Bismuth as a relatively non-toxic and inexpensive metal with exceptional properties has numerous biomedical applications. Bismuth-based compounds are used extensively as medicines for the treatment of gastrointestinal disorders including dyspepsia, gastric ulcers and H. pylori infections. Recently, its medicinal application was further extended to potential treatments of viral infection, multidrug resistant microbial infections, cancer and also imaging, drug delivery and biosensing. In this review we have highlighted the unique chemistry and biological chemistry of bismuth-209 as a prelude to sections covering the unique antibacterial activity of bismuth including a description of research undertaken to date to elucidate key molecular mechanisms of action against H. pylori, the development of novel compounds to treat infection from microbes beyond H. pylori and the significant role bismuth compounds can play as resistance breakers. Furthermore we have provided an account of the potential therapeutic application of bismuth-213 in targeted alpha therapy as well as a summary of the biomedical applications of bismuth-based nanoparticles and composites. Ultimately this review aims to provide the state of the art, highlight the untapped biomedical potential of bismuth and encourage original contributions to this exciting and important field.

Medicinal chemistry and biomedical applications of bismuth-based compounds and nanoparticles.

As energy demand increases, nuclear power plants will continue to be reliable sources of energy though they release toxic byproducts to the environment. Separation of such contaminants before waste disposal to the environmental waters or release to the atmosphere, and then storage of the isolated substances benefits human beings and the environment. Fabricating eco-friendly, chemically durable, and efficient adsorbents have become core task to minimize iodine contamination problems. One group of potential green materials to uptake these contaminants are bismuth-based materials. The intent of this review is to provide updated achievements on the bismuth-based materials applied for aqueous and vapor iodine uptake and storage. Factors that affect iodine capture, such as adsorption capacity, pH of the solution, efficiency, temperature, contact time, and others are summarized and assessed. Iodine uptake mechanisms are discussed in-depth. The new trend for developing more efficient bismuth-based adsorbents for iodine capture has been summarized.

Bismuth-based materials for iodine capture and storage: A review

The synthesis methods, some reactions, and specific features of the structures of aryl compounds of pentavalent antimony and examples of their possible use are systematized and described on the basis of an analysis of the works published since 2009 to the present time. Some earlier works are also reviewed due to this special significance. When discussing the synthesis methods, the main attention is given to the most efficient approaches to the syntheses of the aryl compounds, for example, the reactions of ligand redistribution, substitution, and oxidative addition. The formation of heterocyclic antimony compounds is considered. The data on the biological and catalytic activities of selected antimony derivatives are presented. The bibliography consists of 318 references.

Aryl Compounds of Pentavalent Antimony: Syntheses, Reactions, and Structures

Pnictogen-bonding catalysis based on σ-hole interactions has recently attracted the attention of synthetic chemists. As a proof-of-concept for asymmetric pnictogen-bonding catalysis, we report herein an enantioselective transfer hydrogenation of benzoxazines catalyzed by a novel chiral antimony cation/anion pair. The chiral pnictogen catalyst library could be rapidly accessed from triarylstibine with readily available mandelic acid analogues, and the catalyst displays remarkable efficiency and enantiocontrol potency even at 0.05 mol % loading. Moreover, the properties of the catalyst and the mechanistic insights have been investigated by nonlinear effect studies, 1H NMR, LC-MS, and control experiments.

Asymmetric Pnictogen-Bonding Catalysis: Transfer Hydrogenation by a Chiral Antimony(V) Cation/Anion Pair.

With the abuse and misuse of antibiotics, antimicrobial resistance has become a challenging issue in the medical system. Iatrogenic and non-iatrogenic infections caused by multidrug-resistant (MDR) pathogens pose serious threats to global human life and health because the efficacy of traditional antibiotics has been greatly reduced and the resulting socio-economic burden has increased. It is important to find and develop non-antibiotic-dependent antibacterial strategies because the development of new antibiotics can hardly keep pace with the emergence of resistant bacteria. Gallium (III) is a multi-target antibacterial agent that has an excellent antibacterial activity, especially against MDR pathogens; thus, a gallium (III)-based treatment is expected to become a new antibacterial strategy. However, some limitations of gallium ions as antimicrobials still exist, including low bioavailability and explosive release. In recent years, with the development of nanomaterials and clathrates, the progress of manufacturing technology, and the emergence of synergistic antibacterial strategies, the antibacterial activities of gallium have greatly improved, and the scope of application in medical systems has expanded. This review summarizes the advancement of current optimization for these key factors. This review will enrich the knowledge about the efficiency and mechanism of various gallium-based antibacterial agents and provide strategies for the improvement of the antibacterial activity of gallium-based compounds.

/pdf/advancement-of-gallium-and-gallium-based-compounds-as-3oak6twj.pdf

Advancement of Gallium and Gallium-Based Compounds as Antimicrobial Agents

A series of triphenyl Sb(v) and Bi(v) α-hydroxy carboxylato complexes of the general formula [MPh3(O2CROH)2] and [MPh3(O2CRO)] have been successfully synthesised and characterised, and subsequently assayed for their comparative activity towards Leishmania parasites and human fibroblast cells. Four complexes are novel; [SbPh3Gly], [BiPh3(GlyH)2], [SbPh3(R-ManH)2] and [SbPh3(S-ManH)2], and have been structurally characterised through X-ray diffraction. These were combined in the study with the known complexes; ([SbPh3(R-Man)], [SbPh3(S-Man)], [BiPh3(R-ManH)2], [BiPh3(R-ManH)2], [SbPh3(BenzH)2], [BiPh3(BenzH)2], for which the crystal structures of [BiPh3(S-ManH)2] and [BiPh3(R-Man)2] have now been authenticated (GlyH2 = glycolic acid, R/S-ManH2 = mandelic acid, BenzH2 = benzilic acid). The complexes adopt a typical bipyramidal 7-coordinate geometry with the phenyl rings occupying the equatorial plane, and the ligands on the axial. In contrast to previous studies the Bi(v) compounds show a relatively high degree of stability in DMEM culture media. Promastigote and human fibroblast cell assays showed the Bi(v) analogues to be non-selectively toxic with a respective IC50 range of 3.58-6.33 μM and 5.83-7.01 μM. In contrast, the Sb(v) analogues provided much greater selectivity (promastigotes 12.5-20.7; fibroblasts 72.8-≥100 μM). Assessment of the Sb(v) complexes against amastigotes at 10 μM showed them to be effective with % infection values ranging from 9.5 ± 0.5-30 ± 1.3.

Comparative stability, toxicity and anti-leishmanial activity of triphenyl antimony(V) and bismuth(V) α-hydroxy carboxylato complexes

Comparative stability, cytotoxicity and anti-leishmanial activity of analogous organometallic Sb(V) and Bi(V) acetato complexes: Sb confirms potential while Bi fails the test.

Antimicrobial resistance is becoming an ever-increasing threat for human health. Metal complexes and, in particular, those that incorporate bismuth offer an attractive alternative to the typically used organic compounds to which bacteria are often able to develop resistance determinants. Herein we report the synthesis, characterization, and biological evaluation of a series of homo- and heteroleptic bismuth(III) thiolates incorporating either one (BiPh2L), two (BiPhL2), or three (BiL3) sulfur-containing azole ligands where LH = tetrazolethiols or triazolethiols (thiones). Despite bismuth typically being considered a nontoxic heavy metal, we demonstrate that the environment surrounding the metal center has a clear influence on the safety of bismuth-containing complexes. In particular, heteroleptic thiolate complexes (BiPh2L and BiPhL2) display strong antibacterial activity yet are also nonselectively cytotoxic to mammalian cells. Interestingly, the homoleptic thiolate complexes (BiL3) were shown to be completely inactive toward both bacterial and mammalian cells. Further biological analysis of the complexes revealed the first insights into the biological mode of action of these particular bismuth thiolates. Scanning electron microscopy images of methicillin-resistant Staphylococcus aureus (MRSA) cells have revealed that the cell membrane is the likely target site of action for bismuth thiolates against bacterial cells. This points toward a nonspecific mode of action that is likely to contribute to the poor selectivity's demonstrated by the bismuth thiolate complexes in vitro. Uptake studies suggest that reduced cellular uptake could explain the marked difference in activity between the homo- and heteroleptic complexes.

Is Bismuth Really the "Green" Metal? Exploring the Antimicrobial Activity and Cytotoxicity of Organobismuth Thiolate Complexes.

There is an emerging interest in the application of metal complexes in the treatment of microbial infections and colonization. Their unique modes of action and the difficulty that microbes face in evolving mechanisms for resistance toward metal complexes, makes them attractive. Metal complexes offer a way to incorporate a diverse range of ligands and therefore easily tune physico-chemical properties, which in turn can affect the overall behavior of the complex in a biological system. For more than a decade, we have synthesized and characterized a range of bismuth and antimony complexes in the + III and + V oxidation states and evaluated their efficacy toward the treatment of Leishmania or bacteria, including but not limited to: Helicobacter pylori, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Escherichia coli. In many cases these novel complexes outperform the current medicinal compounds employed. There is still work to be done to understand the relationship between the chemical structure of metal complexes and their corresponding antimicrobial activity. We have compiled recent results in the area of metal complexes against microbes, to uncover some of the trends related to antimicrobial activity.

Rebekah N. Duffin

Papers

Comparative stability, toxicity and anti-leishmanial activity of triphenyl antimony(V) and bismuth(V) α-hydroxy carboxylato complexes

Comparative stability, cytotoxicity and anti-leishmanial activity of analogous organometallic Sb(V) and Bi(V) acetato complexes: Sb confirms potential while Bi fails the test.

Is Bismuth Really the "Green" Metal? Exploring the Antimicrobial Activity and Cytotoxicity of Organobismuth Thiolate Complexes.

Antimony and bismuth as antimicrobial agents

Alkyl gallium(III) quinolinolates: A new class of highly selective anti-leishmanial agents.