n 1968, Fowden wrote that “present information suggests that organic compounds containing covalently bound halogens are found only infrequently in living organisms” ( I ) . Although this observation was undeniable 25 years ago, it is nothing but a myth today.
As shown in Table 1, the number of known natural organohalogens has increased dramatically since 1968, and the current number of identified compounds stands at about 2000 (5). Consequently, this review provides a very limited glimpse of this fascinating field of natural products.
Occurrence Simple alkanes and related compounds. The simplest natural organohalogen compounds-halogenated alkanes-are abundant on our planet (Table 2 ) . Chloromethane is produced by marine algae (101, giant kelp ( I f ) , wood-rotting fungus (12). the ice plant ( l o ) , cultivated mushrooms (131, the pencil cedar 1141, the evergreen cypress ( 1 4 ) , several Fomes fungi (15), and phytoplankton (16). Chloride ion is normally present in plants, wood, soil, and minerals (12, 141, and their combustion inevitably leads to the formation of organochlorine compounds. Consequently, forest fires ( 1 7);brush and vegetation burning ( I 8);and volcanoes ( 14, 19, 201, including the eruptions of Mt. St. Helens ( 2 2 ) and Kilauea (221, all produce sienificant and. in some cases, massive quantities of chloromethane. This global emission rate of chloromethane from the marine and terrestrial biomass is 5 million tons per year (23),whereas anthropogenic chloromethane emissions are only 26,000 tons per year (12). Several other s i m p l e haloalkanes and the first “Internaalso have natural tional Conference on sources (Table 2). GCD?ON W. GRIBBLE Naturally Produced In addition to the Organohalogens” was Iartn b College, Hanovel; N H 037 simple one- and twoheld last year in The carbon halogens (Table Netherlands (3). Not I 21, numerous halogeonly are naturally ocnated alcohols, ketones, curring organohalogen compounds ubiquitous in our carboxylic acids and amides, aldehydes, epoxides, and environment, but concentrations of some of these alkenes have also been isolated and characterized from chemicals exceed their anthropogenic levels. Although marine algae (24-26).Indeed, nearly 100 different chlomyriad examples of chlorine-, bromine-, iodine-, and rinated, brominated, and iodinated compounds have even several fluorine-containing natural products exist been found in Asparagopsis taxiformis, the favorite ed(41, the present review focuses principally on organoible seaweed of most Hawaiians (24).The following are chlorine compounds. samples of those chlorinated compounds (p. 312A): chlorinated and other halogenated chemicals are discharged into our biosphere by plants, marine organisms, insects, bacteria, fungi, and mammals, and by other natural processes. Enzymatic, thermal, and other natural processes are constantly occurring in t h e oceans, in the atmosphere, and in the soil that lead to the formation of chlorinated phenols and myriad other chlorinated chemicals, including dioxins a n d CFCs, that previously were thought to result only from the actions of humans. It is clear that these natural processes have been producing chlorinated compounds and have been a vital component of our ecosystem for eons. Chlorine is in the political and environmental spotlight (21, a n d a n aggressive campaign by the environmental organization Greenpeace to ban summarily a l l production and uses of chlorine (and bro-
-
-
310 A Envimn. Sci. Technol.. VoI. 28. No. 7. 1994
0013-936X/94/0927-31OA$04.50/00 1994 American Chemical Society
0
cgc
K
CI CCI3
Br Br+Br
The simple marine haloalkanes, such as chloroform and bromoform, could arise from in vivo haloform reactions, a mechanism that may enable algae, for example, to secrete continuously these “antipredator” chemicals (24,271. Volcanoes produce large quantities of both hydrogen chloride (up to 3 million tons per year) and hydrogen fluoride (up to 11 million
tons per year) (14, 28). It has been proposed that HCI and HF can react with organic compounds to produce organohalogens ( 2 8 ) . Although the quantities may be small compared with anthropogenic levels, several chlorofluorocarbons (CFCs) have been detected in volcanic gases from the Santiaguito volcano in Guatemala ( 1 9 )and the Kamchatka volcanoes in Siberia ( 1 4 ) . It is estimated that 75% of the world’s 500-700 active volcanoes are capable of producing CFCs ( 1 4 ) . The CFCs and compounds below show the organochlorines produced by these volcanoes.
CHF,Cl
eel 0
2
OH
312A Environ. W.Technol.. Vol. 28. No. 7 , l m
CH,CCI,
F,C=CF, FClCkCF, CCl,FCClF, (Freon 113) Cl,C=CCl,
CI,C=CHCl
The concentrations of these chemicals as measured in and around the solfataric vents of the Kamchatka volcanoes range from 0.4 ppb to 160 ppb of CFCs. Deep drill wells (one mile or deeper) are also a source of several organochlorine compounds and CFCs ( 1 4 ) . Terpenes a n d related compounds. Terpenes are ubiquitous in terrestrial organisms and are essential for life, but marine terpenes were not discovered until 1955,and halogenated marine terpenes were
CFC1, (Freon 11) CF,C1, (Freon 12) CHFCl, 5
i 0
CH,Cl,
uwow are identified by number in the text) “lac’
ci%r
3
-Cl
CI
)i+$cl 4
cI 5:(telfairine) Br
first isolated only in 1963 (2931). Examples of chlorinated terrestrial terpenes were first reported in 1969 (32).Since then, there has been a veritable explosion of activity, and a legion of new chlorinated and brominated terpenes has been isolated and identified (30,31,33,34).Notably, the red algae Laurencia and Plocamium have provided a rich and diverse assortment of chlorinated and brominated terpenes over the past 25 years (structures 1-6). Nearly 20 chlorinated diterpenes and one tetraterpene have been isolated from several soft corals (3539). An example of the structural complexity of these compounds is erythrolide C (Structure 7) (38). Another very large group of halogenated organic compounds is the
“nonterpenes,” compounds that do not arise from an obvious terpenoid pathway. The Guam “bubble shell” (Haminoea cymbalum) contains kumepaloxane (Structure 8 ) (40). a feeding-deterrent chemical that is discharged when this mollusk is disturbed by unwelcome carnivorous fishes. Marine red algae, especially Laurencia, are a source of fantastically complex nonterpenoid chemicals. Thus, L. implicata has yielded six new cyclic ethers, some of which are allenes (e.g., Structure 9) (41, 42). Nostoc blue-green algae are recognized as a threat to human health when they infest drinkingwater sources (43. 44). Cultivation and extraction of Nostoc linckia have yielded four unusual chlorinated paracyclophanes. for exam-
ple, nostocyclophane D (Structure 10)(451. Amino acids and peptides. With the exception of the naturally occurring iodinated tyrosines such as thyroxine, there are relatively few examples of halogenated amino acids and simple peptides. The marine sponge Dysidea herbacea contains four novel trichloromethyl metabolites, including dysidin [ S t r u c t u r e 11) a n d d y s i d e n i n [Structure 12) (46-50). Several Streptomyces and Pseudomonas spp. contain chlorinated amino acids and/or peptides, many of which have potent antibacterial activity. For example, Streptomyces griseosporeus produces y-chloronorvaline (Structure 13) ( 5 1 ) , a n d Streptomyces viridogenes
Environ. Sd. Technol., VoI. 28. No. 7, 1994 3131
he number of naturally occurring organohalogen compounds !ar
Reviewer
168
Fowden
summary ~.
30 organochlorine natural products and a lew containing bromine, iodine. and
fluorine 70 fungal metabolites containing
chlorine
200 organohalogen cornpounds from a sources (150 organochlorine, 50 organobromine) 80 new fungal metabolites containing
chlorine
plants organohalogen compounds from all sources isolated between 1980 130 organochlorines from higher
61 1 new
and 1991
yields Structure 14 (52). Alkaloids. Although terrestrial plant alkaloids have been scrutinized by chemists for more than a century, very few of these nitrogen compounds contain halogen of any kind. Recently, oxypterine [Structure 151, a dichlorinated pyrrolizidine derivative, was found to be present in the herb Lotononis oxyptero (53),and a Streptomyces sp. produces clazamycin A (Structure 16) and B (54-56). Steroids. Steroids rarely contain halogen. However, a few examples of chlorinated steroids are found in the plants Withonio somnifera, Acnistus breviflorus, Phvsolis peruvionu. and johoroso moyelionico. such a5 iaborochlorodiol IStruclure 17) (57).'The first three examples of chlorinated marine steroids-kiheisterones C, D, and E-were recently characterized from the Maui sponge Strongylacidon sp. (58). Fatty acids, prostaglandins, and lipids. Although fluoroacetic acid and fluoro-fatty acids in certain terrestrial plants have been known for many years (59, 60),chloro-fatty acids were unknown until recently. The edible jellyfish and the white sea jellyfish (Auritio ourito) contain six fatty acid chlorohydrins (61). Mammalian prostaglandins are of paramount importance in the regulation of physiological processes. Therefore, it was of enormous interest when chlorinated prostaglandins were discovered in the octocoral Telesto riisei (62) and in the stolonifer Clavuloria viridis (63), a marine animal. A total of eight novel chlorinated prostaglandins have been identified [e.g., punaglandin 1 (Structure 18)) (62),some of which have potent antitumor activity (63). The marine brown alga
Egregio menziesii produces three prostaglandin-like chlorinated oxylipins, for example, egregiachloride A (Structure 19) ( 6 4 ) . Of some 22 freshwater algae species that were examined for chlorosulfolipids, all but one contained quantities of these novel lipids (65, 66). Pyrroles. The pronounced reactivity of pyrroles in electrophilic substitution reactions endorses the observation that chlorinated and brominated pyrroles are found widely in nature. Following the isolation in 1958 of pyoluteorin (Structure 201, a new antibiotic from Pseudomonas oeruginoso (67), numerous additional natural chlorinated and brominated pyrroles have been disi:ovcrorl. 'I'hc soil niicrobe Streptomyces sp. produces pyrrolomycin B (Structure 21) (68),and a soil Streptomyces sp. produces the novel neopyrrolomycin (Structure 221, a metabolite that has biphenyltype optical activity (69). Many of the pyrrolomycins have strong antibiotic activity, and a clinical drug from this structural type seems to be a real possibility. Indoles. The indole ring system has the distinction of being embodied in the indigo derivative Tyrian purple, the ancient Egyptian dye extracted from mollusk shells and the focus of a significant industry in Mediterranean countries (70). The marine acorn worm Ptychodero Povo loysanica produces the unstable 3-chloroindole (Structure 23) and 3-chloro-6-bromoindole compounds that are responsible for the peculiar "iodoform-like" odor of this animal (71).The 4-chloroindole ester (Structure 24) and the corresponding carboxylic acid are found in Pisum sativum and several other terrestrial plants (lentil, sweet pea,
314A Environ. Sci. Technol., Vol. 28, No. 7, 1994
sea pea, vetch) (72, 73). Like 3-indoleacetic acid, these compounds function as very strong plant growth hormones. A blue-green alga, Hapolosiphon fontinolis, contains 12 chlorinated isonitriles, one of which is hapalindole A (Structure 25) (74).
The deep water Bahamas sponge Botzello sp. produces six chlorinated indoles, e.g., batzelline A (Structure 26) ( 7 5 ) ,and nature's virtuosity in organic synthesis is further revealed by the marine hryozoan Chartello popyroceo, which constructs a complement of five halogenated indoles, such as chartelline A (Structure 27) (76-78). Miscellaneous heterocycles. Some interesting halogenated thiophenes are found in certain plants. For example, Pterocaulon virgatum contains five chlorinated thiophenes (79, and six species of Echinops are found to contain Structure 28 (80). Only a few examples of nucleic acid bases are known to contain halogen. An Actinomyces sp. produces 2 ' chloropentostatin (Structure 291 181, 82).The first example of a chlorinated porphyrin was recently isolated in trace quantities from cultures of two Pseudomonasspp. (83), and 2-chloropyridine is embodied both in the potent enediyne antitumor agent kedarcidin (84) and in the novel Ecuadoran poison frog metabolite (Structure 30), which is secreted by several species of Epipedobotes and which has powerful analgesic activity (85). Aromatic compounds. Although most of nature's chlorinated aromatic rings are phenolic, a few examples of simple chlorinated aromatics are known. The Mississippi salt marsh "needlerush" Uuncus roemerianus) contains 1,2,3,4-tetrachlorobenzene (86).A careful study of the ash from the 1980 eruption of Mt. St. Helens has revealed the presence of chloroaromatics (Structures 31 and 32), and, more surprisingly, three previously unknown isomers of pentachlorobiphenyls (PCBs) (Structure 33). The nature of the PCB isomers is not what would be expected from industrial PCBs (87). This landmark observation represents the first (and only) discovery of natural PCBs. The authors surmise that rapid, incomplete hightemperature combustion of chloride-containing plant material in the eruption zone led to these chlorinated aromatics, as well as to chloromethane. Plants typically contain 200-10,OOO ppm of chloride ion (12). Another unusual discovery is
and another Nostoc sp. blue-green alga secretes large quantities of two iBLE 2 chlorinated phenolic furanones, iogenic sources of simple haloalkanes nostoclides I and 11, into the culture medium (99). The acorn worm Ptympound Sources chodera bahamensis produces 1 3 halogenated phenols, including 3,4Mar ne a.gae. giant nelp. YOOO ion ng lm 2s 1,CI ce p ant. c. tivatea mLshrooms wn le cecfar dichloro- and 3,5-dichlorophenol oenc cedar. everoreen cvoress lmai. (ZOO). The “mixed” bromochlorodiphytoplankton. lorest firei,’bush burrhg phenyl ether (Structure 40) is provolcanoes, tobacco smoke duced by a marine sponge and acOceans, marine algae, giant kelp, volcanoes counts for 1.3% of the dry weight Oceans, marine algae, volcanoes (202). It is interesting to note that Marine algae, white cedar, lemon, orange, this compound is a “predioxin” inmoss, barley, volcanoes, drill wells termediate. The red alga Rhabdonia Marine algae, oceans verticillata produces six bromo1 Marine algae, oceans, volcanoes, drill wells chloro phloroglucinols (102). Volcanoes, barle Dioxins and related compounds. “Dioxin,” 2,3,7&tetrachlorodibenzo-p-dioxin (Structure 411, was once generally thought to be the Marine algae, oceans most toxic man-made chemical Marine algae, oceans known (203-1 05). However, extenMarine algae sive evaluations by epidemiologists Marine algae, oceans of people exposed to dioxin, such as Marine algae Vietnam veterans (106,207), inhabMarine algae, oceans itants of Seveso, Italy [the site of a 3r major dioxin release in 1976 (20811, I and industrial plant workers (109. 110),have revealed that dioxin is 421 not the “doomsday chemical” once iBrlCI believed (210-122).Nevertheless, iBr12 the extraordinary toxicity of some polychlorinated dioxins (PCDDs) ,C=CHCI and related compounds, such as the ,C=CCI, Oceans, volcanoes polychlorinated dibenzofurans (PCi,CCI, Oceans DFs) (e.g., Structure 42), in some aniFCI, Volcanoes imals is reason enough for the con=CIS Volcanoes, drill wells tinued study of these compounds, especially because it is now recog-IF& nized that PCDDs and PCDFs are, in iFCI, fact, natural products and are ubiq,C=CF, uitous in our environment. X=CF, The production of chloromethane CCI,FCCIF, a n d other organochlorine compounds when organic material is burned, in association with the omthat an unidentified deep-sea gorgo- (92), have been reported. nipresent chloride ion (see above), Chlorophenols are used industri- led to the belief, now supported by nian, collected at a depth of 350 m, exudes haloazulenes (Structure 34) ally on a large scale and have been evidence, that PCDDs could form classified by EPA as Priority Pollut- during combustion processes ( I 23, (88). Phenols and phenolic ethers. A ants (93). Surprisingly, several of 214). Laboratory studies have renumber of chlorinated tyrosine de- these and other chlorophenols are vealed that PCDDs, including “dirivatives have been isolated from produced naturally. The soil fungus oxin” (Structure 421, and PCDFs marine sponges, seafans, and other Penicillium sp. produces 2,4-di- form in parts-per-billion amounts gorgonians (89-90). These amino chlorophenol (Structure 36) (94). during the combustion of wood acids, when incorporated into and grasshoppers secrete 2,5-di- (treated or untreated) (125-218). structural proteins, may stabilize chlorophenol (Structure 37), which The relatively poor efficiency and the proteins in the organism by im- is repellent to ants (95). The sex incomplete oxidation when damp proving the adhesion between pro- pheromone of the female Lone Star vegetation and wood are burned in tein fibers and sheets (90). The mol- tick (Amblyomma americanurn) the presence of high chloride conand several other hard ticks is 2,6- centrations (70-2100 ppm in wood lusk Buccinum undatum utilizes 3-chloro-5-bromotyrosine (Struc- dichlorophenol (Structure 38) (96, pulp) (14) are conditions conducive 97). Careful studies in the first and to PCDD formation, and two reture 35) in its structural proteins (90). The isolation of 3.4-dichloro- last of these investigations rule out search groups have concluded that tyrosine, as well as Structure 35, the possibility that these com- forest and brush fires are the major from Limulus polyphemus @I),and pounds are artifacts. The blue-green source of PCDDs and PCDFs in the of 3-chlorotyrosine from the cuticle alga Anacystis marina contains environment (125, 229). It is estiof locusts (Schistocerca gregaria) chlorophenol (Structure 39) (98), mated that some 130 lb [l lb =
1
Environ. Sci. Technol., VoI. 28, No. 7, 1994 315 A
0.4536 kg] of PCDDs are produced in Canadian forest fires annually ( 1 2 9). This is 10 times more than the amount formed in the 1976 Seveso plant accident. Because most forest fires are lightning-caused, and there are 200,000 forest fires annually worldwide that burn 27,000 square miles [l mi = 1.609 km] ( 2 4 ) , it is logical to assume that PCDDs have been present in the environment for many centuries. An 1877 soil sample was found to contain PCDDs and PCDFs (220). Another milestone observation is the enzymatic conversion of chlorophenols into both PCDDs a n d PCDFs i n the parts-per-million range by horse-radish peroxidase enzyme (HRP) (Equation 1) ( 2 2 2 ) . This extraordinary revelation opens the door to the possibility that a source of environmental PCDDs and PCDFs may be their completely natural formation from (natural) chlorophenols by soil and water microbes.
p”’ OH
HRP
H202
CI
17h,2OoC
CI
PCDD’s
PCDF’s
(38 compounds identified; (214, CIS,Cl6 isomers dominate; ppm range)
Mechanisms of biogenic chlorination Marine organisms, terrestrial plants, fungi, microorganisms, and mammals all contain haloperoxidase enzymes that can chlorinate, brominate, and iodinate organic compounds i n the presence of chloride, bromide, or iodide ions, respectively ( 2 2 2 - 2 2 4 ) . Of 33 species of Phaeophyceae algae from the Atlantic Coast, 2 2 displayed 316 A
peroxidase enzymatic activity (2251, a n d chloroperoxidase, which occurs in the mold Caldariomyces fumago, has been extensively studied ( 2 2 6 ) . Soil extracts have been shown to have chlorinating ability ( 2 2 2 , 2 2 7 ) , and more than 80 species of Death Valley fungi displayed chloroperoxidase activity ( 1 2 2 ) . Peroxidases are present in the thyroid gland of mammals ( 2 2 8 ) .The enzymes chloroperoxidase, HRP, and vanadium peroxidase are capable of chlorinating phenols and phenol ethers (anisole) in the presence of chloride (229, 230). Lactoperoxidase, an enzyme present in mammalian milk ( 2 3 2 ) ,is capable of chlorinating organic substrates (129, 2 3 2 ) . An electrifying development is the utilization of the halide-peroxidase-hydrogen peroxide chemical system by humans and other mammals to generate active halogen (HOC1, HOBr) in order to destroy microorganisms. T h u s , human white blood cells (eosinophils and neutrophils) contain myeloperoxidase, which, in the presence of chloride, bromide, or iodide, and hydrogen peroxide, rapidly forms active halogen, resulting in the death of bacteria and fungi by halogenation reactions ( 2 3 2 , 2 3 3 ) . It would appear that biohalogenation is an integral component of our immune system!
Natural versus anthropogenic organohalogen compounds
Chloromethane is overwhelmingly biogenic in origin. But what about the relative quantities of the other natural organochlorines and organohalogens vis-&-vis the approximately 20 million tons per year of 150 industrial organohalogens currently in use worldwide (222, 242)? A detailed study of the acorn worm Ptychodera flava has revealed that a known population of these animals (64 million) excrete in their fecal matter 95 lb of organohalogens daily in a 1 km2 habitat in Okinawa ( 2 4 3 ) . Obviously, many more studies of a similar nature are needed in order to estimate the global quantities of natural organohalogens. Several researchers have reported the identification of halogenated phenolic compounds in ocean waters and in soil extracts (129, 244, 2 4 5 ) . The major source of most of these compounds, such as 2,4,6trichlorophenol, is biogenic and from natural halogenation processes such as reactions between humic acid and soil microbes (chloride and chloroperoxidase). Humic acids are present not only in soil, but also in rivers, lakes, and the oceans ( 2 4 6 ) . The yearly net production of environmental humic acid from the decomposition of organic material has been estimated at Metabolism and biodegradation 63 billion tons ( 2 4 6 ) . This can be added to the estimated existing gloContrary to common perception, organohalogen compounds, both bal 1.0-1.5 trillion tons of soil humic acids and one trillion tons of natural and unnatural, are readily metabolized and biodegraded to ha- ocean humic acid ( 2 4 6 ) .Numerous studies have demonstrated the ease lide ion by assorted microorganwith which humic acid model comisms. The simple organochlorines pounds (phenolics)react with chloCH,Cl,, CHCl,, CCl,, Cl,C=CC1,, rine to produce chloroform and and others can be degraded to CO, (or other simple organics) and chlo- other simple organochlorines via ride by soil bacteria ( 2 3 4 ) .The soil chlorophenols ( 2 46-2 4 8 ) . As we bacterium Pseudomonas putida ox- have seen, chloride is ubiquitous in idizes chloro- and other haloben- soil, plants (200-10,000 ppm) (221, zenes to the cis-diol ( 2 3 5 ) .This is a rivers (average 8 ppm) ( 2 4 9 ) ,lakes remarkably general reaction and ( 2 4 9 ) , and, of course, oceans (146, 249). These ingredients, in combisucceeds even with fluorobenzene. The biodegradation of chlorophe- nation with natural chloroperoxinols has been thoroughly studied. dase and other enzymes, provide a plausible rationale for the natural For example, 2,4-dichlorophenol is rapidly metabolized in soils ( 2 3 6 ) , formation of chlorinated phenols. and an exhaustive mechanistic Several studies have demonstrated study of the degradation of this that the natural production of chlocompound to chloride and CO, by rinated phenols and anisoles outweighs their anthropogenic sources the white-rot fungus Phanerochaete (244, 245). chrysosporium has been reported Although a vast number of halo( 2 37).This versatile and remarkable fungus is capable of degrading other genated compounds have been isochlorinated phenols ( 2 3 8 ) , DDT lated from natural sources ( 3 ) ,relatively few marine organisms have ( ~ 3 9 pentachlorophenol ), ( 2 4 0 ) ,and been examined for their chemical PCBs (142).
Environ. Sci. Technol., Vol. 28, No. 7 , 1994
content. For example, whereas some 12,000 natural products of all types have been isolated from terrestrial plants, only 500 had been isolated from marine plants (algae) up to 1987 ( 1 5 0 ) .However, there are some 500,000 known species of marine animals, plants. and bacteria (151). For example, there are 80.000 living species of mollusks (152). 5000 species of sponges (1531, and 4000 species of bryozoans [moss animals) (154). but only six of the latter have been examined (155). Of more than 90 known species of deep-sea gorgonians in the Hawaiian Islands, only 20 have been investigated for their chemical content ( 1 5 6 ) . a n d . of 1 3 Mycole sponges living in the Mediterranean Sea, only one has been investigated (157). The list goes on. The enormous diversity of marine life and, hence, of potential new organochlorine compounds, is epitomized by the Great Barrier Reef. This 100,000-mi' area consists of 2500 separate small reefs. Around just one of these, of less than 1 4 square miles, there have been identified 930 species of fish: 107 corals: and 154 urchins, cone shells, and other mollusks (156). Given such diversity and magnitude of biological species, it is indisputable that a large number of unique organochlorine compounds will be isolated and identified from ocean life, to say nothing about the novel chlorinated and other halogenated compounds waiting to be discovered in terrestrial plants, animals, bacteria, fungi, and perhaps even humans. Indications are that organohalogen compounds have been with us for centuries. For example. halogenated fulvic acids have been isolated from groundwater samples that date hack 1300,4600, and 5200 years (244)! Organohalogen material was identified in sediments dating back to the 13th century (159). Microfossils in Precambrian rocks, which are a billion years old, are identical to the blue-green alga Nostoc, and other microfossils are morphologically indistinguishable from Oscillotoria. two present-day species rich in organohalogen compounds (160). Function of natural organohalogens Why does nature create organochlorine compounds? Many marine and terrestrial organisms use organochlorine and other organohalogen compounds i n chemical defense-feeding deterrents, irritants,
or pesticides-or in food gathering (161-164). A recent, careful study of the sea hare St~vlocheiluslongicouda clearly indicates a feeding deterrent role for its organohalogen compounds (165). The sea hare Apl.vsia brnsiliann is distasteful to fish and rejected by sharks in part because of its panacene. a brominated allene ( 1 6 6 ) . Marine algae store organohalogen compounds in the vesicular cells for facile secretion to discourage predators (27, 167). and the terrestrial blue-green alga Fischerello ombiguo secretes into the medium two chlorinated phenols that show antibacterial, antifungal, and molluscicidal activity (166). The marine algae metabolite telfairine (Structure 5 ) is 100% lethal to mosquito larvae at 10 ppm (1691, and the related chlorinated monoterpene plocamene B is three times more effective than the commercial pesticide Lindane against mosquito larvae (170). An organobromine compound with natural insecticidal properties (against the cotton boll weevil) was recently isolated from the Thai plant Arundo donax (171). and the coral Tubostroea microntha secretes two organobromine compounds that deter the destructive crown-of-thorns sea star from feeding ( 1 72). Recently, it was found that the German cockroach (Blottello germonico) utilizes two chlorinated steroid glycosides, blattellastanosides A and B, as aggregation pheromones (173). One very attractive hypothesis is that natural organohalogen compounds play an essential role in the survival of the organism, and the
i
1. i. i
;2&
~
~, 4
. .~ T , ' ,
1
Conclusion The continued improvements in isolation, purification, and spectroscopic techniques ensure that even the most structurally intricate organohalogen natural products will be identified. Widespread antibiotic, antitumor, antifungal. insecticidal. herbicidal, and other potentially valuable biological activities have been observed with these natural chlorinated chemicals. As our understanding of biohalogenation progresses, it will be possible to differentiate and quantify more accurately the natural and anthropogenic sources of halogenated chemicals. References (11
Foaden. L. Proc. R. SOC.E . 1968. 171. 5.
121 Amato. 1. Science. 1993. 261. 152. ( 3 ) International Confcrcncc on Natural-
ly-l'roducrd Organohalogens: E.W.B. de Leer. Chairman. Sspt. 14-17.1993. Delft. The Notherlands. 14) Gribble. (;. \V. I. Not. Prod. 1992. 55. 1353.
Grilhle. G. W. Prog. Chrm. 0%.Not. Prod.. manuscript in preparation. ( 6 ) Turner. W. B. Fungal Mrtaboliles: Academic: New Yark. 1971. 17) Sioda. I. F.: DeBemardis. I. F. Lloydio (5)
1973. 36. 107. 181 Turner. W.B.: Aldridgo. D. C. Fungo1
Metobolitec, 2nd cd.: Academic: N e w York. 1983. (91 Engvild. K. C. Plt.viochrmi.~lry1986. 25. 781. (10) Wuosmaa. A. M.: Hager. L. P. S c i m m 1990, 249. 1611.
(11) Manlcy. S.L.:Dasloor. M. N. Linmol. Ormnogr. 1987.32, 709. (121 Harper. I). B. Nolure 1985. 315. 55. (13) Tumcr. E. M.ct al. 1. C n n Microhiol. 1975.01.167. (14)Isidorov. V. A. Orgunic Chenri.stry of the Enrth'r A t m o s p h w r ; SpringerVerlag: Berlin. 1990. (15) Cownn, M. I. et nl. 7ions. l k Myrol. SOC.1973. 60. 347. (16) Gschwend. 1'. M.: MacFarland. 1. K.: Newman. K. A. Science 1985. 227.
1
1 ~
ability of the organism to synthesize such compounds for chemical def e n s e and food gathering has evolved over time under the stress of natural selection (174).
Gordon W. (;ribbk! is n professor and former choir mu^^ 0 1 the llepnrtn~entof C1tentistl:t~111 l~urtntouthCollege. He received his B.S.degree from the University of California-Berkelev and his Ph.D. from the University of Oregon. After o year at UCLA os n National Cancer lnstitule Posfdocforal Fello~,,he joined the faculty of Dartmouth College in 1968. His research interests include the synthesis and isolation of biologically active natural products, heterocyclic
chemistry, and environmental organic chemistry.
1033. (17)Palmer. T
Y. Notirrr! 1976.263. 44. (18) Lovelock. J. E. Nolortr 1975. 256. 193. (19) Staiber, R. E. PI nl. Geol. SOC. A,,). Bull. 1971. 82.2299. (20) Rasmussan. R. A. et al. Science 1982. 215, 665. (21) Inn. E.C.Y. et al. Science 1981. 211, 821. (22)
Gerlach, T. M. 1. l/olcanol. Geofherm.
Res. 1980, 7. 295. R. A.
(23)Rasmussen,
et at.
I. Geophys.
Res. 1980. 85. 7350. (24) Moore. R. E. Acct. Chsm. Res. 1977, 10. 40.
Environ. Sci. Technol.. Vol. 28,No. 7. 1994 317 A
(25) Woolard, F. X.; Moore, R. E.; Roller, P. P. Tetrahedron 1976, 32, 2843. (26) Fenical, W. Tetrahedron Lett. 1974, 4463. (27) McConnell, 0. J.; Fenical, W. Phytochemistrylg80, 29, 233. (28) Cadle, R. D. et al. J . Geophys. Res. 1979, 84,6961. (29) Yamamura, S.; Hirata, Y. Tetrahedron 1963, 29,1485. (30) Naylor, S. et al. Prog. Chem. Org. Nut. Prod. 1983, 44, 189. (31) Erickson, K. L. In Marine Natural Products, Vol. V; Scheuer, P. J,, Ed.; Academic: New York, 1983; Chap. 4. (32) Kupchan, S. M. et al. J. Org. Chem. 1969, 34, 3876. (33) Marine Natural Products; Scheuer, P. J., Ed.; Academic: New York, 19781983; VOlS. I-V. (34) Faulkner, D. J. Nut. Prod. Rep. 1993, 20, 497 [and previous papers in this series]. (35) Grode, S. H. et al. J. Org. Chem. 1983, 48, 5203. (36) Look, S. A. et al. J. A m . Chem. SOC. 1984, 206, 5026. (37) Bowden, B. F. et al. A u s t . J. Chem. 1989, 42, 1727. (38) Pordesimo, E. 0. et al. J. Org. Chem. 1991, 56,2344. (39) Kusumi, T. et al. J. Org. Chem. 1990, 55, 6286. (40) Poiner, A.; Paul, V. 7.; Scheuer, P. J. Tetrahedron 1989, 45, 617. (41) Coll, J. C.; Wright, A. D. Aust. J. Chem. 1989,42,1685. (42) Wright, A. D.; Konig, G. M.; Sticher, 0. J. Nut. Prod. 1991, 54, 1025. (43) Gorham, P. R.; Carmichael, W. W. Pure Appl. Chem. 1980, 52,165. (44) Moore, R. E. Bioscience 1977, 27, 797. (45) Chen, J, L.; Moore, R. E.; Patterson, G.M.L. J. Org. Chem. 1991, 56, 4360. (46) Hofheinz, W.; Oberhansli, W. E. Helv. Chim. Acta 1977, 60,660. (47) Kazlauskas, R.; Murphy, P. T.; Wells, R. J. Tetrahedron Lett. 1978,4945. (48) Kazlauskas, R. et al. Tetrahedron Lett. 1977, 3183. (49) Charles, C. et al. Tetrahedron Lett. 1978,1519. (50) Biskupiak, J. E.; Ireland, C. M. Tetrahedron Lett. 1984, 25, 2935. (51) Narayanan, S. et al. J. Antibiot. 1980, 33, 1249. (52) Chaiet, L. et al. J. Antibiot. 1984, 37, 207. (53) Verdoorn, G. H.; van Wyk, B-E. Phytochemistry 1992, 31, 1029. (54) Horiuchi, Y. et al. J. Antibiot. 1979, 32, 762. (55) Nakamura, H.; Iitaka, Y.; Umezawa, H. J. Antibiot. 1979, 32, 765. (56) Dolak, L. A.; DeBoer, D. J. Antibiot. 1980, 33, 83. (57) Fajardo, V. et al. J. Nat. Prod. 1991, 54, 554. (58) Carney, J. R.; Scheuer, P. J.; KellyBorges, M. J. Org. Chem. 1993, 58, 3460. (59) Hall, R. J.; Cain, R. B. N e w Phytol. 1972, 71, 839. (60) Hall, R. J. N e w Phytol. 1972, 72, 855. (61) White, R. H.; Hager, L. P. Biochemistry 1977, 16, 4944. (62) Baker, B. J. et al. J. Am. Chem. SOC. 1985,207,2976. (63) Iguchi, K. et al. Tetrahedron Lett. 1985, 26,5787.
318 A
(64) Todd, J. S.; Proteau, P. J.; Gerwick, W. H. Tetrahedron Lett. 1993, 34, 7689. (65) Haines, T. H. Ann. Rev. Microbiol. 1973, 27, 403. (66) Mercer, E. I.; Davies, C. L. Phytochemistry 1979, 28, 457. (67) Takeda, R. J. Am. Chem. SOC. 1958, 80, 4749. (68) Kaneda, M. et al. J. Antibiot. 1981, 34, 1366. (69) Nogami, T. et al. J. Antibiot. 1990, 43, 3192. (70) Baker, J. T. Endeavour 1974, 33, 11. (71) Higa, T.; Scheuer, P. J. Naturwissenschaften 1975, 62, 395. (72) Marumo, S. et al. Agric. Biol. Chem. 1968, 32, 117. (73) Engvild, K. C.; Egsgaard, H.; Larsen, E. Physiol. Plant. 1981, 53, 79. (74) Moore, R. E. et al. J. Org. Chem. 1987, 52, 1036. (75) Sun, H. H. et al. J. Org. Chem. 1990, 55, 4964. (76) Anthoni, U. et al. J. Org. Chem. 1987, 52, 4709. (77) Anthoni, U. et al. J. Org. Chem. 1987, 52, 5638. (78) Anthoni, U. et al. Comp. Biochem. Physiol. 1990, 96B, 431. (79) Bohlmann, F. et al. Phytochemistry 1981, 20, 825. (80) Abegaz, B. M.; Tadesse, M.; Majinda, R. Biochem. Sys. Ecol. 1991, 19, 323. (81) Smal, E.; Baker, D. C. Abstract No. 8, Division of Carbohydrate Chemistry, 188th ACS Meeting, 1984. (82) Schaumberg, J. P.; Hokanson, G. C.; French, J. C. Abstract No. 7, Division of Carbohydrate Chemistry, 188th ACS Meeting, 1984. (83) Lin, W.; Burkhalter, R. S.; Timkovich, R. Heterocycles 1993, 36, 2191. (84) Zein, N. et al. Proc. Natl. Acad. Sci. U S A 1993,90,8009. (85) Spande, T. F. et al. J. Am. Chem. SOC. 1992, 124, 3475. (86) Miles, D. H. et al. Phytochemistry 1973, 22,1399. (87) Pereira, W. E.; Rostad, C. E.; Taylor, H. E. Geophys. Res. Lett. 1980, 7, 953. (88) Li, M.K.W.; Scheuer, P. J. Tetrahedron Lett. 1984, 25, 587. (89) Roche, J.; Andr6, S.; Salvatore, G. Comp. B i o c h e m . Physiol. 1 9 6 0 , 2 , 286. (90) Hunt, S.; Breuer, S. W. Biochim. Biophys. Acta 1971, 252, 401. (91) Welinder, B. S. Biochim. Biophys. Acta 1972, 279, 491. (92) Andersen, S. 0. Acta Chem. Scand. 1972,26, 3097. (93) Keith, L. H.; Telliard, W. A. Environ. Sci. Technol. 1979, 13,416. (94) Ando, K.; Kato, A , ; Suzuki, S. Biochem. Biophys. Res. Commun. 1970, 39, 1104. (95) Eisner, T. et al. Science 1971, 272, 277. (96) Berger, R. S. Science 1972, 177, 704. (97) Berger, R. S. J . Med. Entomol. 1983, 20, 103, and previous papers. (98) Faulkner, D. J, “Natural Organohalogen Compounds,” in T h e Handbook of Environmental Chemistry, 0.Hutzinger, Ed,; Springer-Verlag: Berlin, 1980; Vol. 1,Part A. (99) Yang, X. et al. Tetrahedron Lett. 1993, 34, 761. (100) J.M. Corgiat, private communication, University of Hawaii.
Environ. Sci. Technol., Vol. 28,No. 7, 1994
(101) Capon, R. et al. J. Chem. Soc., Perkin Trans. 1981, 1, 2464. (102) Blackman, A. J.; Matthews, D. J, Phytochemistry 1982,22, 2141. (103) Gribble, G. W. C h e m i s t r y 1 9 7 4 , 47(2), 15. (104) Poland, A,; Knutson, J. C. Ann. Rev. Pharm. Tox. 1982,22, 517. (105) Poland, A,; Glover, E. Science 1973, 279, 476. (106) Wolfe, W. H. et al. J. Am. Med. A s SOC. 1990,264,1824,1832. (107) Gough, M. A m . J. Public Health 1991, 81, 289. (108) Bertazzi, P. Sci. Total Environ. 1991, 206, 5. (109) Zack, J. A,; Suskind, R. R. J. Occup. Med. 1980, 22, 11. (110) Tschirley, F. H. Sci. A m e r . 1986, 254(2), 29. (111) Eduljee, G. H. Chem. Brit. 1988, 24, 1223. (112) Gough, M. Sci. Total Environ. 1991, 204, 129. (113) Bumb, R. R. Science 1980, 210, 385. (114) Travis, C. C.; Hattemer-Frey, H. A. Risk Anal. 1989, 9, 91. (115) Nestrick, T. J.; Lamparski, L. L. Anal. Chem. 1982,54,2292. (116) Clement, R. E.; Tosine, H. M.; Ali, B. Chemosphere 1985, 24, 815. (117) Olie, K.; v. d. Berg, M.; Hutzinger, 0. Chemosphere 1983, 22, 627. (118) Tierman, T. 0. et al. Chemosphere 1983, 12, 595. (119) Sheffield, A. Chemosphere 1985, 14, 811. (120) Eduljee, G. H.; Atkins, D. H. F.; Eggleton, A. E. Chemosphere 1986, 25, 1577, (121) Svenson, A,; Kjeller, L.-0.; Rappe, C. Environ. Sei. Technol. 1989, 23, 900. (122) Neidleman, S. L.; Geigert, J. Biohalogenation: Principles, Basic Roles a n d A p p l i c a t i o n s ; Halsted Press: New York, 1986. (123) Wever, R. et al. Environ. Sci. Techno]. 1991, 25, 446. (124) Butler, A,; Walker, J. V. Chem. Rev. 1993, 93,1937. (125) Vilter, H.; Glombitza, K-W.; Grawe, A. Bot. Marina 1983, 26, 331. (126) Libby, R. D. et al. J. Biol. Chem. 1982, 257, 5050, and previous papers. (127) Neidleman, S. L.; Geigert, J . Endeavor, N e w Series 1986, 2 1 , 5. (128) Taurog, A.; Howells, E. M. J. Biol. Chem. 1966,242, 1329. (129) Walter, B.; Ballschmiter, K. Chemosphere 1991, 22, 557. (130) Wannstedt, C.; Rotella, D.; Siuda, J. F. Bull. Environ. Contam. Toxicol. 1990, 44, 282. (131) Geigert, J, et al. Appl. Environ. Microbiol. 1983, 45, 366. (132) Klebanoff, S. J. J. Bacteriol. 1968, 95, 2131. (133) Weiss, S. J. et al. Science 1986, 234, 200. (134) Bouwer, E. 7.; McCarty, P. L. A p p l . Environ. Microbiol. 1983, 45, 1286. (135) Boyd, D. R. et al. J. Am. Chem. SOC. 1991, 213, 666, and references cited therein. (136) Smith, A. E.; Aubin, A. J. J. Agric. Food Chem. 1991,39,801. (137) Valli, K.; Gold, M. H. J. Bacteriol. 1991, 273, 345. (138) Hammell, K. E.; Tardone, P. J. Biochemistry 1988,27,6563.
(139) Bumpus, J. A,; Aust, S. D. A p p l . Environ. Microbiol. 1987, 53, 2001. (140) Mileski, G. J. et al. A p p l . Environ. Microbiol. 1988, 54, 2885. (141) Bumpus, J, A. et al. Science 1985, 228,1434. (142) Leisinger, T. Experientia 1983, 39, 1183. (143) Higa, T.; Sakemi, S. J. Chem. Ecol. 1983, 9 , 495. (144) Asplund, G.; Grimvall, A.; Pettersson, C. Sci. Total Environ. 1989, 81/82, 239. (145) Asplund, G.; Grimvall, A. Environ. Sci. Techno].1991, 25, 1347. (146) Humic Substances II, In Search of Structure; Hayes, M.H.B. et al., Eds.; Wiley-Interscience: New York, 1989. (147) Rook, J. J, Environ. Sci. Technol. 1977, 11, 478. (148) Howard, A. G.; Pizzie, R. A,; Whitehouse, J. W. Water Res. 1984, 18, 735. (149) Holland, H. D. T h e Chemistry of the A t m o s p h e r e a n d O c e a n s ; WileyInterscience: New York, 1978. (150) Paul, V. J. Bull. Mar. Sci. 1987, 41, 514. (151) Barbier, M. In Marine Natural Products; Scheuer, P. J., Ed.; Academic Press: New York, 1981; Vol. IV. (152) Scheuer, P. J. Is. J. Chem. 1977, 16, 52. (153) Minale, L. In Marine Natural Products; Scheuer, P. J., Ed.; Academic Press: New York, 1978; Vol. I. (154) Christophersen, C. In The Alkaloids; Brossi, A. Ed.; Academic Press: New York, 1985; Vol. 24, Chap. 2. (155) Chevolot, L. et al. J. A m . Chem. SOC. 1985, 207,4542. (156) Okuda, R. K. et al. Pure Appl. Chem. 1982,54, 1907. (157) Corriero, G. et al. Tetrahedron 1989, 45, 277. (158) Boye, R. In Underwater Paradise; Abrams: New York, 1989. (159) Paasivirta, J. et al. Chemosphere, 1988, 27, 137. (160) Fox, S. W.; Dose, K. Molecular Evolution and the Origin of Life; Marcel Dekker: New York, 1977. (161) Scheuer, P. J. Science 1990, 248, 173. (162) Fenical, W. Science 1982, 215, 923. (163) Schulte, G. R.; Scheuer, P. J. Tetrahedron 1982, 38, 1857. (164) Pawlik, J. R. Chem. Rev. 1993, 93, 1911. (165) Paul, V. 7.; Pennings, S. C. J. Exp. Mar. Biol. Ecol. 1991, 151, 227. (166) Kinnel, R. et al. Tetrahedron Lett. 1977, 3913. (167) Burreson, B. 7.; Moore, R. E.; Roller, P. P. J. Agric. Food Chem. 1976, 24, 856. (168) Falch, B. S. et al. J. Org. Chem. 1993, 58, 6570. (169) Watanabe, K. et al. Phytochemistry 1988, 28, 77. (170) Crews, P. et al. Phytochemistry1984, 23, 1449. (171) Miles, D. H. et al. J. Nut. Prod. 1993, 56, 1590. (172) Sandiya, R.; Alam, M.; Wellington,
G. M. J. Chem. Res. (S) 1986, 450. (173) Sakuma, M.; Fukami, H. Tetrahedron Lett. 1993, 34, 6059. (174) Williams, D. H. et al. J. Nut. Prod. 1989, 52, 1189.
Reagent Chem Eighth Edition
R
eagent Chemicals is the only resource of its kind that provides specifications and analytical procedures t o assure the quality of your chemicals. ACS specified reagent chemicals are the choice of most organizations such as APHA, ASTM, FCC, SEMI, USP, etc., and many regulatory agencies, such as the EPA. Improved and expanded, the eighth edition of this authoritative reference now comes in a user-friendly format that makes look-up quick and easy. In it you’ll find all the necessary information on 0 0 0
0 0 0 0 0 0 0 0 0
atomic absorption spectrophotometry chromatography colorimetry and turbidimetry direct electrometric methods gravimetric methods measurement of physical properties reagent solutions solid reagent mixtures solvents for special purposes specifications and tests standard volumetric solutions titrimetry
New in this edition are a section on determining detection limits, the general elimination of boiling point and density specifications, the use of LC in assay determinations, and a section on preparation of volumetric solutions. Twenty-four new reagents have been added. Updated methods include gas chromatography where capillary columns are now used, water determinations where coulometric methods have been added, and the replacement of flame emission techniques by atomic absorption for metal determinations. In addition, the general methods for chromatography and atomic absorption have been extensively revised t o reflect their practical use in today’s typical analytical laboratory. 815 pages (1993) Clothbound ISBN 0-8412-2502-8 $149.95 L
American Chemical Societv Distribution Office Dept. 51 1155 Sixteenth Street, NW Washington, DC 20036 Or CALL TOLL FREE
800-227-5558 (In Washinqton, DC, 872-4363) and use vour credit cardi
Environ. Sci. Technol., Vol. 28, No. 7, 1994 319 A
