New 3d multifunctional metal chelates of sulfonamide: Spectral, vibrational, molecular modeling, DFT, medicinal and in silico studies

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Highlights

  • Synthetic and spectral design of new sulfonamide ligands and metal complexes.

  • Some usual and unusual computational basis sets to achieve the geometry optimization.

  • FMO, NLO, UV, NBO, MEP, and MAC analysis at highly reliable basis sets.

  • Chelation to play its role to enhance their potency and drug likeness abilities.

  • The experimental and DFT based probing to ensure such compounds as excellent medicinal candidates.

Abstract

We are reporting a new synthetic design of sulfonamide entangled Schiff base ligands as H2L1 and H2L2 from 4-amino-N-(3-methyl-1,2-oxazol-5-yl)benzene-1-sulfonamide and their reaction with the bivalent metals (VO2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) to yield metal complexes (1)–(12). The ligands and metal complexes are studied experimentally with different spectroscopic and analytical approaches (UV–Vis, FT-IR, LC-MS 1H and 13C NMR). The ligands practiced their coordination compounds with the 3d-metal ions through phenyl hydroxyl and azomethine nitrogen, resulting in square-planar (only for vanadium) and octahedral morphologies. All complexes are structured in of 1: 2 (metal: ligand) stoichiometry ratio. The indicators of density functional theory are designed to validate geometric structures and their properties. Comprehensive antimicrobial activities, targeting six pathogenic bacteria and fungi are operated by disk diffusion bioassay. To establish their role as multifunctional ligands, promising in vitro assays have been adopted to benchmark their candidature during Alzheimer's disease (anti-choline inhibitor), microbial resistance, anti-oxidant potentials, as well as HIV protease and α-amylase inhibitory activity. The forecasting of ADMET/toxicity characteristics was conducted out through ADMET Prediction™ to analyze the reliability of the drug-receptor complex. The results show that most compounds show antibacterial properties as well antifungal activities against these organisms. The VO+2 and Co+2 complexes indicated a powerful antibacterial effect against the Gram (-) strains. Anti-oxidant interactions were analyzed using three different strategies..

Introduction

The utilization of multi-target-directed ligands (MTDLs) is a prospective management option for diseases with complicated path mechanisms [1]. They could be more efficient as such ligands to engage with many targets or pathogenic processes at the same time (e.g., decreased cholinergic neurotransmission, and peroxidation, etc.), but unlike pharmacological treatment, they do not create drug-drug interactions [2]. Because of the complexities of multifactorial disorders, single-target medications are not always effective. Recent research suggests that simultaneously modulating numerous targets may increase both pharmacological safety and effectiveness when compared to single-target medicines. A crucial stage in the development of multifunctional ligands is the identification of relevant pharmacological targets preferably those engaged in disease-modifying programs [3]. For example, Alzheimer's disease is a neurological illness that develops with age and for which there is no cure [4]. Available treatment only provides symptomatic alleviation for a limited time. Several explanations for illness etiology have been proposed, whereas compounds produced as potential treatment agents during the previous decade have generally underperformed in clinical trials [5]. To develop novel effects, the sulfonamide moiety is also introduced to recognize physiologically relevant scaffolds. The effective inhibitors for Alzheimer's disease (AD)-associated butyrylcholinesterase (BChE) have been synthesized as sulfonamide analogues by previously used drugs. As a result, the usage of sulfa-drugs has been expanded to include disorders other than microbial infections. Several variables, including acetylcholinesterase deficiency and oxidative stress, may have a character in the growth of Alzheimer's disease [6]. The bio-metals (iron, copper, and zinc) in the brain have also been associated to the expansion of Alzheimer's disease [7]. As a result, targeting these metal ions might be a viable method for developing a medication to treat Alzheimer's disease. The rising number of contemporary studies demonstrates the growing interest in multifunctional ligand-based treatments [8], as well as several medications having a multifunctional characteristic.

The chemo-coordination applications of biologically essential elements with Schiff bases has gotten a lot of consideration over the past [9]. Conventional organic antimicrobials primarily target particular biochemical processes including proliferation, replication, or translation. The establishment and spreading of antimicrobial resistance, on the other hand, represents a rising concern to humans. As a result, it is critical to create novel drug development techniques that target numerous biological processes in order to improve their efficacy against a variety of pathogens such as bacteria, viruses, and fungi. This is mostly owing to its widespread use in the pharmaceutical business [10]. Several investigations have found that Schiff bases and associated compounds have remarkable antibacterial, antitumor, and antioxidant effects [11]. The first-row transition metals like vanadium, iron, cobalt, nickel, and copper are found to have substantial biological activity among metal complexes [12]. Because a considerable range of antimicrobial medications can disrupt plasma membranes and interfere with invasion and metastasis, transfer, and diffusion, there is a pressing need to create novel chemotherapeutic medicines [13]. These metals are very significant, versatile, and trace bimetal in the first row of transition metal series, capable of forming a wide range of complexes with a wide range of organic ligands. Because of its versatility in retaining a variety of stable and controlled oxidation states, these are widely used in biological[14] and catalytic[15] processes. Owing to the presence of one or more nitrogen in a ring with a confined pair of electrons, heterocyclic derivatives such as pyridine and similar compounds, are powerful ligands.

Sulfonamides are one-of-a-kind moieties with a wide range of applications in, pharmacological, enzymatic, and diagnostic fields [16]. Sulfonamide Schiff bases form coordination complexes with diverse types of coordination depending on the configurations and oxidations of distinct metals [17]. Additionally, due to the attendance of the N–H moiety close enough to the azomethine group, the sulfonamides can self-assemble themselves by hydrogen bonding, in both free and complexation mode [18]. Owing to cheapest, having ease of synthesis with remarkable chemical and thermal robustness in both solid and liquid phases, a vast range of metal complexes with imine-based Schiff bases are extensively utilized as oxidation catalysts in several types of key organic processes [19]. So as a continuation of our previous reports, we have designed a new and efficient structure of Schiff bases resulting from a sulfonamide moiety 4-amino-N-(3-methyl-1,2-oxazol-5-yl)benzene-1-sulfonamide with two carbonyl compounds; 1-(5‑bromo-2-hydroxyphenyl)ethan-1-one and 1-(2-hydroxyphenyl)ethan-1-one. The highly pure ligands were interacted with the biologically important transition metals to develop their transition metal. All the synthesized compounds were undergone through promising in vitro assays to insight their medicinal probing.

Section snippets

Synthesis of ligands (H2L1 and H2L2)

H2L1 was synthesized by refluxing 0.225 gs of ethanolic 4-amino-N-(3-methyl-1,2-oxazol-5-yl)benzene-1-sulfonamide into to 0.136 g of 1-(2-hydroxyphenyl)ethan-1-one in pure ethanol (2o mL each). The reaction mixture was allowed to cool after 1 hour of refluxing [20] (Scheme 1). A yellowish-green solid chemical was isolated throughout this process. After that, it was filtered, rinsed, precipitated from diethyl ether, and vacuum desiccated.

4-{[1-(2-Hydroxyphenyl)ethylidene

Results and discussion

We synthesized, highly pure, two new sulfonamide ligands and their twelve metal complexes of VO2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+. The metal complexes of formed owing to a molar ratio (1:2) reaction involving metal ions and ligands (M: L) (scheme 1). In this paper, the empirical formula, melting temperatures, elemental composition, and molar conductance values are provided. The aforesaid condensation products were collected were air-stable with their solublities in solvents like in

Conclusions

The metal (VO2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) complexes of two newly synthesized sulfonamide moieties have been synthesized and characterized using a variety of analytical and spectral techniques. The design of these recently synthesized compounds was validated by all analytical/spectral parameters. The ligands behaved through the N atoms of the azomethine and hydroxyl phenyl group. The complexes appeared octahedral in geometry, according to physical, magnetic, and spectral measurements,

Credit author statement

A. U. Hassan: Writing-original draft-Equal, Methodology-Equal, Software-Equal

S. H. Sumrra: Investigation-Equal, Project administration-Equal, Supervision-Equal, Resources-Equal

M. Imran: Data curation-Equal, Formal analysis-Equal

Z. H. Chohan: Validation-Equal, Formal analysis-Equal, Writing-review & editing-Equal

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors are thankful to Higher Education Commission (HEC) Islamabad, Pakistan for financially supporting their research project by funding through a project, NRPU 7800. One of the author (Muhammad Imran) also express his appreciation to the Deanship of Scientific Research at King Khalid University Saudi Arabia for funding through research groups program under grant number RGP 2/28/43.

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