Synthesis and Complex-Forming Pro­perties of Thio-Containing Complexons: S,s'- Ethylenedithiodialanine and S,s'- Carboxy- Ethylenedithiodialanine

Abstract

Two thio-containing complexones – S,S'-ethy­lenedithiodialanin (EDAL) and S,S'-carboxy-ethylenedithiodialanin (СEDAL) – were synthesized by the alkylation reaction of L-cysteine with dibromoethane. The developed technique has a number of advantages compared to those described in the literature: the absence of ammonia and metallic sodium as synthesis reagents, a decrease in the synthesis temperature and time, an increase in the yield of the final product to ~95%. The physicochemical properties of complesones were investigated using (1H, 13C) NMR, pH-potentiometry, UV-VIS, IR-spectroscopy, DTA and non-quantitative mass spectrometry. The acid dissociation constants of EDAL (pКN1=9.79; pКN2=8.79; pКCOO1=3.25) and СEDAL (pКN1=9.81; pКN2=8.17; pКCOO1=2.82; pКCOO2=3.34) were calculated and the scheme of protonation of complexons depending on pH was proposed. On the basis of NMR spectroscopy data, it is shown that the complexons have a folded structure, mobile along the S-CN2СНСООН and N–CH–COOH axes, in which betaine nitrogen atoms form two intramolecular five-membered glycine cycles due to the rapid exchange of labile protons of СООН groups. In addition, there is an intermolecular cycle in the molecule, which includes an ethylenethioamine fragment.
 DTA data show the presence of adsorbed and crystallization water in molecules of thio-complexons, which is eliminated at 100–170 0С. Intraspherical water molecules are located between molecular layers and form a branched system of hydrogen bonds. The final tempe­rature of the decomposition of compounds is ~4600C. Probably, the end products of EDAL and СEDAL decomposition are non-stoichiometric sulfates or sulfides.
 Complex formation of thio-complexons with Mo(VI) and Cu(II) at their equimolar ratio was investigated in aqueous solutions in a wide pH range (1÷10). The formation of complexes of the composition MoO3CEDAL and CuEDAL in the range of pH 4–9 is shown and the structure of the complexes is proposed.
 The biological activity of carboxy-ethylenedithiodialanin and its complexes with Cu(II) was studied. It has been proven that the compounds exhibit fungistatic properties against pathogenic bacteria Candida spp. (main causative agents of fungal infections).