Imipenem-metal complexes: Computational analysis and toxicity studies with wastewater model microorganisms.

The occurrence of antibiotic residues in diverse water sources has long been acknowledged as a potential health concern due to the emergence and spread of antibiotic-resistant bacteria and genes. However, there have been limited studies into the presence of antibiotic-metal complexes (AMCs) in real-time wastewater matrices, and their impact on wastewater microbial communities. The present work, in this regard, investigated the stability of Imipenem-metal complexes (Me = Mg (II), Ca (II), Fe (II), Cu (II), and Al (III)) with computational studies, stoichiometry with potentiometric measurements, and their antibacterial activity towards wastewater model microorganisms- Bacillus subtilis (B. subtilis) and Escherichia coli (E. Coli) by Colony Forming Unit (CFU) method. The lower energy of Imipenem-metal complexes than the parent antibiotic- Imipenem, during energy optimization using density functional (DFT) methods, revealed that metal interactions of Imipenem stabilize the drug by minimizing its energy. Further, CFU studies indicated that these complexes display higher antimicrobial activity than parent antibiotics. The electron delocalization over the entire chelated system (AMCs) reduces polarity and increases the lipophilicity of the complexes, thereby facilitating stronger interaction between AMCs and the bacterial cell membrane. Results indicate increased antibacterial activity of Imipenem-metal complexes for both E. coli and B. subtilis. The antibacterial activity, was however, more pronounced in B. subtilis, with >97% growth inhibition for metal complexes of Imipenem (at a Minimum Inhibitory Concentration of 20 nM or 6 ppb (i.e., MIC90)), for both the stoichiometric ratios (metal to ligand) ratios (M: L 1: 1 and 2: 1). All around, with increased stability and toxicity, AMCs are emerging as contaminants of concern and demand immediate attention to devise methods for their removal.

Antibiotic-metal complexes in wastewaters: fate and treatment trajectory.

Unregulated usage, improper disposal, and leakage from pharmaceutical use and manufacturing sites have led to high detection levels of antibiotic residues in wastewater and surface water. The existing water treatment technologies are insufficient for removing trace antibiotics and these residual antibiotics tend to interact with co-existing metal ions and form antibiotic-metal complexes (AMCs) with altered bioactivity profile and physicochemical properties. Typically, antibiotics, including tetracyclines, fluoroquinolones, and sulphonamides, interact with heavy metals such as Fe2+, Co2+, Cu2+, Ni2+, to form AMCs which are more persistent and toxic than parent compounds. Although many studies have reported antibiotics detection, determination, distribution and risks associated with their environmental persistence, very few investigations are published on understanding the chemistry of these complexes in the wastewater and sludge matrix. This review, therefore, summarizes the structural features of both antibiotics and metals that facilitate complexation in wastewater. Further, this work critically appraises the treatment methods employed for antibiotic removal, individually and combined with metals, highlights the knowledge gaps, and delineates future perspectives for their treatment.