Bismuth(III) saccharinate and thiosaccharinate complexes and the effect of ligand substitution on their activity against Helicobacter pylori

Five bismuth(III) saccharinate and thiosaccharinate complexes, [Ph(2)Bi(sac)](infinity) 1, [Bi(sac)(3)](n) 2, [Ph(2)Bi(tsac)](infinity) 4, [PhBi(tsac)(2)](n) 5, [Bi(tsac)(3)](n) 6 (sacH = saccharin, tsacH = thiosaccharin), have been synthesized and fully characterized. The tendency for ligand redistribution in [Ph(2)Bi(sac)](infinity) has been investigated in solution by NMR spectroscopy. The structures of [Ph(2)Bi(sac)](infinity) I and [Ph(2)Bi(tsac)](infinity) 4 have been confirmed by X-ray crystallography. In Ph(2)Bi(sac) the sac ligand is bound to a four-coordinate bismuth center via its imino nitrogen atom with an accompanying long-range Bi-O interaction. However, in the structure of [Ph(2)Bi(tsac)](infinity) the ligand is sigma-bound through the exocyclic sulfur atom, giving a thiolate complex, confirming the more thiophilic nature of bismuth(III). Both complexes consist of polymeric chain structures with formally four-coordinated bismuth atoms. The complexes were assessed for their activity against H. pylori. The activity is both ligand dependent and sensitive to the degree of ligand substitution. The saccharinate complexes, 1 and 2, show activity comparable with standard tris-carboxylato bismuth(III) compounds, 6.25 mu g/mL, while the activity of the thiolato complexes, 4-6, increases dramatically on increasing the number of thiolate groups from one to three (range 50-6.25 mu g/mL). Saccharin, thiosaccharin, and BiPh(3) were found to be inactive.