Chemical & Chemical Engineering News (80th Anniversary Issue), Vol. 81, No. 36, 2003, Sept. Edited by X. Lu Introduction

In combination with nitrogen, sulfur forms sulfur nitride (S4N4), precursor to the sulfur-nitrogen inorganic polymer (SN)x, which was shown in 1975 by my colleagues at the University of Pennsylvania, Alan G. MacDiarmid and Alan J. Heeger, to be a metal at room temperature with a conductivity similar to iron. This pioneering work eventually led to the fundamental discovery of organic conducting polymers, and in turn to the award of the Nobel Prize in Chemistry to MacDiarmid, Heeger, and Hideki Shirakawa in 2000.

Organosulfur compounds, equally widespread in nature, are essential for all living organisms. Particularly important are the amino acids cysteine and methionine. Cysteine possesses the unique thiol (–SH) functionality, which plays a critical role in the folding and three-dimensional structures of proteins through formation of cross-linking disulfide bonds. Methionine, in the form of S-adenosylmethione, is nature's methylating agent. Other important sulfur-containing biomolecules include keratin, biotin, thiamine, coenzyme A, glutathione, and lipoic acid.

In synthetic chemistry, sulfur plays a central role, especially in its oxidized forms. Dimethylsulfoxide (DMSO), a commonly used organic solvent with invaluable solubility properties, is the key reagent in the widely used Swern oxidation of alcohols. Enantiomerically pure sulfoxides, sulfoximines, and derivatives make superb chiral auxiliaries and reagents for many asymmetric reactions (for example, Davis oxidation and Johnson resolution), while sulfones and dithianes are utilized extensively to form - and -carbon-carbon bonds (for example, Julia olefination and Corey-Seebach umpolung chemistry). In our and others' laboratories, dithianes have found extensive use in mono- and multicomponent fragment unions for the construction of complex natural products possessing important bioregulatory properties.

Amos B. Smith III is the Rhodes-Thompson Professor of Chemistry and a member of the Monell Chemical Senses Center at the University of Pennsylvania.

SULFUR AT A GLANCE Name: From the Sanskrit sulvere and the Latin sulphur.

Atomic mass: 32.07. History: Known to ancient civilizations.

Occurrence: Found near hot springs, geysers, and volcanoes.

Appearance: Pale yellow, brittle solid.

Behavior: Elemental sulfur is relatively nontoxic, but its simple derivatives can be harmful. SO2 is indicated in atmospheric air pollution.

Uses: Used in fireworks, gunpowder, fungicides, and preservatives.

SELENIUM

LIU TUNGSHENG, CHINESE ACADEMY OF SCIENCES, BEIJING

I I n 1935, a terrible disease was spreading wantonly in some rural areas of Heilongjiang province in northeastern China. Women of childbearing age and children were its primary victims. Particularly cruel, the disease frequently occurred without warning and led to the death of a large number of people. At the time, nobody understood the cause of this disease, so it was called "Keshan disease" because it was first reported in Keshan County of Heilongjiang province. Today, Keshan disease is known to be an endemic myocardial disease. It still occurs in some rural areas.

The idea that environmental selenium deficiency could be the cause of Keshan disease came about as the result of the discovery of a special ecological phenomenon in the Keshan disease region. In the summer of 1967, my colleagues and I went to Heilongjiang province to investigate the geological and geochemical environment of the disease districts. We were surprised to learn that local residents believed that Keshan disease was coming from the local water and soil, because, they reasoned, a person could avoid the disease by moving from the disease district to another place. In particular, we were told by a local veterinarian that sheep in the disease district were contracting white muscle disease. The main pathological change for white muscle disease is injury of the sheep's heart. This was noted as similar to the pathological changes seen in Keshan disease patients. The cause of the white muscle disease was attributed to selenium deficiency in the environment. And, indeed, by adding appropriate selenium in the form of Na₂SeO₃, white muscle disease can be treated and prevented in sheep. So we had a clue for investigating Keshan disease in humans.

For the next 10 years, Chinese scientists studied Keshan disease in three ways. First, they used fluorospectrophotometry with 2,3-diaminonaphthalene to determine trace levels of selenium. Simultaneously, a multidisciplinary research team consisting of both Earth and medical scientists was established and studied environmental geology, geochemistry, geography, hydrology, soil science, epidemiology, nutrition, and pathology. The investigation plan was based on a unique geo-ecological phenomenon that I had previously discovered, that is, that Keshan disease has a distribution that forms a belt crossing China from northeast to southwest. The belt region is a transitional area from the eastern plane, which has a wetter climate, to the western mountains, which are drier and where weathering and leaching actions are strong and both loss of water and soil erosion are serious problems.

A research team took samples of rock, soil, water, and staple food grains (corn, wheat, millet, and so on). Human hair specimens were obtained from people who lived in the disease districts and in the nondisease districts. A number of chemical components, including selenium and more than 10 other trace elements, as well as some organic compounds, were analyzed. The data indicated that the concentrations of selenium are lower in the disease-district samples.

So we suggested that adding selenium to the diets of local residents could halt the spread of Keshan disease. Chinese medical scientists carried out a series of animal studies designed to determine the metabolic, toxicological, and biochemical characteristics of selenium supplementation. On the basis of the results of these studies, residents of disease-prone districts took supplements of Na₂SeO₃ under medical supervision. At the same time, a series of biochemical and environmental observations were made. Ten years' worth of data show that taking Na₂SeO₃ tablets is an effective measure for controlling the spread of Keshan disease.

While we still do not know for certain whether selenium deficiency is the only factor leading to Keshan disease, it is certainly one of the most important factors. And we can also say that lack of selenium in the environment is potentially harmful to the health of humans and animals and is thus worth our attention.

Liu Tungsheng is a research professor at the Institute of Geology & Geophysics, Chinese Academy of Sciences, Beijing. Hong Yetang, a professor at the Institute of Geochemistry, Chinese Academy of Sciences, contributed to this essay.