Biomethylation and Environmental Transport of Metals
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S. Krishnamurthy U S . Environmental Protection Agency, Risk Reduction Engineering Laboratory, Edison, NJ 08837 Toxic heavy metals are ubiquitous in the environment. They are found as metal or oxide dust in air, metal ions attached to humic substances in surface and ground water, and as metal ions bound to soils and sediments. The transformations, mobilization, transport, and bioaccumulation of these toxic metals are of fundamental environmental importance. There is a balance between the use of metals for important catalytic process in cells of higher organisms and the bioaccumulation of metals to a toxic level. Biological methylation of metals is a mechanism that plays an important role in the mobilization and transport of the metals. This review covers the literature to early 1991. Organometallic compounds containing a metalkarbon bond constitute a large class of metal containing species with properties quite different from those of the metal ions. The neutral organometallic compounds tend to be lipid soluble, a property that enables their facile movement across biological membranes (1).They remain intact during movement through membranes and thus get distributed in these systems as lipid soluble compounds. Methylation is the attachment of a methyl group to heavy elements (metals and metalloids) and is a significant uatural process that is responsible for much of the environmental mobility of these elements (2).The fact that methylation changes the solubility and volatility of the resulting species obviously affects the movement of these species through water, air, andlor living organisms. Biological methylation proceeds through the formation of a methylated intermediate on the substrate surface, followed by movement of the metal out of the solid lattice into the surrounding solution. As has been mentioned already, methylation brings about a large difference in such physical properties as boiling point and solubility. These changes arise primarily from the fact that the methyl groups have neither empty orbitals nor non-bonding electrons available for intermolecular interaction. Methylation also can increase the toxicity of metals due to the aforementioned changes in physical properties (3).The increase in volatility and lipophilicity caused by methylation brings about the mobility of the metals under environmental conditions. Biological methylation of metals can take place both in homogeneous aqueous media and in heterogeneous media (4, 5).Example of methylation in homogeneous media are the following: Pb(N03),
+ CH,
I
3 (CH,),Pb
RKSCH3 + AdOH), + CH3 As03H2+ RR'S
+H '
Thayer (6) studied the mechanism and kinetics of methylation in homogeneous systems, using aqueous methyl iodide as the methylating agent. Aqueous solution of methyl iodide was passed at constant flow rate over a metal solution. A metal substrate need not be dissolved in aqueous solution for undergoing methylation. Using methylcobalamine, it was shown that several metal oxides in dilute, buffered acetic acid, underwent methylation. Tetramethyl lead and tin compounds were detected by reaction of the dioxides with methylcobalamin. Aqueous solutions of methvl iodide reacted with metal sulfides or selenides and
sevcral binary and ternary ores involving metals combined with sulfur and selenium, us exemplified by the following: Thayer, using a flow technique, observed a sharp increase in the concentration of dissolved metal, when the methylating agent came into contact with the substrate. The initial increase of dissolved metal concentration followed first-order kinetics. The dissolution of nickel dioxide by methylcobalamin solution, the dissolution of ferrous sulfide by methyl iodide solution, and the dissolution of iron out of Baltimore Harbor sediment by methyl iodide flow, were all demonstrated. Biomethylating Agents and Mechanism of Methylation The principal naturally occurring methylating agents are (a) Methylcobalamin (vitamin Biz); (b) S-adenosyl methionine and (c) methyl iodide, probably formed by the methylation of the iodide ion by S-adenosyl methionine. The mechanism of methylation has been reviewed (7). The methylating agents and their mechanisms of action will be discussed briefly and later, individual metal and metalloids will be considered. Methylcobalamin This is one of the coenzyme forms of vitamin B12found in bacteria and animals. It is a crystalline cobalt complex synthesized by microorganisms. It belongs to a group of a m ~ o u n dnamed s corrinoids. All corrinoids contain four reduced pyrrole rings, joined into a macrocyclic ring by four links. Three of the links are formed bv the methvlene =Cm u n s and the fourth by a G C bond. ?he centraicobalt atok isln oxidation state Co(IU).It has the capacity to coordinate up to six ligands. Of these coordinate positions, four are occupied bv the four nitrogen atoms of the corrin rine. The fifth wsiis tion is occupied by a heterocyclic chain. t he-sixth usuallv occu~iedbv a methvl e r o u ~or a water molecule. Meth$cobalarnin ;an be reir&ent'ed by the abbreviated structure below. where BZ is 5.6-dimethvl benzimidazole. Of all the biomethilating agents, kethylcobalamin is unique in that it is capable of transferring a methyl group by all three possible mechanisms, namely, as a carbanion (CHd, acarbonium ion (CHH)and a methyl radical (CH:), schematized as follows. Of these three, the carbanion (CH; ) and the free radical BZ (CHj) transfer mechanisms are predominant. ~
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Electrophilic Attack on the Co-C Bond: (Ce)Transfer Methvlcobalamin reacts r a ~ i d l vwith a number of metal ions, i n aqueous media under aerobic conditions, to give metal alkvls and aauoeobalamin as the reaction ~roducts. For example, the reaction between methylcobal~minand mercuric acetate involves a carbanion transfer. The secVolume 69 Number 5 May 1992
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ganisms is well documented. Nothing was known about the existence of organic forms of lead in the environment. I t was first shown bv Wone et al. (16) that microoreanisms in lake sediments can transform certain inorganic and organic lead compounds to volatile lead-tetramethyl. Arsenic The investigations concluded from the results of 50 experiments that incubation of some lead-containine sediments This element is widelv distributed in the environment. (not all) generates PbMe4, and that the converkon of lead The chemical and biolo&cal transformations of arscnlc are nitrate and lead chloride to PbMe* occurred on several ocoxidation. reduction. methvlation. which affect the volatilcasions in the presence of certainsediments and that the ity, absorption, and dissolution of the arsenic species inconversion is a purely biological process. The reaction bevolved. The transuort of arsenic in the environment is tween lead nitrate and methyl iodide to form PbMe4 was largely mntrolled dy adsorption/desorption process in soils investigated by Ahmad et al. (17) and Jarvia et al. (18). and sediments. Therefore, sediment movement is responThayer (19) showed that methylcobalamin reacted with sible for transfer of arsenic to their ultimate sinks in deep lead dioxide to give PbMe4. The lead redox couple oceans and sediments. Conversion of arsenic to volatile alPb(N)/Pb(II) has a high potential of + 1.46 V and this kylarsines leads to air transport loss from soils. Methylawould expect us to predict that Pb (IV) should react election of arsenic occurs in both fresh water and marine systmphilically, It has been shown by Taylor et al. (20) that tems and where arsenic is detected as arsenite, arsenate, prolonged contact of rnethylcobalamin with a fine suspenmethylarsenic acid, a n d dimethylarsenic acid. sion of Pb (N)oxide. results in uartial demethvlation of Methylcobalamin brings about the methylation of arsenic, the corriuoid. 'Racer' studies with [14-Cl methi1 labeled leading to various products as follows: methylcobalamin indicated that demethylation was accompanied by a proportional with Pb (N) 0 Me volatilization of the label. Pb(I1) salts did not show this behavior. It is clear from these obserH3 As04 % Me- &OH M ~ - ~ O H Me$H vations that lead reacts according to an e l e b philic heterolytic mechanism, the methylcobalamin transferring a methyl group as OH a carbanion. It is also to be noted that it is the higher oxidation state of the element that is imMe portant. It has been stated that, under humid conditions, arsenic in plaster and wallpaper pigMe ments could be biomethylated. It is quite possi&-Me Me- - A s 4 ble that lead paint in old buildings could be biomethylatedto PbMe4. This compound could be released to air or water. From air, it could be Me Me absorbed bv the skin or uroduce elemental lead as dust that could be inhiedor deposited on &ill Further, in lead battery superfund sites where lead dioxide is a contaminant, biomethylation could conBiomethylation of arsenic is responsible for numerous cases arsenic poisoning in Europe during 1880's. Under vert it into PbMeLwith serious conseouences to the environment. The lead dioxide is singled o i t since studies have humid conditions, arsenic in plaster and wallpaper pigshown that in biomethvlation. the hieher oxidation state is ments was converted into biomethvlated forms. a s maniimportant. fested by the strong garlic odor of tge products, and people sleeoindworkina in the moms became ill from inhaline the orgino&senic compounds. Trimethylarsine has been ;denChromium tified as the toxic aaseous arsenical produced bv the reacThe methylatiou of Cr(I1) by rnethylcobalamin appears with intion of certain mol& growing on wali paper to proceed by a homolytic pathway involving the transfer organic arsenic compounds present in the wallpaper. By of a methyl radical. Cobalamin [Co(II)Iand CH&r (HzOa2+) using I4C- labeled methylcobalamin and 74As-labeled disare the products of this reaction, but the latter is rapidly odium arsenate, it has been demonstrated that methano cleaved under acidic conditions to give methane and bacteria strain M.O.H. reduces and methylates arsenic to Cr(II1). dimethylarsine. The methyl donor of choice was The biomethvlation of metals and metalloids in soils and methylcobalamin (14). Microorganisms are believed to be sediments apdears to be a widespread phenomenon. The capable of reducing arsenic to mono and dimethylarsenic methylated compounds owing to their altered physical acids and arsines. Such reactions are not completely unproperties like volatility and lipid solubility, are important derstood. in the mobilization. transuort, and bioaccumulation of As(II1) is reportedly 25-60 times as toxic as As(V). The The adaptability of mitrace metals in the &ironment. increased toxicity of As(II1) relative to A&), is due to the croorganisms i s phenomenal and several reactions ability of As(II1) to react with sulfhydryl groups, thereby brought about by them await discovery Some methylated increasine its residence time in the bodv. A recent review compounds, for example those of Cd, Te, and Be, may have (15)summarizes the fate, mobilization; and transport of escaped detection owing to their reaction with water or air. arsenic in the environment, especially, groundwater. Most attention has been given to methyl metals in the environment, concentrating on their detection and toxicity, Lead In order for the compounds to be seen, they must be stable Lead is one of the most toxic metals found in the environenough to reach the detector being used. compounds not ment and is of great concern because of its widespread ocmeeting this requirement are not observed, although their currence in nature. The fate of lead in the environment existence may be indicated by indirect evidence. ~;ocelluwas largely unknown. As has already been indicated, the lar methylatingagcnts may react under natural conditions methylation of Hg and As in the environment by microorto form methyl metals. Ewn ifthey not be sufficiently long cmssa (13).Such a n alkylating system could be regarded as a conjugation mechanism for the microorganisms, but certainly they create unexpected environmental hazards to higher animals.
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Volume 69 Number 5 May 1992
349
lived to be detected directly, they may well play an important and unrecognized part in the movement of metals through the biosphere. Well-planned experiments should be conducted to detect these fugitive metal methyls and to unravel their role in the movement of such metals in the environment. The adaptability of microorganisms is indeed phenomenal. Many new reactions have been discovered, some favorable and some not favorable from the environmental standpoint. The omnipresence of the microbial population and their massive action and their importance in the maintenance of the total biota, underscore the need for further studies of this area. The biosvnthesis of metal methvls is a microbial response to the toxicity of ingested metal ions. Metal methyls may dilute local cellular concentration of metal ions, because small nonpolar molecules such as metal methyls are dissipated by diffusion controlled processes. The views presented here are those of the author, and do not reflect the views and policies of the United States Environmental Protection Agency.
350
Journal of Chemical Education
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Seuvell, W M. J Am. Chem. Soe 1374,96,34513456. Challeneer. . . F Chom Rou. 1945.36.315. Thayer, J. 3.: Olson, G. J.; ~rin!&k,F.E.Enuimn. Sci. l k h n a l . 1984, 18, 7626. Chu,V C. W.; G ~ w m w e d e lD. , W. Bioinorg. Chpm 1917,7, 169. Landner L.Nafuro 1911.230 452. MeBride, B.C.: Wolf, R. S. Blochemrslrv 1911.10.4312 Korte,M. S.; Fernando, Q. CCt.Reu. inEnuimn. Canfml 1991.21, (1),1-39. Won& P T. S.; Chsu, Y K ; Luxon,P. L Nolum 1916,253,263. Ahmad, J.; Chau,Y K; Wong,P.T. S.; Carty,A. J.;Taylm,L.Nofum 1980,287,716. JaMe.A. W P;Whitmare.A. PEnuImn. Tpehnol. Lett. 1981.2.197. Thayer. J.S.Enuimn. SciHmlth-Enuimn. Sei. E n g 138?,A18,471. Taylor, R. T.; Hannah. M. J. Enuiron. Sci. Health-Enuimn. Sei. E M . 1916.3, M I .
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