Interaction of Metal(II) Ion–Ciprofloxacin–Glycine in Solution

Abstract

Purpose

The aim of this work is to study the metal–drug–amino acid ternary complex formation kinetically, thermodynamically and computationally and explore the possibility of developing some potent new drugs for biological applications.

Methods

Metal(II)–ciprofloxacin–glycine ternary complexes (metal = MnII, CuII, ZnII) were synthesized. The slow kinetics and thermodynamics of imine formation were investigated spectrophotometrically. The geometry optimizations of ternary complexes were studied by the density functional theory (DFT) using TURBOMOL 6.5 software. The in vitro antibacterial activities of the ternary complexes against gram-positive and gram-negative bacteria were evaluated by disc diffusion method.

Results

It turns out that Cu(II) is the most and Mn(II) is the least efficient in terms of thermodynamics control, while Zn(II) is the most active and Cu(II) is the least active in terms of kinetic control of the ternary imine complex formation, a consequence of kinetic–coordination–template process. The biological screening showed that the ternary metal complexes are as active as the parent drug (cf). However, the uncharged ternary complex may be better career of the drug to the active site due to the presence of metal ion, entailing further detailed investigation.

Conclusion

Kinetics, thermodynamic and in vitro antibacterial activities of metal complexes were investigated. Metal complexes show similar activity towards bacteria as free drug, but they have several advantages over the neat drug (cf), such that increase in lipophilicity of the ternary complex enhances the passage into the cell wall of the microorganism more efficiently than the free drug and blocks the growth of organism; increases the time of post-bacterial activity; and meets the deficiency of metals Cu, Zn, Mn and glycine (gly) which are essential for different metabolisms in biological domain.

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Acknowledgements

The authors are thankful to Prof. A. C. Dash (Retd.Professor, Utkal University) for his constant guidance for completion of this paper. One of the authors, J Panda, is thankful to the Head of the Department of Chemistry, Utkal University, Bhubaneswar, for providing research facilities and also thankful to UGC and Govt. of Odisha for sanctioning teacher fellowship. The authors express their gratitude to Dr. Sharanappa Nembenna, Scientist-F, NISER, Odisha, for his whole-hearted cooperation for mass and NMR spectral analysis and Dr. Himansu Sekhar Biswala, Associate Prof. Chemistry, NISER, Odisha, for computational analysis.

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Correspondence to Ajaya K. Patnaik.

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Panda, J., Das, S., Patnaik, A.K. et al. Interaction of Metal(II) Ion–Ciprofloxacin–Glycine in Solution. J Pharm Innov (2020). https://doi.org/10.1007/s12247-020-09451-3

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Keywords

  • Ciprofloxacin (cf)
  • Glycine (gly)
  • Metal(II) ions
  • Kinetics
  • Antibacterial activity
  • Computational study