Design, Synthesis and Evaluation of a Series of Zinc(II) Complexes of Anthracene-Affixed Multifunctional Organic Assembly as Potential Antibacterial and Antibiofilm Agents against Methicillin-Resistant Staphylococcus aureus

Abstract

A novel class of zinc(II)-based metal complexes, i.e., [Zn 2 (acdp)(μ-Cl)]•2H 2 O (1), [Zn 2 (acdp)(μ-NO 3 )]•2H 2 O (2), and [Zn 2 (acdp)(μ-O 2 CCF 3 )]•2H 2 O (3) (Cl − = chloride; NO 3 − = nitrate; CF 3 CO 2 − = trifluoroacetate) of anthracene-affixed multifunctional organic assembly, H 3 acdp (H 3 acdp = N,N′-bis-[anthracene-2-ylmethyl]-N,N′-bis[carboxymethyl]-1,3-diaminopropan-2-ol), have emerged as promising antibacterial and antibiofilm agents in the domain of medicinal chemistry. Accordingly, complexes 1−3 were synthesized by utilizing H 3 acdp in combination with ZnCl 2 , Zn(NO 3 ) 2 •6H 2 O, and Zn(CF 3 CO 2 ) 2 •H 2 O respectively, in the presence of NaOH at ambient temperature.The complexation between H 3 acdp and Zn 2+ was delineated by a combined approach of spectrophotometric and spectrofluorometric titration studies. The stoichiometry of acdp 3− /Zn 2+ in all three complexes is observed to be 1:2, as confirmed by spectrophotometric/spectrofluorometric titration data. Elemental analysis (C, H, N, Zn), molar conductance, FTIR, UV−vis, and thermoanalytical (TGA/DTA) data were effectively used to characterize these complexes. Besides, the structures of 1−3 were established by density functional theory (DFT) calculation using B3LYP/6-311G, specifying a self-assembled compact geometry with average Zn•••Zn separation of 3.4629 Å. All three zinc complexes exhibited significantly high antibacterial and antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA BAA1717). However, complex 1 showed a more recognizable activity than 2 and 3, with minimum inhibitory concentration (MIC) values of 200, 350, and 450 μg/mL, respectively. The antimicrobial activity was tested by employing the minimum inhibitory concentration (MIC) and time-kill assay. The crystal violet (CV) assay and microscopic study were performed to examine the antibiofilm activity. As observed, complexes 1−3 had an effect on the production of extracellular polymeric substance (EPS), biofilm cell-viability, and other virulence factors such as staphyloxanthin and hemolysin production, autoaggregation ability, and microbial cell-surface hydrophobicity. Reactive oxygen species (ROS) generated due to inhibition of staphyloxanthin production in response to 1−3 were also analyzed. Moreover, complexes 1−3 showed an ability to damage the bacterial cell membrane due to accumulation of ROS resulting in DNA leakage. In addition, complexes 1−3 displayed a synergistic/additive activity with a commercially available antibiotic drug, vancomycin, with enhanced antibacterial activity. On the whole, our investigation disclosed that complex 1 could be a promising drug lead and attract much attention to medicinal chemists compared to 2 and 3 from therapeutic aspects.

Structures and Properties of a Series of High-Spin [CoII2] Complexes Supported by Ancillary Benzoate, Ortho-Hydroxybenzoate, and Para-Hydroxybenzoate Ligands

“…This versatility of the carboxylate group as a ligand has oriented its use to build an extended family of coordination complexes showing potential applications as magnetic materials . Again, continuing our research on biological activities of metal complexes of carboxylate-based ligands, we have also reported anticancer, antidiabetic, antibiofilm, and glycosidase/phosphatase activities of iron­(III), nickel­(II), copper­(II), and zinc­(II) complexes. ,− The multidentate ligand, N , N ′-bis­[2-carboxybenzomethyl]- N , N ′-bis­[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H 3 cpdp) incorporating two benzoate and two pyridine functionalities, has been well-established in studying coordination complexes with diverse applications in biological activities and magnetic properties. − ,− Therefore, motivated by our ongoing research interests in designing of smart scaffolds for exploration of magnetic and biological features in a synchronized manner, we extended our attention to synthesize a new family of high-spin cobalt­(II) complexes. In the present contribution, we report the syntheses, X-ray crystal structures, variable temperature magnetic properties, and in vitro antibacterial activities of a series of high-spin dinuclear cobalt­(II) complexes [Co 2 (cpdp)­(μ-O 2 CC 6 H 5 )] ( 1 ), [Co 2 (cpdp)­(μ- o -O 2 CC 6 H 4 (OH))]·H 2 O ( 2 ), and [Co 2 ­(cpdp)­(μ- p -O 2 ­CC 6 ­H 4 ­(OH))]·5H 2 O ( 3 ).…”

“…Among the different bridging ligands explored, the carboxylate-based ligands appear very appealing because of their varied conformations, specifically syn-syn , syn-anti, and anti-anti that can lead to the formation of various di- and multinuclear complexes with novel topologies and interesting properties. In this context, the research and associated studies on carboxylate containing metal complexes as magnetic materials and therapeutic drugs are in continuous development. , In case of carboxylate-bridged high-spin cobalt­(II) complexes, a very few examples with magneto-structural correlations are known where moderate antiferromagnetic interactions occur across the syn-syn conformations and ferro–/antiferromagnetic interactions take place through syn-anti and anti-anti conformations. This versatility of the carboxylate group as a ligand has oriented its use to build an extended family of coordination complexes showing potential applications as magnetic materials .…”

Electropolymerization of Pyrrole-Tailed Imidazolium Ionic Liquid for the Elaboration of Antibacterial Surfaces

“…This strategy is also original as the anchoring PPy polymer will not act as an “innocent” anchoring group as it is always the case in classical chemical grafting. Concerning the choice of IL’s anion, we have decided to work with a halometallate anion containing Zn­(II) ions that are known to present good antibacterial properties and can be regarded as safe . Here, we present the synthesis of our pyrrole-tailed imidazolium IL with the determination of its antibacterial properties by determination of its minimal inhibitory concentration (MIC).…”

“…Concerning the choice of IL's anion, we have decided to work with a halometallate anion containing Zn(II) ions that are known to present good antibacterial properties and can be regarded as safe. 37 Here, we present the synthesis of our pyrrole-tailed imidazolium IL with the determination of its antibacterial properties by determination of its minimal inhibitory concentration (MIC). We then report the methodology developed to prepare the antibacterial surfaces via the electropolymerization of our pyrrole-tailed IL.…”

Rapid Semiconducting Supramolecular Mg(II)-Metallohydrogel: Exploring Its Potential in Nonvolatile Resistive Switching Applications and Antiseptic Wound Healing Properties

“…Minimum inhibitory concentrations (MICs) of Mg@PEHA metallohydrogel were determined against KP using the standard broth micro dilution method. 77 Briefly, overnight-grown bacterial cell suspension was used as inoculum after 1:10 dilution, from where 100 μL was added in 3 mL of fresh broth, supplemented with different concentrations of Mg@PEHA dissolved in 1% DMSO, ranging from 1 mg/mL to 8 mg/mL. For the positive control set, a solution was prepared using 1% DMSO (v/v) along with an equal volume of bacterial inoculum in the media.…”