INTRODUCTION:

Hydrazone complexes have undergone a phenomenal growth during the recent years because of the versatility offered by these complexes in the field of industries,^1,2 catalysis³ and in biological system.^4,5 etc. In this way, the synthesis, structural investigation and reaction of transition metal Schiff bases have received a special attention, because of their biological activities as antitumoral, antifungal and antiviral activities.⁶ Thus, Schiff base hydrazones are also interesting from the point of view of pharmacology. Derivatives of hydrazones have been reported to exhibit antibacterial, antitubercular, anticonvulsant, and anti-inflammatory properties.^7,8,9,10 Carcelli et al. specifically investigated and reported on the antibacterial and antifungal effects of hydrazones and their complexes with certain transition metal ions.¹¹

Furthermore, it was demonstrated that salicylaldehide benzoyl hydrazone complexes were a strong inhibitor of DNA synthesis and cell proliferation.¹² Additionally, a number of analogues of this hydrazone have been researched as possible ion chelating medications for genetic illnesses including thalasemia. It also has a small amount of bacteriostatic activity.^13,14 Given these observations, we report here the synthesis and structural studies of the complexes of Cu(II), Co(II), Ni(II), and Zn(II) with some hydrazone derivatives containing triazine moieties, such as 6-tert-butyl-4-{[1-(2-methoxyphenyl)ethylidene]amino}. This work is part of our ongoing research on the coordination chemistry of multidentate ligands. In this work, 6-tert-butyl-4-{[1-(2-methoxyphenyl)ethylidene]amino}-3-(methylsulfanyl)-1,2,4-triazin-5(4H)-one is abbreviated as TBMO, and MMAO stands for 4-{[(E)-(2-methoxyphenyl) methylidene]amino}-3-methyl-6-phenyl-1,2,4-triazin-5(4H)-one.

EXPERIMENTAL:

MATERIALS AND METHODS:

All the chemicals used were of Analytical Reagent grade. Prior to usage, the solvents underwent conventional procedures for purification. The materials such as 4-amino-6-tert-butyl-3-methylsulfanyl-1,2,3-triazine-5-one (Metribuzin with CAS number, 21087-64-9), 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,3-triazine-5-one, (Metamitron with CAS number, 41394-05-2) and 2-methoxybenzaldehyde, (o-anisaldehyde with CAS number: 135-02-4) were purchased from Sigma Aldrich chemical company.

Preparation of Ligands:

The ligands used in the present investigation are triazine-5-hydrazones of an aldehyde, o-anisaldehyde. These have been synthesized by condensing metribuzin and metamitron with o-anisaaldehyde in the following manner.

Ethanolic solutions of metribuzin and metamitron (0.01 mol in 20 mL) were added to ethanolic solution of o-anisaldehyde (0.01 mole in 20 mL), subsequently adding two to three drops of piperidine to the solution described above as a condensing agent. For three hours, the resultant solutions were each refluxed in a water bath. The coloured precipitates formed were concentrated and allowed to stand overnight before they were separated out in each case. These precipitates were filtered, washed and recrystallised from ethanol.¹⁵ The samples were then dried in vacuum over fused calcium chloride and then analysed (schemes 1and 2).

Preparation of the complexes: Hot ethanolic solutions of the ligands TBMO/MMAO (0.02 mole in 20 mL) were treated with ethanolic solution of respective hydrated metal (II) chloride (0.01 mole in 20 mL). The reaction mixtures were refluxed on a water bath for two hours while being continuously stirred. The resulting liquids were filtered and allowed to cool when coloured crystals of the corresponding metal complexes separated out in each case. The complexes underwent filtration, an ethanol and ether wash, and a vacuum-assisted drying process over fused CaCl₂.^15,16,17

Analysis and Physical measurements:

Weighed quantities of the compounds (0.2-0.3 g) were treated with few drops of concentrated H₂SO₄ and 1 mL of concentrated HNO₃. They were heated till all the organic matter decomposed and sulphur trioxide fumes were liberated. For the substance to totally break down, the same procedure was carried out three times in each case. Then were dissolved in water and the resulting solutions were used for analysis of metal ions. Gravimetric analysis was used to determine the complexes' metal contents in accordance with established protocol.¹⁷ Using a 1×10^-3 M solution of the complexes in DMSO, the molar conductance measurements were performed at room temperature using a Toshniwal conductivity Bridge (model CL-01-06, cell constant 0.5 cm-1). A MLW-CHN micro analyzer was used to determine the complexes' carbon, hydrogen, and nitrogen contents. Using an Australian Varian FTIR spectrophotometer, FTIR spectra in KBr pallets were recorded. A Perkin-Elmer spectrophotometer was used to record the electronic spectra of the complexes in DMSO. The Netzch-429 thermo analyzer was used to perform the thermogravimetric analysis. The compounds' ¹H-NMR spectra were captured using JEOL, GSX-400 type equipment in DMSO-d6 medium.

RESULTS AND DISCUSSION:

Molar conductance measurements support the suggested equations for the complexes that were constructed based on the analytical data (Table 1). The complexes exhibit color and are soluble in strongly coordinating solvents like DMSO, dioxane, and DMF, but insoluble in water and typical organic solvents. They are non-hygroscopic, highly stable under normal conditions and all of them decompose above 250^oC. The complexes' molar conductance data values in DMSO show that they are not electrolytes by nature.

IR spectra: The IR spectra of the ligands TBMO and MMAO and their metal complexes have been studied in concert for the appraisal of the structure of the complexes. The formation of the above ligands via the condensation of o-anisaldehyde with the ligands have been confirmed by the disappearance of band due to ν_NH2 and the discovery of a new band at about 1600 cm^-1, which is most likely the result of the recently added azomethine (C=N) group. The presence of -OCH₃ group in TMBO is also indicated by the appearance of the band at ~2840 cm^-1 in their respective spectrum assignable to ν_CH3 group of o-anisaldehyde.^18,19 The position of the above bands remains practically unaltered in the IR spectra of complexes there by suggesting non-participation of methoxy oxygen atom in coordination.

The triazine group's vC=N (cyclic) and νC-N (exocyclic) are attributed to the distinctive infrared bands found in the ligands' spectra at approximately 1560 and 1303 cm^-1, respectively. Analogous to the previous complexes, the position of both bands remain unaltered suggesting there by non-participation of ring N atom (-C=N) in complexation. However, ν_NH band of triazin ring (-N-H) group was found invariably shifted 20-10 cm^-1 towards negative side indicating the coordination of triazine ring NH group to the metal ions. Whereas band occurring at ~3100 cm^-1 due to ν_N-H exocyclic remains practically unaltered indicating it’s non-involvement either in coordination or enolisation. In addition to the previously mentioned, the bands at approximately 1600 and 1010 cm^-1, which correspond to the azomethine (vC=N) group and (vN-N) groups, respectively, moved during complexation.

As in earlier instances, the νC=N band experiences a red shift in this instance, while the νCN band displays a blue shift, signifying the coordination of the nitrogen atom in azomethine with metal ions. With this we further confirmed by the presence of a band at ~525 cm^-1 due to ν_NN. It is noteworthy to notice that electron-releasing units like -OCH₃ and -C-O-C-only strengthen conjugation; they do not participate in coordination when they are close to the condensation site most probably due to steric hindrance. Although evidence of ν_M-Cl band could not be brought in the present investigation due to instrumental limitation, the insolubility of the complexes in water and their non-electrolytic nature provide sufficient proof that the counterions Cl- coordinate to produce neutral complexes.

Thermal analysis:

Thermal characteristics of the complexes formed by TBMO and MMAO are recorded in Table 2. The thermal decomposition patterns of these compounds are the same. A quick examination of the thermograms of the complexes reveals that, the complexes remain almost stable up to ~235^oC indicating absence of water molecules. The complexes quickly break down and leave their stable residues above this threshold. The rapid decomposition denotes loss of ligand moiety. It has been noted that the residue's composition matches the corresponding metal oxides. The decomposition temperature varies for different complexes. The representative thermogram of Cu(TBMO)₂Cl₂ complex is shown in Fig. 1. The complexes' thermal stability is discovered to be in the following order:

TBMO Complexes: Co(II) < Zn(II) < Cu(II) < Ni(II)

MMAO Complexes: Co(II) < Ni(II) < Cu(II) < Zn(II)

Table 1: Analytical and physical data of the ligands and their complexes

Sl. No.	Compounds	Colours	Yields (%)	Λa	C Found (Calcd)	H Found (Calcd)	N Found (Calcd)	Cl Found (Calcd)	M Found (Calcd)
1	TBMO	Light yellow	80	-	40.78 (40.82)	5.23 (5.26)	44.41 (44.44)	-	-
2	MMAO	Light brown	83	-	41.23 (41.26)	4.38 (4.42)	40.06 (40.11)	-	-
3	Co(TBMO₂Cl₂	Silver grey	65	23.10	54.34 (54.38)	2.08 (2.11)	16.89 (16.92)	10.68(10.72)	8.88 (8.91)
4	Ni(TBMO)₂Cl₂	Royal ivory	62	21.35	54.39 (54.41)	2.09 (2.11)	16.90 (16.93)	10.70(10.73)	8.80 (8.84)
5	Cu(TBMO)₂Cl₂	Cannery yellow	63	21.90	53.98 (54.01)	2.07 (2.10)	16.76 (16.80)	10.61(10.65)	9.48 (9.53)
6	Zn(TBMO)₂Cl₂	White	64	22.12	53.81 (53.86)	2.05 (2.09)	16.74 (16.76)	10.59(10.62)	9.69 (9.73)
7	Co(MMAO)₂Cl₂	Brown	60	18.35	49.44 (49.48)	1.69 (1.72)	19.21 (19.24)	12.15(12.19)	10.11(10.13)
8	Ni(MMAO)₂Cl₂	Pale green	61	23.68	49.48 (49.51)	1.70 (1.72)	19.22 (19.25)	12.18(12.20)	10.02(10.06)
9	Cu(MMAO)₂Cl₂	Steel grey	63	21.65	49.08 (49.10)	1.68 (1.71)	19.05 (19.09)	12.06(12.10)	10.79(10.82)
10	Zn(MMAO)₂Cl₂	White	60	20.25	48.91 (48.95)	1.64 (1.70)	19.01 (19.04)	12.04(12.07)	11.01(11.05)

Table 2: Important features of thermo gravimetric analysis (TGA)

Sl. no.	Compounds	Total wt. of TG (mg)	Decomposition temperature (^oC)	% weight of residue Found (calcd.)	Composition of the residue
1	Co(AIAB)2Cl2	19.2	237-560	11.29 (11.33)	CoO
2	Ni(AIAB)2Cl2	21.2	258-555	11.23 (11.26)	NiO
3	Cu(AIAB)2Cl2	17.5	247-540	11.91 (11.93)	CuO
4	Zn(AIAB)2Cl2	15.8	240-550	12.08 (12.12)	ZnO
5	Co(FIAB)2Cl2	22.3	236-570	12.84 (12.88)	CoO
6	Ni(FIAB)2Cl2	21.7	240-570	12.78 (12.81)	NiO
7	Cu(FIAB)2Cl2	20.1	252-575	13.52 (13.55)	CuO
8	Zn(FIAB)2Cl2	16.4	260-585	13.75 (13.77)	ZnO

Electronic spectra and magnetic properties:

The electronic spectral data and room temperature effective magnetic moment values of Co(II) complexes with the ligands TBMO and MMAO are recorded. The room temperature µ_eff value of these complexes lies in the range 4.40-4.63 B.M. i.e., lower than expected for high spin pesudo-octahedral Co(II) species. This lower µ_eff value may be due to distorted structure of Co(II) complexes under C₂ symmetry. Similar to C2 symmetry, the metal ion's ground state degeneracy will be removed, resulting in an orbital singlet state that has a substantially lower magnetic moment than anticipated.²⁰ Thus, electronic spectrum data further supports the assumption that the current Co(II) complexes most likely contain an orbital singlet ground state with a deformed octahedral environment.

Figure 1: Thermogram of Cu(TBMO)2Cl2.

The electronic spectra of these complexes show a broad band at ~9000 cm^-1 (1111 nm) and a split band at ~19,200- 20,500cm^-1 (520-487 nm). Under Oh geometry, the first band is ascribed to 4T1g(F)→4T2g(F) (v1), while the second band is caused by 4T1g(F)→4T1g (P) (ν3) transitions. The ν1 band superimposes other bands, as seen by the large asymmetrical curve observed as v1. It is possible to calculate the values of Dq and B using band position of ν₁ and ν₃, following same method as in previous cases. Value of ν₂ has been calculated to be around ~19000 cm^-1 (526 nm). Thus, the observed weak shoulder near ~19000 cm^-1 may be tentatively assigned to ν₂ transition. From this it is concluded that the band around ~16000-16,500 cm^-1 is most likely due to spin for- bidden ⁴T_1g(F)→²T_2g (G) transition and not due to ⁴T_1g (F)→⁴A_2g (F) (ν₂) transition.

The spectral characteristics of Co(II) complexes with TBMO and MMAO ligands with Cl^- as co ligand do not indicate pure octahedral or D_4h symmetry, instead, it implies that the C2 geometry has distorted six coordinates, as indicated by the µeff values. This, nevertheless, necessitates dividing the ν3 and v1 bands because the symmetry is lowered.²⁰ The electronic spectra displays bands between approximately 19,200 and 20,500 cm^-1, which might be interpreted as the split constituent of the ν3 band. Additionally, one of the split components of the ν3 band may potentially be present in the shoulder around 19,000 cm^-1. Although no split Component of ν band is observed, yet the presence of a broad envelope suggests superimposition of the different components into a single one.

The electronic spectral data and µ_eff value room temperature for Ni(II) complexes with ligands TBMO and MMAO with Cl^- as co ligand have recorded. For these complexes, the measured µeff values support the idea of a tetragonal six-coordinated spin-free Ni(II) species.²⁰ Numerous bands in the range of approximately 8,600 cm^-1 (1160 nm), 10,400 cm^-1 (961 nm), 14,000 cm^-1 (714 nm), and 26,000 cm^-1 (386 nm) may be seen in the electronic spectra of the complexes. These types of spectral features can be explained on the basis of energy level schemes derived by Ballhausen and coworkers²¹ for D_4h symmetry. The first two bands are associated with the split components of 3T2g (F), specifically 3B1g→3Eg and 3B1g→3B2g, whereas the third and fourth bands are related to the split components of 3T1g (F) term, 3B1g→3A2g and 3B1g→3Eg. The transition 3B1g (P)→3T1g (P) can be associated with the sixth one. In this instance, the 3B2g term under D4h symmetry has replaced the ground state term A2g under Oh symmetry.²¹

The electronic spectral data and room temperature µ_eff values of Cu(II) complexes with ligands TBMO and MMAO are recorded. The µ_eff value in these cases lie in the range 1.82-1.88 B.M. as expected for hexa-coordinated spin free Cu(II) complexes in distorted octahedral environment. In the electronic spectra of these complexes one broad envelope is seen at ~16,000 cm^-1 (625 nm). Suggesting super-imposition of ν₁, ν₂ and ν₃ transitions because of similar energy. Hence, in a distorted octahedral environment, the aforementioned band corresponds to the 2Eg→2T2g transition. Evidence of distortion is provided by the band's breadth. Figure 2 displays the representative spectrum of the Ni(MMAO)2Cl₂ complex.

1H-NMR spectra: In the ¹H NMR spectrum of the ligand TBMO, the multiplet is observed at δ 8.0-8.7 ppm correspond to 4 aromatic protons of aldehyde group. A signal observed at δ 9.2 ppm correspond to the exocyclic -NH-N= proton. Besides the above peaks, a sharp signal at δ 9.4 ppm and δ 4.7 ppm observed due to azomethine (-N= CH-) protons and O-CH₃ group respectively. In the context of TBMO complexes, the azomethine proton exhibits an upfield shift in conformity with the coordination of the azomethine group in complexes, but the exocyclic -NH-N proton of the triazine group shows a downfield shift, indicating hence the coordination of the ring NH group to the metal ions.²²

Figure 2: Electronic spectra of Ni(FIAB)2Cl2

Figure 3: M = Co(II), Ni(II), Cu(II) and Zn(II).

Figure 4: M = Co(II), Ni(II), Cu(II) and Zn(II).

In the ¹H NMR spectrum of the ligand MMAO, the multiplet is observed at δ 8.0-8.7ppm correspond to 4 aromatic protons of the aldehyde group and 5 aromatic protons of the phenyl group attached to the triazine ring. A signal observed at δ 9.0ppm correspond to exocyclic -NH-N= proton. In addition to the aforementioned peaks, azomethine (-N=CH-) protons are responsible for a strong signal at δ 9.4ppm. In the context of MMAO complexes, the azomethine proton exhibits an upfield shift in conformity with the coordination of the azomethine group in complexes, but the exocyclic -NH-N proton of the triazine group shows a downfield shift, indicating hence the coordination of the ring NH group to the metal ions. It is to be noted that the multiplet due to aromatic proton undergoes downfield shift to some extent probably due to the involvement of ring NH group to the complexation because of lowering electron density in the ring system. For the current complexes, the structures (Figs. 3 and 4) are suggested in light of the previously mentioned observations.^23,24

Antibacterial and antifungal activity:

The Antibacterial activities of the synthesized complexes were evaluated by the Agar Well Diffusion Assay Technique against two Gram positive bacteria, i.e., Bacillus subtilis and Bacillus stearothermophilus and two Gram negative bacteria, i.e., Escherichia coli and Salmonella typhi. Solutions of the ligands and its complexes in DMF were plated onto the cultured agar medium and incubated for a period of 24h at 37^oC. The plates were checked for zones of inhibition (measured in centimeters) post incubation period. Two fungal strains, A. niger and A. flavus, were used to test the complexes' antifungal properties. The complexes showed good antibacterial and antifungal activities (Table 3) against the species. This could be explained by the fact that C=N bonds predominate in their structures. Additionally, coordination lessens the metal ion's polarity^25,26,27, primarily as a result of The chelate ring formed during coordination has a partial shared positive charge with the metal ion. Through this process, the core metal atom becomes more lipophilic, increasing its ability to penetrate the lipid layer of microorganisms and cause more aggressive destruction.^28,29,30 The antibacterial properties of these metal complexes may also be due to a variety of other variables, including conductivity, dipole moment, and solubility, all of which are impacted by the metal ion.^31,32,33,34

Table 3: Antibacterial and antifungal activities of the compounds (for a concentration of 100 µg mL^-1)

Compound	*B. subtilis*	*B. stearothermophilus*	*E. coli*	*S. typhi*	*A. niger*	*A. flavus*
TMBO	17.38	15.63	18.43	20.11	12.53	11.49
MMAO	16.76	13.39	19.54	21.67	7.84	9.28
Co(TMBO)₂Cl₂	41.53	36.64	43.61	46.82	37.54	34.32
Ni(TMBO)₂Cl₂	22.39	25.78	29.42	27.28	28.81	31.73
Cu(TMBO)₂Cl₂	19.91	21.45	26.65	24.45	21.34	23.62
Zn(TMBO)₂Cl₂	20.42	19.37	21.63	28.21	16.26	17.47
Co(MMAO)₂Cl₂	28.23	19.87	31.73	33.57	18.28	20.78
Ni(MMAO)₂Cl₂	21.85	26.27	28.49	25.32	20.61	17.58
Cu(FIAB)₂Cl₂	25.83	22.19	27.46	28.32	12.23	16.34
Zn(MMAO)₂Cl₂	22.48	18.67	24.52	19.34	15.47	14.38

CONCLUSION:

The synthesis of hydrazone ligands and their metal complexes, which have antibacterial and antifungal activities, was the focus of the completed research. The compounds were synthesized and characterized using efficient techniques. The recently created compounds are strong inhibitors of the microorganisms under research, according to the results of antimicrobial investigations of the compounds.

ACKNOWLEDGEMENT:

The director of the Central Laboratory in Port-Harcourt, Nigeria, provided the services for which the writers are very grateful.

CONFLICT OF INTEREST:

The authors wish to infer that there is no conflict of interest to declare.

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Received on 27.04.2024 Revised on 10.08.2024

Accepted on 12.10.2024 Published on 22.10.2024

Available online from October 31, 2024

Asian J. Research Chem.2024; 17(5):257-263.

DOI: 10.52711/0974-4150.2024.00045