An Introduction to Boron: History, Sources, Uses, and Chemistry William G

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An Introduction to Boron: History, Sources, Uses, and Chemistry William G. Woods Office of Environmental Health and Safety, University of California, Riverside, California Following a brief overview of the terrestrial distribution of boron in rocks, soil, and water, the history of the discovery, early utilization, and geologic origin of borate minerals is summmarized. Modern uses of borate-mineral concentrates, borax, boric acid, and other refined products include glass, fiberglass, washing products, alloys and metals, fertilizers, wood treatments, insecticides, and microbiocides. The chemistry of boron is reviewed from the point of view of its possible health effects. It is concluded that boron probably is complexed with hydroxylated species in biologic systems, and that inhibition and stimulation of enzyme and coenzymes are pivotal in its mode of action. - Environ Health Perspect 102(Suppl 7): 5-11 (1994) Key words: boron, borax, colemanite, glass, boric acid, health effects, enzyme, review

Introduction retardants, as micronutrients in fertilizers were an important source of boric acid in Boron is an ubiquitous element in rocks, and for many other purposes, as well. Europe from about 1820 to the 1950s. soil, and water. Most of the earth's soils The varied chemistry and importance Borax also was made from Italian boric have <10 ppm boron, with high concen- of boron is dominated by the ability of acid in England, France, and Germany. trations found in parts of the western borates to form trigonal as well as tetrahe- The borate industry in Turkey com- United States and in other sites stretching dral bonding patterns and to create com- menced in 1865 with mining of the calci- from the Mediterranean to Kazakhstan. plexes with organic functional groups, um borate pandermite (priceite, The average soil boron concentration is many of biologic importance. 4CaO5B203 7H20). At about the same 10 to 20 ppm, with large areas of the The present review will give an time, several borate deposits were found world boron deficient. Boron concentra- overview of boron from its sources to its in California and Nevada, including ulex- tions in rocks range from 5 ppm in uses and chemistry to provide a back- ite (Na 202CaO 5B 20 3 16H 20) and basalts to 100 ppm in shales, and averages ground for the following papers dealing colemanite (2CaO3B203 5H20) in 10 ppm in the earth's crust overall. Soils with its health effects. Death Valley. These minerals could be have boron concentrations of 2 to 100 converted to borax by reaction with trona ppm. Seawater contains an average of 4.6 History and Sources (Na2CO 3-NaHCO 32H 20). ppm boron, but ranges from 0.5 to 9.6 The Babylonians have been credited with The Kramer deposit, at what is now ppm. Freshwaters normally range from importing borax from the Far East over Boron, California, in the Mojave Desert, <0.01 to 1.5 ppm, with higher concentra- 4000 years ago for use as a flux for work- was discovered in 1913, first as a cole- tions in regions of high boron soil levels ing gold. Mummifying, medicinal and manite ore source. In 1925, tincal ore was (1,2). metallurgic applications of boron are found and in 1926, the new mineral Highly concentrated, economically sometimes attributed to the ancient rasorite (kernite, Na202B20 34H 20) sized deposits of boron minerals, always Egyptians. None of this very old borax was encountered (4). It is the largest in the form of compounds with boron history has been verified, but solid evi- borate deposit outside of Turkey and has bonded to oxygen, are rare and generally dence exists that tinkar (i.e., supplied a sizable portion of world borate are found in arid areas with a history of Na 2B4 0 7- 10H 20, tincal, the mineral demand for over 50 years. volcanism or hydrothermal activity. Such borax) was first used in the eighth century Turkey has supplied colemanite for deposits are being exploited in Turkey, around Mecca and Medina, having been many years to boric acid producers in the United States, and several other coun- brought there (and to China) by Arab Europe. Sodium borates were discovered tries (3). Borate-mineral concentrates traders (4). The use of borax flux by at Kirka in 1960 and other deposits have and refined products are produced and European goldsmiths dates to about the since been found and developed in sold worldwide. They are used in a myri- 12th century. Anatolia. As a result, today Turkey is the ad of ways: in glass and related vitreous The earliest source of borax is believed largest producer of borate products in the applications, in laundry bleaches, in fire to have been Tibetan lakes. The borax world (5), exporting mineral concentrates was transported in bags tied to sheep, of tincal, colemanite, and ulexite, plus which were driven over the Himalayas to refined borax decahydrate, borax pen- This paper was presented at the International India. tahydrate (Na2O°2B203-5H20), anhy- Symposium on Health Effects of Boron and Its Compounds held 16-17 September 1992 at the Volatility of boric acid with steam is drous borax (Na2O-2B20 3 ), and boric University of California, Irvine, California. believed by geologists to be the primary acid (B[OH]3). Address correspondence to Dr. William G. Woods, mechanism for the formation of borate Borates in the United States are pro- Office of Environmental Health and Safety, University of California, Riverside, Riverside, CA 92521. deposits (3). A prime example of this are duced entirely in the Mojave Desert of Telephone (909) 687-1568. Fax (909)787-5122. the geysers (soffioni) in Tuscany, which southern California. United States Borax

Environmental Health Perspectives 5 W G. WOODS

Table 2. Estimated consumption of boron minerals and chemicals in the United States (6). Use Percent Glass and ceramics Insulation fiberglass 28 Textile fiberglass 12 Glass 9 Enamels and glazes 3 Detergents and bleaches 12 Alloys and metals 6 Fire retardants 5 Agriculture 4 Adhesives 2 Other chemicals 19

low sodium, so boric acid or colemanite are used. Glass batch melting is aided by B203 which acts as a flux to improve the melting rate of more refractory components (e.g., U..~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. ... . SiO2). As an added benefit, water given off Figure1 Aerial. view of the US Borax mine and refineryeat Boron CA (U Borax Inc photo) by the borates also accelerates the melting. The alkali/alkaline earth oxide content Figure 1. Aerial view of the US Borax mine and refinery at Boron, CA. (US Borax, Inc. photo) is quite important to the effect of B203 on the structure and properties of glass. Adding Na2O, for example, progressively Table 1. Important refined borate products and mineral concentrates. changes trigonal B03 groupings to tetrahe- Name Formula Percent B203 dral B04- groups, which initially causes an increase in the glass transition temperature Borax pentahydrate Na2[B405(OH)4] 3H20 47.8 (Tg). Further addition of Na)O converts Borax (tincal) Na2[B405(OH)4]F8H20 36.5 B04- bonding groups to nonbonding Colemanite Ca[B304(OH)3] H2O 50.8 BO3-n units, which decreases Tg as well as Ulexite NaCa[B506(OH)6]F5H20 43.0 the melt viscosity. The latter helps in elimi- Boric acid B(OH)3 56.3 nating bubbles from the finished glass and Anhydrous borax Na2B407(glass) 69.2 gives good homogeneity and flattens the viscosity-temperature curve. The latter allows more latitude during manufacture & Chemical Corporation, a subsidiary of and the former USSR also produce some (forming) of the finished glass product, and Rio Tinto Zinc (RTZ), is the largest borates. the lower viscosity allows higher pro- source, producing borax pentahydrate Table 1 gives a list of the commercially duction rates. and decahydrate, and anhydrous borax important refined borate products and Borosilicate glass has increased thermal from tincal ore, and boric acid from ker- mineral concentrates. The formulas are shock resistance because B203 lowers the nite ore (Equation 1). written in a form reflecting their structures. expansion coefficient. In fiberglass, boric Na2B407 4H20+H 2S04 + H20 oxide gives desirable drawing qualities and Uses increases mechanical strength and chemical 4B(OH)3 + Na2SO4 [1] Table 2 lists the uses ofboron minerals and durability. An aerial photo of the US Borax mine chemicals in the United States glass and Another 12% of United States B203 is and refinery is shown in Figure 1. Another related uses consume about half of the consumed in detergents and bleaches; the US Borax plant at Los Angeles harbor pro- borates as boric anhydride (B203) in the percentage is even higher in Europe. Borax duces ammonium and potassium borates, United States (6). Fiberglass accounts for has been used as a laundry additive since boric oxide, zinc borate, and spray dried the largest share, comprising about 77% of about 1900. It can contribute to the soft- polyborates, in addition to serving as an the total (54% for insulation fiberglass, ening of hard water by tying up calcium export terminal. 23% for textile grade). Heat-resistant pyrex ions, as well as acting as a buffer agent. A North American Chemical recovers and other low-thermal expansion glasses traditional use as a sweetening agent for borax and boric acid as byproducts from consume about 18%, while enamels, frits, diaper pails is thought to involve the borate potash, soda ash, and salt-cake extrac- and ceramic glazes consume 5%. Small inhibition of the urease enzyme, (prevent- tion operations on Searles Lake brine. amounts are used in sealing and optical ing ammonia formation). The same effect Ore concentrates are produced by glasses, Vycor, and vitrifying nuclear waste. has been patented for deodorizing animal Newport Mineral Ventures on the edge Boric oxide can be added to the glass litter (8). Products based on borax and for- of Death Valley. formulation as borax pentahydrate, boric mulated with additives can give bleachlike Peru and Chile produce ulexite concen- acid, or colemanite, with price and cation activity when added to the wash. trates and boric acid, and Boroquimica in compatibility determining which is used Sodium perborates [NaBO3' 1 H 20 or Argentina operates a tincal deposit. China (7). For example, textile fiberglass requires 4H20; PBS1 or PBS4] are true persalts

6 Environmental Health Perspectives INTRODUCTION TO BORON: HISTORY, SOURCES, USES, AND CHEMISTRY

that traditionally have been blended into powdered detergents in Europe as bleach- HO, ing agents. Dilution in alkaline wash water results in hydrolysis of PBS to give hydroperoxide ion (Eq. 2). Na2[(HO)2B(OO)2B(OH)2 ] *6H20 + 20H--- 2NaB(OH)4 + 200H- + 4H20 [2] B303(O0H)4 B303(OH)S Sodium perborate (PBS) is effective as a broad-range bleach only at washing tem- 0 peratures above about 60°C, unless an acti- vator is present. Activators are organic acyl derivatives, which react with the hydroperoxide ion formed by hydrolysis of the perborate leading to peracid formation (Eq. 3). These peracids are effective bleaching agents at low temperature. HOW CH3(CH 2) 7COO Q S0 3Na SNOBS or B40s(OH)4 Bs06(OH) (CH3CO) 2NCH 2CH 2N(COCH3 )2 TAED Figure 2. Polymeric borate anions (14).

+ 1 or2-00H-* crops (2). Some crops susceptible to Adequate boron is required for incorpora- boron deficiency are apples, alfalfa, sugar tion of phosphorus into RNA and DNA. beets, and oil palms. Boron is one of the Lack of boron also is suspected of elevating CH3(CH2)7COOOH or 2 CH3COOOH more important essential elements for indoleacetic acid (IAA) in plants by [3] plant growth, and can be applied either to inhibiting IAA oxidase (2). the soil or to the foliage. Although small Borates are used extensively in treating At present, sodium 4-nonanoyloyben- amounts of boron are needed by all wood to protect against decay by brown zenesulfonate (SNOBS) is used in several plants, high concentrations can be toxic and white rot, and staining by fungi (11). detergents with bleach products in the to certain species. Borates and combina- Insecticidal use of borates is attractive United States, and tetraacetylethylenedi- tions of borates with organic herbicides because of their low mammalian toxicity amine (TAED) is used widely in Europe as are used to control weeds. and lack of insect resistance compared with well as in many other countries. The exact role of boron in plant metab- the organic insecticides. The literature con- PBS-based powdered bleach also is sold in olism is not known. Boron deficiency alters tains over 150 references in this field. the United States. Borax or boric acid can the plasmalemma of root cells, which Species showing promise for control by be used to stabilize protease enzymes in results in reduced absorption of potassium, borate-based insecticides are the powder liquid laundry detergents (9,10). chloride, and rubidium, as well as cessation post beetle (Lyctus brunneus) in hardwoods Alloy and metal production consume of root growth. Enzymes such as glucan (12) and larvae of several other beetles another 5.5% of the total B203. Welding synthetase involved in pollen tube cell wall which attack soft wood. Some species of rods and other fluxes use borates because growth apparently require boron. Boron subterranean termites like Coptotermes of their excellent metal oxide solubilizing also may control the amount of phenols in and Reticulitermes which contain gut pro- ability. Boron usage in amorphous metal cells. Apical meristem abnormalities may tozoa are susceptible, because boron is toxic alloys for electrical equipment and mag- be a secondary effect of vascular tissue to these cellulose-digesting organisms and nets is slowly increasing. Borates are used damage caused by lack of boron. An ade- leads to starvation of the host as well as sys- extensively as fire retardants, particularly quate supply of boron is essential for prop- temic effects. Less research has been done borax and boric acid in shredded cellu- er seed set and normal fruit development. on drywood termites, but some success has losic insulation and zinc borate in plas- Breakdown of parenchyma in cell walls been obtained with Cryptotermes. Sodium tics. Concerns about the toxicity of other which results in reduced lignification is octaborate, a highly soluble polyborate, is treatments have increased the interest in another symptom of boron starvation. of interest both for pre and posttreatment borates for wood preservation. Sugar buildup in leaves of boron-deficient ofwood. Agriculturally, borates are used in fer- plants is attributed to reduced sugar con- Control of cockroaches with boric acid tilizer (4% of United States B203) to cor- sumption and plasmalemma abnormalities has had great success, particularly against rect trace boron-deficiency in certain inhibiting sugar transport out of the leaves. the German roach Blattella germanica in

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tions have been shown by NMR and Raman spectra, as well as by titrimetric evi- dence, to contain polyborate ions of the types shown in Figure 2 (14). The distribution of these species as a function ofpH is given in Figure 3 (15). At the pH of human blood (7.4), the expected low concentrations of borate will be present as 98.4% B(OH)3 and only 1.6% as the B(OH)4- ion because of the weak acidity (PKa 9.2) ofboric acid. Simple alcohols react with boric acid to give esters (Eq. 4). In aqueous solution, B303(OH)4- this 040 equilibrium usually lies far to the left. B(OH)3 + 3ROH -> B(OR)3 + 3H20 [4] B506(OH) -B0( 020 The partially esterified species (RO)2BOH and ROB(OH)2 probably also are involved (16). Polyhydric alcohols B4OsOHg- form cyclic esters with boric acid. For example, hexylene glycol boric anhydride 0A (Structure 1) 4 6 8 10 12 id pH Figure 3. Distribution of polyborate species as a function of pH, 0.40M boric acid (15).

Structure 1

and 1,3-butylene glycol biborate (Structure 2) o 0

0'~~~ H C B O Ca++ Structure 2 * o00 0 Figure 4. Diastereomeric borate-saccharate complexes showing calcium coordination (18). are mixed to give the jet fuel microbiocide Biobor JF. This additive prevents the the US Boric acid does not act as a repel- ductor dopants, and a multitude of other growth of Cladosporium resinae and lant, (a problem with many organic blatti- small uses comprise 21% of the utilization Pseudomonas in fuel tanks cides), and it is aeruginosa by inexpensive, safe, and effec- of B203 in the United States. distributing itself between the water and tive (13). When powdered boric acid is fuel This combined with an Chemistry phases. hydrocarbon-metaboliz- anticaking agent, the ing fungus and bacterium grow at the roach contacts the chemical and eventually The aqueous chemistry of the borates is fuel-water interface and can cause corro- dies through cuticular absorption and dependent on concentration and pH. sion as well as foul the fuel filter (17). ingestion by grooming. Dilute aqueous boric acid solutions are with the of Promising work also has been Sugars proper disposition done with comprised solely of B(OH)3 and B(OH)4- hydroxyl groups also form ester complexes boron insecticides on ants, carpet beetles, species. Rapid exchange on the nuclear with boric acid. A striking example is the and fleas. magnetic resonance (NMR) time scale diacid disodium saccharate Miscellaneous sugar (glu- applications in starch results in a single peak in the boron- 11 carate) which forms a 2:1 sugar acid:borate adhesives, raw material for sodium borohy- NMR spectrum which moves steadily up as complex in aqueous solution that has the dride, borides, boron trifluoride, semicon- the pH is increased. Concentrated solu- ability to complex calcium ions. The two

8 Environmental Health Perspectives INTRODUCTION TO BORON: HISTORY, SOURCES, USES, AND CHEMISTRY

His-57

Figure 5. Boromycin (20). Figure 6. Borate intermediate in serine hydrolase inhibition.(32) diastereomeric forms of this complex are shown in Figure 4. Proton and carbon-13 NMR spectra showed that the 3,4-diol portion of the tetrol fragment was involved CONH2 in coordinating with the boron atom (18). These complexes are of interest as biodegradable builders to replace phos- phate in detergents (19). Adenosine<®-®. 0 - A small group of boron-containing antibiotics contain a single tetrahedral boron atom in the center of the structure, complexed with two vicinal diol groups. The tll~ first to be isolated and identified was boromycin (20) (Figure 5) from Strepto- myces antibioticus. The related aplasmomycin was obtained from S. griseus (21); both show antibiotic activity against gram-positive bacteria and represent the only isolated natural products containing boron. 7. Borate inhibition of coenzyme by fibityl group complexing (31). Bis(salicylato)borate salts (Structure 3) Figure hydrogenase are readily formed in aqueous solution from salicylic acid solution and boric A recent mechanistic study of boric ited by boric acid (24), and simple borates acid (22). , acid complexation with 4-isopropyl- have been patented as protease stabilizers in tropolone and with chromotropic acid, a liquid detergent formulations (9,10). 1,8-dihydroxynaphthalene derivative, has Reactions such as acylation and deacy- shown that the rate-determining step is the lation are catalyzed by enzymes through change in boron coordination from trigo- lowering of the energy of activation. nal to tetrahedral (23). Binding and stabilization of the near tetrahedral oxyanion transition state by the 0 active site of the enzyme is how this is Structure 3 accomplished. Thus, a transition state ana- B log inhibitor is a species which binds the 2-Aminoalkanols form borate esters readily active site in a way similar to that of the because of the added stabilization of the substrate. Serine hydrolase enzymes react N-B dative bond. A striking example is the with various borates, boronates, and bori- formation of triethanolamine borate nates by forming a tetrahedral complex (Structure 4) from a 1:1 aqueous solution Structure 4 between the serine hydroxyl group and the ofboric acid and triethanolamine (16). boron atom. Hydrogen bonding to the Boron in plant roots is believed to be Tetrahedral borate or boronate com- imidazole ring of an adjacent histidine adds reversibly bound as polysaccharide-borate plexes have been shown to be involved in further stabilization. complexes (2). enzyme inhibition. Serine proteases were X-ray structures have been worked out proposed in early Russian work to be inhib- for the benzeneboronic and 2-phenyl-

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ethaneboronic acid (PEBA) complexes of matin (31). It was concluded that good environment and it is likely that life subtilisin BPN'(Novo) (25) and for the boronate inhibitors of CHT, like PEBA, evolved in the presence of the element. PEBA complex of a-chymotrypsin inhibit cell replication and that this effect is Boron is essential to plant life, but can (a-CHT) dimer (26). Further stabilization expected to be higher in rapidly proliferat- be herbicidal at high levels. Borates have of the hydroxyls on boron is gained by ing cancer cells than in normal tissue (30). effects on a variety of bacteria, fungi, hydrogen bonding to other amido groups Complexing of the ribose group of and insects. Boron in biological systems lining the oxyanion hole (Figure 6). nicotinamide adenine dinucleotide (NAD) can be expected to be associated with Subtilisin Carlsberg (27) and choles- is preferred electrostatically over that of one or more OH groups. terol esterase (28,29) also are inhibited by a reduced nicotinamide adenine dinucleotide Borates are used widely in industrial range of aliphatic and aromatic boronic (NADH), leading to inhibition of this and domestic applications. Boron has acids. Work on inhibiting a-CHT and cell coenzyme system (Figure 7) (32). The been shown to influence a variety of replication with a variety of boronic acids effects of boron compounds on enzyme enzymes, involving both stimulation and concluded that the a-CHT activity was catalyzed reactions have been thoroughly inhibition. Enzyme interactions proba- associated with chromatin in normal and reviewed through 1979 by Kliegel (33). bly represent the most important feature tumorous tissue of mice (30). It has been of boron chemistry from the point of demonstrated that certain boronic acids Conclusions view of the health effects considered in inhibit protease activity in rat liver chro- Boron is present in every part of the the following papers.

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10 Environmental Health Perspectives INTRODUCTION TO BORON: HISTORY, SOURCES, USES, AND CHEMISTRY

cell replication. Biochem Pharmacol 35:3587-3591 (1986). 32. Smith KW, Johnson SL. Borate inhibition of yeast dehydrogenase. 31. Carter DB, Ross DA, Ishaq KS, Suarez GM, Chae C-B. The inhi- Biochemistry 15:560-564 (1976). bition of rat liver chromatin protease by cogeners of the phenyl- 33. Kliegel W. Bor in biologie, medizin und pharmazie. New boronic acids. Biochim Biophys Acta 484:103-108 (1977). York:Springer-Verlag, 1980.

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