A sweeter way to combat Helicobacter pylori? Bismuth(III) complexes and oxido-clusters derived from non-nutritive sweeteners and their activity against H. pylori

Eight new homo-and hetero-leptic bismuth(III) complexes and two new polynuclear bismuth(III) oxido clusters derived from acetosulfame (AceH) and cyclamic acid (CycH2) have been synthesised and characterised. Complexes, [Ph2Bi(Ace)] 1, [Bi(Ace)3] 2, [PhBi(Ace)2] 3, [Bi(CycH)3] 6, [Ph2Bi(CycH)] 7 and [PhBi(CycH)2] 8 were synthesised by treating BiPh3 with the appropriate acid in 1:1, 1:2 and 1:3 stoichiometric ratios under solvent-free or solvent-mediated conditions. Complex 4, [Bi(OH)(Ace)2], was obtained from the hydrolysis of 3. [Bi2(Cyc)3] 9 was obtained from the reaction of cyclamic acid with (Bi(OtBu)3) in a 3:2 ratio under inert conditions. The polynuclear bismuth oxido clusters, [Bi50O64(Ace)22(H2O)10] 5 and [Bi38O45(CycH)24(H2O)14] 10 were obtained using Bi2O3 under sonication in water and their composition confirmed through elemental and thermogravimetric analyses. The DMSO soluble complexes, 1, 2, 4, 5, 6, 7 and 9, were all assessed for their in-vitro activity against three strains of H. pylori (251, 26695 and B128). All compounds gave an MIC value of 6.25 μg/mL, indicating that bactericidal activity is insensitive to increased substitution by acetosulfamate or cyclamate at the Bi(III) centre.

Graphical abstractEight new homo-and heteroleptic bismuth(III) compounds and two polynuclear oxido-clusters derived from the non-nutritive sweeteners acetosulfame and cyclamic acid have been synthesised by solvent-mediated and solvent-free methods. Bactericidal studies against Helicobacter pylori (MIC 6.25 μg/mL for all compounds) suggest activity is independent of ligand-type and degree of substitution.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of homo-and heteroleptic bismuth acetosulfamate and cyclamate complexes from BiPh3. ► Large bismuth oxido-clusters from reaction of Bi2O3 with acetosulfamate or cyclamic acid in water. ► High bactericidal activity of bismuth complexes and oxido-clusters against Helicobacter pylori. ► Bactericidal activity insensitive to increasing number of acetosulfamate and cyclamate ligands.