Cp and indenyl ruthenium complexes containing dithione derivatives: Synthesis, antibacterial and antifungal study

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Highlights

  • Ruthenium binds preferentially through the sulfur atoms of dithione derivatives.

  • The dithione ligands (L1, L2 & L3) lacked antibacterial and antifungal activity.

  • Complexes 3 and 4 shows exceptional antibacterial and antifungal activity.

Abstract

A series of cationic complexes [(Cp/Ind)Ru(к2(SS)-L)(PPh3)]PF6 (16) are obtained by the reaction of [CpRu(PPh3)2Cl] or [(Ind)Ru(PPh3)2Cl] (Cp = η5-C5H5, Ind = η5-C9H7) with respective dithione derivatives 1,2-di(piperidin-1-yl)ethane-1,2-dithione (L1), 1,2-dimorpholinoethane-1,2-dithione (L2) and 1,2-dithiomorpholinoethane-1,2-dithione (L3). All the compounds are characterized using spectroscopic techniques. The molecular structures of complexes 1, 2 and 4 are established by single-crystal X-ray diffraction studies. Antimicrobial studies were tested against three strains of bacterial microorganisms Staphylococcus aureus (gram + ve), Bacillus subtilis (gram + ve), Klebsiella pneumoniae (gram -ve) and one strain of fungal microorganism Candida albicans.

Introduction

Bacterial infections have remained the largest problem to humans due to their increasing resistance towards multiple antibacterial drugs (multiple drug resistance) and even to new antibacterial agents that the bacteria have never encountered before. Thus, the search for a new and efficient antibacterial agent that can counteract this problem has become the emerging trend in pharmaceutical and biological fields. This fact has driven us to synthesize and characterize new complexes that have potential antimicrobial properties. We have zeroed-in/focussed our attention to investigating new half-sandwich ruthenium complexes because of their ease to form complexes with a variety of ligands [1,2] and their vast applications in catalysis and biology. Although transition metal complexes containing dithiolene ligands have been extensively studied; those of half-sandwich ruthenium complexes have not been investigated yet. The study of dithiolenes has long been associated with inorganic chemistry, only recently they have become subject of interest to those scientists studying biological systems. Dithiolene ligands are found in the biomolecule of organisms throughout the entire kingdom of life [3]. These biomolecules are enzymes that help to catalyze chemical reactions crucial to the host organisms [4,5].

However, it is certainly the coordination of the metal and the dithiolene that is, along with the protein, responsible for the biological function in these enzymes. Research on dithiolenes was energized by the recognition that the majority of molybdenum and tungsten enzymes contain dithiolene-like moiety in their active site [6,7]. A metalladithiolene ring is a five-membered ring consisting of one metal, two sulfur atoms and two unsaturated carbons. Metalladithiolene complexes exhibit dual nature of both the aromatic and the unsaturated characters [8]. The former property renders the metalladithiolene ring to carry out substitution reactions [9], while the latter property allows addition reactions of Lewis bases (e.g., PR3) to the unsaturated metal center [10]. It is worth mentioning that these ligands are also termed as ‘non-innocent’ ligands as the manner in which they bond with the metal center is unclear. The oxidation form (usually neutral or anionic) of the ‘non-innocent’ ligand present in the complex is not certain. Consequently, the oxidation state of the central atom is not clear [11]. Dithiolene bearing secondary amine substituents such as piperidine, morpholine and thiomorpholine are chosen for this work. These secondary amines were chosen because of their good antibacterial property in the biological system. Several researchers have reported compounds containing piperidine or morpholine or thiomorpholine showed better antimicrobial and anticancer activity (Chart 1) [12].

Section snippets

Physical methods and materials

All the reagents were purchased from commercial sources and used as received. Glyoxal and elemental sulfur were obtained from Sigma Aldrich. Piperidine, morpholine and thiomorpholine were obtained from Alfa Aesar. The solvents were purified and dried according to standard procedures. The starting metal precursor [CpRu(PPh3)2Cl] [13] and [(Ind)Ru(PPh3)2Cl] [14] were prepared following the reported procedure. Infrared spectra were recorded on a Perkin-Elmer 983 spectrophotometer by using KBr

Synthesis of ligands and complexes

In this work, we have carried out the synthesis, characterization and antimicrobial activity evaluation of dithiolene ligands and complexes of ruthenium (Cp/Ind) containing dithiolene derivatives. On reacting [(arene)Ru(PPh3)2Cl] (arene = cyclopentadienyl, indenyl) with ligand (L1/L2/L3) in 1:1 (M:L) ratio, a series of cationic bidentate sulfur-sulfur bonded five-membered chelating ruthenium complexes 16 with the chemical formula [(arene)Ru{κ2(S∩S)L}(PPh3)]+, L = L1/L2/L3 were obtained. The

Conclusion

All the complexes were isolated as cationic species with PF6 counter ion. The ligands and complexes were obtained in good yields and were characterized by analytical and spectral methods. Single crystal X-ray diffraction study reveals that the dithiolene derivatives ligands coordinated to the metal center through the two sulfur atoms forming cationic five-membered chelate complexes. Antimicrobial activity against Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 441 strains, Klebsiella

Declaration of competing interest

None.

Acknowledgment

Lincoln Dkhar thanks the Department of Science and Technology (DST), India for providing financial assistance under the Innovation in Science Pursuit for Inspired Research (INSPIRE) fellowship. Lincoln Dkhar also thanks SAIF-NEHU for spectral analyses and DST-PURSE SCXRD, India for providing Single Crystal X-ray analysis.

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