A tridentate Schiff base ligand, (E)-2-(4-dimethylbenzydimino) glycylglycine (glygly-DAB), derived from the condensation of 4-Dimethylaminobenzaldehyde (D AB) and glycylglycine (glygly) together with its Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized and characterized using various physico-chemical methods including C,H,N elemental analysis, melting point determination, molar conductivity measurement, IR, 1H NMR and UV-Vis. The ligand and metal complexes were screened in vitro for antimicrobial and antifungal activities on four bacterial strains (Staphylococcus aureus, Escherichia coli, Salmonella thyphi and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). glygly-DAB showed remarkable antifungal activities on all the fungal strains and antibacterial activities on one bacterial strain.
Schiff bases are an important class of ligands due to their synthetic flexibility, their selectivity, their ability to act as multidentate N- and O-donor ligands and their structural resemblance to natural biological substances [
The emergence of drug-resistant bacterial strains has become a world-wide cause for concern [
All reagents were analytical grade, obtained from commercial sources and were used without further purification. The metal contents in the complexes were estimated by complexometric titrations. C, H and N elemental analyses were performed using a PE 2400 CHN/O/S Elemental Analyser. IR spectra were recorded using a KBr disc on an ALPHA-P spectrometer obtained from BRUKER in the 3800 ~ 400 cm−1 region. Electronic spectra were recorded on a HACH DR-3900 UV/VIS spectrometer. Molar conductance measurements of aqueous solutions of the complexes (10−3 M) were measured using a CD810 Solea Tacussel conductivity meter. The melting points of the compounds were determined using a KOFLER bench from LEICA VMHB. The micro-organisms were obtained from the Phytobiochemistry Laboratory of the University of Yaoundé 1.
The Schiff base ligand, glygly-DAB was synthesized according to the general synthetic procedure [
An ethanolic solution of 4-Dimethylaminobenzaldehyde (5 mmol) was added drop wise to a solution of glycylglycine (5 mmol) and KOH (5 mmol) in ethanol and the mixture heated under reflux for 3 hours. After concentrating the solution, a yellowish precipitate was obtained which was filtered, washed several times with ethanol and air-dried at room temperature. Yield: 72%, m.p 56˚C; Anal. Calc. (Found): C: 51.81 (51.93); H: 5.35 (5.57); N: 13.94 (13.84). 1H NMR (DMSO; ppm): δ 9.85 (s, 1H; -CH=N); 8.40 (s, 1H; N-H); 7.1 - 7.9 (m, 4H; phenyl ring H); δ 3.2 - 3.4 (s, 4H; -CH2); 2.75 (m, 6H; -CH3).
A methanoic solution of the metal Chloride (1 mmol) was added drop wise to a solution of (E)-2-(4-dimethylbenzydimino) glycylglycine (1mmol) in ethanol. The mixture was heated under reflux for 3hours and the coloured precipitates obtained were filtered, washed several times with methanol and air-dried at room temperature.
In vitro Antimicrobial activity of the ligands and corresponding complexes were done in the Laboratory unit of Yaoundé Central Hospital and the phytobiochemistry laboratory of the University of Yaounde 1, and tested against four bacterial species: Staphylococcus aureus, Escherichia coli, Salmonella thyphi and Pseudomonas aeruginosa and two fungal species: Candida albicans and Cryptococcus neoformans.
The antimicrobial and antifungal screening were performed by the disc diffusion method [
40 mg of each compound was dissolved in 1 ml of 10% DMSO to obtain a final concentration of 40 mg/ml. A wattman N˚3 filter paper, 5mm diameter was placed on the surface of the sowed medium. 10µl of the compound was then added to every corresponding disc and allowed to stand for 15 minutes for pre-diffusion at room temperature before being hatched at 37˚C for 24 hours for the bacteria and 48 hours for the fungi. Every test was repeated three times. The antimicrobial and antifungal activities of each compound were determined by measuring its inhibition zone diameter in mm and the compounds with an inhibition zone diameter ≥ 13 mm are kept for the determination of their inhibitory minimal concentration [
The physical characterization and analytical data of the ligands and their complexes are given in
Compounds | Formula | Color | Molar conductance (Ω−1∙cm2∙mol−1) | Melting point (˚C) | Analysis % calculated (found) | ||
---|---|---|---|---|---|---|---|
C | H | N | |||||
GLYGLY-DAB (L) | C13H16N3O3K | yellow | / | 56 | 51.81 (51.93) | 5.35 (5.57) | 13.94 (13.84) |
[ZnL(H2O)]2SO4∙2H2O | ZnC13H22N3O10S | white | 238.8 | >260 | 32.68 (32.02) | 4.64 (5.18) | 8.79 (8.93) |
[CuL(H2O)]Cl∙5H2 O | CuC13H20N3O5Cl | blue | 119.2 | 224 | 33.27 (33.33) | 6.01 (6.08) | 8.95 (8.55) |
[CoL(H2O)]Cl∙3H2 O | CoC13H24N3O7Cl | Pink | 159.2 | >260 | 36.42 (36.09) | 5.64 (4.13) | 9.80 (8.97) |
[NiL(H2O)]Cl∙5H2 O | NiC13H28N3O9Cl | Pale green | 159.0 | 196 | 33.61 (33.77) | 6.03 (5.21) | 9.05 (8.26) |
The 1H-NMR spectrum of glygly-DAB was recorded on an AC 250 NMR spectrometer using DMSO as internal standard in the 3 - 10 ppm region.1H-NMR spectrum of glygly-DAB shows the azomethine proton (H-C=N) signal at 9.8 ppm and amide proton (-CONH-) signal at 8.4 ppm. The aromatic protons show the multiplet (aromatic-CH‚ CH-) at 6.8 - 7.5 ppm. The two aliphatic protons (-CH2-) in the chain show the multiplet signal at 3.2 - 3.7 ppm and the methyl group signal (-CH3) appear at 2.75 ppm. Based on the above analysis, the 1H-NMR spectrum and proposed structure of glygly-DAB is given in
The IR spectra of glygly-DAB and its complexes are given in
composes | ν(C=N) | ν(N-H) | ν(C-O) | ν(M-O) | ν(M-N)Azomethine | ν(M-N)peptide | ν(O-H) | |||
---|---|---|---|---|---|---|---|---|---|---|
glygly-DAB (L) | 1625 | 3412 | 1382 | / | / | / | / | |||
[ZnL(H2O)]2SO4 | 1587 | 3385 | 1064 | 649 | 476 | 415 | 3303 | |||
[CuL(H2O)]Cl | 1587 | 3396 | 1337 | 618 | 442 | 396 | 3414 | |||
[CoL(H2O)]Cl | 1568 | 3349 | 1336 | 475 | 457 | 438 | 3237 | |||
[NiL(H2O)]Cl | 1585 | 3334 | 1280 | 481 | 465 | 399 | 3301 | |||
The UV-Visible spectrum of the ligand and its complexes were measured in distilled water at room temperature and the obtained spectra of the complexes are given in
The antibacterial and antifungal activities of glygly-DAB and its metal complexes were tested against E. coli, S. thyphi, C. albicans, P. aeruginosa, S. aureus and C. néoformans. The susceptibility of these strains of bacteria and fungi towards these compounds was judged from the measurement of the size of the inhibition diameter growth. The results obtained are presented in
The Schiff base ligand, glygly-DAB was more active against E. coli, S. thyphi, C. albicans, C. néoformans and no activity against P. aeruginosa, S. aureus. The Co(II) complex show greater activity on E. coli and C. néoformans than the free ligand glygly-DAB. In the same way, the Cu(II) complex shows greater activity on E. coli; P. aeruginosa; C. albicans and C. néoformans compared to the free ligands while the Ni(II) complex shows greater activities on S. thyphi; S. aureus and C. néoformans compared to the free ligands. This increase in activity on chelation might be due to the delocalization of charge on the metal in the chelated complex thus increase in the lipophilic character of the metal chelate. Cu(II) and Ni(II) complexes show better activity on C. néoformans than the standard antibiotic, fluconazole. Compounds with a diameter of zone of inhibition ≥ 13 mm were used for the determination of their inhibitory minimal concentration.
Bacterial species | Fungal species | |||||
---|---|---|---|---|---|---|
compound | E. coli | S. thyphi | P. aeruginosa | S. aureus | C. albicans | C. néoformans |
glygly-DAB (L) | 07 | 12 | 00 | 00 | 09 | 13 |
Zn-glygly-DAB | 05 | 00 | 07 | 16 | 00 | 00 |
Cu-glygly-DAB | 09 | 08 | 07 | 00 | 10 | 00 |
Co-glygly-DAB | 09 | 09 | 00 | 00 | 00 | 06 |
Ni-glygly-DAB | 00 | 15 | 00 | 00 | 00 | 00 |
The minimal concentration at which the compound inhibits 100% visible growth of microorganism, (MIC) was further determined using the compounds with a diameter of inhibition zone greater than 13 mm [
Compound | Bacterial species | Fungal species | ||
---|---|---|---|---|
S. thyphi | S. aureus | C. néoformans | ||
glygly-DAB | / | / | 2 × 10−2 | |
Zn-glygly-DAB | / | 2 × 10−3 | / | |
Ni-glygly-DAB | 2.5 × 10−2 | / | / |
The (E)-2-(4-dimethylbenzydimino) glycylglycine Schiff base ligands and their Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized and characterized. The Schiff base ligand glygly-DAB is tridentate, bonding using the azomethine nitrogen, peptide nitrogen and carboxyl oxygen, forming Tetrahedral complexes except Cu(II) complex which is square planar. Antimicrobial tests show that some of the complexes are more active as compared to the free ligand.
We thank Pr. Aminou Mohamadou (University of Reims, France) for the 1H-NMR spectra.
The authors declare no conflicts of interest regarding the publication of this paper.
Kuate, M., Conde, M.A., Nchimi, K.N., Paboudam, A.G., Ntum, S.-J.E. and Ndifon, P.T. (2018) Synthesis, Characterization and Antimicrobial Studies of Co(II), Ni(II), Cu(II) and Zn(II) Complexes of (E)-2-(4-Dimethylbenzydimi- no)-Glycylglycine, (Glygly-DAB) a Schiff Base Derived from 4-Dimethylaminobenzalde- hyde and Glycylglycine. International Journal of Organic Chemistry, 8, 298-308. https://doi.org/10.4236/ijoc.2018.83022