprazolam drug and their metal complexes which have been screened
against ‘‘B. subtilis, S. aureus, E. coli and S. typhi’’ and fungi such as
Aspergillus flavous, Penicillium tricticena, Fusarium species, and Aspergillus
niger have studied and results are presented in Table number 4.
Infra-red and Elemental Analysis:
The IR
spectra have been recorded by using Perkin –Elmer 842 spectrometer in the KBr
disc and the elemental analysis of elements (C, H and N)
of all compounds has been done by using the Elemental analyzer Carlo Erba 1108
analyzer at CDRI, Lucknow, Uttar Pradesh India, and metal ions were determined
volumetrically and chloride ions were determined gravimetrically.
RESULT AND DISCUSSION:
In this research, the molar formula of
ligand alprazolam is C17H13Cl N4, and their
complexes of Cr(III) and Co(II) are [C17H13ClN4.Cr(NO3)3]
and [C17H13Cl N4 .Co (NO3)2]
accordingly. The molar mass of metallic complexes of Cr (III) and Co (II) ions
are 546.79 and 491.73 respectively. The molecular mass of these complexes has
been determined by the analysis of elements (C, H and N).The results of
elemental analysis are shown in table number 2.
The main IR bands are listed in Table no.
3. The band of ligand alprazolam at 1628 cm-1 which is indicating the frequency
to lower wave numbers ( 1614 and 1613 cm-1 ) in the complexes of
Chromium (III) and Cobalt (II) correspondingly which indicated that nitrogen of
azomethine group is coordinated to the metal ions. The Cr (III) and Co (II)
metal complexes bands are attributed to the vibrational mode arising at 1264
and 1265 cm-1 representing the frequency shifted towards the lower
side in comparison to alprazolam ligand that indicates nitrogen
(1) is coordinated to the cobalt and chromium metal ions. IR spectrum of
ligands, belongs to the vibrational mode ‘‘u[-C6H5], u[-Cl], u[CH2],
u [CH3]’’ arise at the frequency
1600,740, 2960 and 1355 cm-1 the position of these bands indicating
little positive shift in metal complex formation and the other bands present in
the region 480 and 346 cm-1 in Cr (III) complex and 492 and 340 cm-1
in Co(II) complex, which is ascribed to the (Metal-Nitrogen) linkage12.
Presence of other bands in the region 1390, 908, and 830 cm-1 in the
complex of Cr (III) and 1370 and 890 cm-1 in the Co (II) complex,
thus the presence of strong bands indicated the presence of monodentate NO2
group in these complexes. Finally, the results of IR studies provide strong
evidence for the complex formation of alprazolam ligands with Cr(III) and
Co(II) metal ions. IR spectra are shown in figure number 4,5 and 6. The
expected structure of complexes of metal ions Chromium (III) and Cobalt (II)
are shown in figure number 2 and 3.Spectroscopic study of new substituted
heterocyclic compounds have been done by researchers13recently.
Figure 2: Metal complex (trivalent), M=
chromium
Figure 3: Metal complex (bivalent), M=
cobalt
Figure 4: IR spectrum of alprazolam
Figure 5: IR spectrum of Co (II)-AZ complex
Figure 6: IR spectrum of Cr (III)-AZ complex
Antimicrobial studies of ligand and
complexes:
The antibacterial and antifungal results
are systematized in Table 4. For the study of ligand alprazolam, metallic
nitrate, and their complexes have been examined against a few selected
bacterial and fungal species14-24. Here selected bacteria are B. subtilis, S. aureus, E.
coli and S. typhi, and the fungi are Aspergillus flavous, Penicillium
tricticena, Fusarium species, and Aspergillus niger. In this
study, the zone of inhibition is measured by this formula, percentage
inhibition = [(C-T)/ C] X 100, here C is the diameter of the microbial colony
in the control plate in mm and T is the diameter of the microbial colony in the
treated (test) plate. In this study, Streptomycin was used as the
standard antibacterial drug and Nyastatin was used as the standard
antifungal drug for comparison under similar conditions.
As shown in the above results, the study
found that the activity of metal complexes increased in comparison to the metal
nitrate and the ligand alone. Infigure number 6 and 7the graph is plotted in
between the percentage of zone of inhibition and the compounds used in the
antimicrobial study at 500ppm concentration. Graph number 6 is plotted for the
zone of inhibition against bacteria and graph number 7 is plotted for zone of
inhibition against fungi. From the graph 6 and 7 it is clear the metal
complexes inhibit the growth of bacteria and fungi much more in comparision of ligand
alprazolam. The enhanced activity of metal complexes is the result of their
increased chelating tendency and it has been proved by many researchers25,26,27,28.
So due to the chelating tendency of metal complexes, the complexes are more
powerful that inhibit the growth of bacteria and fungi than the parent Schiff
base (alprazolam ligand).
Figure 6: Zone of Inhibition against
bacteria
Figure 7: Zone of inhibition against fungi
CONCLUSION:
In this research paper, the synthesis,
Infrared studies (IR), and antibacterial and antifungal studies of complexes of
Cr (III) and Co(II) with ligand alprazolam have been studied. Determination of
molecular weight, molecular formula, and melting point of complexes of metal
ions [Cr (III) and Co (II)] have been done by elemental analysis and TLC
confirms the purity of compounds. Results obtained from IR studies confirm the
complex formation of Chromium (III) and Co (II) with alprazolam ligand. The
present research shows that the complex of Co (II) is more effective on
bacteria and fungi than Cr (III) and alprazolam alone. Metal complexes are more
active due to their increased chelating tendency and lipo-soluble nature.
CONFLICTS OF INTEREST:
Conflicts of interest are not present.
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