This paper includes synthesis and characterization of mixed ligand complexes derived from mefenamic acid and metformin using transition metal ions such as Co(II) and Cu(II). These complexes have been characterized by magnetic susceptibility, molar conductance, TG analyses, and spectral techniques such as FTIR and UV spectra. The theoretical study of the ligands and their complexes using semiempirical (PM6) method was used to measure IR and UV spectroscopy, HOMO-LUMO categories of the ligands. These synthesized complexes are also studied for their biological activities. The studies made on these complexes proposed a six octahedral geometry
Mefenamic acid [L1] 2-[(2,3- dimethylphenyl)amino]benzoic acid], an anthranilic acid derivative, which is widely used to relieve mild to moderate pain [
All the chemicals were supplied from Samarra Laboratories for Drugs Industry (IRAQ), BDH, and Fluka; these materials were used without further purification.
Atomic absorption using Shimadzu model 6809, FTIR-8300 Shimadzu spectrophotometer, in the frequency range of 4000-400 cm−1, UV-visible spectrophotometer using Varian model, and conductivity meter using Philips. The melting points were recorded in Coslab melting point apparatus. The magnetic susceptibility of the solid complexes was obtained at room temperature using Magnetic Susceptibility Balance Johnson Matthey. Elemental analysis (EA) was carried out using elemental analyzer.
Synthesis of mixed drug complexes was carried out using template method. A hot ethanolic solution (10 ml) of respective transition metal salts (1 mmol) was mixed with a hot solution (1 mmol) of mefenamic acid and metformin (1 mmol). Few drops of dil. NH3 10% were added to the mixture. The resulting mixture was then left under reflux for 2 hours. After refluxing for 2hrs appropriate complexes were precipitated out on cooling the reaction mixture. Those were then filtered, washed with ethanol, and washed using cold water [
Synthesis of mixed drug complexes.
All the synthesized complexes were thermally stable and colored. The magnetic moments of the solid complexes were measured by Farady’s method at 300 K and the values observed for copper(II) complex were 1.69-1.78 BM which fall in one of the expected electrons for d9 configurations [
Physicochemical properties of ligands and synthesized complexes.
Comp. | M.Wt | Color | Melting Point (°C) | Yield(%) | Molar Conductance (ohm−1.mol−1.cm2) | B.M( |
---|---|---|---|---|---|---|
C15H15NO2 [L1] | 241 | White | 230-231 | - - - - - - | - - - - - - - | - - - - |
C4H11N5 [L2] | 129 | White | 221-222 | - - - - - - | - - - - - - - | - - - - - |
| 481 | Violet | >300 | 71 | 18 | 4.7 |
| 486 | Pink | >300 | 83 | 11 | 1.65 |
Figure
HOMO-LUMO categories of the ligands (mefenamic acid and metformin).
The ligand (metformin) shows three sharp absorption bundles at regions 3373cm−1 and 3159-3298 cm−1 assigned to groups NH and NH2, respectively; peak C = N appears at 1583- 1626cm−1 and 1276-1419cm−1 assigned to C=N; and N-N appears at 937cm−1. Mefenamic acid has N-H band appearing at 3340cm−1. The vibrational spectrum of the synthesized complexes showed the difference in the severity of the packs C = N and NH, respectively, having clearer deviations than in the free ligand. This is evidence of the participation of the nitrogen atom in the uniformity of the metal ion. This is shown by resonance and the change in the intensity of the group C = N towards the red displacement in the complex was recorded in the free ligand (1583-1626cm−1) (1612-1629cm−1) in the metal complex due to consistency and the formation of the motor stabilized system [
Experimental and theoretical IR spectrum bands of ligands and their complexes.
Comp. | | | | |
---|---|---|---|---|
C15H15NO2 [L1] | 3340 | 1730 | 1673-1422 | - - - - - - |
| | | ||
C4H11N5 [L2] | 3373 | - - | - - - - | - - - - - |
| ||||
[Co(L1)(L2) H2OCl] | 3327 | - - - | 1678-1492 | 486 |
| | | ||
[Cu(L1)(L2) H2OCl] | 3336 | - - - - - | 1614-1462 | 491 |
| | |
The IR spectra of the ligand metformin (L2).
The IR spectra of the complex [Cu(L1)(L2) H2OCl].
The electronic spectra of the ligands L1, L2 and their metal complexes were measured in ethanol and DMSO solutions. The mefenamic acid and metformin base ligand L1, L2 displayed absorption around and in the 220 nm region assigned to the
Experimental and theoretical UV-Vis spectrum bands of ligands and their complexes.
Compounds | Bands (nm) | Geometry |
---|---|---|
C15H15NO2 [L1] | 324 – 247 | - - - |
| ||
C4H11N5 [L2] | 237 – 266 | - - - - |
| ||
[Co(L1)(L2) H2OCl] | 610 – 489 - 341 | Octahedral |
| ||
[Cu(L1)(L2) H2OCl] | 580 – 370 - 290 | Octahedral |
(670 – 365 – 296) |
UV-Vis spectra of the complex Co(L1)(L2) H2OCl].
Thermogravimetric analyses (weight changes) were performed in the temperature up to 600°C under argon atmosphere at the heating rate 20 C/min. The thermogram of
TG/DTG and DSC thermogram of [Co(L1)(L2) H2OCl] in argon atmosphere.
TG/DTG and DSC thermogram of [Cu(L1)(L2) H2OCl] in argon atmosphere biological activity.
Biological activities of these complexes against different bacterial isolates were studied. The biological activities of the test compounds were evaluated by the well diffusion method against
Biological activities of the ligands and their complexes against different bacterial isolates.
Bacterial isolates | DMSO | Ligand 1∖DMSO | Ligand 2/DMSO | Ligand | Co ligand | Cu-ligand |
---|---|---|---|---|---|---|
1+2/DMSO | 1+2/DMSO | 1+2/DMSO | ||||
| - | 21 | 15 | 14 | 14 | 15 |
| - | 14 | - | - | 13 | 10 |
| - | 15 | - | - | 15 | 12 |
| - | 15 | - | 12 | 15 | 11 |
| - | 14 | 14 | 12 | 16 | 13 |
Effect of ligands and their complexes in the inhibition of different kinds of bacteria.
We concluded in this work that the synthesized complexes, prepared from mixed drugs (mefenamic acid and metformin), had octahedral geometric shapes; the biological activity of these drugs against different kinds of bacteria increased after being mixed with Cu(II) and Co(II). We concluded that there is a great convergence between experimental and theoretical results using semiempirical (PM6) method.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there are no conflicts of interest.
This work was performed in the Laboratories of the Chemistry and Biology Departments in Al-Mustansiriyah University.