Synthesis and Antimicrobial Activities of Zn (II) Complex
of 2,5-diamino-1,3,4-thiadiazole.
Vinita Gupta1, Sanchita Singh1,
Y.KGupta2*
1Department of Chemistry, Agra College, Agra, U.P, India
2Head Department of Chemistry, B K Birla Institute of
Engineering and Technology, Pilani, Rajasthan, India
*Corresponding
Author Email: ykgbkbiet@rediffmail.com, ykgbkbiet@yahoo.com,ykgbkbiet123@gmail.com
ABSTRACT
Aim:
The ligands contain O, N, S-Sequence and
their metal complexes have their various chemical and structural
characteristics and their wide application in the field of pharmacology. The extreme efforts have been made to design novel drug
to strains of resistant micro-organisms.
This has required the need to search for more efficient drugs.
The Zn (II) metal complexes with a tridentate
ligand 2,5-diamino-1,3,4-thiadiazole has been
prepared by cyclisation of bithiourea in a 3% hydrogen peroxide medium. 2,5-diamino-1,3, 4-thiadiazole acts as neutral
tridentate ligand and coordinates through the sulphur atom and nitrogen of the
amines. The complexes are non-electrolyte in DMF. The complexes exhibited
octahedral geometry. The antimicrobial activities of ligand and its complexes
were screened using sensitivity test, minimum inhibition concentration and
minimum bacterial concentration method. Metal chelates showed greater
antimicrobial activities as compared to the control and the ligand. The metal
chelates and the ligand did not exhibited activity against Aspergillus niger and Penicillin species.
Elemental
analyses, IR spectra, magnetic susceptibilities by using Faraday Balance, molar
conductance by using Genway 4200 conductivity meter. Metal estimation by using
Alpha 4 Atomic Absorption Spectrophotometer. Thin layer chromatography was
carried out using TLC plate coated with silica gel.
Results:
The
results of the elemental analyses are in good agreement with those calculated
for the suggested formulae, 1:2 (M: L) solid chelates are isolated and found to
have the general formulae [(ML2)] X2; M=Zn (II) (X=Cl).
The
IR spectra revealed that the ligand L is a neutral tridentate ligand. It
coordinated to the metal ions via the nitrogen of the amines and sulphur atom.
The molar conductance value of the Zn (II) complex was low which indicate the non-electrolytic nature of the complex. The
ligand and metal complexes show antimicrobial effect against the tested organism
species except against molds of penicillin and Aspergillius . Niesseria
gonorrhoea was probably the most sensitive organism to the
2,5-Diamino-1,3,4-Thiadizole and its metal complexes. Metal complexes showed
greater activity against some of the micro-organisms compared to the parent
compounds
Conclusion:
In
this paper we conclude from combined results of the chemical and physical
analysis that the ligand (2,5-diamino-1,3,4-thiadiazole) coordinated with Zn.
The metal complexes possess better physical
properties than the parent compound. Metal complex of
2,5-diamino-1,3,4-thiadiazole would be a better therapeutic drug for
antibacterial treatment.
KEY WORDS: Zn (II) complex, Cyclisation,
2,5-diamino-1,3,4-thiadiazole, Antimicrobial
Activities.
INTRODUCTION
The efforts have already been made to design novel compounds to confront
new strains of resistant micro-organisms. The on-going seek out novel and
innovative drug delivery systems is predominantly a consequence of the
well-established fact that the convectional dosages are not sufficiently
effective in conveying the drug compounds to its site of action and it has
necessitated the need to search for more potent drugs [1]. The recognition of
the potential employment of metal complexes and chelates in therapeutic
application provides useful outlets for basic research in transition metal
chemistry [2].
A number of antibiotics such as bleomycin, streptonigrin and bacitracin
have already been reported to operate properly upon coordination with metal
ions [3]. Metallo-antibiotics can interact with several biomolecules such as
DNA, RNA, protein receptors and lipids, making them very unique and
specifically bioactive [4,5]. The efficacies of some therapeutic agents are
known to improve upon coordination; hence metal-based drug is seen as possible
replacement for most of the present drugs [6].
There is great interest about synthesis and characterisation of ligands
which contain O, N, S-sequence and their metal complexes. The significance of
the compounds, besides their diverse chemical and structural characteristics,
stems not merely from their potential but in addition their proved application
as biologically active molecules and an extensive spectral range of activity
[7]. In my previous work some metals such as Iron play important roles in
general body metabolism. [8]
Semicarbazide and thiosemicarbazide derivatives are associated with some
important biological activities such as Antitubercular [9,10,11], anthelmintic,
fungicidal, antitumor [12], antimalarial and antibacterial activity [14,15].
They are found to be pharmacologically and physiologically active [16]. The
difficulty of treating bacterial diseases induced us to assess the biological
properties of these novel metal complexes. This method might provide interesting
compounds with greater biological activity in pharmacological research [13].
EXPERIMENTAL:
The chemicals used in the preparation of the complexes and in solutions
studies were of the highest purity grade. Semicarbazide hydrochloride,
potassium thiocynate and 3% hydrogen peroxide were supplied from Sigma
Chemicals. Zn (II) Sulphate Hepta hydrate from BDH were used as supplied. The
organic solvents used; absolute ethanol and methanol were also obtained from
BDH.
Elemental analyses (C, H, N and S) were carried out using
micro-analytical techniques on Heraens-rapid analyser. The IR spectra were
recorded using SP3-30 Perkin-Elmer FT-IR spectrometer in the region 4000 – 400
cm-1. The spectra were recorded as KBr disks. The molar magnetic
susceptibilities of the powdered samples were measured using Faraday Balance
Model 7650 using Hg [Co (SCN)4] calibrant. The ultraviolet/visible
analysis was carried out on Genesys.10S V1.200 spectrophotometer. The molar
conductance measurements of the
complexes were carried out in DMF using Genway 4200 conductivity meter. Metal
estimation of the complexes was determined using Alpha 4 Atomic Absorption
Spectrophotometer with PM8251 simple-pen recorder. Thin layer chromatography
was carried out using TLC plate coated with silica gel.
Antimicrobial screening
The stimulatory or inhibitory activity of the ligand and the metal
complex synthesized were determined according to the procedure previously
reported with slight modification [17, 18, and19]. The bacteria species useful
for this test include clinical cultures of Escherichia coli, Staphylococcus aureus, Klebsiella species,
Niesseria gonorrhoea, Salmonella typhi, Shigella species, Penicillium species,
Pseudomonas aeruginosa and Aspergillus species. The antibacterial activities
of the compounds were determined using sensitivity test, minimum inhibitory
concentration and minimum bacterial concentration.
Preparation of the 2,5-diamino-1,3,4-thiadiazole (L)
A 30 g (0.2 mol) of bithiourea was introduced into a 250 cm3
round bottomed flask and 40 cm3 of 3% H2O2 was
added. The mixture was refluxed at 50 – 60°C for 1 hr with continuous stirring.
The product was then filtered under vacuum and dried at 100°C in the oven and
the percentage crude yield was determined. It was thereafter recrystallised
from boiling water.
Synthesis of the metal complexes
The complex was prepared based on previous reported procedures with
slight modifications [20]. An aqueous or ethanolic solution of the metal salt
(ZnSO4.7H2O) was mixed with an aqueous ethanolic solution
of 2,5-diamino- 1,3,4-thiadiazole (which was dissolved in minimum amount of the
solvent) in 0.01 mol each. The reaction mixture was heated in a 250 cm3
round bottomed flask for 15 min on a water bath and there was change of colouration,
indicating the precipitates of the complexes appearing. The reaction mixture
was reduced to about one third when the metal complex separated out on cooling.
The complexes formed were recovered from the solution by filtration. It was
washed and recrystallised from ethanol and then dried in vacuum over CaCl2.
RESULTS AND DISCUSSION:
Preparation and characterization of the ligand
The cyclisation of bithiourea were performed by 3% hydrogen peroxide, H2O2,
a proposed mechanism of the cyclisation is shown in Scheme 1:
Bithiourea undergoes tautomerism in the mercapto form and by
protonation; a molecule of hydrogen sulphide is detached. This provides a
positively charged carbon nucleus with a lone pair of electrons on the second
sulphur atom which makes cyclisation possible. The structure of the ligand (L)
was elucidated based on elemental data (Table
1) and spectral data. Its IR spectra
Scheme 1
(Table 2) showed the
absorption bands of NH2 and C−S at 3195 and 1430 cm-1,
respectively. Compound L are separated in high yield (96.4%). The results of
the elemental analyses (C, H, N, S and metal content) with the proposed
molecular formulae are presented in (Table
3). The results obtained are in good agreement with those calculated for
the suggested formulae, 1:2 (M: L) solid chelates are isolated and found to
really have the general formulae [(ML2)]. The solid complex are
prepared and characterized by different tools of analyses like IR, molar
conductance, magnetic moment, UV/Visible (Table
4) and atomic absorption spectroscopy to throw more light on the
coordination behaviour of this ligand towards some biologically active metals
under study.
The metal salt react with ligand L (L = 2, 5-diamino-1, 3,
5-thiadiazole) according to the following proposed general equation: [M (II) L2]
where M = Zn2+ metal salt. The complex synthesized was found to be
non-hygroscopic solids with white colour, (as shown in Table 1). The complexes
are well soluble in DMSO and DMF and hot distilled water. They have sharp
melting points. The average percentage yield was very high. The retention
factor (Rf) values was calculated from the developed single spot for the
complexes indicating the purity of the compound [21]. The retention factor of
the metal complex was found to be greater than that of the ligand. The
conductivity value shown in Table 3
is too low to account for any dissociation of the complexes in DMF. Hence this
complex could be regarded as
non-electrolyte. The analytical data of the metal complex showed 1:2
stoichiometry.
Infrared spectra and mode of bonding
The IR spectra of the free ligand and their metal complex were carried
out in the range of 4000 – 400 cm-1 and listed in Table 2. The assignments have already
been carried out based on literature values obtained for similar structural
compounds [22, 23, and 24]. The important IR frequencies of the ligand, L and
the metal complex (in KBr) with their tentative assignments are given. Both the
free ligand and the metal complex are characterized by υ (N−H), δ (NH2), υ (C−S) and υ (C=S) Bands. [25]. the
absorption patterns look quite similar to that of the free ligand that is in
agreement with coordination through nitrogen atom. The band around 3400 – 3100
cm-1 is assigned to υ (NH) and is supported
by the presence of δ(NH2)
deformation bands around 1600 − 1500 cm-1. A blue shift was
observed in the υ (C−S) frequency
of the complexes, compared to the free ligand, which indicates coordination
through the sulphur atom. Bands between 800 – 900 cm-1 that have
been absent in the free ligand are assigned to M−L that is the metal
ligand coordination. The IR spectra showed that the ligand L is a neutral
tridentate ligand. It coordinated to the metal ions via the nitrogen of the
amines and sulphur atom.
Molar conductance data
The molar conductance of the solid complexes (λm, Ω -1 cm2 mol-1)
was calculated. The DMF solubility of the above complex made calculations of
the molar conductivity (λm) of 10-3 mol dm-3
solution at 25°C possible. The data in Table
3 revealed that the molar conductance is of relatively low value for Zn
(II), indicating the nonelectrolytic nature of the complex. Therefore, the
molar conductance data confirm the outcome of the elemental analyses and IR
spectra data.
Structural interpretation
Consequently, the structures proposed are based on octahedral geometric
structures. The 2,5-diamino-1,3,4- thiadiazole coordinate via nitrogen of the
amines and sulphur atom forming three binding chelating sites.
Proposed structure of Bithiourea metal
complex (M=Zn)
Table 1: Magnetic moment and elemental data of Ligand and their metal
complexes.
|
Compounds |
Emperical Formula |
Formula Weight |
μeff (BM) |
Elemental Analysis Calculated (Found) |
||||
|
C |
H |
N |
S |
Me |
||||
|
L |
C2H4N4S |
116.00 |
-- |
20.69 (20.67) |
3.45 (3.42) |
48.28 (48.22) |
13.79 (13.73) |
--- |
|
Zn(L)2 |
ZnC4H8N8S2 |
297.00 |
4.65 |
16.16 (16.14) |
2.70 (2.71) |
37.71 (37.70) |
10.77 (10.75) |
21.89 (21.87) |
Table 2: IR spectral assignment of Land its metal complexes.
|
Ligand/Complexes |
υ(NH2) |
υ(C-S)cm-1 |
Δ(NH2) cm-1 |
|
L |
3195.31,b |
1430,str |
1536.55,str |
|
Zn(L)2 |
3214.06,b |
1429.98,s |
1536.92,s |
Table 3: Physical properties of Land its metal complexes.
|
Compounds |
Melting Point(0C) |
Colour |
% Yield |
Conductivity (Ω-1 cm-1 dm-3) |
|
L |
208 |
White |
96.4 |
--- |
|
Zn(L)2 |
220 |
White |
54.7 |
1.2× 10-6 |
Table 4: Ultraviolet/visible spectral assignment of L and its metal complexes.
(Wavelength, nm (cm-1)
|
Compounds |
Band-1 |
Band-2 |
Band-3 |
|
L |
205(48780) |
238(42017) |
------- |
|
Zn(L)2 |
229(43668) |
340(29412) |
346(28902) |
CONCLUSION:
It is concluded from combined results of the chemical and physical
analysis and from previous reports that the ligand
(2,5-diamino-1,3,4-thiadiazole) employed in this work coordinated with Zn. The
metal complex possesses better physical properties than the parent compound.
Based on antimicrobial activities, metal complex of 2,5-
diamino-1,3,4-thiadiazole would be a better therapeutic drug for antibacterial
treatment.
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Received on 11.12.2013 Accepted
on 24.12.2013
Modified on 28.12.2013 ©A&V
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Research J. Science and Tech 5(4): Oct.- Dec.., 2013 page 462-465