title: Homo- and heteroleptic bismuth(III/V) thiolates from N-heterocyclic thiones: synthesis, structure and anti-microbial activity.
abstract: Homo- and heteroleptic bismuth thiolato complexes have been synthesised and characterised from biologically relevant tetrazole-, imidazole-, thiadiazole- and thiazole-based heterocyclic thiones (thiols): 1-methyl-1H-tetrazole-5-thiol (1-MMTZ(H)); 4-methyl-4H-1,2,4-triazole-3-thiol (4-MTT(H)); 1-methyl-1H-imidazole-2-thiol (2-MMI(H)); 5-methyl-1,3,4-thiadiazole-2-thiol (5-MMTD(H)); 1,3,4-thiadiazole-2-dithiol (2,5-DMTD(H)2 ); and 4-(4-bromophenyl)thiazole-2-thiol (4-BrMTD(H)). Reaction of BiPh3 with 1-MMTZ(H) produced the rare Bi(V) thiolato complex [BiPh(1-MMTZ)4 ], which undergoes reduction in DMSO to give [BiPh(1-MMTZ)2 {(1-MMTZ(H)}2 ]. Reactions with PhBiCl2 or BiPh3 generally produced monophenylbismuth thiolates, [BiPh(SR)2 ]. The crystal structures of [BiPh(1-MMTZ)2 {1-MMTZ(H)}2 ], [BiPh(5-MMTD)2 ], [BiPh{2,5-DMTD(H)}2 (Me2 CO)] and [Bi(4-BrMTD)3 ] were obtained. Evaluation of the bactericidal properties against M. smegmatis, S. aureus, MRSA, VRE, E. faecalis and E. coli showed complexes containing the anionic ligands 1- MMTZ, 4-MTT and 4-BrMTD to be most effective. The dithiolato dithione complexes [BiPh(4-MTT)2 {4-MTT(H)}2 ] and [BiPh(1-MMTZ)2 {1-MMTZ(H)}2 ] were most effective against all the bacteria: MICs 0.34 μM for [BiPh(4-MTT)2 {4-MTT(H)}2 ] against VRE, and 1.33 μM for [BiPh(1-MMTZ)2 {1-MMTZ(H)}2 ] against M. smegmatis and S. aureus. Tris-thiolato Bi(III) complexes were least effective overall. All complexes showed little or no toxicity towards mammalian COS-7 cells at 20 μg mL(-1) .
authors.affiliation: School of Chemistry, Monash University, Clayton, Melbourne, VIC 3800 (Australia).
authors.forename: Ahmad
authors.initials: A
authors.lastname: Luqman
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Blair
authors.forename: Rajini
authors.initials: R
authors.lastname: Brammananth
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crellin
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.forename: Philip C
authors.initials: PC
authors.lastname: Andrews
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001729:Bismuth / Q000737:chemistry*; D019556:COS Cells; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D056831:Coordination Complexes; D007093:Imidazoles; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D013871:Thiones; D014230:Triazoles; D001729:Bismuth
keywords: bacteria; bismuth; structure elucidation; synthesis; thiolate