Rare earth elements in soil and in soil-grown plants

Concentrations of the rare earth elements (REEs) La, Ce, Nd, Sm, Eu, Gd, Tb, Yb and Lu were determined in leaves of 6 plant species (Norway spruce, silver fir, maple, ivy, blackberry, and wood fern), and in pertinent soils and soil extracts, also taken from the same site. The distribution of the individual REEs in plants showed little or no agreement with that in the soil or the soil extracts. Ce had a negative anomaly with respect to the soil in all plants. The REE distribution patterns of fir and spruce were almost identical, but differed profoundly from that of the other species. In most cases, concentration ratios between species were a smooth function of the atomic number of the REE. Very similar results were obtained at 2 additional sites.     

感耦等离子体发射光谱法研究土壤-铁芒萁系统中稀土元素的分布、累积和迁移特征

用感耦等离子体发射光谱法(ICP-AES)测定了江西赣南地区非稀土矿区和处不同稀土矿区内,土壤-铁芒萁系统中La、Ce、Pr、Nd、Sm、Gy、Db、Yb和Y的含量,并对其在土壤剖面层及铁芒萁植物体内的分布、迁移特征进行了研究.结果表明,土壤剖面层的底土层含量最高,但表土层铈相对富集.稀土元素总量(∑REE)在铁芒萁植物体内的分布规律是叶＞根＞茎＞叶柄,单一稀土元素的分布规律各异,La、Ce、Pr、Nd的分布规律表现为:叶＞根＞茎＞叶柄;Sm和Gd在不同采样点表现为叶＞根＞茎＞叶柄或根＞叶＞茎＞叶柄;Dy、Yb和Y均有3种不同的分布模式:叶＞根＞茎＞叶柄、根＞叶＞茎＞叶柄及根＞茎＞叶＞叶柄.稀土元素在铁芒萁体内的迁移过程中,发生了明显的分馏作用,茎、叶柄、叶中的重稀土相对贫乏.     

Rare earth elements in soil and plant systems - A review

The rare earth elements (REEs) form a chemically uniform group and include yttrium (Y), lanthanum (La) and the lanthanides cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), and lutetium (Lu). Their average abundance in the Earth’s crust range from 66μg g⁻¹ in Ce to 0.5μg g⁻¹ in Tm and ?0.1μg g⁻¹ in Pm. Recent great improvements in more routine analytical technique, the use of REEs as fertilisers, at least in East Asian agriculture, and the importance of these elements as indicators in both pedological and physiological processes and reactions have contributed to an increased interest in these previously less considered elements in environmental sciences. This review of recent and current literature deals with REEs in primary and secondary soil minerals, concentrations in surface soils, factors influencing adsorption, solubility and transport in soils, including weathering and transformations of REE minerals, and vertical distribution in soil profiles. Reviewed and discussed are also concentrations, distribution and localisation of REEs in plants and plant organs, soil-plant relationships and interactions, effects on plant growth and crop production and their importance in plant physiology and biochemistry. The REEs are found, usually several elements together, as phosphates, carbonates and silicate minerals finely dispersed especially in magmatic and metamorphic rocks. REE concentrations in surface soils of humid climates, such as the A(E)-horizons of Podzols and Laterites, are usually lower than in the parent material, due to higher weathering and leaching rates than of the average soil constituents. Some fractionation may occur due to the formation of more element-specific secondary minerals. Transfer from soil to plant is usually low, but extreme accumulators are found, e.g., among several species of ferns. Roots have generally higher concentrations than shoots. Possible uptakemechanisms of REEs are discussed. Uptake is positively, though often weakly, correlated with soil acidity and easily soluble concentrations of the elements, but rarely well related to their total concentrations in the soil. Under certain conditions, low concentrations of at least some REEs seem to favour plant growth and productivity, but the physiological mechanisms are still not well understood. Some considerations concerning the boundary between essential and non-essential micro nutrients are discussed.     

Assessment the Exposure Level of Rare Earth Elements in Workers Producing Cerium,Lanthanum Oxide Ultrafine and Nanoparticles

In order to assess occupational exposure level of 15 rare earth elements (REEs) and identify the associated influence, we used inductively coupled plasma mass spectrometry (ICP-MS) based on closed-vessel microwave-assisted wet digestion procedure to determinate the concentration of Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu in urinary samples obtained from workers producing ultrafine and nanoparticles containing cerium and lanthanum oxide. The results suggest that La and Ce were the primary component, together accounting for 97 % of total REEs in workers. The urinary levels of La, and Ce among the workers (6.36, 15.32 μg.g^?1 creatinine, respectively) were significantly enriched compared to those levels measured in the control subjects (1.52, 4.04 μg.g^?1 creatinine, respectively) (p < 0.05). This study simultaneously identified the associated individual factors, the results indicate that the concentrations in over 5 years group (11.64 ± 10.93 for La, 27.83 ± 24.38 for Ce) were significantly elevated compared to 1–5 years group (2.58 ± 1.51 for La, 6.87 ± 3.90 for Ce) (p < 0.05). Compared the urinary levels of La and Ce at the separation and packaging locations (9.10 ± 9.51 for La, 22.29 ± 21.01 for Ce) with the other locations (2.85 ± 0.98 for La, 6.37 ± 2.12 for Ce), the results show urinary concentrations were significantly higher in workers at separation and packaging locations (p < 0.01). Inter-individual variation in levels of La and Ce in urine is the result of multi-factorial comprehensive action. Further researches should focus on the multiple factors contributing to the REEs levels of the occupationally exposed workers.     

Study on binding of REEs with water-soluble polysaccharides in fern

The binding of rare earth elements (REEs) with water-soluble polysaccharides of nondeproteinization and deproteinization in the leaves of the fernDicranopteris dichotoma was studied by molecular activation analysis (MAA). Two cold-water-soluble polysaccharides (extracted by 75% ethanol and 90% ethanol, respectively) and one hot-water-soluble polysaccharide (extracted by 90% ethanol) were separated using biochemical separation techniques. The eight rare earth elements (La, Ce, Nd, Sm, Eu, Tb, Yb, and Lu) in these polysaccharides were determined by instrumental neutron activation analysis. Our new results showed that the REEs were bound firmly with the water-soluble polysaccharides in the plant, regardless of whether nondeproteinization or deproteinization was used. The molecular-weight (MW) measurement demonstrated that REEs were mainly bound with low-MW (10,000–20,000) polysaccharides.     

感耦等离子体发射光谱法研究土壤—铁芒萁系统中稀土元素的分布、累积和迁移特征

用感耦等离子体发射光谱法（ICP－AES）测定了东西赣南地区非稀土矿区和4处不同稀土矿区内,土壤－铁芒萁系统中La、Ce、Pr、Nd、Sm、Gd、Dy、Yb和Y的含量,并对其在土壤剖面层及铁芒萁植物体内的分布、迁移特征进行了研究,结果表明,土训层的底土层含量最高,但表土层铈相对富集、稀土元素总量（∑REE）在铁芒萁植物体内的分布规律是叶＞根＞茎＞叶柄,单一稀土的分布规律各异,La、Ce、Pr、Nd的分布规律表现为：叶＞根＞茎＞叶柄;Sm和Gd在不同采样点表现为叶＞根＞茎＞叶柄或根＞叶＞茎＞叶柄;Dy、Yb和Y均有3种不同的分布模式：叶＞根＞茎＞叶柄、根＞叶＞茎＞叶柄及根＞茎＞叶＞叶柄,稀土元素在铁芒萁体内的迁移过程中,发生了明显的分馏作用,茎、叶柄、叶中的重稀土相对贫乏。     

Bioaccessibility and health risk assessment of rare earth elements in Porphyra seaweed species

In this study, the content and bioaccessibility of rare earth elements (REEs) in Porphyra spp. Samples before and after thermal treatments were investigated. Additionally, the risks of REEs exposure to human health were assessed. REEs content significantly reduced after thermal processing (P < 0.01), and the removal rate of REEs was approximately 30%. Thermal treatment increased REEs bioaccessibility from 44% to 64.34%. The concentration and bioaccessibility of Ce, La, Y, Nd were high in raw and thermally treated Porphyra samples, and there was no correlation between REEs content and bioaccessibility. Based on the following parameters: highest content of REEs in the studied seaweed samples (13.45 mg/kg), the highest daily seafood consumption (44.9 g/day), and the highest bioaccessibility (64.34%), the ratio of the calculated daily intake (DI) to daily allowable intake by diet (DAI_diet) of REEs did not exceed the reference value in rare earth mining areas or under extreme conditions. The DI via seafood consumption would be exceeded when the content of REEs in the seafood sample is greater than 15.77 mg/kg. In this study, the concentration of REEs did not exceed 15.77 mg/kg in any sample. Thus, the human health risks of REEs associated with seafood are low.     

Criticality of the Rare Earth Elements

Recent constraints on supplies of the rare earth elements (REEs) have led to concerns about their long‐term availability as well as the consequences that shortages would pose for modern technology. To assess this situation, we apply a comprehensive “criticality” methodology to the REE: lanthanum (La); cerium (Ce); praseodymium (Pr); neodymium (Nd); samarium (Sm); europium (Eu); gadolinium (Gd); terbium (Tb); dysprosium (Dy); holmium (Ho); erbium (Er); thulium (Tm); ytterbium (Yb); lutetium (Lu); and yttrium (Y). Assessments are made on national (U.S. and China) and global levels for the year 2008. Evaluations of each indicator are presented and the results plotted in “criticality space” on a 0 to 100 scale. Over the medium term (5 to 10 years), supply risk (SR) for all REEs is moderate with minimal variation (62.8 to 65.1). Over the long term (10 to 100 years), SR is low (42.1 to 49.2). Environmental implications scores, reflecting the economic allocation of environmental burdens, range from 4.2 for La to 34.4 for Lu. Eu, Er, and Dy have the highest vulnerability to supply restriction (VSR) at the global level (50.6, 49.2, and 47.4, respectively), whereas Sm has the lowest (15.1). This is mainly a reflection of their substitution potential. Similarly, at the national level for the United States and China, Eu and Sm have the highest and lowest VSR scores, respectively, although there are notable differences in scores among the REEs and between countries. Although China's export restrictions render REE supplies inadequate to meet demand at present, our analysis indicates a lower criticality for REEs over the longer term than for a number of other industrially used metals.     

The variation of REE (rare earth elements) patterns in soil-grown plants: a new proxy for the source of rare earth elements and silicon in plants

Rare earth elements (REEs) in five species of soil-grown plants (Taxodium japonicum, Populus sieboldii, Sasa nipponica, Thea sinensis and Vicia villosa) and in the soil on which each plant grew were determined with an inductively coupled plasma mass spectrometer (ICP-MS) in order to observe the variation in the distribution of REEs and to elucidate their source in soil-grown plants. The plant samples were divided into root (secondary root and main root), trunk (stem) and leaf; the soils into water soluble (soil_{soluble fraction}), HCl and HNO₃ soluble (soil_{non-silicate fraction}) and HF soluble (soil_{silicate fraction}). The REE abundances of samples were compared using REE patterns where the abundances were normalized to those of a chondrite and plotted on a logarithmic scale against the atomic number. All the plants showed similar REE patterns independent of species and location, and a W-shape variation (W-type tetrad effect) and abundance depletion of cerium (negative Ce anomaly) were found in each REE patterns of plants, more conspicuous tetrad effect being observed in HREE (heavier rare earth elements) region than in LREE (lighter rare earth elements) region. The overall variation of REE patterns of each secondary root was not similar to that of soil_{soluble fraction}, but similar to that of soil_{silicate fraction} except for the tetrad effect and Ce anomaly. The REE patterns can be interpreted by the idea that plants of different species take in REEs and Si from different parts in the soil. The results of this study seem to imply that Sasa nipponica and Vicia villosa take in free REEs and Si rather directly from silicate in the soil, and that a majority of REEs and Si in Taxodium japonicum and Thea sinensis are originated from the soluble fraction in the soil.     

Population growth responses of Tetrahymena shanghaiensis in exposure to rare earth elements

This article presents the population growth responses of Tetrahymena shanghaiensis s₁ in exposure to rare earth elements (REEs). Both the light REEs (La, Sm) and the heavy REEs (Y, Gd) were investigated with 24- and 96-hr population growth assays to evaluate their aquatic toxicity. Four end points, cell count, frequency of neutral red (NR) uptake, total protein, and nucleic acid content were employed in the 24-h assay, and a population growth curve was plotted in the 96-h assay. The results of 24- and 96-h assays suggest a dual effect of REEs on T. shanghaiensis of the stimulated growth at low concentrations and the toxicity at higher ones. In the promoted growth of T. shanghaiensis, however, the cell density increased with an increased growth rate and the protein and nucleic acid content per 10⁴ cells undertook no remarkable changes, which suggests possible cell growth control by REE.     

Rare earth elements and relation between their potential bioavailability and soil properties, Nidda catchment (Central Germany)

Rare earth elements (REEs) are widely used in industry and the entry of REEs into the pedosphere is assumed. Data about REEs in soils are scarce since only a few studies discuss their ecologically relevant behavior. Hence, we investigated total contents (aqua regia digestion) and potentially bioavailable contents (EDTA extraction) of REEs in soils from the Nidda catchment in Hesse (Central Germany). The study site covers a 1,600 km² sized area and 232 soil samples from 63 soil profiles were examined. The total REE content varied considerably, ranging from 544 mg kg^?1 to 41 mg kg^?1 (mean 201.1 mg kg^?1) with a high proportion of light REEs. Highest REE contents were found in the soilscape VB, followed by LVB, WNE, T, WSW and BF with the smallest concentrations. With respect to the parent material the contents decreased in the following order: basalt > clay slate > loess > sandstone. On average 15.9% of the total REEs belong to the potentially bioavailable fraction. They range greatly by a factor of 100, between 1.3 and 171.3 mg kg^?1 (average 33.5 mg kg^?1). Remarkably, Yttrium has a maximum available proportion of 75%. In contrast, Ce showed the highest total contents with the smallest potentially bioavailable proportion of all elements. Regression analyses established relation between soil properties and the potential bioavailability of REEs. Around 53% (range from 29.9 to 76.8%) of the REE’s potential bioavailability variations could be explained by the chosen variables (pH, clay and C_org contents and the total element concentrations). Occurrence patterns and concentrations of REEs lie within the range of the results found in the available literature. Bioavailability is linked to soil properties and varies greatly according to the individual element. In comparison with the chosen soil properties the pH value shows the least impact on bioavailability.     

Accumulation and fractionation of rare earth elements (REEs) in the naturally grown Phytolacca americana L. in southern China

The widespread use of rare earth elements (REEs) has resulted in problems for soil and human health. Phytolacca americana L. is a herbaceous plant widely distributed in Dingnan county of Jiangxi province, China, which is a REE mining region (ion absorption rare earth mine) and the soil has high levels of REEs. An investigation of REE content of P. americana growing naturally in Dingnan county was conducted. REE concentrations in the roots, stems, and leaves of P. americana and in their rhizospheric soils were determined. Results showed that plant REEs concentrations varied among the sampling sites and can reach 1040 mg/kg in the leaves. Plant REEs concentrations decreased in the order of leaf > root > stem and all tissues were characterized by a light REE enrichment and a heavy REE depletion. However, P. americana exhibited preferential accumulation of light REEs during the absorption process (from soil to root) and preferential accumulation of heavy REEs during the translocation process (from stem to leaf). The ability of P. americana to accumulate high REEs in the shoot makes it a potential candidate for understanding the absorption mechanisms of REEs and for the phytoremediation of REEs contaminated soil.     

Rare earth elements (REEs) in PM10 and associated health risk from the polymetallic mining region of Nandan County,China

A total of 26 samples were collected from Dachang, Chehe and Liuzhai in Nandan County, China, in order to investigate the concentrations of rare earth elements (REEs) and associated health risk in particulate matter. The concentrations of REEs in Dachang (23.54 ng/m³), Chehe (20.29 ng/m³) were significantly higher than those in Liuzhai (8.1 ng/m³). The light rare earth elements (LREEs) account for 87.08%, 87.09%, and 86.17% of the total REE burden in PM10 at Dachang, Chehe, and Liuzhai, respectively, indicating that the distribution pattern of REEs in PM10 was characterized by the obvious fractionation of LREEs. Enrichment factor calculation indicated that EFs for La, Ce, Nd, Pr, and Nd in PM10 from Dachang and Chehe were greater than 2, indicating moderate enrichment. Source identification indicated that REEs in PM10 from Dacheng and Chehe originated from anthropogenic activities such as mining and smelting activities, while REEs in PM10 from Liuzhai were associated with natural sources, like soil erosion. Noncarcinogenic and carcinogenic risks associated with the exposure of REEs in PM10 were negligible based on the health risk assessment models. However, greater noncarcinogenic risk for children was found in studied areas compared with the adults.     

Rare earth element, Al, and Sc partition between soil and Caatinger wood grown in north-east Brazil by instrumental neutron activation analysis

Seven representative wood species constituting Caatinger forest in north-east Brazil were chosen to analyze La, Ce, Sm, Eu, Yb, Sc, and Al by instrumental neutron activation analysis (INAA). Soil profiles were prepared where the trees were downed. Then soil and root samples from each horizontal soil layer, as well as the upper part of the wood, ground-level bark, and the bark at 1 m above were collected. In woods, the rare earth element (REE) was found to be mainly accumulated in root, which concentration was in the same order as that of soil. In all samples, concentration of La and Ce were found to be about ten times higher than those of the other REEs. The REE accumulation became higher, in both root and soil, in the order of La, Ce, and Sm. The partition rate of La and Eu was higher from soil to root, whereas Ce tended to be concentrated from root to bark. In the case of bark, there was no tendency of specific REE accumulating from ground level to the upper part. The correlation of La concentration to the other REE was higher in root than that of corresponding soil. Roots also showed higher correlation of REE to Al and Sc than that of soil or bark.     

Bioaccumulation of rare earth elements in cultured hela cells

HeLa S-3 cells were grown in minimal essential medium supplemented with 10% calf serum and 1 mM L-glutamine without adding any rare earth elements (REEs). Exponentially growing cells were collected, and dried materials were used to analyze their REE content by inductively coupled plasma-mass spectrometry. The results showed that the cells accumulated REEs in individually different manners; namely the accumulation ratio was higher in the lighter REEs than in the heavier REEs. To deduce the implication of the accumulation of REEs in HeLa cells, the accumulation ratios for REEs were compared with those of other biologically important elements. It was seen that the accumulation ratios obtained for REEs (from 31.8 [Ce] to 14.7 [Lu]) were intermediate among those of many bioelements: Fe (124), Mg (54.5), K (38.8), Cr (12.7), Na (11.8), Mn (11.3), Zn (10.7), Ca (8.8), and V (6.7).     

Identification and application of amino acids as chelators in phytoremediation of rare earth elements lanthanum and yttrium

Aims

This study aimed to identify amino acids that could act as chelators in enhancing absorption and translocation capabilities of a rare earth element (REE) lanthanum and yttrium in a non-hyperaccumulator plant.

Methods

We analysed correlations between amino acid, La and Y concentrations in xylem saps of the REE hyperaccumulator Phytolacca americana L., to identify functional amino acids in long-distance transportation processes. These were used as chelators to observe the efficacy of La uptake and translocation in REE non-hyperaccumulator tomato seedlings. Pot culture experiments were conducted using modified Hoagland solution artificially contaminated with REEs.

Results

Eighteen xylem sap amino acids were identified and measured in the xylem sap, using reversed-phase high-performance liquid chromatography. Aspartic acid, asparagine, histidine and glutamic acid may be related to xylem La and Y long-distance transportion in P. americana L. Extraneous aspartic acid, asparagine, histidine and glutamic acid enhanced La absorption in the whole tomato, compared with La alone. Moreover, the whole tomato La content increased by 449 μg and 139 μg in the presence of aspartic acid and asparagine as compared to P. americana L. Tryptophan insignificantly affected La uptake and translocation in tomato seedlings.

Conclusions

Aspartic acid and asparagine could potentially promote remediation of La contamination in soil when used as a chelator.     

Accumulation of rare earth elements in human bone within the lifespan

For the first time, the contents of rare earth elements (REEs) in a rib bone of a healthy human were determined. The mean value of the contents of Ce, Dy, Er, Gd, La, Nd, Pr, Sm, Tb, and Yb (10 elements out of 17 total REEs), as well as the upper limit of means for Ho, Lu, Tm, and Y (4 elements) were measured in the rib bone tissue of 38 females and 42 males (15 to 55 years old) using inductively coupled plasma mass spectrometry (ICP-MS). We found age-related accumulation of REEs in the bone tissue of healthy individuals who lived in a non-industrial region. It was calculated that during a lifespan the content of REEs in a skeleton of non-industrial region residents may increase by one to two orders of magnitude. Using our results as indicative normal values and published data we estimated relative Gd accumulation in the bone tissue of patients according to magnetic resonance imaging with contrast agent and La accumulation in the bone tissue of patients receiving hemodialysis after treatment with lanthanum carbonate as a phosphate binder. It was shown that after such procedures contents of Gd and La in the bone tissue of patients are two to three orders of magnitude higher than normal levels. In our opinion, REEs incorporation may affect bone quality and health similar to other potentially toxic trace metals. The impact of elevated REEs content on bone physiology, biochemistry and morphology requires further investigation.     

Use of GEOCHEM-PC to predict rare earth element (REE) species in nutrient solutions

The interpretation of results of some experiments examining effects of rare earth elements (REE) on plant growth may have been complicated by rare earth phosphate precipitation. Simulations were undertaken using the computer model GEOCHEM-PC to define REE solubility limits and predict REE species in low and high ionic strength nutrient solutions. In low ionic strength solutions containing 5 M P, lanthanum phosphate (LaPO₄) precipitation is predicted to occur at solution pH>4.0, reaching a maximum (>95% of total) at pH 5.5. In high ionic strength solutions (1000 M P) over 95% of the La is predicted to precipitate as phosphate at pH>4.0. The predicted behaviour of cerium (Ce) was closely similar to that for La.At pH 5.5, the concentration of REE species in solution can be increased only after virtually all the P has been precipitated. Consequently, it is important to consider REE-P interactions in nutrient solutions when investigating REE effects on plant growth.     

Use of rare‐earth elements in the phyllosphere colonizer Methylobacterium extorquens PA1

Until recently, rare‐earth elements (REEs) had been thought to be biologically inactive. This view changed with the discovery of the methanol dehydrogenase XoxF that strictly relies on REEs for its activity. Some methylotrophs only contain xoxF, while others, including the model phyllosphere colonizer Methylobacterium extorquens PA1, harbor this gene in addition to mxaFI encoding a Ca²⁺‐dependent enzyme. Here we found that REEs induce the expression of xoxF in M. extorquens PA1, while repressing mxaFI, suggesting that XoxF is the preferred methanol dehydrogenase in the presence of sufficient amounts of REE. Using reporter assays and a suppressor screen, we found that lanthanum (La³⁺) is sensed both in a XoxF‐dependent and independent manner. Furthermore, we investigated the role of REEs during Arabidopsis thaliana colonization. Element analysis of the phyllosphere revealed the presence of several REEs at concentrations up to 10 μg per g dry weight. Complementary proteome analyses of M. extorquens PA1 identified XoxF as a top induced protein in planta and a core set of La³⁺‐regulated proteins under defined artificial media conditions. Among these was a REE‐binding protein that is encoded next to a gene for a TonB‐dependent transporter. The latter was essential for REE‐dependent growth on methanol indicating chelator‐assisted uptake of REEs.     

New complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin

New solid complex compounds of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin were synthesized. The molecular formula of the complexes is Ln(C₁₅H₉O₇)₃ · nH₂O, where Ln is the cation of lanthanide and n = 6 for La(III), Sm(III), Gd(III) or n = 8 for Ce(III), Pr(III), Nd(III) and Eu(III). Thermogravimetric studies and the values of dehydration enthalpy indicate that water occurring in the compounds is not present in the inner coordination sphere of the complex. The structure of the complexes was determined on the basis of UV-visible, IR, MS, ¹H NMR and ¹³C NMR analyses. It was found that in binding the lanthanide ions the following groups of morin take part: 3OH and 4CO in the case of complexes of La, Pr, Nd, Sm and Eu, or 5OH and 4CO in the case of complexes of Ce and Gd. The complexes are five- and six-membered chelate compounds.