A series of heterocyclic organobismuth(III) carboxylates 4 and 5 [RCO2Bi(C6H4-2-SO2C6H4-1′-)] derived from diphenyl sulfone was synthesized to determine the influence of the carboxylate ligand structure on the lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae. In contrast to the clear structure–activity relationship between the size of the inhibition zone and the value of ClogP for specific substitution on diphenyl sulfone scaffold 1 [ClBi(5-RC6H3-2-SO2C6H4-1′-)], scaffolds 4 and 5 showed similar inhibition activities irrespective of the ClogP value. This suggests that these molecules function inside the yeast cell by separating into the cationic heterocyclic bismuth scaffold and the anionic carboxylate moiety, and that the bismuth scaffold plays an important role in the inhibition activity.Graphical abstractHighlights► Heterocyclic bismuth carboxylates derived from diphenyl sulfone are synthesized. ► Antifungal activity of the bismuth carboxylates is tested against Saccharomyces cerevisiae. ► The cationic bismuth scaffold plays an important role in the antifungal activity.

A series of heterocyclic organobismuth(III) compounds 2 [ClBi(5-R-C6H3-2-SO2C6H4-1'-): R = Me, Ph, MeO, Cl, H, t-Bu, CF3, F, Me2N] was synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae. A clear structure–activity relationship between the size of the inhibition zone and the value of ClogP was found for 2. These results suggest that the higher the lipophilicity, the lower the antifungal activity. Thus, 2e (R = H) and 2h (R = F), which had ClogP values of 1.18 and 1.45, respectively, were most active. In contrast, 2b (R = Ph) and 2f (R = t-Bu) had ClogP values of 3.06 and 3.00, respectively, and exhibited no antifungal activity. Compound 6b ClBi[5-(OH)C6H3-2-SO2-5′-(OH)C6H3-1'-] had an estimated ClogP value of 0.81 but exhibited only low activity in spite of its low ClogP value, suggesting that such a considerable decrease in lipophilicity lowers inhibition activity. Bismuth carboxylate 7b derived from p-nitrobenzoic acid and 2e exhibited inhibition activity comparable to those of 2e and 2h despite its higher lipophilicity (ClogP = 2.68).Graphical abstractA series of heterocyclicorganobismuth(III) compounds derived from diphenyl sulfones was synthetized. A clear structure–activity relationship between the antifungal activity and the lipophilicity was found for these compounds.Research highlights► Bismuth heterocycles based on a diphenyl sulfone scaffold are synthesized. ► Antifungal activity of the bismuth heterocycles is tested against S. cerevisiae. ► The higher the lipophilicity, the lower the antifungal activity.

Dithienobismoles having a bismole ring fused with a bithiophene system were prepared by the reactions of β,β′-dilithiobithiophenes with aryldihalobismuthanes, as novel phosphorescence materials.

Inhibitory activity of organobismuth compounds, triarylbismuthanes 1 and their dihalides 2 and 3, was examined against jack bean urease. Besides triarylbismuth dichlorides 2, triarylbismuth difluorides 3 and bismuthanes 1 exhibited the activity. Of all these compounds, triphenylbismuth difluoride 3a and tris(4-fluorophenyl)bismuth dichloride 2b showed the highest activity. These results indicate that generation of the inhibitory effect is not always governed by the Lewis acidity at the bismuth center. Such a tendency of inhibition by the organobismuth compounds is in good accord with that observed in the antibacterial activity against Helicobacter pylori, suggesting that H. pylori-produced urease may be a therapeutic target by bismuth-based drugs.Inhibitory activity of organobismuth compounds was tested against jack bean urease. Triphenylbismuth difluoride showed the highest activity. The tendency of the inhibition is in good agreement with that observed in the antibacterial activity against Helicobacter pylori.

Competitive oxidative chlorination of p-substituted triarylstibines 3 [(p-XC6H4)3Sb; a: X = OMe, c: Cl, d: CO2Et, e: CF3, f: CN, g: NO2] by sulfuryl chloride was carried out against 3b (X = H) and the electronic effect of these substituents on the chlorination of 3 was compared with that of homologous triarylbismuthanes 1. The relative ratios 4/4b (Ar3SbCl2/Ph3SbCl2) decreased with increasing electron-withdrawing ability of the substituents (a: 53/47, c: 49/51, d: 46/54, e: 44/56, f: 40/60, g: 37/63), but the tendency was not so pronounced as observed in the chlorination of 1. A Hammett plot of the 4/4b ratios against the σp constants exhibited a good linear relationship with a negative slope, the value of which was almost half of that deduced from the 2/2b (Ar3BiCl2/Ph3BiCl2) ratios. The difference in the reactivity between 1 and 3 may be explained by the effect of the electron-withdrawing substituents in the aromatic rings, which affects the p-character of the lone pair on the pnictogen atoms by increasing the positive metal charge and appears more remarkably in 1 than in 3. The 13C NMR study of 3 revealed that the chemical shifts of the ipso carbons (C1) attached to the antimony show a linear relationship against the σp constants with a positive slope (14.5). The value was smaller than that deduced from 1 (17.0), suggesting that the antimony center of 3 is less sensitive to the substituent effect. This is in accord with the tendency of the chlorination.Oxidative chlorination of p-substituted triarylstibines was carried out and the effect of the p-substituents on the chlorination was compared with that of the bismuth congeners. The spectroscopic characteristics of the stibines and their dichlorides were studied by 13C NMR spectrum.

Antifungal activity of organobismuth(III) and (V) compounds 1–9 was examined against the yeast, Saccharomyces cerevisiae. A clear structure–activity relationship was observed in these compounds. Thus, triarylbismuth dichlorides 2 {(4-YC6H4)3BiCl2: Y=MeO, F, Cl, CF3, CN, NO2} and halobismuthanes 6 {2-tBuSO2C6H4(4-YC6H4)BiX: Y=MeO, Me, H, Cl; X=Cl, Br, I}, 7 {Bi(X)(C6H4-2- SO2C6H4-1′-): X=Cl, Br, I}, 8 {2-Me2NCH2C6H4(Ph)BiX: X=Cl, Br} and 9 {4-MeC6H4(8-Me2NC10H6-1-)BiCl} showed the growth inhibition effect, while triarylbismuth difluorides 3 {(4-YC6H4)3BiF2} and triarylbismuthanes 1 {(4-YC6H4)3Bi}, 4 {2-tBuSO2C6H4(4-YC6H4)2Bi} and 5 {4-YC6H4Bi(C6H4-2-SO2C6H4-1′-)} were not active at all irrespective of the nature of the substituents. Generation of the inhibition effect is governed by the facility of nucleophilic reaction at the bismuth center and the Lewis acidic bismuth center is an active site. Of all the bismuth compounds attempted, halobismuthanes 7 derived from diphenyl sulfone exhibited the highest activities. An X-ray crystallographic study of 7a {Bi(Cl)(C6H4-2-SO2C6H4-1′-)} revealed that the bismuth center adopts a seven-coordinated geometry, which is unusual in organobismuth(III) compounds, through the intramolecular and intermolecular coordination between the bismuth and oxygen atoms. The marked inhibition effect of 7 may be attributed to such a highly coordinated geometry, which allows the bismuth center to bind tightly with some biomolecules playing important roles in the growth of S. cerevisiae.

Competitive chlorination of p-substituted triarylbismuthanes 1 [(p-XC6H4)3Bi; a: X = OMe, c: Cl, d: CO2Et, e: CF3, f: CN, g: NO2] and trimesitylbismuthane (2,4,6-Me3C6H2)3Bi 1h by sulfuryl chloride was carried out against 1b (X = H) and the effect of these substituents on the formation of triarylbismuth dichlorides 2 was studied. The relative ratios 2/2b decreased with increasing electron-withdrawing ability of the substituents (2a/2b = 53/47, 2c/2b = 33/67, 2d/2b = 35/65, 2e/2b = 29/71, 2f/2b = 16/84, 2g/2b = 0/100, 2h/2b = 46/54), indicating a lowering of reactivity of the lone pair on the bismuth atom. Pd-Catalyzed degradation of 2a–g and their difluorides 3 giving biaryls 4 was promoted by the electron-withdrawing p-substituents in the equatorial aryl groups but suppressed by the more electronegative fluorine atoms in the apical positions. This is in fairly good accord with the stability of the trigonal bipyramidal geometry. The 13C NMR study of 1–3 showed that the signals due to the ipso carbons (C1) attached to the bismuth atom shift downfield with increasing electron-withdrawing nature of the p-substituents. No such tendency was observed in other aromatic ring carbons. The electronic effect on the C1 atoms, similar to that on the chlorination of 1 and degradation of 2 and 3, indicates the significant participation of the C1 atoms in these reactions through the Bi–C1 bonds.The electronic effect of the p-substituents on the oxidative chlorination of triarylbismuthanes, Pd-catalyzed coupling reaction of triarylbismuth dihalides and spectroscopic characteristics of these organobismuth compounds was studied. The π-accepting substituents were revealed to markedly affect their reactivity and spectroscopic properties.