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Bismuth is the heaviest nonradioactive element and is essentially a nontoxic neighbor of lead and thallium in the periodic table. It is mined as bismuth oxide (Bi2O3, also known as bismite) or bismuth sulfide (Bi2S3, bismuthinite), and the brittle, silvery elemental form is one of a few substances (water is another) for which the solid is less dense than the liquid.

Although bismuth has been extensively used in alloys, pharmaceuticals, electronics, cosmetics, pigments, and organic synthesis ("Chemistry of Arsenic, Antimony, and Bismuth," N. C. Norman, editor, Kluwer Academic Publishers, 1997; "Organobismuth Chemistry," Hitomi Suzuki and Yoshihiro Matano, editors, Elsevier, 2001), the chemistry of bismuth is perhaps the least well established of the group-15 elements (known as the pnictogens). Compounds of bismuth typically have low solubility in most solvents, so that definitive formula assignments are usually based on X-ray diffraction studies of crystalline samples that have been isolated in small or indefinite quantities. Most isolated compounds are unique rather than members of a series of related compounds illustrating fundamental chemical trends.

The bioutility of bismuth compounds has a 250-year history that includes numerous medicinal applications [Chem. Rev., 99, 2601 (1999)]; however, the mechanisms of bioactivity are not understood. Moreover, as for most compounds of bismuth, the chemical characterization of biorelevant complexes remains incomplete. Although the "heavy metal" designation has impeded application of bismuth chemistry in medicine, two compounds have been extensively used for gastrointestinal medication for decades. Pepto-Bismol contains bismuth subsalicylate (BSS), and De-Nol contains colloidal bismuth subcitrate (CBS). The use of these compounds for the treatment of travelers' diarrhea, non-ulcer dyspepsia, nonsteroidal anti-inflammatory drug damage, and various other digestive disorders extends from the previous use of bismuth compounds in the treatment of syphilis and tumors, in radioisotope therapies, and in the reduction of the renal toxicity of cisplatin.

Systematic synthetic studies coupled with bioactivity assessments of tropolone derivatives [Coord. Chem. Rev., 163, 345 (1997)] and thiobismuth compounds [Dig. Dis. Sci., 43, 2727 (1998)] have revealed relationships between specific structural features and bioactivity. Assessments have included antimicrobial behavior against Clostridium difficile, Helicobacter pylori (a bacterium associated with the pathogenesis of gastroduodenal ulcers), Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, as well as gastric ulcer healing efficacy studies in rats.

CRYSTAL CLEAR Crystals of bismuth have a pink sheen that is unusual among metals.
The binding of bismuth to proteins of exposed ulcer tissue and the formation of a protective coating is proposed as a mode of action for the ulcer-healing behavior of some bismuth compounds. In this context, the chemistry of bismuth complexes involving biomolecules as ligands represents an important component in understanding aspects of the bioactivity. The thiophilicity of bismuth has prompted speculation that sulfur-containing biomolecules represent the primary target for pharmaceuticals such as CBS and BSS.

Bismuth complexes involving biomolecules have been characterized by 13C NMR spectroscopy and X-ray absorption spectroscopy [Coord. Chem. Rev., 185­186, 689 (1999); Pure Appl. Chem., 70, 863 (1998)]. More definitive data are obtained using mass spectrometry, which enables formula assignments for molecules and molecular fragments, and, specifically, the identification of new bismuth complexes involving weakly donating functional groups [Inorg. Chem., 42, 3136 (2003)]. Most important is the identification of glutathione and cysteine complexes of bismuth, which provide support for the thiolation of bismuth as the primary biochemical fate of bismuth pharmaceuticals [Chem. Commun., 2003, 146].

The array of medicinal uses for bismuth compounds indicates a diverse biorelevance for the element that has not yet been unequivocally defined. The indisputable antimicrobial activity of various bismuth compounds at appropriate concentrations, the relatively low elemental human-cell cytotoxicity, and the apparent gastric cytoprotective properties of certain bismuth salts highlight the chemistry of bismuth as an important focus for the development or discovery of new gastrointestinal pharmaceutical agents. The efficiency of such developments will depend on the systematic assessment of bismuth chemistry as a foundation for understanding biochemical interactions.

Neil Burford is the Harry Shirreff Professor of Chemical Research and a Canada Research Chair in the department of chemistry at Dalhousie University in Halifax, Nova Scotia. He received his B.Sc. from the University of Cardiff and a Ph.D. from the University of Calgary in 1983.


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From the German weisse masse, white mass.
Atomic mass: 208.98.
History: Known since the 15th century; was often confused with tin and lead.
Occurrence: Found in the ores bismite and bismuthinite.
Appearance: Mostly white, heavy, brittle metal with a pinkish tinge at room temperature.
Behavior: The most diamagnetic metal. One of the few species that expands from a liquid to a solid.
Uses: Metallurgists often use it in alloys so that a metal's volume will remain the same when it solidifies. Bismuth alloys are also used extensively in fire alarms and fuses; a large electrical current will melt the alloy, breaking the circuit.

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