Synthesis, characterisation and biological activity of 2-(methylthiomethyl)anilines, 2-(methylthio)anilines, their Schiff-base derivatives and metal(II) (Co, Ni, Cu) complexes
- Olalekan, Temitope Elizabeth
- Authors: Olalekan, Temitope Elizabeth
- Date: 2013
- Subjects: Aniline , Schiff bases , Ligands , Nuclear magnetic resonance spectroscopy , Chelates , X-ray crystallography , Antimalarials
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4562 , http://hdl.handle.net/10962/d1020868
- Description: A series of 31 sulfur-nitrogen donor ligands and 64 metal(II) complexes have been investigated. The thiomethylated aniline ligands 2–(methylthiomethyl)aniline 2MT and 2–(methylthio)aniline 2MA were synthesized with their substituted derivatives (-Me, -MeO, -Cl, -Br, -NO2) to serve as chelating agents. These ligands behave as bidentate ligands with SN donor group with Co(II), Ni(II) and Cu(II). The Co(II) and Ni(II) complexes have the ML2Cl2 molecular formula while the Cu(II) complexes formed with MLCl2 stoichiometry where L is the bidentate ligand. The ligands and their metal(II) complexes have been characterized by elemental analysis and with spectroscopic techniques. The trend observed in the NMR spectra and IR frequencies of the thiomethylated compounds shows there is a significant difference between the 2MT and 2MA series as a result of sulfur lone pairs extending the conjugation of the aromatic ring in the case of the latter. The effect of the position and electronic nature of ring substituent on the NMR shifts of the amine protons is discussed. The 6- and 5-membered chelate complexes formed by the 2MT and 2MA ligands respectively do not show significant diversity in their spectroscopic properties. From the elemental analysis for the Co(II) and Ni(II) complexes, their compositions reveal 1:2 M:L stoichiometry with 2 chlorine atoms from the respective metal salts. In addition, the spectroscopic data are largely indicative of tetragonally distorted structures for these solid complexes. The X-ray crystallography data reveal the Cu(II) complexes exist as square pyramidal dimers and with long Cu–Cl equitorial bonds fit into the tetragonally distorted octahedral structure. The electrolytic nature of Co(II) and Cu(II) complexes in DMF were found to be similar, they behave as non electrolytes in contrast to Ni(II) complexes which are 1:1 electrolytes. The electronic spectra of these metal(II) complexes were found to be different for both their solid forms and in solutions of DMF and DMSO and this has been discussed. The thiomethylated aniline ligands possess the amine and thioether groups which are present in many known biologically active compounds, hence the biological activity of the ligands and their metal complexes were tested against three strains of bacteria and one fungus. The methoxy-substituted derivatives were found to possess better inhibitory activity and this was similarly reflected in the metal(II) complexes. The activity of the complexes can be said to be in the order, Cu(II) > Co(II) > Ni(II). The Schiff-base derivatives were prepared from the ligands and para-methoxysalicylaldehyde and their Cu(II) complexes were synthesized in order to determine their biological activity. The Schiff-base ligands were found to be less active than their parent ligands. The Cu(II) complexes are not soluble in water, DMSO or DMF, as a result and could not be evaluated for their biological activity. Based on the good results from the antimicrobial evaluation, the antiplasmodial activity of some of the Co(II), Ni(II) and Cu(II) complexes of the thiomethylated ligands against Plasmodium falciparum (FCR-3) was determined. At 50 μM concentration level, the Cu(II) complexes show activity equal or better than the prophylactic chloroquine. The Cu(II) complexes with the methoxy-substituted demonstrated exceptional activity but their Co(II) and Ni(II) analogues did not show any activity. The cytotoxicity of the active Cu(II) complexes at 50 μM concentration was determined against the breast cancer cell line (MDA-MB-231). The compounds destroyed the cancer cell in the range of 28–40%, thus showing their preferred activity against the parasitic cell instead of the cancer cell. The selectivity demonstrated by these compounds have shown them to be potential antimalarial agents and this could be further investigated.
- Full Text:
- Date Issued: 2013
- Authors: Olalekan, Temitope Elizabeth
- Date: 2013
- Subjects: Aniline , Schiff bases , Ligands , Nuclear magnetic resonance spectroscopy , Chelates , X-ray crystallography , Antimalarials
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4562 , http://hdl.handle.net/10962/d1020868
- Description: A series of 31 sulfur-nitrogen donor ligands and 64 metal(II) complexes have been investigated. The thiomethylated aniline ligands 2–(methylthiomethyl)aniline 2MT and 2–(methylthio)aniline 2MA were synthesized with their substituted derivatives (-Me, -MeO, -Cl, -Br, -NO2) to serve as chelating agents. These ligands behave as bidentate ligands with SN donor group with Co(II), Ni(II) and Cu(II). The Co(II) and Ni(II) complexes have the ML2Cl2 molecular formula while the Cu(II) complexes formed with MLCl2 stoichiometry where L is the bidentate ligand. The ligands and their metal(II) complexes have been characterized by elemental analysis and with spectroscopic techniques. The trend observed in the NMR spectra and IR frequencies of the thiomethylated compounds shows there is a significant difference between the 2MT and 2MA series as a result of sulfur lone pairs extending the conjugation of the aromatic ring in the case of the latter. The effect of the position and electronic nature of ring substituent on the NMR shifts of the amine protons is discussed. The 6- and 5-membered chelate complexes formed by the 2MT and 2MA ligands respectively do not show significant diversity in their spectroscopic properties. From the elemental analysis for the Co(II) and Ni(II) complexes, their compositions reveal 1:2 M:L stoichiometry with 2 chlorine atoms from the respective metal salts. In addition, the spectroscopic data are largely indicative of tetragonally distorted structures for these solid complexes. The X-ray crystallography data reveal the Cu(II) complexes exist as square pyramidal dimers and with long Cu–Cl equitorial bonds fit into the tetragonally distorted octahedral structure. The electrolytic nature of Co(II) and Cu(II) complexes in DMF were found to be similar, they behave as non electrolytes in contrast to Ni(II) complexes which are 1:1 electrolytes. The electronic spectra of these metal(II) complexes were found to be different for both their solid forms and in solutions of DMF and DMSO and this has been discussed. The thiomethylated aniline ligands possess the amine and thioether groups which are present in many known biologically active compounds, hence the biological activity of the ligands and their metal complexes were tested against three strains of bacteria and one fungus. The methoxy-substituted derivatives were found to possess better inhibitory activity and this was similarly reflected in the metal(II) complexes. The activity of the complexes can be said to be in the order, Cu(II) > Co(II) > Ni(II). The Schiff-base derivatives were prepared from the ligands and para-methoxysalicylaldehyde and their Cu(II) complexes were synthesized in order to determine their biological activity. The Schiff-base ligands were found to be less active than their parent ligands. The Cu(II) complexes are not soluble in water, DMSO or DMF, as a result and could not be evaluated for their biological activity. Based on the good results from the antimicrobial evaluation, the antiplasmodial activity of some of the Co(II), Ni(II) and Cu(II) complexes of the thiomethylated ligands against Plasmodium falciparum (FCR-3) was determined. At 50 μM concentration level, the Cu(II) complexes show activity equal or better than the prophylactic chloroquine. The Cu(II) complexes with the methoxy-substituted demonstrated exceptional activity but their Co(II) and Ni(II) analogues did not show any activity. The cytotoxicity of the active Cu(II) complexes at 50 μM concentration was determined against the breast cancer cell line (MDA-MB-231). The compounds destroyed the cancer cell in the range of 28–40%, thus showing their preferred activity against the parasitic cell instead of the cancer cell. The selectivity demonstrated by these compounds have shown them to be potential antimalarial agents and this could be further investigated.
- Full Text:
- Date Issued: 2013
Synthesis, characterization and antimicrobial activity of copper (II) complexes of some hydroxybenzaldimines and their derivatives
- Authors: Sobola, Abdullahi Owolabi
- Date: 2012
- Subjects: Copper , Schiff bases , Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4534 , http://hdl.handle.net/10962/d1016258
- Description: This study focuses on the antimicrobial activity of Cu(II) complexes of some orthohydroxybenzaldimines and its derivatives. Four different categories of Schiff base ligands were prepared by condensing salicylaldehyde, o-vanillin, p-vanillin and vanillin with p- and osubstituted anilines; 1-aminonaphthalene; 2- and 3-aminopyridine; 2- and 3- aminomethylpyridine as well as 2-aminobenzimidazole. The last category was prepared from ophenylenediamine and o-vanillin. The Schiff base ligands have been characterized by a combination of elemental analysis and spectral (¹H- and ¹³C-NMR, UV/Visible, infrared and Raman) data. The existence of strong intramolecular hydrogen bonding in the orthohydoxybenzaldimines was evident from the chemical shift values of the hydroxyl proton in the ¹H-NMR spectra of the Schiff base ligands. The hydroxyl proton resonates at high frequency and thus absorbed far downfield at 13.46-11.83 ppm, reflecting the presence of hydrogen bonding between the hydroxyl proton and the imine nitrogen. In the p-substituted aniline analogues of the Schiff base, a plot of the chemical shift values of the hydroxyl proton against the Hammett's substituent parameters gave a linear correlation between the electronegativities of the substituents and the chemical shift values. The nitro group with the highest electronegativity caused the least deshielding of the hydroxyl proton and thus absorbed upfield compared to the less electronegative substituents such as the CH3 and OCH3 analogues. Likewise, in the solid state infrared spectra of the ligands, the hydroxyl stretching band of the ortho-hydroxyl Schiff base ligands was observed as a very broad band and at much lower frequency, 3100-2100 cm⁻¹, indicating the existence of strong intramolecular hydrogen bonding. In the same vein, ¹H- and ¹³C-NMR spectral data for the Schiff base ligands indicated that the prepared compounds exist in the enol form in aprotic solvent, chloroform. The methine proton appeared as singlet and there was no carbonyl signal in the ¹³C-NMR spectra of the Schiff base ligands. This was supported by the infrared data having no vibrational band attributable to the carbonyl stretching of the keto-form of the Schiff base ligands in solid state. However, the UV/Visible study of the Schiff base ligands in protic solvent, methanol, suggested the existence of some of the Schiff base ligands in keto-enol form. A band at greater than 400 nm was observed in the UV/Visible spectra of the ligands and this has been attributed to the presence of the keto form of orthohydroxyl Schiff base ligands in solution. A plot of the molar absorptivity (ε) of the band at greater than 400 nm against Hammett substituent parameters revealed that the intensity of the bands increased with the electronegativity of the substituents. The Cu(II) complexes of salicylaldehyde, o-vanillin and a few p-vanillin based Schiff base ligands are reported in this work. It was observed that introduction of Cu(II) ions into the ligand system resulted in the hydrolysis of the imine band in few cases. All the isolated complexes have been characterized by elemental analysis, conductivity measurement, infrared and UV/Visible spectral data. The structures of three of the Cu(II) complexes were further confirmed by X-ray single crystal diffraction. The Schiff base ligands either coordinated as neutral base through the imine nitrogen or via the imine nitrogen and the phenolic oxygen atoms. In addition, the benzimidazole-based and ovan-2-pico analogues equally coordinated through the imidazole N-3 nitrogen and the azine nitrogen respectively; thus acted as tridentate. In general, the synthesized Cu(II) complexes fell into seven categories viz: [Cu(LH)Cl(H₂O)]Cl; [Cu(LH)₂Cl₂].xH₂O; [CuL₂]; [Cu₂L₂]; [Cu(LH)Cl(H₂O)]Cl; and [MLCl]. The Cu(II) complexes of the form, M(LH)₂Cl₂.xH₂O were either 1:1 or non-electrolyte in methanol and DMF. The third category, CuL₂, was however, non-electrolyte existing as neutral four coordinate Cu(II) complexes. X-ray single crystal structure of Cu(II) complexes derived from the ammonia-based Schiff bases revealed a square planar geometry for the complexes and this agreed with the planar geometry that has been reported for Cu(II) complexes of N-arylsalicylaldimines of the type studied in this work. The complexes, [Cu₂L₂], resulted from the ortho-hydroxyaniline analogues and were polymeric with the Schiff base ligands coordinating to the Cu(II) ions as tridentate dibasic via the imine nitrogen, phenolic oxygen and the aminophenolic oxygen atoms. Cu(II) complexes prepared from ovan-2-ampy and ovan-2-pico Schiff bases were of the forms [Cu(LH)Cl(H₂O)]Cl and [CuLCl] respectively. The X-ray crystal structure of [Cu(ovan-2- pico)Cl] revealed a four-coordinate square planar geometry for the complex. In the same vein, the o-phenylenediamine complexes were of the form [Cu(L)(H₂O)], with the X-ray crystal structure of [Cu(bis-ovanphen)(H₂O)] revealing a square pyramidal geometry. The Schiff base ligands and the isolated Cu(II) complexes have been evaluated for their antimicrobial activity against three bacterial strains (Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™* and Bacillus subtilis subsp. spizizeni ATCC® 6633™*) and one fungal strain, Candida albicans ATCC® 2091™*, using agar disc diffusion and broth dilution techniques. It was observed that the presence of the methoxyl group at the ortho-position of the aldehyde moiety of the Schiff base ligands enhanced the activity of the ligand tremendously and thus the o-vanillin analogues showed the highest potency against the tested organisms. In addition, the hydroxyaniline analogues were equally the most promising of all the substituted aniline based Schiff bases. The o-vanillin analogues of the aminopyridines and aminomethylpyridines also exhibited significant activity against the tested organisms. All the 2-aminobenzimidazole series were active against the tested organisms. It should be noted that E. coli was the least susceptible of all the microorganisms while the highest potency was exhibited against the fungus of choice, Candida albicans. Lastly, chelation of the Schiff base ligands with Cu(II) ions did not have significant influence on the activity of the free ligands.
- Full Text:
- Date Issued: 2012
- Authors: Sobola, Abdullahi Owolabi
- Date: 2012
- Subjects: Copper , Schiff bases , Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4534 , http://hdl.handle.net/10962/d1016258
- Description: This study focuses on the antimicrobial activity of Cu(II) complexes of some orthohydroxybenzaldimines and its derivatives. Four different categories of Schiff base ligands were prepared by condensing salicylaldehyde, o-vanillin, p-vanillin and vanillin with p- and osubstituted anilines; 1-aminonaphthalene; 2- and 3-aminopyridine; 2- and 3- aminomethylpyridine as well as 2-aminobenzimidazole. The last category was prepared from ophenylenediamine and o-vanillin. The Schiff base ligands have been characterized by a combination of elemental analysis and spectral (¹H- and ¹³C-NMR, UV/Visible, infrared and Raman) data. The existence of strong intramolecular hydrogen bonding in the orthohydoxybenzaldimines was evident from the chemical shift values of the hydroxyl proton in the ¹H-NMR spectra of the Schiff base ligands. The hydroxyl proton resonates at high frequency and thus absorbed far downfield at 13.46-11.83 ppm, reflecting the presence of hydrogen bonding between the hydroxyl proton and the imine nitrogen. In the p-substituted aniline analogues of the Schiff base, a plot of the chemical shift values of the hydroxyl proton against the Hammett's substituent parameters gave a linear correlation between the electronegativities of the substituents and the chemical shift values. The nitro group with the highest electronegativity caused the least deshielding of the hydroxyl proton and thus absorbed upfield compared to the less electronegative substituents such as the CH3 and OCH3 analogues. Likewise, in the solid state infrared spectra of the ligands, the hydroxyl stretching band of the ortho-hydroxyl Schiff base ligands was observed as a very broad band and at much lower frequency, 3100-2100 cm⁻¹, indicating the existence of strong intramolecular hydrogen bonding. In the same vein, ¹H- and ¹³C-NMR spectral data for the Schiff base ligands indicated that the prepared compounds exist in the enol form in aprotic solvent, chloroform. The methine proton appeared as singlet and there was no carbonyl signal in the ¹³C-NMR spectra of the Schiff base ligands. This was supported by the infrared data having no vibrational band attributable to the carbonyl stretching of the keto-form of the Schiff base ligands in solid state. However, the UV/Visible study of the Schiff base ligands in protic solvent, methanol, suggested the existence of some of the Schiff base ligands in keto-enol form. A band at greater than 400 nm was observed in the UV/Visible spectra of the ligands and this has been attributed to the presence of the keto form of orthohydroxyl Schiff base ligands in solution. A plot of the molar absorptivity (ε) of the band at greater than 400 nm against Hammett substituent parameters revealed that the intensity of the bands increased with the electronegativity of the substituents. The Cu(II) complexes of salicylaldehyde, o-vanillin and a few p-vanillin based Schiff base ligands are reported in this work. It was observed that introduction of Cu(II) ions into the ligand system resulted in the hydrolysis of the imine band in few cases. All the isolated complexes have been characterized by elemental analysis, conductivity measurement, infrared and UV/Visible spectral data. The structures of three of the Cu(II) complexes were further confirmed by X-ray single crystal diffraction. The Schiff base ligands either coordinated as neutral base through the imine nitrogen or via the imine nitrogen and the phenolic oxygen atoms. In addition, the benzimidazole-based and ovan-2-pico analogues equally coordinated through the imidazole N-3 nitrogen and the azine nitrogen respectively; thus acted as tridentate. In general, the synthesized Cu(II) complexes fell into seven categories viz: [Cu(LH)Cl(H₂O)]Cl; [Cu(LH)₂Cl₂].xH₂O; [CuL₂]; [Cu₂L₂]; [Cu(LH)Cl(H₂O)]Cl; and [MLCl]. The Cu(II) complexes of the form, M(LH)₂Cl₂.xH₂O were either 1:1 or non-electrolyte in methanol and DMF. The third category, CuL₂, was however, non-electrolyte existing as neutral four coordinate Cu(II) complexes. X-ray single crystal structure of Cu(II) complexes derived from the ammonia-based Schiff bases revealed a square planar geometry for the complexes and this agreed with the planar geometry that has been reported for Cu(II) complexes of N-arylsalicylaldimines of the type studied in this work. The complexes, [Cu₂L₂], resulted from the ortho-hydroxyaniline analogues and were polymeric with the Schiff base ligands coordinating to the Cu(II) ions as tridentate dibasic via the imine nitrogen, phenolic oxygen and the aminophenolic oxygen atoms. Cu(II) complexes prepared from ovan-2-ampy and ovan-2-pico Schiff bases were of the forms [Cu(LH)Cl(H₂O)]Cl and [CuLCl] respectively. The X-ray crystal structure of [Cu(ovan-2- pico)Cl] revealed a four-coordinate square planar geometry for the complex. In the same vein, the o-phenylenediamine complexes were of the form [Cu(L)(H₂O)], with the X-ray crystal structure of [Cu(bis-ovanphen)(H₂O)] revealing a square pyramidal geometry. The Schiff base ligands and the isolated Cu(II) complexes have been evaluated for their antimicrobial activity against three bacterial strains (Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™* and Bacillus subtilis subsp. spizizeni ATCC® 6633™*) and one fungal strain, Candida albicans ATCC® 2091™*, using agar disc diffusion and broth dilution techniques. It was observed that the presence of the methoxyl group at the ortho-position of the aldehyde moiety of the Schiff base ligands enhanced the activity of the ligand tremendously and thus the o-vanillin analogues showed the highest potency against the tested organisms. In addition, the hydroxyaniline analogues were equally the most promising of all the substituted aniline based Schiff bases. The o-vanillin analogues of the aminopyridines and aminomethylpyridines also exhibited significant activity against the tested organisms. All the 2-aminobenzimidazole series were active against the tested organisms. It should be noted that E. coli was the least susceptible of all the microorganisms while the highest potency was exhibited against the fungus of choice, Candida albicans. Lastly, chelation of the Schiff base ligands with Cu(II) ions did not have significant influence on the activity of the free ligands.
- Full Text:
- Date Issued: 2012
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