First Divalent Metal Complexes of the Polyether Ionophore Monensin A:X-Ray Structures of [Co(Mon)2(H2O)2] and [Mn(Mon)2(H2O)2] and their Bactericidal Properties

Abstract

The complexation of carboxylic acid Monensin A (MonH, 1a) with CoCl2.6H2O and MnCl2.4H2O leads to the formation of mononuclear complexes [Co(Mon)2(H2O)2], 2a and [Mn(Mon)2(H2O)2], 2b, respectively. The unique crystal structures of 2a and 2b were determined by X-ray crystallography. The complexes crystallize in the monoclinic space group P2 1 with an octahedrally coordinated transition metal center forming the crystallographically centrosymmetric chromophore CoO6 or MnO6, respectively. Two molecules of Monensin A act bidentately through their carboxylate moiety and a hydroxyl group, and two water molecules are additionally trans-coordinated. Although the transition metal ions are not bound into the cavity of the ligand, the unusual bidentate coordination mode of the ionophore induces its "pseudo-cyclization" forming 22-membered cycles further stabilized by a number of H-bonds. The complexes are the first example of divalent metal complexes of the monovalent polyether ionophore. The parallel study on the complexation ability of the potassium complex of Monensin A (MonK, 1b) towards Co(II) and Mn(II) showed the formation of the isostructural complexes 2a and 2b accompanied by loss of the potassium ion due to the new coordination mode of the ligand. The biological tests performed with the antibiotic MonH and the corresponding metal(II) complexes show greatly enhanced antimicrobial activity of complexes 2a-b against Gram(+)-bacteria.

Cytotoxicity of Monensic Acid and its Biometal(II) Complexes Against Anaerobic Bacterial StrainClostridium PerfringensSpp.

“…the complexes of ni(ii) (5) and Zn(ii) (6) are effective against B. subtilis, B. mycoides and C. perfringens, although they do Pantcheva et al (7,8,9,10) B. mycoides c Pantcheva et al (7,8,9,10) not show toxicity against S. lutea in the studied concentration range. notably, the Mn(ii) complex (4) was shown to be the least toxic among the metal(ii) compounds against Gram-positive aerobic bacteria.…”

“…Monensic acid (Monh) and its biometal(ii) complexes with ions of Mg(ii), ca(ii), co(ii), Mn(ii), ni(ii) and Zn(ii) were prepared as previously reported (8,9,10). their structural characteristics have also been previously described (8,9,10).…”

“…in this respect we have recently studied the ability of these antibiotics, especially Monensin, to coordinate divalent bio-and toxic metal ions. We were able to characterize complexes of various compositions and different structures depending on the antibiotic applied (acidic or sodium form) as well as on the metal(ii) ion tested (7,8,9,10). our studies revealed that the activity of metal(ii) complexes of Monensin and Salinomycin is enhanced compared to the non-coordinated antibiotics against Gram-positive aerobic bacteria.…”

“…For comparative purposes, data obtained using Grampositive aerobic bacteria are also included (7,8,9,10). the bacterial assay showed that metal(ii) salts are ineffective by themselves and do not affect the growth of aerobic and anaerobic microorganisms.…”

In VitroActivity of Biometal(II) Complexes of Monensin Against Virus-Induced Transplantable Animal Tumors

“…Dulbecco's modified Eagle's medium (D-MeM) and fetal bovine serum were purchased from Gibco-invitrogen (UK). Dimethyl sulfoxide (DMSo), neutral red (nR), trypan blue (tB) and trypsin were supplied from AppliChem (Germany); purified agar (Difco) and thiazolyl blue tetrazolium bromide (Mtt) were from Sigma- (22,23). the compounds were prepared as stock solutions in DMSo (1 mg/ml) due to their low solubility in water.…”