ISSN 2319-7625 (Online)
(An International Research Journal), www.chemistry-journal.org
Biological Studies and Characterisation of Sulfa Drug
Based Ligand and Transition Metal Complex
V. A. Modhavadiya
Department of Chemistry,
Shree M. M. Science College, Morbi-363642.Saurashtra University, Rajkot, Gujarat, INDIA.
email:[email protected]
(Received on: November 11, Accepted: November 13, 2017)
ABSTRACT
The sulfa drug based ligand and transition metal complex have been synthesized and the constitution of the products have been settled on the basis of spectroscopic data. The products have been evaluated for antimicrobial activity. Some compounds are found to have antimicrobial activity comparable to that of standard drugs, viz.sulfamethoxazole, sulfadiazine. The products have also been characterized by elemental analysis, conductivity measurement, molecular weight determination and magnetic susceptibility measurements and PH metric method.
Keywords: Synthesis, ligand, metal complex, characterization.
INTRODUCTION
Sulfonamide was introduced in therapy about half a century ago for prevention and
cure of bacterial infections in humans1.Due to low cost, low toxicity, and excellent activity
against bacterial diseases, sulfonamides are among the most widely used as antibacterial as well as an antimalarial drug. However, it is mostly used now in combination therapy with
pyrimethamine to treat chloroquine resistant malaria parasite2-7. Studies related to new
developments in metal based drugs are both promising and of great interest in the development of therapeutic agents8-9.
Metal complexes of azo dye ligand have played a central role in the development of co-ordination chemistry. Azo dyes (V) of sulfa drugs are well known for their antiseptic
activity10-11 and some are useful as chemotherapeutic agents12. A large number of metal
sulphonamide complexes are found to be more potent than the parent sulphonamides13-14. In
EXPERIMENTAL
The titled compounds have been synthesized by the reaction of alcoholic solution of 3-ethyl-2-hydroxy-5-methyl-4’-methyl carbonyl sulphonamido - azobenzene ( ligand ) with aqueous solution of Fe (II) metal salts. The later of ligand have been synthesized by coupling of diazotized sulfacetamide with 2-ethyl-5-methyl phenol. 2-ethyl-4-methyl phenol have been
synthesized by the clemmensen reduction15-16 (Zn/Hg, Conc.HCl) on 2-acetyl-4-methyl
phenol. The later was synthesized by the fries migration17 on P-cresyl acetate have been
synthesized by the acetylation18 of P-cresol with acetic anhydride in presence of pyridine.
The products have been evaluated for antimicrobial activity. Some compound are found to have antimicrobial activity comparable to that of standard drugs, viz. sulfamethoxazole, sulfadiazine. The product have also been characterized by elemental analysis, absorption spectra, conductivity measurements, molecular weight determination,
magnetic susceptibility measurements and stepwise stability constants by PH metric method.
By using the results of above study, structure of metal complex is proposed.
OH O O O acetic anhydride O O p-cresylacetate p-Cresol
+ Reflux 2Hrs
Pyridine
(I) Fries Migration
Anhydrous AlCl3
O OH 2-acetyl-4-methylphenol (II) OH 2-ethyl-4-methylphenol (III) Clemmensen's reduction Zn/Hg, conc.HCl 1.
2.H2N SO2NHCOCH3 Cl N N SO2NHCOCH3
Sulphacetamide Diazonium salt (IV) Diazotisation
Conc. HCl + NaNO2
3. ( III ) + (IV) HO
N SO2NHCOCH3 N
C2H5
H3C
3-Ethyl-2-hydroxy-5-methyl-4'-methylcarbonylsulphonamido-azobenzene (V)
REACTION SCHEME
4. (Alcoholic sol.)
(V) + Metal Salts
aqueous sol. O
N
H3COCHNO2S N C2H5
H3C
O N
SO2NHCOCH3
N
C2H5
CH3
M+2
(VI a)
RESULTS AND DISCUSSION
IR Spectral data of the ligand.
IR ( KBr ): 3360 ( O-H str.), 3257(N-H str.), & 3075 ( = C-H str.), 2966 (C-H str.),
2967 (C-H str. -CH2 ), 2932 (C-H str.sym.-CH3 ),2870(C-H str. ), 1618 N=N- str.),1581
(-C=C- str.), 1581 (N-H def.), 1472 ( C-H def.), 1417( -N=N- str.), 1315 ( S=O str.asym.),1318 (O-H def.),1163 ( S=O str.sym.), 765 (N-H wag).
NMR Spectral data of the ligand.
1H NMR (CDCl
3): 1.24-1.25 δ(3H,t,-CH2 - CH3 ),2.34 δ(3H,s,-Ar - CH3), 2.67-2.70
δ(2H,q,-CH2 - CH3 ),5.09 δ(1H,s -NH) 7.15 δ ( 1H, s, Ar-H ) 7.64 δ ( 1H, s, Ar-H ),7.95-7.97
δ ( 2H, d, Ar-H ),8.07-8.09 δ ( 2H, d, Ar-H ), 12.94 (1H,s,Ar-OH ).
Mass Spectra: (m/z): 362 (M+), 303, 287, 267, 255, 239, 223, 205, 195, 163, 150, 135, 120,
105, 91, 77, 65, 55, 41.
Absorption Spectra: λ max (nm): 231, 323, 362,412.
log ε : 4.3410, 4.2859, 4.3267, 4.1747.
Antimicrobial Activity : The testing were carried out by cup-plate method at a concentration
of 50 μg using gram positive bacteria as B.megaterium and B. subtilis and gram negative bacteria as E. coli. And P. fluorescens and fungi as A. awamori and A.niger.Most of the compounds were moderately active against different strains of bacteria and fungi. However, comparatively significant was observed in compounds ( along with zone of inhibition in mm) having azodye ligand (V)-(17), Fe( II ) complex (VI)-(18) against B. mega, azodye ligand (V)-(19), Fe ( II ) complex (VI)-(20) against B. subtilis, azodye ligand (V)-(19), Fe( II ) complex (VI)-(19) against E. coli., azodye ligand (V)-(19), Fe ( II ) complex (VI)-(20) against A. arogens, azodye ligand (V)-(20), Fe ( II ) complex (VI)-(19) against A. awamori, azodye ligand (V)-(17), Fe ( II ) complex (VI)-(22) against A. niger
Physical method: Molar conductivities of 10-3 M solutions of the complexes in DMF were
measured on a Toshniwal conductivity bridge, using a dip type cell at room temperature. Magnetic susceptibilities were measured at room temperature on a Gouy balance using mercury (II) tetrathiocynato cobaltate (II) as the calibrant. IR spectra were obtained using KBr disc on NICOLET MEGNA-IR 550 SERIES II.
Table-1: Some Physical Properties of metal complex
Compound Molecular weight Found/ (Req.)
Elemental analysis % found/ calculated)
Conducivity (Mohs.cm2
Mole-1)
μ eff.
B.M.
M C H N
Fe(C17H18O4N3S)2(H2O)2 805.24 6.81 50.21 4.91 10.33 12.5 Diamagnetic
PH-metric measurements: for the determination of stepwise stability constants an expanded
scale systronic PH meter with accuracy ±0.02 units was employed. All experiments were
carried out at 30 ± 0.2 0C and temperature was mentioned constant using thermostat. The three
sets acid, acid + ligand, acid + ligand + metal were prepared.
In each case total volume was made up to 40 ml by adding required amount of double distilled water or purified dioxane as the case may be. The ionic strength was maintained by adding appropriate amount of sodium nitrate (0.01M) and mixtures were titrated with standard
NaOH solution. A modified form of Irving-Rosstti19 titration technique was used for
calculating the stability constants. The PH meter was calibrated with aqueous buffers. In the
calculations for pL the pH meter reading ‘B’ was used instead of converting it to true pH value (Corresponding to aqueous medium). The use of pH meter reading ‘B’ instead of true pH
values did not make any differences20-21 in the calculation of free ligand concentration and
was usually valid for water dioxane media.
Table 2: Stepwise stability constants of metal complexes of 3-ethyl-2-hydroxy-5-methyl-4’-methyl carbonyl sulphonamido- azobenzene in ( 60 : 40 ) Dioxane : Water, μ =0.1M, Temp 30 ± 0.20 C.
Ligand logK1H logK2H logB2H
C17H19O4N3S 10.547 3.511 14.058
Complex logK1 logK2 logK3
Fe(C17H18O4N3S)2(H2O)2 6.1123 4.6579 9.7702
Conductance measurements: Molar conductance values of all the complex in 10-3 M DMF
solutions are given in Table-1. This values are consistent with the non-electrolytic22 nature of
this complex.
Magnetic measurements: The observed magnetic moments of the resulting complex are
given in Table-1. This value shows that Fe(II) complex is diamagnetic nature.
From this observation it is concluded the Fe(II) complex is distorted octahedral in nature.
Potentiometric study: The PH metric study of the metal complex show the n values as 1.91,
indicating two ligands per metal ion, the result of stepwise stability constants shown in (Table-2).
UV and Visible spectra: The iron complex show a very diffused band at 795 n showing
Octahedral structure. The Mossbauer spectra show two symmetrical bands indicating distorted octahedral geometry which is support of the fact that there are two water molecules and two ligand molecules attached with Fe (II) ion.
CONCLUSION
ACKNOWLEDGDMENTS
The authors are thankful to the Head, Department of Chemistry, Saurashtra University, Rajkot, India for providing the necessary laboratory facilities.
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