Synthesis, Structural Characterization and Evaluation of the Chelating Potential in C. Elegans Involving Complexes of Mercury (Ii) with Schiff Bases Derived from Amino Acids

Abstract

Two series of neutral mercury(II) complexes have been obtained from the reaction of HgPh(OCOCH 3 )( 1 , 2 , and 3 ) or Hg(OCOCH 3 ) 2 ( 4 , 5 , and 6 ) with N-(2-hydroxynaphtalidene)β-alanine (L1H 2 ), N-(5-bromo-salicylidene)β-alanine (L2H 2 ), and N-(5-bromo-salicylidene)β-phenylalanine (L3H 2 ), respectively. The complexes were characterized by elemental analysis, IR, NMR ( 1 H, 13 C, and 199 Hg) and X-ray crystallography ( 1 and 2 ). X-ray diffraction analyses are similar for complexes 1 and 2 , consistent with mononuclear compounds bearing a primarily di-coordinated Hg II nucleus with several additional Hg—O interactions, which give rise to supramolecular assemblies. Solution NMR analyses indicate that the primary coordination is retained in DMSO for 1 , 2 and 3 , but the additional interactions observed in solid state are lost in solution. Complexes 4 , 5 and 6 are also mononuclear and all analyses, both in solution and solid state, point to a di-coordinated Hg II nucleus with a di-anionic Schiff base ligand. The biological evaluation of the Schiff base (L1H 2 ) chelating potential was performed by pretreating Caenorhabditis elegans ( C. elegans ) nematodes with the L1H 2 (1mM) followed by phenylmercury acetate exposure (LC 50 = 290 μM).The pretreatment with L1H 2 resulted in a significant protection of worm survival against phenylmercury acetate toxicity. Together, these data show that the chelating potential of these ligands is a crucial factor in reducing the toxic effects caused by metals in the worm, suggesting them as promising agents in chelation therapy.

Keywords: Schiff bases, amino acids, mercury(II) complexes, crystal structures, 199Hg NMR spectroscopy, Caenorhabditis elegans, chelating potential.