Synthesis and structural characterisation of bismuth(III) hydroxamates and their activity against Helicobacter pylori.
Seven new bismuth(iii) hydroxamate complexes derived from the hydroxamic acids N-methylfurohydroxamic acid (H-MFHA), N-benzoyl-N-phenylhydroxamic acid (H-BPHA), salicylhydroxamic acid (H2-SHA), benzohydroxamic acid (H2-BHA), and acetohydroxamic acid (H2-AHA) have been synthesized and characterized. The complexes formed are either tris-hydroxamato complexes containing only mono-anionic ligands, [Bi(H-SHA)3], [Bi(MFHA)3] and [Bi(BPHA)3]; mixed-anion complexes, [Bi(SHA)(H-SHA)] and [Bi(AHA)(H-AHA)]; and potassium bismuthate complexes, K[Bi(SHA)2] and K[Bi(BHA)2]. The solid-state structure of three complexes has been determined through single crystal X-ray diffraction; [Bi(MFHA)3]2·Me2C[double bond, length as m-dash]O, {[Bi(SHA)(H-SHA)(DMSO)2][Bi(SHA)(H-SHA)(DMSO)]·DMSO}∞ and [Bi(BPHA)3]2·2EtOH. All the complexes and their parent acids were assessed for the bactericidal activity against three strains of Helicobacter pylori (26695, B128 and 251). Of the acids, only acetohydroxamic acid showed any activity at low concentrations (MIC 6.25 μg mL(-1); 83.26 μM) while the others were not toxic below 25 μg mL(-1). In contrast, their bismuth(iii) complexes all showed excellent activity across all three strains (e.g. 0.28 μM for [Bi(H-SHA)3] to 6.01 μM for K[Bi(BHA)2] against strain 251) with only minor variations in activity being both ligand and composition dependant.
School of Chemistry, Monash University, Clayton, Melbourne, VIC 3800, Australia.
Amita
A
Pathak
Victoria L
VL
Blair
Richard L
RL
Ferrero
Peter C
PC
Junk
Richard F
RF
Tabor
Philip C
PC
Andrews
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001729:Bismuth / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D006868:Hydrolysis; D006877:Hydroxamic Acids / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation
D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D006877:Hydroxamic Acids; D001729:Bismuth