Unusual coordination mode of aroyl/acyl thiourea ligands and their π‐arene ruthenium (II) piano‐stool complexes: Synthesis, molecular geometry, theoretical studies and biological applications

Abstract

Two mononuclear ruthenium complexes (1 and 2) with aroyl/acylthiourea as an ancillary ligand of type, [(η6‐p‐cymene)RuCl(L‐N,S)], where [L1 = 2,4‐dichloro‐N‐(o‐tolylcarbamothioyl)benzamide] and L2 = N‐(phenylcarbamothioyl)cyclohexanecarboxamide] were synthesized and well characterized. The single crystal X‐ray diffraction studies revealed the coordination mode and the geometry of the complexes. The two complexes adopted general piano‐stool (three‐legged) geometry with a novel coordination mode of aroyl/acylthiourea through amide N (anionic) and thiocarbonyl S (neutral). This type of monobasic bidentate coordination of the aroyl/acylthiourea ligand was witnessed the first time around the metal ion. The coordination of the complexes was well explained through geometric parameters and frontier molecular orbital parameter values computed at the B3LYP/SDD level. The synthesized complexes were also screened for their antibacterial, antifungal, antioxidant and in vitro antiproliferative activities. Complexes exhibited good antimicrobial agents against various pathogens. The antioxidant activity of the complex 2 has shown most potent activity with IC50 value of 48.55 ± 1.7 μM compared to the reference drug. In addition, the in vitro antiproliferative activity of the complex 2 showed excellent activity against HepG‐2 cell line with the IC50 value of 24.30 ± 1.20 μM which is close to Doxorubicin standard drug.

Cationic RuII Cyclopentadienyl Complexes with Antifungal Activity against Several Candida Species

“…[21] Although numerous compounds based on various other metals (Cu, Ni, Zn, Co, Ag, Pd, etc) were previously reported for their activity against a wide range of fungal species including Candida, [22][23][24][25][26][27][28][29][30] our long-standing interest in the biological activity of ruthenium complexes prompted us to investigate the promising antifungal potential of compounds based on this particular metal. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] It is noteworthy that ruthenium complexes are currently extensively studied for their anticancer properties and are even now considered as potential alternatives to cisplatin, a chemotherapeutic agent currently widely used in clinical settings. [51][52][53][54][55] For instance, Turel et al reported Ru II complexes bearing antifungal azole-containing drugs clotrimazole, miconazole, and tioconazole that could inhibit the growth of Curvularia lunata.…”

“…[33] Notably, several ruthenium species were also previously studied for their potential anti-Candida properties ( Figure 1). [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] Some of the first examples were reported by Günal et al (1999) and consisted of a series of Ru II -cymene complexes with promising activities against different fungal species including C. albicans and C. tropicalis. [44] Since then, most reports of ruthenium species with an anti-Candida activity ( Figure 1) showed a superior antifungal activity for the complexes compared to their corresponding ligands, suggesting an important role of the ruthenium moiety in the observed antifungal activity.…”

“…Indeed, metal complexes display reactivities that differ from simple organic molecules, and could potentially lead to the discovery of therapeutics with unique properties and/or modes of action [21] . Although numerous compounds based on various other metals (Cu, Ni, Zn, Co, Ag, Pd, etc) were previously reported for their activity against a wide range of fungal species including Candida , [22–30] our long‐standing interest in the biological activity of ruthenium complexes prompted us to investigate the promising antifungal potential of compounds based on this particular metal [31–50] . It is noteworthy that ruthenium complexes are currently extensively studied for their anticancer properties and are even now considered as potential alternatives to cisplatin, a chemotherapeutic agent currently widely used in clinical settings [51–55] …”

Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group

“…Acyl thiourea derivatives can coordinate metals in either a bidentate fashion through both the carbonyl oxygen and the thiocarbonyl sulfur [14,15], or a monodentate fashion via the thiocarbonyl sulfur only [16,17] (Figure 3). Thiourea itself can coordinate metals through its sulfur or through one of its nitrogen atoms [18][19][20].…”

Design, synthesis and docking study of acyl thiourea derivatives as possible histone deacetylase inhibitors with a novel zinc binding group

“…5 thiocarbonyl sulfur only [15,16] (Figure 3). Thiourea itself can coordinate metals through its sulfur or through one of its nitrogens [17][18][19].…”