Synthesis and Characterisation of Bismuth(III) Aminoarenesulfonate Complexes and Their Powerful Bactericidal Activity against Helicobacter pylori

Abstract

The synthesis and characterisation of nine new tris-substituted bismuth(III) aminoarenesulfonates of the general formula [Bi(O3S-R(N))3] (R(N) = o-aminophenyl 1, m-aminophenyl 2, 6-amino-3-methoxyphenyl 3, p-aminophenyl 4, 2-pyridyl 5, o-aminonaphthyl 6, 5-aminonaphthyl 7, 4-amino-3-hydroxynaphthyl 8 and 5-isoquinolinyl 9) is described. Two synthetic strategies, using Ag2O and [Bi(OtBu)3], were explored and compared. The possibility to access heteroleptic bismuth(III) complexes with the new silver(I) metathesis reaction is demonstrated with the synthesis of the heteroleptic bismuth(III) aminoarenesulfonate complexes [PhBi(O3S-P2)2(dmso)] 10, [Ph2Bi(O3S-P2)]∞ 11 and [PhBi(O3S-P2)2]∞ 12, of which the solid state structures 10 and 12 are presented (2P-SO3(-) = 2-pyridinesulfonate). These complexes offer remarkable in-vitro activity against three standard laboratory strains of Helicobacter pylori (H. pylori) as demonstrated by their exceptionally low minimum inhibitory concentration (MIC) values of 0.049 μg mL(-1) for the strains 251 and B128, which places most MIC values in the nano-molar region. These results demonstrate the importance of the amino functionality in addition to the sulfonate group on the bactericidal properties against H. pylori.

Bismuth(iii) complexes derived from α-amino acids: the impact of hydrolysis and oxido-cluster formation on their activity against Helicobacter pylori

“…These activity results are comparable with the bismuth(III) sulfonate 70 and amino arenesulfonate 35 complexes. The inclusion of the nitrogen atom in the heterocycle showed no effects, as the tris-substituted bismuth(III) derived from L-proline, 2, displayed results that were comparable with exocyclic bismuth(III) compounds.…”

“…35 These complexes were ultimately accessible in high yield through either a metathesis reaction of the silver(I) amino-arenesulfonates with BiCl 3 , or through direct reaction of the amino-arenesulfonic acids with [Bi(O t Bu) 3 ]. 35 These complexes were ultimately accessible in high yield through either a metathesis reaction of the silver(I) amino-arenesulfonates with BiCl 3 , or through direct reaction of the amino-arenesulfonic acids with [Bi(O t Bu) 3 ].…”

Homo‐ and Heteroleptic Coordination Polymers and Oxido Clusters of Bismuth(III) Vinylsulfonates

“…pylori relative to BiPh 3 and the essentially ineffective sulfonic acids . The same or higher bactericidal activities have been determined for heteroleptic 5‐sulfosalicylates, homoleptic arenesulfonates, and aminoarenesulfonates . These bismuth sulfonates are more effective against H .…”

“…pylori than the commercial preparations BSS, CBS, and RBC . However, only a few examples of mononuclear bismuth(III) sulfonates have been fully characterized, including by means of crystallographic studies: [{Ph 2 Bi(O 3 SR)} n ] (R=CF 3 , R=2,4,6‐mesityl, S ‐(+)‐10‐camphoryl, 2,4‐xylyl, 2,5‐xylyl), [{PhBi(O 3 SR) 2 } n ] (R=4‐tolyl, 2,4,6‐mesityl, 2,5‐xylyl, 2‐pyridyl), [{PhBi(Hssal)(solv)} n ] (H 3 ssal=5‐sulfosalicylic acid; solv=H 2 O, EtOH), [{[Bi(Hssal)(H 2 ssal)(H 2 O) 3 ] 2 ⋅2 H 2 O} n ], and [Bi(H 2 O) x ](OTf) 3 (OTf=triflate; x= 4, 9)…”

Review: Bismuth complexes: synthesis and applications in biomedicine

“…A solution of 2,2′-dilithiated diphenyl sulfone generated from diphenyl sulfone and butyllithium in THF was added dropwise at −40°C to a suspension of dichloro(4-methylphenyl)bismuthane in ether and the resulting mixture was stirred for 3 h to reach ambient temperature [41]. The synthesis of nine [42]. Unfortunately, the long reaction time weakens the advantages of this method.…”