Ni(II) Cd(II) mixed ligand complexes as dual antimicrobial and anti inflammatory agents Original paper

What was studied?

Ni(II) Cd(II) mixed ligand complexes were synthesized and characterized to evaluate their in vitro antimicrobial and anti-inflammatory activities. The authors prepared mixed ligand complexes of Ni(II) and Cd(II) using 2,4-dinitrophenylhydrazine (DNPH) and dimethylglyoxime (DMG) in a 1:1:1 metal to ligand ratio, then performed comprehensive physicochemical characterization and biological testing. Elemental CHNO analysis, molar conductance, UV–visible spectroscopy, FTIR, powder X ray diffraction, thermal analysis, magnetic measurements, and SEM imaging were used to confirm complex formation, non-electrolytic behavior, octahedral geometry, nanocrystalline structure, and thermal stability. The central aim was to determine whether these Ni(II) Cd(II) mixed ligand complexes, which incorporate nitrogen and oxygen donor atoms and the classic nickel chelator DMG, exhibit meaningful antibacterial, antifungal, and anti-inflammatory effects that could justify further exploration as bioactive coordination compounds.

Who was studied?

No human or animal subjects were included. Instead, the study employed reference microbial strains and an in vitro protein denaturation system as experimental models. Antimicrobial activity was assessed against Gram positive bacteria Bacillus subtilis and Staphylococcus aureus, Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the fungal species Aspergillus niger and Candida albicans, all obtained from MTCC culture collections. These taxa include clinically relevant pathobionts commonly implicated in soft tissue, device-associated, and mucosal infections that intersect with microbiome research. Anti-inflammatory activity was modeled using egg albumin (bovine serum albumin analogue) denaturation in phosphate-buffered saline, with diclofenac sodium as the reference nonsteroidal anti-inflammatory drug. Thus, the biological data reflect direct effects on key bacterial and fungal taxa plus a generic protein denaturation model rather than host tissue or in vivo outcomes.

Most important findings

Structurally, both Ni(II) and Cd(II) complexes behaved as non-electrolytes in DMF with low molar conductance, showed IR shifts consistent with coordination through DNPH and DMG donor atoms, and exhibited electronic spectra and magnetic moments consistent with octahedral geometry. PXRD patterns demonstrated crystalline materials with nanoscale crystallite sizes of approximately 56.7 nm for Ni(II) and 69.3 nm for Cd(II), and thermogravimetric analyses showed multistep decomposition, confirming reasonable thermal stability suitable for further formulation work.

Biologically, both complexes demonstrated measurable antimicrobial activity that increased with concentration. At 30 and 60 μg/ml, the Ni(II) complex showed particularly good activity against B. subtilis and E. coli, with inhibition zones of 15 and 17 mm for B. subtilis and 11 and 19 mm for E. coli, relative to chloramphenicol standards. In contrast, the Cd(II) complex was more potent against P. aeruginosa and especially C. albicans at 60 μg/ml, where inhibition of C. albicans reached 18 mm compared with very weak action of the Ni(II) complex against this yeast. Activity against A. niger was modest for both complexes. This pattern indicates that complexation to DNPH and DMG alters metal bioavailability and broadens activity across a clinically relevant spectrum that spans Gram positive and Gram negative bacteria and opportunistic fungi.

From a microbiome signatures perspective, the inclusion of E. coli, P. aeruginosa, S. aureus, B. subtilis, and C. albicans is notable, since these taxa frequently emerge as major microbial associations in dysbiotic mucosal and device related infections and are of interest when designing microbiome targeted interventions or co therapies. The differential sensitivity of C. albicans to the Cd(II) complex in particular suggests that mixed ligand metal chelates could in principle be tuned to selectively suppress fungal pathobionts such as Candida while exerting varying pressure on bacterial community members.

For anti-inflammatory effects, both Ni(II) and Cd(II) complexes inhibited egg albumin denaturation in a concentration dependent fashion. At 500 μg/ml, the Ni(II) complex achieved 84.56 percent inhibition, the Cd(II) complex 79.55 percent, and diclofenac sodium 96.05 percent. Calculated IC50 values were 230.75 μg/ml for diclofenac, 257.31 μg/ml for the Ni(II) complex, and 270.83 μg/ml for the Cd(II) complex, indicating that while less potent than the reference NSAID, the complexes display meaningful anti-denaturation activity. The authors attribute the bioactivity partly to chelation effects, where coordination reduces metal ion polarity and increases lipophilicity, facilitating penetration into microbial cells and interaction with protein targets.

Key implications

For clinicians and microbiome researchers, these findings position Ni(II) Cd(II) mixed ligand complexes as proof of concept scaffolds rather than ready translational candidates. The complexes show that combining DNPH and the classical nickel chelator dimethylglyoxime around a transition metal center can yield thermally stable, nanocrystalline coordination compounds with broad antimicrobial spectra against several clinically relevant taxa, including E. coli, P. aeruginosa, S. aureus, B. subtilis, and C. albicans, while also delivering moderate anti-inflammatory effects via inhibition of protein denaturation.

However, systemic use of Ni and particularly Cd raises substantial toxicity and metallotoxicity concerns, limiting realistic applications to highly localized or surface bound contexts such as coatings, dressings, or device surfaces. From a microbiome signatures standpoint, the work supports the broader concept that metal coordination chemistry and chelation can be leveraged to modulate pathobionts that are strongly represented in dysbiotic states, potentially informing the design of safer metal based or metal chelator based agents that target C. albicans and other MMAs without introducing toxic metals into the host environment. Future work should focus on metal substitution to less toxic centers, evaluation in biofilm models that better replicate microbiome architecture, and an explicit assessment of collateral effects on beneficial commensals before any clinical application is considered.

Citation

Muthuppalani M, Al Otaibi A, Balasubramaniyan S, Manikandan S, Manimaran P, Mathubala G, Manikandan A, Kamal T, Khan A, Marwani HM, Alamry KA, Asiri AM. An in-vitro anti-inflammatory and anti-microbial essential on Ni(II), Cd(II) mixed ligand complexes by using 2,4-dinitrophenyl hydrazine and dimethylglyoxime. Journal of King Saud University – Science. 2022;34:102114. doi:10.1016/j.jksus.2022.102114.