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ISSN 2229-5518
Complexes of 2-amino-4-thiazoleacetic acid hydrazide(ATAH), salicylaldehyde-2-amino-4- thiazoleacetic acid hydrazone(ATASH) and
acetone-2-amino-4-thiazoleacetic acid
hydrazone(ATAAH), each with copper(II)sulphate
M. C Enedoh (megnedoh@yahoo.com)
Department of Chemistry, Imo State University, P.M.B. 2000, Owerri, Nigeria.
Abstract: Four complexes obtained from 2-amino-4-thiazoleacetic acid hydrazide [keto- (ATAH) and enol- (ATA) forms), salicylaldehyde- 2- amino-4-thiazoleacetic acid hydrazone (ATASH) and acetone -2-amino-4-thiazoleacetic acid hydrazone (ATAAH) each complexed with copper(II) sulphates have been synthesized. The complexes were characterized by elemental analyses, conductance, infrared and electronic spectral studies. The ligands and complexes were screened for antimicrobial activity and the compounds were relatively inactive against the organism tested. The electronic data indicate a square planar coordination for the all the complexes synthesized. The IR spectra data are diagnostic of bidentate coordination via the carbonyl oxygen and the azomethine, the SO42- anions are in their inner coordination spheres. The conductivity analyses indicate a non-electrolytic nature for the chelates.
Key Words: acetone, 2-amino-4-thiazoleacetic acid, antimicrobial, bidentate, enol, hydrazide, hydrazone, keto, Salicylaldehyde, sulphates
—————————— ——————————
The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. Much attention is given to hydrazones and some other hydrazine derivatives because of their biological and physiological activities [J.N. Nwabueze (1997),
Complexes of Copper (II) with Acetone hydrazones derived from some cyclocarboxylic acids, Synth. React.Inorg. Met.-Org. Chem. 27,
673.] They generally exhibit very strong antibacterial activity. This antibacterial activity is enhanced on complexation to some transition metal ions[Bontchev et al; 1981]. 4-isopropylthiazole-2- carbohydrazide is known to be a novel class of potential antibacterial, antifungal and antitubercular agents [B. P. Mallikarjuna et al, 2008, 2009]. Also of interest is the coordination mode of hydrazones. This is due to the fact that other ligating sites may be present in addition to the carbonyl O and the
azomethine N depending on the nature of R and R1
in RCONHNCR 1 2 . Hydrazones derived from 6-
amino-5-formyl-1, 3-dimethyl uracil and nicotinic and isonicotinic acid hydrazides formed four – coordinate complexes with Cu2+ which are monomeric with three binding sites occupied by the dinegative tridentates ligand and the fourth position by water. The donor atoms are the deprotonated N of the 6- amino group, the azomethine N and the carbonyl O of the hydrazone moity. Neither the
carbonyl O atoms of the uracil ring nor the endocyclic N atom of the pyridine are involved in the coordination to the metals[Enedoh and Nwabueze; 2011, Fransisco et al; 2000]
This work aims at synthesizing for the first time complexes of the title metal with 2-amino-4- thiazoleacetic acid hydrazide(ATAH &ATA), salicylaldehyde-2-amino-4-thiazoleacetic acid hydrazone (ATASH) and acetone -2-amino-4- thiazoleacetic acid hydrazone (ATAAH) for
possible use | as | antibacterial | agent. | Then, |
characterizing | the | complexes | by | some |
physicochemical properties while subjecting the ligands and complexes to antimicrobial screening.
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Ethyl-2-amino-4-thiazoleacetate, acetone and salicylaldehyde were obtained from Sigma –
Aldrich Chemical Company Ltd, while the copper(II) sulphates and acetates were obtained
from BDH Chemical Ltd England. All were used without further purification
2- amino-4-thiazoleacetic acid hydrazide was
prepared from 1mole of ethyl-2-amino-4- thiazoleacetate and 1 mole of the hydrazine hydrate using standard methodas in literature [Nwabuezeto ;
1992].
25.00ml (0.40moles) of hydrazine hydrate was added to 70g (0.40moles) of ethyl-2-amino-4- thiazoleacetate in 300mls of absolute ethanol. It was refluxed on a water bath for 6 hours. The solution was left to crystallize for 3 days. The light brown crystals obtained were filtered , recrystallized from ethanol, filtered and dried over silica gel in a desiccators. (yield , 46.1g; 65.86%)
8.6g, (0.05 mole) of 2-amino-4-thiazoleacetic acid
hydrazide (ATAH) was mixed with 5.3ml( 6.01g,(
0.0.05 moles) of salicylaldehyde in 130ml ethanol
and refluxed for 4 hours in a 250ml round bottom flask on water bath. The solution was left for 24 hours to crystallize. The yellow crystals obtained were filtered and were recrystallized from ethanol.s They were then dried in a desiccator over silica gel.( Yield,9.7g; 80.78%).
8.6g, (0.05 mole) of 2-amino-4- thiazoleacetic acid hydrazide (ATAH)
was mixed with 3ml (0.05 moles]) of acetone in 120ml ethanol and refluxed for
4 hours in a 250ml round bottom flask on water bath. The solution was left for 7days
to crystallize. The milky crystals obtained were filtered and were recrystallized from
ethanol.s They were then dried in a desiccator over silica gel.( Yield,6.1g;
40%).
The complexes were prepared by the
reaction between aqueous solutions of the metal salts and ethanolic solutions of the ligand in a 1,2 molar ratio
The preparation of the Cu-ATAH
complexes
0.86 gram (0.005mole) of 2-amino-4- thiazoleacetic acid hydrazide(ATAH) was
dissolved in 10ml of ethanol and slightly warmed, while 0.61g (0.0025 moles) of
CuSO4 .5H2 O was dissolved in 10ml of water. The ligand was then added gently while stirring continuously into the copper(II) solution and a light brown coloured crystals were formed. The crystals were filtered and dried over silica gel in a desiccator for 2 days. (Yield, 1.1g;
43%).
The preparation of the Cu-ATASH
complexes
1.22 gram (0.005mole) of salicylaldehyde-
2-amino-4-thiazoleacetic acid hydrazone was dissolved in 10ml of ethanol and slightly warmed, while 0.61g (0.0025moles) of CuSO4.5H2 O was dissolved in 10ml of water. The ligand was then added gently while stirring continuously into the copper(II) solution and a brown coloured crystals were formed. The crystals were filtered and dried over silica gel in a desiccator for 2 days. (Yield, 1.3g; 60%).
The preparation of the Cu-ATAAH
complexes
0.985gram (0.005mole) of acetone-2- amino-4-thiazoleacetic acid hydrazone
was dissolved in 10ml of ethanol and slightly warmed, while 0.61g (0.0025
moles) of CuSO4 .5H2 O was dissolved in
10ml of water. The ligand was then added
gently while stirring continuously into the copper(II) solution and a coffee brown coloured crystals were formed. The
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crystals were filtered and dried over silica gel in a desiccator for 2 days. (Yield,
1.15g; 61%).
The preparation of enolhydrazide, Cu- ATA
This was obtained by adding a little quantity of sodium ethoxide into the
mixture of copper (II) sulphate and 2- amino-4-thiazoleacetic acid hydrazide
during the complexation
Elemental Analysis [Jeffrey et al;
1979]
Using EDTA the percentage of metals in
the complexes were determined complexometrically while that of sulphur was gravimetrically determined as sulphate by precipitation using BaCl2.
Instrumental Measurement
IR spectra in nujol were taken using 8400S Fourier Transform Infrared
Spectrophotometer.Electronic absorption spectra of the ligand and complexes were
done in ethanol solution using Spectronic
21D Milton Roy UV – VIS
SpectrophotometeR. The conductivity measurement in EtOH of the complexes were made using the pH/ conductivity meter, JENWAY 430.
different solutions of the ligand and complexes(0.005g/ml ethanol).Drying and sterilization in the oven at a temperature of
37oC for 24 hours followed. The Petri-
dishes containing already gelled nutrient agar were innoculated with the micro- organisms. These Petri-dishes were impregnated with the disks containing the solutions of the ligands and the complexes differently and separately. They were arranged radially from the centre of the dishes and incubation was done for 24 hours. This was done in duplicate . Antibacterial activity was measured as zone diameter of inhibition around the disk.
The chemical equation below represents the preparation of the thiozolehydrazone
from the thiozolehydrazide
Assignment of band above 3000cm-1 are only tentative since band due to the symmetric vibrations of OH, NH and NH2 groups appear in this region as unresolved
[Jeffery et al; 1979]. Bands around 3400cm-1 in the
spectra of the hydrated complexes are assigned to υ(OH) of water of crystallization [Ikekwere et al; 1989]. The υ(C=O) band located in the spectrum of the ligand at
-1
Antimicrobial Screening
ca1669cm
is lowered in the spectra of the complexes
Antimicrobial screening of the ligands, the copper salts and the complexes in aqueous methanol was carried out using nutrient Agar. In-vitro susceptibility testing of the chemicals were carried out on four types of micro-organisms viz staphylococcus aureus, Escherichia coli, streptococcus, klebsialla aero genes. Disks were sterilized in the oven at a temperature of
60oC for one hour and allowed to cool and
then they were coated accordingly with the
-
by 02 – 128cm-1 indicating coordination via the carbonyl oxygen.
The υ(C=N) group is also affected because the azomethine N is used for ligation [Ikekwere et al; 1989, Nwabueze 1999]. Uncoordinated sulphate group has infrared active vibration located around 1120cm-1. Whenever this anion coordinated, it lowers its Td symmetry and split this band. As the sulphate band is split in all the relevant complexes, it indicates that the anion is in the inner coordination sphere.
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CH2CONHNH2
CH2CONHNCR2
N
+
NH2
S
R2CHO
N
NH2
S
The reaction between the ligands and the metal salt yield complexes with 1:1, 2:1, or3:1
stoichiometries
The analytical data and some physical constants for the complexes are shown in table 1
1. ATAH
2. ATA
3 ATASH
4 ATAAH
5 [Cu(ATAH)3 ]SO4 .
6 [Cu(ATA)2 ]H2 O
7 [Cu(ATASH)2 SO4. H2 O
8 [Cu(ATAAH)]SO4
Figures In parenthesis are theoretical values
These complexes are monometric non-electrolytes, proved by their solubility in common organic solvents, insolubility in H2 O, not too high melting points and very low conductivity [Ikekwere et al 1989]
The diagnostic IR bands for the ligands and complexes are shown in Table 2
ATAH 3322 3120 1701 1508 600 423
ATASH 3788 1750 1589 423
ATAAH 3395 1628 1528 432
[Cu(ATAH)3 ]SO4 . 3310 3124 1627 -74 1522 +14 1119 599 423 699 [Cu(ATA)2 ]H2 O 3308 3112 1626 1521 603 510 693 [Cu(ATASH)2 SO4. H2 O 3382 3131 1622 -128 1521 -68 1104 614 460
[Cu(ATAAH)]SO 4 3312 3139 1630 -02 1516 -12 1130 412 698
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The electronic spectra data for the complexes are shown in table 3
Compound | λnm | Assignment | Stereochemistry |
1 [Cu(ATAH)3 ]SO4 . | 610 | d → d | Square planar |
2. [Cu(ATA)2 ]H2 O | 670 | d → d | Square planar |
3. [Cu(ATASH)2 ]SO4 .H2 O | 682 | d → d | Square planar |
4 [Cu(ATAAH)]SO4 | 680 | d → d | Square planar |
The spectra of the copper(II)complexes show a single band located at610nm, 670nm, 682nm and 680nm. This is the d→d band which indicates a square planar
geometry for the complexes [Nwabueze; 1997, Nicholis;
!974]
The result of the antimicrobial screening of the compounds is shown in table 4
1. | 1. | ATAH | - | - | ++ | - |
2. | ATASH- | - | - | - | - | |
3. | ATAAH- | + | + | - | + | |
4. | [Cu(ATAH)3 ]SO4 | + | + | - | ++ | |
5. | [Cu(ATASH)2 ]SO4 .H2O | - | - | + | - | |
6. | [Cu(ATAAH)]SO4 | - | + | - | - |
Key - resistance, + (fairly active) ++ (active)
The microbial activity of the compounds is insignificant, probably due to the presence of few nitrogen atoms.
The ligands (1). 2-amino-4-thiazoleacetic acid hydrazide
(2). salicylaldehyde-2-amino-4-
thiazoleacetic acid hydrazone and (3). acetone-2-amino-4- thiazoleacetic acid hydrazone with their complexes which was each done with copper (II) sulphate was successfully synthesized. The ligands acted as a neutral bidentate donor via the azomethine
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N and the carbonyl O. The copper complexes are square planar. The anions apparently are in the inner coordination sphere. No significant antimicrobial activity was shown by the compounds.
J. N Nwabueze, (1997), Complexes of copper (II) with acetone hydrazones derived from some cyclocarboxylic acids, Synthesis and Reactivity in Inorganic Metal Organic Chemistry. 27, 673
P. R Bontchev,, M. Boneva, and M. Miter, (1981), Copper (II)complexes of hydrazides,Journal of Inorganic and Nuclear Chemistry, 43, 3163
B.P Mallikarjuna, B.S Sastry, G.V Suresh Kumar, Y.Rajendraprasad and S.M Chandrashekar, K.Sathisha.(2008) Synthesis of new 4- isopropylthiazole hydrazide analogs and some derived clubbed triazole, oxadiazole ring systems--a novel class of potential antibacterial, antifungal and antitubercular agents. Department of Medicinal Chemistry, PES College of Pharmacy, Hanumantha Nagar, BSK Ist Stage, Bangalore 560050, Karnataka, India. mallibp@gmail.com
B. P. Mallikarjuna, B. S. Sastry, Suresh, Y. Rajendraprasad, S. M. Chandrashekar and K. Sathisha (2009), Synthesis of new 4-isopropylthiazole hydrazide analogs and some derived clubbed triazole, oxadiazole ring systems--a novel class of potential antibacterial, antifungal and antitubercular agents European Journal of Medicinal Chemistry doi:10.1016/j.ejmech.2009.06.008 Key: citeulike:5013595 Posts Export Citation Find Similar
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