Synthesis of Aromatic Heterocyclic Ketimines: Part-II.
Synthesis, Characterization and Biological Studies of
Copper complex of Biomolecule
C. J. Patil1, M. C. Patil2*, N.
A. Patil3, Dhiraj Kolhe4
1Department
of Chemistry, Smt. G. G. Khadse College, Muktainagar, Dist-Jalgaon-425306
2Department
of Zoology, Smt. G. G. Khadse College, Muktainagar, Dist-Jalgaon-425 306, M.S.,
India
3Department
of Zoology, Dr. A. G. D. Bendale Mahila College, Jalgaon, Dist-Jalgaon-425001
4Department
of Biotechnology, Smt. G. G. Khadse
College, Muktainagar, M.S., India
*Corresponding Author E-mail: nandapatil10@rediffmail.com
The
Cu-complex of Biomolecule or Ketimine was synthesized by reacting
the Biomolecule and metal salt by conventional method. The synthesized
Cu-complex of biomolecule was characterized by colour, TLC, physical constant
and UV-Vis spectra and FTIR spectral method. The complex, Cu-biomolecule was
also tested for the in-vitro biological activity and the results
obtained were compared with biomolecule itself as well as Ciprofloxacin as
known and standard drug.
KEYWORDS: Biomolecule
(BM), Ketimines,
2-Amino-6-(1-pyridin-3-ylethylideneamino)-hexanoic acid(as BM) Cu-complex,
TLC and UV-Vis, FTIR and Biological studies.
INTRODUCTION:
The compound formed by the reaction between an
aldehyde or ketone and an aliphatic or aromatic amino compound is known as
Ketimine or Schiff base. Schiff bases were first discovered by Hugo Schiff[1]
and hence they are referred as Schiff bases. The condensation products formed
from ketone with an aromatic amine are referred as Ketimine[2]. It is a
intermediate in Strecker degradation reaction where amino group of α-amino
acid is transferred to a carbonyl group via ketimine formation[3]. Many types
of reaction Ketimines or Biomolecule are involved in metal complex formation[4]
oxidations[5], hydrolysis[6] and reduction[7] have been studied with ketimines.
Survey of the literature shows report[8] on synthesis, crystal structure and anticancer
activities of transition metal complex with Ketimine derived from L-tryptophan
and 2-acetylpyridine.
L + Metal
Salt L- Metal Complex
Herein, we report the preparation of
2-Amino-6-(1-pyridin-3-ylethylideneamino)-hexanoic acid(as BM) from
3-Acetylpyridine with L-Lysine monohydrochloride and its copper complex as
biomoleculer complex: It is also studied for its biological activity.
EXPERIMENTAL:
Preparation
of Schiff base metal complex:
The complexation of the ketimine is performed as per
reported methods[9-10]. The Ketimine, synthesized, 2-Amino-6-(1-pyridin-3-ylethylideneamino)-hexanoic
acid(BM) and reported[2a] from our lab, was complexed with
a calculated quantity of metal salt to
form the complex.
Preparation
of Ketimine-metal complex:
The
ketimine ligand (2.5 mmol) solution of CuCl.6H2O dissolved in
ethanol is mixed with 50 ml, 5 mM solution of Ligand, BM in (2:1)
Ligand: Metal ratio. The reaction mixture was refluxed for 4–5 hrs. The
coloured powdered product appeared on standing and cooling the solution. The
precipitated compound is filtered, washed with ethanol and dried under vacuum
to a constant weight at 60°C. Record its dried weight and
the physical constant. The purity of the
ketimine-complex were ascertained by recording the melting point(uncorrected)
and by analyzing them for carbon, hydrogen, nitrogen and the metal content. The
elemental analysis indicates that all the metal complex have 2:1 (L:M) ratio.
The yield of complex obtained was calculated.
Safety:
During
the above type of work always wear personal
safety protective equipments including safety goggles, gloves and the
lab-coat made of cotton must be used at all times during performing the
experiment. Also, the long pants should be worn along with close-toed shoes. No
food or drink is allowed in the laboratory. Always work using the fume-hood. Be
careful when handling the products, they are deeply coloured and it may stain
your skin and cloth on exposure for a long period of time. Do not wipe gloves
on the lab-coat.
Antibacterial
Activity:
To
study the in-vitro antibacterial activity of Schiff Base following setup will
be required. The following experimental procedure will be adopted.
Newly
synthesized compounds were screened for their antibacterial activities against
four strain of bacteria E. coli, B.
subtilis, P. aeruginosa and S.
aureus using disk diffusion method [11-13]. Activity of each
compound was compared with that of standard drug. Before testing, the test
bacterial strains were cultured in Nutrient broth(NB) about 0.1 ml suspension
(above NB) spread over the entire surface of the sterile Nutrient agar plates,
which were then allowed to dry. The discs with compounds (100 and 500 mg/ml) were applied into each inoculated plate and the plates were
incubated at 37°C for bacteria, with readings taken after 24 hours[14]. The
diameter zone diameters for disks were measured in mm and compared with that of
control disk.
RESULTS
AND DISCUSSION:
The
complexation of the ketimine is performed as per reported methods[9-10]. The
Ketimine, synthesized, 2-Amino-6-(1-pyridin-3-yl-ethylideneamino)-hexanoic acid(BM), was complexed with
a calculated quantity of Metal salt to
form the complex.
The abbreviation of ketimine-complex (BM-Cu),
colour, nature and melting point of the ketimine-complex were summarized in Table-1.
The yield of the complex and
the elemental analysis data for ketimine-Cu complex were depicted in Table-2.
The complex was analyzed by
colour and UV-Vis spectral measurement. The data obtain is shown in following Table-3.
Glimpses
of In-vitro antibacterial activity of Biomolecule (Ketimine) Cu-complex
1)
Among the biomolecules or
ketimines and the Cu complex studied for the MIC for bacterial strain, E. coli was
found more than B. subtilis, P. aeruginosa and S. aureus.
2)
BM-Cu complex also showed moderate
activity on the bacterial strains.
3)
The Biomolecule and its Cu complex
showed less anti-bacterial activity than the known standard
drug(Ciprofloxacin).
4)
A comparative study of inhibition values of the Biomolecule and their
complex indicates that the complex exhibit higher antibacterial activity than
the free Biomolecule.
The overall and a comparative study of inhibition
values of the Schiff base ligands and their complex indicate that the complex
exhibit higher antimicrobial activity than the free ligands.
These findings are in concurrence with that of the
findings in case of amino acid (Arginine and Glycine) aldimines of
2-Hydroxy-naphthaldehyde with respect to comparative activity of free ligand
and its complex[18].
CONCLUSIONS:
The
compounds were tested for the anti-bacterial activity at the concentrations 100
and 500 (µg/ml) in DMSO and compared with known antibiotics viz
Ciprofloxacin it is found that the inhibition by metal chelates is higher
than that of a Biomolecule(BM) and results are in good agreement with
that of previous findings reported.
ACKNOWLEDGEMENT:
The
authors (NAP and MCP) are thankful to WRO, UGC, Pune for sanctioning the
Minor research project under UGC Scheme (XIth Plan, File No.
47-1896/11(WRO), DATE: 11-01-2012). They are also thankful to the Management
and Principal of Smt. G. G. Khadse College, Muktainagar, Dr. A. G. D. Bendale
Mahila College, Jalgaon, for the permission of the present work.
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