The Study of Biological Activities of Various Mixed Ligand Complexes of Nickel(II)

Review Article

Austin Biochem. 2020; 5(1): 1025.

The Study of Biological Activities of Various Mixed Ligand Complexes of Nickel(II)

Paison F, Su B*, Pan D, Yan T and Wu J

College of Chemistry and Chemical Engineering, Xi’an Shiyou University, China

*Corresponding author: Biyun Su, College of Chemistry and Chemical Engineering, Xi’an Shiyou University, P.O. Box: 710065, Xi’an, China

Received: February 10, 2020; Accepted: April 21, 2018; Published: April 28, 2020


This review focuses on research undertaken over the past decades about biological activities of nickel complexes with mixed ligands of different types such as mixed ligand complexes of Ni(II) with furfuralurea and thiourea, mixed ligand complexes of Ni(II) dialkyldithiophosphates with 2-acetylpyridine semicarbazone and 2-acetylpyridine benzoylhydrazone, Ni(II) complexes of thiosemicarbazone and isothiosemicarbazone-based ligands, Ni(II) complexes of morpholinedithiocarbamates and diamines, mixed ligand complex of Ni(II) with nicotinanilide and thiocyanate, mixed-ligand Ni(II) complexes containing sulfathiazole and cephalosporin, Ni(II) complexes with sparfloxacin in the presence or absence of N,NO-donor ligand, Ni(II) mixed ligand complexes of bis(phenylimine) Schiff base ligands incorporating pyridinium moiety, Ni(II) complexes of azo dyes and thiamine hydrochloride, Ni(II) complexes of moxifloxacin imidazole mixed ligands, Ni(II) thiosemicarbazone complexes, mixed ligand Ni(II) complexes with isatinmonohydrazone Schiff base ligands and heterocyclic nitrogen base, mixed ligand complexes of Ni(II) based on 1,10-phenanthroline and novel thiosemicarbazone, Ni(II) mixed ligand complexes of 2-Amino-3-Hydroxypyridine (AHP) and imidazoles. This study focuses on the antimicrobial biological activities of various kinds of mixed ligands Ni(II) complexes.

Keywords: Mixed ligands; Ni(II) complexes; Biological activities; Antibacterial activities; Anti-fungal activities; Shiff base ligands


M: Ni(II); Fu: Furfural-urea; A: Thiourea; CHP: Chloramphenicol, G+ve: Gram positive, Pr: Propyl; G-ve: Gram negative; MICs: Minimum Inhibitory Concentrations; NI: No Inhibition; C: Candida; S: Staphylococcus; E: Escherichia; H2L1: (4-(p-fluorophenyl) thiosemicarbazone); H2L2: (4-(p-bromophenyl) thiosemicarbazone), H2L3 : (4-(p-methoxyphenyl)thiosemicarbazone) of salicylaldehyde; PPh3: Triphenylphosphine; µ-4,4’-byp: (4,4’-bipyridine); Py: Pyridine; Imz: Imidazole; (4-Pic): 4-picoline; MOX: Moxifloxacin; Him: Imidazole; Hstz: Sulfathiazole; L1: Cefazolin; HL2: Cephalothin; HL3: Cefotaxime; HL4: Ceftriaxone; HL5: Cefepime; Hstz: sulfathiazole.


Transition metal ions are playing an important role in biological processes in the human body [1,2]. Coordination compounds combine the features of metals, which have a wide range of coordination numbers, geometries, variable oxidation states, and ability to bind a variety of organic ligands or mixed ligands in an attempt to get the optimal stability and the biological in vitro activity, where the action of many drugs depends on the coordination with metal ions or the inhibition on the formation of metallo-enzyme [3,4]. Researchers have published reviews about complex metals and their contributions to biological activities; it was made clear that a number of antibiotics contain a metal-binding site. Sometimes, transition metal ions are tightly bound forming stable coordination connections, which have an important structural function and/or are responsible for effective antibiotic action. There are a number of antibiotics that require metal ions to function properly and complexes often show better physicochemical properties and are much more effective than parents drugs. Therefore, bioinorganic chemistry provides a powerful weapon for overcoming numerous challenges encountered in antibiotic chemistry [5], researchers showed the importance of metal chelation to tetracycline which is an antibiotic used to treat many different bacterial infections, such as urinary tract infections, acne, gonorrhea, chlamydia, and others [6]. Coordination chemistry of mixed-ligands with transition and non-transition metal ions is important in metallo-enzymes and other biological activities [7]. In most cases, metal complexes show higher bioactivities than the free ligands[8], and some side effects and drug-resistance may be reduced upon complexation [9]. Mixed ligand complexes differ from traditional complexes in the sense that they are having at least two different kinds of ligands associated with the same metal ion in a complex. The presence of more than one type of ligand in a complex increases chances of variation in properties expected for the complex. This makes the researchers interested in the synthesis of mixed ligand complexes with varying properties. In recent years, many publications are devoted to synthesis and characterization of mixed ligand complexes [10]. Numerous mixed ligands transition metal complexes have been investigated by various techniques and their biological activitiesand, exhibit many neurophysiological and neuro pharmacological effects like antimicrobial, antiviral, anticonvulsant, anticancer, anti-mycobacterial, antimalarial, cysticidal, herbicidal and anti-inflammatory activity were extensively studied [11-15]. Chelating ligands containing O, S and N donor atoms and metal complexes containing nitrogen and Sulphur donors have been proved to show broad biological activity [16-18], to be potential antibacterial and fungal agents [19] as well as component of several vitamins and drugs [20,21]. Nickel(II) complexes with nitrogen and sulfur donor ligands are highly interesting because several hydrogenases and carbon monoxide dehydrogenases contain such nickel complexes as their active site [22,23]. The role of mixed ligand complexes in biological process has been well recognized. The stabilities of mixed chelates are of great importance in biological systems as many metabolic and toxicological functions are dependent upon this stability. Many attempts have been made to correlate the stability of the metal-ligand complexes with their antimicrobial activity [24], biological important metal ions with mixed ligands where mixed ligand complexes are used for storage as well as for transport of active material through membrane [25].Schiff bases were important class of ligands, such ligands and their metal complexes had a variety of applications including biological, clinical, analytical and industrial in addition to their important roles in catalysis and organic synthesis [26-28]. Mixed ligand complexes are found to be more active biologically than the ligand itself and its binary complexes and it was widely reported that transition metal mixed ligand complexes are used in fighting microbial infections [29-31]. In his most recent article for the first time, Lobana also reported some nickel(II) complexes of thiosemicarbazones with a co-ligand [32], the biological activities of both above mentioned ligands are attributed to their chelating ability with transition metal ions coordinating to them through either thione or thiolate sulfur, and one of the nitrogen atoms [33,34]. In addition, various applications transition metal complexes of thiocarbazones have been described such as catalytic activity [35, 36], imaging and therapy [37], in sensor [38], antimicrobial [39], antiviral [40], cytotoxic [41], antibacterial [42], anticancer [43], antioxidant activities [44], antiparasital [45], antitumor activities [46], fungicidal [47], and antineoplastic [48]. It is well known that some drugs exhibit increased activity when administered as metal complexes and several metal chelates have been shown to inhibit tumor growth [49,50]. Among all transition metals, this work is much emphasized on nickel, which is an important transition metal normally stable in the +2 oxidation state and it more attracted by the researchers in recent years because of their numerous importance in biological systems. The role of nickel in bioinorganic chemistry has been rapidly expanded since the discovery that urease is a nickel enzyme in 1975. Since then, the list of nickel-dependent enzymes has been significantly increased [51,52], Ni(II) complexes as antibacterial, antifungal, and anticancer agents have been studied and proposed as potent catalysts in homogenous and heterogeneous reactions [53-56]. The coordination chemistry of nickel ion is significant because of its participation in redox cycles of several metallo-enzymes. Square planar nickel complexes can cause cleavage of plasmid DNA, under special factors [57]. A large number of nickel complexes with capability of acting as vitamins are known [58]. Nickel possesses an important role in physiological processes as a co-factor in absorption of iron from the intestine. It can increase absorption of iron from the diet in iron deficient rats (female) under the condition that dietary iron is in the unavailable ferric form [59]. In this review, the focus is placed on anti-bacterial and anti-fungal activities of various kinds of mixed ligands nickel(II) complexes.

Anti-Microbial Activities of Various Kinds of Mixed Ligands Nickel(II) Complexes

Antimicrobial activities of mixed ligand complex of Ni(II) with furfuralurea and thiourea

In vitro antimicrobial efficacy of pneumonia the mixed ligands and their corresponding Ni(II) complexes which are discussed in this work were all evaluated by the agar well diffusion method [60-63] and the paper disc diffusion method [64, 65]. This mixed ligand complex of the Ni(II) with furfuralurea and thiourea was tested against Proteus mirabilis, Staphlococus aureus, Klebsiella, Pseudomonas aeriginosa, and E. coli. The results of antimicrobial activity of the complex were described in Table 1; the complex shows appreciable activity against all the test organisms at 60µg/ml/disc. It was carried out in dimethylsulfoxide solution at concentrations of 15, 30 and 60 µg/ml/disc. The positive control was chloranphenicol at 60µg. The highest zone of exhibition that was 14mm was seen against Klebsiella pneumonia compared to 21mm inhibition of the control. The complex showed activity against E. coli and Klebsiella pneumonia at all the concentrations used. The complex is active against Staphylococcus aureus at the concentration of 60µg/ml/disc while it showed no activity against Proteus mirabilis and Pseudomonas aeriginosa at 15µg/ml/disc. The higher the concentration, the higher the zone of inhibition. The in vitro evaluation of the biological studies of the mixed ligand complex showed greater activity against Proteus mirabilis and Klebsiella pneumonia at 60µg/ml/disc with the minimum zone of inhibition of 13mm and 14mm respectively [66].