Synthesis and Antimicrobial Screening of Metal-ligand Complexes Derivative from (2-chloroquinolin-3-yl)methylene)hydrazine) and their Biological Studies

Introduction

The chemistry of transition metal complexes has garnered significant interest due to their catalytic and bioinorganic properties. These complexes are also noteworthy for their potential biological activities, including anticancer¹, antimicrobial², antimalarial³, and antitumor⁴. antibacterial⁵, antiviral⁶, antinflammatory⁷, antioxidant⁸. Schiff base compounds, which are formed through thecompression of prime amines by carbonyl compounds (aldehydes) and the elimination of water molecules, are particularly important in this context. The formation of Schiff bases is often facilitated by the presence of a dehydrating agent (Scheme 1).

The choice of metal integrated into the complex and the particular Schiff base utilized have a substantial impression on their biological activity. Metal-Schiff base compounds demonstrate more potent drug action mechanisms than their decently organic counterparts. Owing to the biologically active azomethine group, Schiff bases serve as highly effective ligands for metal compounds. This azomethine structure, with its electron-deficient carbon and electron-rich nitrogen, facilitates diverse electrophilic and nucleophilic reactions at these specific sites^9-11.

Schiff bases that coordinate with oxygen, nitrogen, and other similar donor atoms, and their complexes, have been extensively studied and statedto exhibit a comprehensivevarietyof biological activities, with activity beside bacteria, fungi, and certain types of tumors. These compounds possess numerous biochemical, clinical, and pharmacological properties¹². The synthesis of the metal complexes followed procedures reported in the literature^13,14.

The chemistry of Schiff bases represents a significant area of study within coordination chemistrybecause of their capacity to form stable multiplexes with various metal ions, leading to applications across multiple disciplines. A notable focus in this field has been theusageofSchiff-base ligands to progressphenoxo-bridged binuclearmultiplexesby eitherhomometalliccenters. These Schiff-base complexes are crucial in biomedical, biomimetic, and catalyticorganizationsand also support liquid crystalline phases^15-22. Schiff bases synthesized from aliphatic aldehydes tend to be more unstable and prone to polymerization compared to those derived from aromatic aldehydes, which exhibit greater stability due to more effective conjugation. Aldehydes, which are less sterically hindered and more electrophilic than ketones, react more readily, facilitating the formation of Schiff bases. The simplicity of synthesis and the ready availability of Schiff bases have made them a subject of considerable interest. The development of several applications in the fields of inorganic²³, bioinorganic²⁴, organic synthesis²⁵, environmental²⁶, and coordination chemistry²⁷ are the significant interest. 

Materials and Methods

All the procured substances used were methodical mark, distilled solvents were used.

Metal salts were used without further refinement. 

Scheme 1: Synthesis of hydrazine derivative.Click here to View Scheme

In 50 ml round bottom flask to stirred solution of compound (1) (1mmol) in ethanol (10 mL) was treated by hydrazine hydrate (2) (6 mmol) and 1-2 drops of rigorous sulphuric acid at room temperature. The reaction mixture was refluxed in a preheated oil bath for four hours, resulting in the formation of 2-chloro-3-(hydrazonomethyl)quinolone (3). Subsequently, an extra 1 mmol of 2-chloroquinolin-3-carbaldehyde (4) and 1–2 drops of concentrated H₂SO₄ were introduced, and the mixture was further refluxed for another four hours. Upon conclusion of the reaction, as observed by T. L.C. by means of an ethyl acetate: n-hexane (3:7) system, the solvent was evaporated. The resulting crude product was precipitated by adding ice, followed by filtration, drying, and recrystallization from ethanol.The isolated yellow solid was confirmed by NMR and Mass spectroscopic analysis. IR (KBrcm^-1): 3402 (OH), 3011 (Ar-H), 1668 (Imine C=N), 1579 (C=C), 1170 (C-O-C).

Preparation procedure

Scheme 2: Preparation procedureClick here to View Scheme

The metal salts (1mmol) were addition the ethyl alcohol solution of the ligand (5) (2 mmol). A some what basic pH of the reaction was carried out in slightly basic condition by adding 1 mmol of ammonia, and then this contentswere refluxedup to 5 to 6 hrs. The development of the reaction was checked by using T.L.C. and also monitored the colour changes. The subsequent yield was poured on petri dish and cool, filtration and dehydrated (6a-h). Each product was recrystallized from ethanol andthen take out its melting point, confirmed by IR and UV spectroscopy. Physical data of synthesized compounds are shows in table 1.

Table 1: Physical information of manufactured complexes 

Spectroscopic data of Synthesized metal Complexes

The N-H stretching band of the free ligand exhibited a shift towards lower frequencies in the spectra of all complexes, suggesting the involvement of the N-H group in complex formation. The infrared spectral data (ν, cm^-1) for C=N, M-N, and C-H bonds in the metal complexes is provided.

The (6a) complex have Lemon yellow colour solid with melting point 274°C infrared Spectral values (cm^-1) 1672 (C=N), 639 (M-N), 3068 (C-H), 3268 (O-H), UV spectra of the (6a) metal complex werenotedin ethanol solvents λ_maxvalue is 344.99 nm.

(6b) Complex have grey colour solid with melting point >300⁰C Infrared Spectral values (cm^-1) 1611 (C=N) 687(M-N), 3071(C-H), 3486 (O-H), UV Spectra of the (6b) metal complex were noted in ethanol solvents λ_maxvalue is 201.58 nm.

(6c) Complex have yellowish brown colour solid with melting point 280⁰C Infrared Spectral values (cm^-1)1611 (C=N), 687 (M-N), 3072 (C-H), 3407 (O-H), UV spectra of the (6c) metal complex were noted in ethanol solvents λ_maxvalue is 385.53 nm.

(6d) Complex have brown colour solid with melting point 298⁰C Infrared Spectral values (cm^-1)1580 (C=N), 689 (M-N), 3055 (C-H), 3180 (O-H), UV spectra of the (6d) metal complex were noted in ethanol solvents λ_maxvalue is  nm.

(6e) Complex have yellow colour solid with melting point >300⁰C Infrared Spectral values (cm^-1) 1581 (C=N), 646 (M-N), 3060 (C-H), 3133 (O-H), UV spectra of the (6e) metal complex were noted in ethanol solvents λ_maxvalue is 383.28 nm.

(6f) Complex have white colour solid with melting point >300⁰C Infrared Spectral values 1610 (C=N), 688 (M-N), 3069 (C-H), 3389 (O-H), UV spectra of the (6f) metal complex were noted in ethanol solvents λ_maxvalue is 350.06 nm.

(6g) Complex have yellowish green colour solid with melting point 270⁰C Infrared Spectral values cm-1611 (C=N), 689 (M-N), 3070 (C-H), 3497 (O-H), UV spectra of the (6g) metal complex were noted in ethanol solvents λ_maxvalue is 203.6 nm.

(6h) Complex have lightYellow colour solid with melting point 286⁰C Infrared Spectral values 1596 (C=N), 686 (M-N) 3065 (C-H), 3429 cm-1 (O-H). UV spectra of the (6h) metal complex were noted in ethanol solvents λ_maxvalue is 343.06 nm.

Result and Discussion

Antifungal activity (in vitro)

The newly manufacturedcomplexes were evaluated for theirin vitroAntifungal activity in contradiction ofnumerous fungal pathogens. MICstandards were resoluteby means of the normal agar technique, with Miconazolehelping as the reference drug. Dimethyl sulfoxide was used as the solvent control. TheMIC values (µg/mL) for the tested compounds and Miconazole are presented in Table 2. According to the data in Table 1, all synthesized compounds demonstrated decentto reasonableantifungalefficacy in contradiction of the examined fungal strains.

Table 2: Antifungal activity of complexes

^a Values are theordinaryof threeevaluations

The results revealed that the entire Schiff base metal complex complexesexhibition antifungal activity. The compounds with the decent antifungal outlineswere 6b, 6e, and 6h, each awarding at slightestone MIC value reachingbetween10-40 µg mL^-1. Table 1 results observations show that the Schiff base metal complex compounds are more active than their respective Schiff base. The Ni complex i.e. 6ewas found to be highly active towards all the selected fungi strains. A good effectiveness is exhibited by Zn complex i.e. 6h, which acts in the range 14–35 µg mL^-1 toward C. albicans, C.glabrata, A. fumigates, A. flavusand Cryptococcus neoformans.

Antibacterial activity (in vitro)

The antibacterial properties of the newly manufacturedcomplexeswere assessed in vitro against three distinct bacterial strains. MIC standards were measured by means of the normal agar process, with Ampicillin serving as the reference drug and DMSO as the solvent control. The results, as shown in Table 3, indicate that the synthesized compounds exhibited moderate to strong antibacterial effects in contradiction ofE.  coli, B. subtilis, and S. aureus.

Table 3: Antibacterial activity (in vitro) data

^a Values are the ordinary of three evaluations

The consequences ofAntibacterial activity (in vitro) as obtainablein Table 3,indicate that the manufacturedcomplexes6b and 6hwereoriginateto beadditional equipotent to that oftypical drug Ampicillin against Escherichia coli IC₅₀values 46 µg/mL and 48 µg/mL correspondingly. The synthesized complexes 6hwerefound to be equipotent to that of standard drug Ampicillin against Bacillus subtilis IC₅₀value 50 µg/mL. It was also noticed that the derivatives with the “Zn” and “Cd” metal in their structure were found to be potent compounds among the other synthesized derivatives.

Conclusion

In conclusion, a new ligand was synthesized using aldehydes, vanillin and 2-chloro-3-carbaldehyde,along with amine hydrazine hydrate. This ligand was further utilized for the synthesis of metal-ligand complexes. The anewmanufactured ligand and metal complexes were categorizedby means of various spectroscopic methods, including ¹H NMR, Mass spectrometry, IR spectroscopy, UV spectroscopy, and antibacterial and antifungal activity assays. The monodentate Schiff base substituted hydrazineLigand and its metal developments were positivelymanufactured and categorized using the aforementioned spectroscopic techniques. The antifungal and antibacterial activities of themanufactured metal complexes were evaluated, revealing that the compound Ni exhibited significantly good in vitroantifungal activity against C.albicans, C.glabrata, A.fumigatus, A.flavus, and C.neoformans. Complexes with Cd and Zn demonstrated in vitroantifungal activity when compared to the standard drug Miconazole against the fungiform strains C.albicansand C. glabrata.

Acknowledgement

The authors extend their heartfelt appreciation to the Principal and Head of the Chemistry Department, Deogiri College, ChhatrapatiSambhajinagar, Maharashtra, India, for generously providing access to the laboratory facilities essential for conducting this research. This article does not involve any studies conducted with human or animal participants by any of the authors.

Funding Sources

There is no any funding for this research

Conflict of Interest

We announced no conflicts of interests.

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