Heteroleptic NiII complexes: Synthesis, structural characterization, computational studies and amoebicidal activity evaluation

J Inorg Biochem. 2020 May:206:111043. doi: 10.1016/j.jinorgbio.2020.111043. Epub 2020 Feb 19.

Abstract

In this work, we present the synthesis, characterization, electrochemical studies, DFT calculations, and in vitro amoebicidal effect of seven new heteroleptic NiII coordination compounds. The crystal structures of [H2(pdto)](NO3)2 and [Ni(pdto)(NO3)]PF6 are presented, pdto = 2,2'-[1,2-ethanediylbis-(sulfanediyl-2,1-ethanediyl)]dipyridine. The rest of the compounds have general formulae: [Ni(pdto)(NN)](PF6) where N-N = 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (44dmbpy), 5,5'-dimethyl-2,2'-bipyridine (55dmbpy), 1,10-phenanthroline (phen), 4,7-dimethyl-1,10-phenanthroline (47dmphen) and 5,6-dimethyl-1,10-phenanthroline (56dmphen). The size of NN ligand and its substituents modulate the compound electronic features and influence their antiproliferative efficiency against Entamoeba histolytica. 56dmphen derivative, shows the biggest molar volume and presents a powerful amoebicidal activity (IC50 = 1.2 μM), being seven times more effective than the first-line drug for human amoebiasis metronidazole. Also, increases the reactive oxygen species concentration within the trophozoites. This could be the trigger of the E. histolytica growth inhibition. The antiparasitic effect is described using NiII electron density, molar volume, estimated by DFT, as well as the experimental redox potential and diffusion coefficients. In general, amoebicidal efficiency is directly proportional to the increment of the molar volume and decreases when the redox potential becomes more positive.

Keywords: Amoebiasis; Amoebicidal activity; DFT calculations; Nickel (II) complexes; pdto ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amebicides / chemistry
  • Amebicides / pharmacology*
  • Animals
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • Entamoeba histolytica / drug effects
  • Entamoeba histolytica / growth & development*
  • Models, Molecular
  • Nickel / chemistry*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*

Substances

  • Amebicides
  • Coordination Complexes
  • Organometallic Compounds
  • Nickel