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The diversity of natural organochlorines in living organisms
08/2008 More than 3,100 organohalogen chemicals are produced by living organisms and more than 1,800 of these contain chlorine as an innate part of their molecular structure. These chlorinated compounds are biosynthesized by marine organisms (sponges, corals, tunicates, seaweeds, sea slugs, bryozoans, etc.), plants, trees, fungi, lichens, bacteria, fresh water algae, insects, a few amphibians, and some mammals, including humans. The ocean is probably the single greatest source of known organochlorines. Nearly 50 different organochlorine compounds occur naturally in the favorite edible seaweed of most Hawaiians. Other seaweeds produce chloroform, carbon tetrachloride, dichloromethane, and numerous other chlorinated chemicals, some of which have important medicinal properties. One chlorine-containing monoterpene from a red seaweed is in preclinical development against human cancer. About four million tonnes of chloromethane, the simplest organochlorine compound, are released into the atmosphere annually, and much of this is believed to be produced by marine algae and phytoplankton. A species of marine worm from the Gulf of Mexico secretes 20 different halogenated compounds, including several chlorinated phenols. Chlorinated natural marine compounds have been discovered in soft coral and sponges living as deep as 1,000 feet in the ocean. Terrestrial sources of natural chlorine compounds are also abundant. For example, chloromethane is produced by fungi, cypress and cedar trees, mushrooms and potatoes: it is also released on combustion of biomass, e.g. during forest fires. A fungus produces several organochlorines with multiple chlorine atoms, e.g. Mollisia ventosa produces a metabolite that contains eight chlorine atoms (70% chlorine by weight), more chlorine than in any PCBs. A natural plant growth regulator, 4-chloroindoleacetic acid, is biosynthesized and utilized by peas, lentils, and beans, and 3,5-dichlorohexaphenone is produced by a slime mold as a signal chemical to trigger transformation of undifferentiated cells into fruiting bodies. A Chinese folk medicine plant contains five natural chlorinated terpenoids. A recent discovery is that Australian termites in the outback produce chloroform within their mounds; it is estimated that up to 100,000 tonnes/year of chloroform is produced by termites worldwide. The German cockroach utilizes two chlorinated steroids as communication pheromones. More than a dozen species of ticks produce 2,6-dichlorophenol as a sex pheromone, and locusts and some crustaceans have evolved to employ chlorinated proteins to strengthen the cuticle. A Penicillium mold produces 2,4-dichlorophenol, which is also a common industrial chemical used to make the herbicide "2,4-D". A tiny Ecuadorian tree frog produces a chlorinated alkaloid, epibatidine, which has powerful analgesic activity - several hundred times more potent than morphine. Several chlorinated dioxins and dibenzofurans have been found in remote Canadian peat bogs, and these compounds are believed to be natural from chloride-labeling studies and the fact that the chlorine substitution patterns are different from that of atmospheric deposition. It is proposed that the in vivo oxidative coupling of chlorophenols, which are also present in the peat bogs, leads to these compounds. A study of the edible Japanese lily has revealed that this plant produces seven new chlorinated orcinols as natural fungicides in response to attack by a pathogenic fungus. A liverwort contains 11 novel polychlorinated bridged biphenyls, the bassanins, the structures of which have no counterpart in manmade chemicals. The natural antibiotic vancomycin - our last defense against hospital staph infections - contains two chlorine atoms, and, pyrroindomycin B is a chlorine-containing metabolite active against vancomycin-resistant bacteria. In fact, many of the numerous recently discovered natural organochlorine compounds have potent antibacterial, anticancer, and other important medicinal properties. An example is the extremely powerful anticancer agent, spongistatin, which is a chlorine-containing metabolite of a marine sponge that occurs in the Indian Ocean. An Oregon forest moss produces the chlorine-containing ansamitocin, which has been found to exhibit potent anticancer activity, as do the cryptophycins, which are produced by a blue-green alga and which have extraordinary activity against solid tumors. Ambigol, a natural polychlorinated biphenyl produced by a terrestrial blue-green alga, has been demonstrated in laboratory studies to show promising activity against HIV, the AIDS virus. More remarkable is that our immune system uses chlorine to fight infection and kill invading microorganisms (bacteria, yeast, fungi, and even tumor cells). Cellular peroxidase enzymes in mammalian white blood cells transform natural blood chloride to free chlorine or hypochlorite (bleach). A by-product of this chlorination, 3-chlorotyrosine, has recently been isolated from human tissues and other human organochlorines will soon be identified. Biological chlorination is as natural a process as blood clotting or salivation. Research has shown that these organochlorine compounds are not derived from man-made chemicals, but, rather, they are biosynthesized by individual organisms for very specific purposes. These natural organochlorines appear to play an essential role in the survival of the organism, and its ability to synthesize these compounds has evolved over time under the stress of natural selection. Although the function of most of these myriad natural chlorinated compounds remain to be determined, there is no doubt that nature has chosen to use chlorine as an atomic building block, in the same way that it uses carbon, oxygen, hydrogen, nitrogen, and other elements to construct the molecules of life. |
