ANTIMONY

NINA ULRICH, UNIVERSITY OF HANNOVER, GERMANY

A
ntimony is one of the least famous chemical elements. If you ask someone on the street about it, you'll be met with a blank stare. Not like the response you would get if you mentioned everyday elements such as oxygen or elements famous for their toxicity, such as arsenic. Even a chemist might respond: "Well, antimony, it's just like arsenic. Toxic, you know. Its chemical properties are quite similar, fifth main group. But less useful, except maybe for some alloys."

That was also my point of view when I started antimony speciation analysis 10 years ago. But I quickly realized that this element has been part of history for a long time and has many important functions in the present. In the future, there could be even more applications, especially in the medical field.

Antimony's use is first documented by the ancient Egyptians. They loved the beautiful colors of compounds like the bright orange antimony sulfide, especially for cosmetic purposes. But even in that period, antimony was taken as medicine for different fevers and skin irritations, as old papyri show. And medicine stayed one of the main fields for antimony application (besides alchemy). In the 13th century, Roger Bacon described several of its properties, and in the 17th century, Theodor Kerckring wrote the first monograph of a chemical element about antimony. In addition, antimony is part of the canon of homeopathy and has been widely applied in the past few centuries.

ANTIMONY AT A GLANCE
Name: From the Greek anti and monos, not alone. The symbol is from the Latin stibium, mark.
Atomic mass: 121.76.
History: Antimony was recognized in compounds by ancient civilizations and was known as a metal at the beginning of the 17th century.
Occurrence: Found in many minerals.
Appearance: Bluish white, solid metal.
Behavior: Antimony is highly toxic.
Uses: Addition of antimony to alloys increases the hardness and mechanical strength of lead and other metals.
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AFFLICTED A young Sudanese boy with visceral leishmaniasis. A. CRUMP, TDR, WHO/SCIENCE PHOTO LIBRARY

Back in the early-20th century, antimony was discovered to be extremely useful in the therapy of tropical diseases, especially leishmaniasis. This is a deadly parasitic infection; there are millions of people at risk and, according to the World Health Organization, an estimated 2 million cases occur every year. In some areas of South America, leishmaniasis is endemic and its cutaneous form is simply viewed as a children's disease. The more severe form, visceral leishmaniasis, however, leads to fever and massive enlargement of the intestines, liver, and spleen and, sadly, when untreated it has a mortality rate of 98%. The vector is a small insect, a sand fly, that lives in human houses, and the reservoir contains not only humans but also many kinds of mammals and even some reptiles like crocodiles. Therefore, it is nearly impossible to exterminate the disease.

Although the mechanism of antimony toxicity to the parasite remained unclear, several therapeutic agents have been developed. In the early years, mainly trivalent antimony had been applied, which showed a nice ability to kill the parasite but unfortunately also to kill the human host. So the antimony was switched to the pentavalent oxidation state in the 1950s, resulting in much lower toxicity. Nowadays, mainly sodium stibogluconate (pentostam) and meglumine antimonite (glucantime) are used.

In the past decade, health officials noted that the disease was becoming resistant to antimony treatment. That led to increased efforts for the development of new therapeutic agents and the understanding of their mode of action. New techniques--both on the biomedical and on the chemical side--were developed for cell samples. Scientists succeeded in cultivating the parasite cells, the amastigotes, on media, giving the opportunity for direct investigation of antimony toxicity on them.

Meanwhile, in analytical chemistry, advances were being made in the field of speciation analysis, which deals with different oxidation states and the chemical bindings of metals and metalloids. Ideally, the conformation of the chemical compounds can directly be determined. Although there are numerous problems--for example, the stability of the compounds, the low concentrations of the species, and insufficient separation--much progress has been made in the past few years. It has been possible to differentiate between trivalent and pentavalent antimony in cell samples. In addition, the formation of chemical bindings between organic compounds in the cells, such as enzymes or proteins, and antimony has been observed.

The chemical analysis led to these results for the biological processes: The pentavalent antimony is reduced in the amastigote cells to the trivalent oxidation state. Afterward, the trivalent antimony takes effect on the parasite. The antimony resistance of some strains of the leishmaniasis parasite is possibly caused by the inability of these cells to effect the reduction, thereby interrupting the chemical reactions. In addition, some cell groups show a reduced antimony uptake or accelerated antimony excretion.

Speciation analysis in combination with biomedical experiments has helped explain much about the biochemistry of antimony in leishmaniasis. But much more research is needed before the mode of action of antimony in the parasite is fully understood. This knowledge then might be used as a basis for the development of new therapeutic agents that are more toxic to the parasites and cause fewer side effects.


Nina Ulrich is a professor of inorganic chemistry at the Institute of Inorganic Chemistry, University of Hannover, Germany.




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