Organobismuth Research Articles

Development of Reactivity for Organobismuth (III, V) Toward Sulfur-Containing Compounds

Organobismuth compounds have been used in various areas of science, like biology and organic synthesis, because they are normally nontoxic and exhibit unique properties. Bismuth induces metallothionein production and is known to exhibit thiophilicity. However, few reports on the reactions between bismuth and sulfur compounds exist. This article reviews studies on the reactivity of bismuth (III and V) with sulfur compounds. A simple approach for the reaction of azole-2-thiones, which contains a heterocyclic ring, with triaryl bismuthines in the presence of a copper catalyst affords the S-arylated coupling product. When a palladium catalyst is used instead of a copper catalyst, desulfinative C-C bond formation occurs. These reactions indicate that trivalent bismuth compounds can be used as novel aryl sources. Triphenylbismuth dichloride, an organobismuth (V) reagent, successfully promotes the cyclodesulfurization of thioureas within short reaction times under mild conditions. The reaction affords N-substituted benzoxazol-2-amines in excellent yields. Tafamidis, a drug used to treat transthyretin amyloidosis, can be synthesized using this reaction.

Effect of La3+ on the Formation of Endohedral Zintl Clusters Featuring In/Bi Shells.

Investigating the interactions of f-block metal ions with p-block polyanions in multinary cluster compounds is becoming increasingly attractive but remains a challenge in terms of both the synthetic approach and the control of the structures that are formed during the syntheses. So far, two types of reactions were dominant for the formation of corresponding clusters: the reaction of binary anions of p-block elements in 1,2-diamino-ethane (en) solutions or the reaction of organobismuth compounds with corresponding f-block metal complexes in THF. Herein, we report the synthesis of [La@In2Bi11]4- (1) and its doubly μ-Bi-bridged analogue in the doubly [K(crypt-222)]+-coordinated {[K(crypt-222)]2[La@In2Bi11](μ-Bi)2[La@In2Bi11]}4- (2) as their [K(crypt-222)]+ salts [K(crypt-222)]41 and [K(crypt-222)]42, respectively, achieved by reactions of [InMes3] and [La(C5Me4H)3] (Mes = mesityl, C5Me4H = tetramethylcyclopentadienyl) with K10Ga3Bi6.65/crypt-222 (crypt-222 = 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) in en. In the absence of [La(C5Me4H)3], the otherwise unchanged reactions afford the anions [Bi6(InMes)(InMes2)]3- (3) and [Mes3In-InMes3]2- (4) instead, which can be isolated as their [K(crypt-222)]+ salts [K(crypt-222)]33 and [K(crypt-222)]24·tol (tol = toluene), respectively. The {Bi6} fragment observed in anion 3 is assumed to be one of the key intermediates not only toward the formation of 1 and 2 but also on the way to more general bismuth rich compounds.

Phosphorescence Properties of Boron/Bismuth Hybrid Conjugated Materials.

By introducing main-group elements such as boron and bismuth to π-conjugated systems, it is possible to modify the optical properties of π-conjugated materials through orbital interactions between the orbital on the elements and π/π*-orbitals, and the heavy atom effect. Moreover, bismuth, which is the heaviest stable element, induces a significant heavy atom effect, making organobismuth compounds promising for applications as phosphorescent materials. In this study, we synthesized new room-temperature phosphorescent materials by incorporating bismuth into thiophene units. The phosphorescence properties of these materials, such as emission lifetime and wavelength, could be further controlled by combining tricoordinate boron with the thienylbismuth structures. The synthesized bismuth- and boron-containing thiophene compounds exhibited phosphorescence at room temperature in both solution and solid states. Furthermore, the introduction of boron raised the energy of the triplet state in the π-conjugated system, resulting in a blue shift of the phosphorescence wavelength. The analysis of photoluminescence properties and TD-DFT calculations revealed that the introduction of bismuth enhances phosphorescence properties, whereas the introduction of boron further promotes intersystem crossing.

Mechanochemical synthesis of bismuth active pharmaceutical ingredients, bismuth(iii) gallate and bismuth citrate

Organobismuth compounds have been known for centuries as substances of medical interest, and continue to be used in medicine today.

New organobismuth(III) compounds based on a tetrahydro-dibenzo[c,f][1,5] azabismocine heterocyclic framework

Organobismuth chalcogenides of type [CH3OCH2CH2N(CH2C6H4)2Bi]2E [E = S (1), Se (2)], containing two butterfly-like tetrahydro-dibenzo[c,f][1,5]azabismocine heterocyclic frameworks, were prepared and their solution behavior was investigated by multinuclear NMR spectroscopy (1H, 13C and 77Se, as appropriate) and mass spectrometry. Crystals of [CH3OCH2CH2N(CH2C6H4)2BiO]2SeO (3) were serendipitously formed during the synthesis of compound 2. The molecular structure of 3 was determined by single-crystal X-ray diffraction and revealed, besides a strong transannular N→Bi interaction, an additional O‧‧‧Bi interaction involving the oxygen of the NCH2CH2OCH3 pendant arm from the organic fragment attached to the metal atom, thus resulting in a 12Bi5 hypercoordinate species.

Effects of Hypervalent Bismuth on Electronic Properties of the Azobenzene Tridentate Ligand and Roles of Lewis Acidity in Controlling Optical Properties.

Organobismuth compounds have been studied in various fields, including electronic states, pnictogen bonds, and catalysis. Among them, one of the unique electronic states of the element is the hypervalent state. So far, many issues regarding the electronic structures of bismuth in hypervalent states have been revealed; meanwhile, the influence of hypervalent bismuth on the electronic properties of π-conjugated scaffolds is still vailed. Here, we synthesized the hypervalent bismuth compound, BiAz, by introducing hypervalent bismuth into the azobenzene tridentate ligand as a π-conjugated scaffold. The influence of hypervalent bismuth on the electronic properties of the ligand was evaluated from optical measurements and quantum chemical calculations. The introduction of hypervalent bismuth revealed three significant electronic effects: first, hypervalent bismuth shows position-dependent electron-donating and electron-accepting effects. Second, BiAz can have a larger effective Lewis acidity than the hypervalent tin compound derivatives reported in our previous research. Finally, the coordination of dimethyl sulfoxide transformed the electronic properties of BiAz, similar to the hypervalent tin compounds. The data from quantum chemical calculations showed that the optical properties of the π-conjugated scaffold were able to be changed by introducing hypervalent bismuth. To the best of our knowledge, we first demonstrate that the introduction of hypervalent bismuth should be a new methodology for controlling the electronic properties of π-conjugated molecules and developing sensing materials.

Synthesis, Isolation, and Characterization of Two Cationic Organobismuth(II) Pincer Complexes Relevant in Radical Redox Chemistry.

Herein, we report the synthesis, isolation, and characterization of two cationic organobismuth(II) compounds bearing N,C,N pincer frameworks, which model crucial intermediates in bismuth radical processes. X-ray crystallography uncovered a monomeric Bi(II) structure, while SQUID magnetometry in combination with NMR and EPR spectroscopy provides evidence for a paramagnetic S = 1/2 state. High-resolution multifrequency EPR at the X-, Q-, and W-band enable the precise assignment of the full g- and 209Bi A-tensors. Experimental data and DFT calculations reveal both complexes are metal-centered radicals with little delocalization onto the ligands.

Bi2O3 Nanoparticle-Loaded Plastic Scintillator for High-Energy X-Ray Detection

In this study, we successfully fabricated a Bi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O3 nanoparticle-loaded plastic scintillator (PLS) with high detection efficiency for high-energy X-rays. Such a heavy-metal-oxide-loaded PLS is useful for the measurement of high-energy X-rays with a high count-rate >10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> s <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> . Bi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O3 nanoparticles were synthesized by surface modification with aliphatic carboxylic acid from a triphenylbismuthine starting material. Up to 50 wt% surface-modified Bi <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O3 nanoparticle-loaded plastic scintillator (50 wt% Bi-PLS, 31 ± 1 wt% bismuth in the plastic) successfully maintained transparency after polymerization by mixing monomers consisting mainly of styrene or vinyltoluene and 2-(4-tert-butylphenyl)-5-(4-biphenylyl)-1,3,4-oxadiazole as the fluorophore. The Bi content of the Bi-PLSs was greater than that of PLSs using organobismuth compounds. The optical properties of each Bi-PLS (8 mm diameter and 3 mm thickness) were measured for transmittance, photoluminescence, and quantum yield. The average transmittance between 380 and 780 nm was over 70% (except for 50 wt% Bi-PLS) and was sufficiently high for practical use. In the recorded photoluminescence spectra, the peak attributed to fluorophore emission was clearly observed at 386 nm, even for 50 wt% Bi-PLS. We tested the Bi-PLS mounted on a photomultiplier tube using a synchrotron X-ray beam (67.41 keV at beamline BL-14A of the Photon Factory). The detection efficiency of 50 wt% Bi-PLS reached 36.8 ± 0.5%, 5.0 times higher than that of a commercially available 5 wt% Pb-loaded PLS. A superior time resolution (full width at half maximum) of 0.21 ± 0.06 ns was obtained using 20 wt% Bi-PLS.

Electrochemical Studies of the Cycloaddition Activity of Bismuth(III) Acetylides Towards Organic Azides Under Copper(I)-Catalyzed Conditions.

Time-dependent monitoring of the reactive intermediates provides valuable information about the mechanism of a synthetic transformation. However, the process frequently involves intermediates with short lifetimes that significantly challenge the accessibility of the desired kinetic data. We report in situ cyclic voltammetry (CV) and nuclear magnetic resonance (NMR) spectroscopy studies of the cycloaddition reaction of organobismuth(III) compounds with organic azides under the copper(I)-catalyzed conditions. A series of bismuth(III) acetylides carrying diphenyl sulfone scaffolds have been synthesized to study the underlying electronic and steric effects of the tethered moieties capable of transannular oxygen O···Bi interactions and para-functionality of the parent phenylacetylene backbones. While belonging to the family of copper-catalyzed azide-alkyne cycloaddition reactions, the reaction yielding 5-bismuth(III)-triazolide is the sole example of a complex catalytic transformation that features activity of bismuth(III) acetylides towards organic azides under copper(I)-catalyzed conditions. Stepwise continuous monitoring of the copper(I)/copper(0) redox activity of the copper(I) catalyst by cyclic voltammetry provided novel insights into the complex catalytic cycle of the bismuth(III)-triazolide formation. From CV-derived kinetic data, reaction rate parameters of the bismuth(III) acetylides coordination to the copper(I) catalyst (KA) and equilibrium concentration of the copper species [cat]eq. are compared with the overall 5-bismuth(III)-triazolide formation rate constant kobs obtained by 1H-NMR kinetic analysis.

Triphenylbismuth dichloride inhibits human glyoxalase I and induces cytotoxicity in cultured cancer cell lines.

Organobismuth compounds, i.e., organic-inorganic hybrid molecules composed of an organic structure and bismuth metal, have been reported to induce cytotoxicity in cancer cells; however, the target proteins associated with this cytotoxicity have not been elucidated. Herein, we investigated the inhibitory effect of five organobismuth compounds on human glyoxalase I (hGLO I), a promising target candidate for cancer therapy. Among these compounds, triphenylbismuth dichloride (Bi-05) exerted a strong inhibitory effect on hGLO I. Indeed, Bi-05 inhibited hGLO I in a dose-dependent manner with an IC50 value of 0.18 µM. Bi-05 also induced cytotoxicity in human leukemia HL-60 cells and human lung cancer NCI-H522 cells, both of which exhibit high expression levels of GLO I. However, the hGLO I-inhibiting and cytotoxic effects of Bi-05 disappeared when the bismuth atom was replaced with an antimony or phosphorus atom. Bismuth(III) nitrate had little inhibitory effect on hGLO I activity and only slightly reduced the viability of cancer cells. In the culture medium of Bi-05-treated HL-60 cells, the concentration of the GLO I substrate methylglyoxal was markedly elevated. In addition, Bi-05 treatment more strongly inhibited human lung cancer NCI-H522 cell (exhibiting high GLO I expression) proliferation than human lung cancer NCI-H460 cell (exhibiting low GLO I expression) proliferation. Furthermore, the cytotoxicity of Bi-05 was significantly decreased by pre- and co-treatment with the methylglyoxal scavengers N-acetyl-L-cysteine and aminoguanidine. Overall, these results suggest that Bi-05 treatment leads to the accumulation of methylglyoxal via GLO I inhibition, resulting in cytotoxic effects in cancer cells.

Heteroelement organobismuth compounds in 2010–2020: A review

The present review, which includes a description of modern achievements in the field of synthesis methods, the study of structural features and the possibility of practical use of organometallic compounds of bismuth, is based on an analysis of the literature published for the period from 2010 to 2020. Some of the earlier works are presented in the review because of their importance. The bibliography includes 100 references.

AN OVERVIEW OF BIOMEDICINAL PERSPECTIVES OF ORGANOBISMUTH COMPOUNDS

There is the enormous potential of metal-based drugs as they have more efficacy against different chronic and acute diseases. The transition and non-transition metal played significant roles in the synthesis of active potential scaffolds as a catalyst and also played a significant role in enhancing the biomedical importance of organic and organometallic drugs. Members of group-15 put up an important signature in this area as they are used in the treatment of microbial infections and also as antitumor, antiulcer, antiasthamatic, antitubercular and gastric disorders. The present review article highlights the potential applications of organobismuth compounds on the human body both clinically and industrially

Liebeskind-Srogl-type cross-coupling reaction of azole-2-thiones with triarylbismuthines: Synthesis of 2-arylazoles

Liebeskind-Srogl-type C(HetAr)–C(Ar) bond formation using trivalent organobismuth compounds as a new class of arylating reagents is described. The reaction of benzazole-2-thiones with triarylbismuthines in the presence of 10 mol% Pd(dba)2 and 2.0 equiv. Cu(OAc)2 at 80 °C affords 2-arylbenzothiazoles, benzoxazoles, and N-methyl benzimidazole in moderate-to-high yield. The reaction is sensitive to the electronic nature of triarylbismuthines: compounds bearing an electron-withdrawing group on the phenyl ring showed higher reactivity than those having an electron-donating group.

SYNTHESIS AND CHARACTERIZATION OF NOVEL ORGANOBISMUTH FOR ANTIMICROBIAL AND ANTITUMOR STUDIES

Objectives: The major objective of this manuscript is to present synthesis and biomedical screening of some organic derivatives of bismuth having general formula (R3BiL2) by the method reported and characterized with the help of M.P., elemental, I.R., and NMR spectral analysis along with their antimicrobial and in vitro antitumor activity against human breast (MCF-7) and mammary cancer (EVSA-7) cell line.&#x0D; Methods: All the newly organobismuth having general formula [R3BiL2] were synthesised by the method reported especially using oxidative addition and complexation reactions.&#x0D; Results: It was found that organobismuth compounds have trigonal bipyramidal structure as per their elemental and spectral analysis and show potentiality as antimicrobial and antitumor agents.&#x0D; Conclusion: The newly synthesized organobismuth(V)substituted carboxylates were fully characterized chemically to ascertain their structure by sophisticated instrumental and spectral analysis resulted as trigonal bipyramidal structure. The compounds were also screened 1st time for antitumor and antimicrobial studies. The observations clearly indicated that organobismuth carboxylates show potent antimicrobial and antitumor activity.

Modular bismacycles for the selective C-H arylation of phenols and naphthols.

Given the important role played by 2-hydroxybiaryls in organic, medicinal and materials chemistry, concise methods for the synthesis of this common motif are extremely valuable. In seeking to extend the lexicon of synthetic chemists in this regard, we have developed an expedient and general strategy for the ortho-arylation of phenols and naphthols using readily available boronic acids. Our methodology relies on in situ generation of a uniquely reactive Bi(V) arylating agent from a bench-stable Bi(III) precursor via telescoped B-to-Bi transmetallation and oxidation. By exploiting reactivity that is orthogonal to conventional metal-catalysed manifolds, diverse aryl and heteroaryl partners can be rapidly coupled to phenols and naphthols under mild conditions. Following arylation, high-yielding recovery of the Bi(III) precursor allows for its efficient re-use in subsequent reactions. Mechanistic interrogation of each key step of the methodology informs its practical application and provides fundamental insight into the underexploited reactivity of organobismuth compounds.

Upregulation of nuclear factor (erythroid-derived 2)-like 2 protein level in the human colorectal adenocarcinoma cell line DLD-1 by a heterocyclic organobismuth(III) compound: Effect of organobismuth(III) compound on NRF2 signaling

An increasing number of metal-based compounds, including arsenic trioxide, auranofin, and cisplatin, have been reported to have antitumor activity. Their beneficial effects are controlled by a transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2). In response to oxidative stress, NRF2 induces the expression of cytoprotective genes. NRF2 protein levels are regulated by Kelch-like ECH-associated protein 1 (KEAP1) via ubiquitination. Bi-chlorodibenzo[c,f][1,5]thiabismocine (compound 3), a bismuth compound, is known for its potent anti-proliferative activity against various cancer cell lines. In the present study, we investigated the effect of compound 3 on NRF2 signaling in the human colorectal adenocarcinoma cell line DLD-1 in terms of cell viability as well as mRNA and protein expression levels of NRF2. Compound 3 upregulated NRF2 protein levels in a time- and concentration-dependent manner, accompanied by a marked increase in heme-oxygenase-1 (HO-1) mRNA and protein levels. We observed that brusatol, an NRF2 inhibitor, as well as small interfering RNA (siRNA)-mediated knockdown of NRF2 in DLD-1 cells suppressed compound 3-induced HO-1 expression. The anticancer activity of compound 3 was enhanced by compounds that downregulate NRF2. These results suggest that compound 3 upregulates HO-1 via NRF2 activation and that the NRF2-HO-1 pathway is the cellular response to compound 3. We also discovered that compound 3 slightly downregulated KEAP1; thus, NRF2 activation may be associated with KEAP1 modification. Collectively, our results indicate that compound 3 simultaneously activates an anti-oxidative stress pathway, such as NRF2 and HO-1, and a pro-cell death signal in DLD-1 cells. Our findings may provide useful information for the development of a potent anticancer organobismuth(III) compound.

Heterocyclic organobismuth(III) compound induces nonapoptotic cell death via lipid peroxidation.

Heterocyclic organobismuth compounds, such as N-tert-butyl-bi-chlorodibenzo[c,f][1,5]azabismocine (compound 1) and bi-chlorodibenzo[c,f ][1,5]thiabismocine (compound 3), exert potent antiproliferative activities in vitro in human cancer cell lines. We showed that compound 3 induced both apoptotic and nonapoptotic cell death via reactive oxygen species production and mitotic arrest in a dose-dependent manner. The mechanisms underlying the dose-dependent effect of these organobismuth compounds were not clear. In the present study, we examined the dose-dependent mechanism underlying cell death induced by compound 1 in a human pancreatic cancer cell line, SUIT-2, and a human colorectal cancer cell line, DLD-1. Compound 1 inhibited cell growth in a dose-dependent manner and induced cell death. Treatment with the pan-caspase inhibitor zVAD-fmk reduced cell death induced by compound 1, whereas the inhibitory effect of zVAD-fmk was limited. Moreover, compound 1 significantly induced lipid peroxidation with concomitant induction of caspase-independent cell death. Our results suggested that eight-membered ring organobismuth compounds induce nonapoptotic cell death via lipid peroxidation.

Синтез, строение и применение арильных соединений висмута

On the basis of analysis of the literature published in the period from the end of the 20th century to the beginning of the 21st century, the methods of preparation, some reactions, structure features of organic bismuth compounds, as well as examples of their possible use, have been systematized and described. Over the past ten years, the number of works in the field of bismuth compounds has increased significantly, and their inclusion in this review would substantially enhance the scope of this article. However, some later references have still been included in the review due to their particular importance. In 1950–1952, the Nobel laureate G. Wittig first obtained pentaphenyl compounds of phosphorus, arsenic, antimony, and bismuth and studied some of their reactions. Since then, few foreign researchers continued Wittig's studies in the field of reactivity of pentaphenyl bismuth since the synthesis experiment was quite complex, and its reproduction for many researchers seemed an impossible task. In 1974, one of the authors of the present article synthesized pentaphenyl bismuth for the first time in Russia and published a series of papers on its reactivity. Another Nobel laureate, D. Barton, drew attention to the published works. He was interested in the fascinating results obtained by Russian chemists. In the last years of his life, D. Barton concentrated his efforts in the direction of using organobismuth compounds in fine organic synthesis. A series of remarkable papers were published, the results of which allowed the chemist to be nominated for the second time for the title of Nobel laureate in chemistry, but this did not happen. Research on the reactivity of pentaphenyl bismuth and its derivatives is currently continued in Russia only at the South Ural State University. The following review covers the description of modern achievements in the field of synthesis methods, the study of the reactivity and structural features of bismuth compounds.

Oxidative addition of Bi-C bonds to Pt(0): reaction of Pt(PEt3)3 with cyclic organobismuth compounds.

The reaction of cyclic organobismuth compounds, 12-phenyl- and 12-chloro-5,6,7,12-tetrahydrodibenz[c,f][1,5]azabismocines, with Pt(PEt3)3 was examined. Oxidative addition of the exocyclic Bi-C bond to Pt(0) selectively took place in the reaction of the 12-phenyl derivative. Oxidative addition of the exocyclic Bi-Cl bond reversibly took place and was kinetically preferred, while endocyclic Bi-C bond oxidative addition products were thermodynamically favored and became the final products in the reaction of 12-chloro derivatives. These results demonstrate the oxidative addition of a Bi-C bond to a transition metal complex for the first time.

Three-phenyl transfer in palladium-catalyzed C[sbnd]C coupling reactions by triarylbismuths: A mechanistic study

The unusual reactivity of organobismuth compounds in cross-coupling processes, where they act as multi-aryl sources, opens up new and exciting possibilities in the field of organic synthesis. In particular, the high reactivity of arylbismuths in multifold couplings with arylhalides suggests that three catalytic cycles occur simultaneously. Here, we carry out a computational investigation of a cross-coupling model reaction between bromobenzene (Ph-Br) and triphenylbismuthine (Ph3Bi), catalyzed by Pd(0). The energetic profile evidences the exergonic behavior of the overall reaction with a ΔrG of −38.2 kcal mol−1, in good agreement with the experimental results. Moreover, the largest activation energy (39.8 kcal mol−1) is found for the first Ph3Bi aryl transfer (PhP’1Ph1 → PhP’2Ph1), identified as the rate-determining step. Additional dynamical computations on these potential profiles are needed to confirm these findings. We expect this research to allow for a better understanding of organobismuth palladium-catalyzed CC coupling reactions and organobismuth chemistry in general.