BDTH2: Difference between revisions

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 399537633

| ImageSize = 260

| ImageAlt = Central benzene ring, with two identical strings of CNCCCS attached to non-adjacent carbon atoms in the ring: the first "C" in each string is double-bonded to an O.

| ImageFile1 = BDTH2-3D-spacefill.png

| ImageSize1 = 240

| ImageAlt1 = Space-filling model of the BDTH2 molecule

| PIN = ''N''¹,''N''³-Bis(2-sulfanylethyl)benzene-1,3-dicarboxamide

| OtherNames = BDET; BDTH₂; BDETH₂; ''N'',''N''′-Bis(2-mercaptoethyl)-1,3-benzenedicarboxamide; N1,N3-bis(2-mercaptoethyl)isophthalamide; NBMI;

|Section1={{Chembox Identifiers

| MeSHName = 1,3-benzenediamidoethanethiol

| InChI = 1/C12H16N2O2S2/c15-11(13-4-6-17)9-2-1-3-10(8-9)12(16)14-5-7-18/h1-3,8,17-18H,4-7H2,(H,13,15)(H,14,16)

| CASNo_Ref = {{cascite|correct|??}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 4U7K5X4ANS

| ChemSpiderID =19238563

| PubChem = 16043475

| SMILES = O=C(NCCS)C1=CC(C(NCCS)=O)=CC=C1

|Section2={{Chembox Properties

| C=12 | H=16 | N=2 | O=2 | S=2

| Appearance =

| Density = 1.23 g/mL

| MeltingPtC = 132 to 135

| MeltingPt_ref = <ref name=Blue/>

| BoilingPt =

| Solubility = }}

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

'''BDTH₂''' (also called '''BDET''' and '''BDETH₂'''; trade names '''B9''', '''MetX''', and '''OSR#1''') is an [[organosulfur compound]] that is used as a [[chelation]] agent.<ref name=Blue_Diss>Blue LY, Immobilization of mercury and arsenic through covalent thiolate bonding for the purpose of [[environmental remediation]], Dissertation, University of Kentucky, 2010</ref> It is a colourless solid. The molecule consists of two [[thiol]] [[functional group|groups]] and linked via a pair of [[amide]] groups.<ref name=Clarke_Diss>[https://search.proquest.com/docview/910887793 Clarke D, Efficacy of a Novel Chelator for Mercury Chelation and Distribution], Dissertation, Arkansas State University, December 2012</ref>

The compound was reported in about 1994 after a search for chelating agents selective for mercury. It was licensed in 2006 to CTI Science with the long-term goal of using BDTH₂ to treat mercury poisoning.<ref name=C&EN /> This compound is prepared by treating [[isophthalic acid|isophthaloyl dichloride]] with two equiv of [[cysteamine]]:<ref name=Blue/><ref name=Blue_Diss/>

== Use ==

=== Environmental remediation ===

BDTH₂ can be used to chelate [[heavy metals]] like [[lead]], [[cadmium]], [[copper]], [[manganese]], [[zinc]], [[iron]], and [[Mercury (element)|mercury]] from [[ground water]], coal tailings, gold ore, waste water of battery-recycling plants, and contaminated soil.<ref name=Blue_Diss/>

BDTH₂ appears to bind mercury more strongly than do other chelators. The mercury-BDT complex does not break down even at high [[pH]] and in the presence of [[cyanide]]s, as in [[gold cyanidation|waste water of gold mines]]. The particular stability of the mercury bond can be attributed to the linear position of the two [[thiol]]s.<ref name="stable">{{cite journal | url=http://www.sciencedirect.com/science/article/pii/S0043135407007580 | doi=10.1016/j.watres.2007.12.010 | title=Low-level mercury removal from groundwater using a synthetic chelating ligand | journal=Water Research | date=April 2008 | volume=42 | issue=8 | pages=2025–2028 | last1=Blue | first1=Lisa Y. | last2=Van Aelstyn | first2=Mike A. | last3=Matlock | first3=Matthew | last4=Atwood | first4=David A. | bibcode=2008WatRe..42.2025B }}</ref> The company Covalent Research Technologies had investigated BDTH₂ for the removal of mercury from flue gas without success.<ref name=C&EN />

=== Clinical use ===

Animal experiments with inorganic mercury showed, that BDTH₂ effectively binds mercury in the body, and the resulting mercury derivative is excreted in the feces. Experimental animals showed no signs of poisoning. It is unclear, how the BDTH₂-mercury-chelate behaves in the long term. BDTH₂ is lipophilic, as opposed to [[2,3-Dimercapto-1-propanesulfonic acid|DMPS]] and [[Dimercaptosuccinic acid|DMSA]]; this enables it to cross lipid membranes, including the [[blood-brain-barrier]], and enter bone marrow.<ref name=C&EN>{{cite journal|last=Mullin|first=Rick|title=A mercury chelator|journal=C&EN Online|date=3 March 2014|volume=92|issue=9|pages=18–19}}</ref> In animal experiments, mercury in brain tissue neither increased nor decreased. There are indications that the BDTH₂-mercury-compound moves into adipose tissue.<ref name=Clarke_Diss/> It is unknown how BDTH₂ works with methyl-mercury.

BDTH₂ appears to bind copper and zinc in vivo weakly. In contrast, DMPS und DMSA bind these ions more strongly. Its affinity is low for other [[HSAB theory|"hard" ions]], e.g., Ca²⁺, Mg²⁺, Na⁺, and K⁺.<ref name=Clarke_Diss/>

Until July 2010, CTI Science sold BDTH₂ as a nutritional supplement under the name OSR#1.<ref name=forrest>Forrest Health Online:{{cite web|url=http://www.forresthealth.com/osr-1-30-100mg-caps.html |title=OSR#1 - 30 100mg caps - Forrest Natural Health Supplements |accessdate=2014-07-15 |url-status=dead |archiveurl=https://web.archive.org/web/20101223175448/http://www.forresthealth.com/osr-1-30-100mg-caps.html |archivedate=2010-12-23 }} </ref> Since OSR#1 didn't fulfill criteria of a nutritional supplement, its sale was stopped under pressure of the U.S. [[Food and Drug Administration]].<ref>[https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm216216.htm Warning letter CIN-10-107927-14] 17 June 2010 FDA to CTI Science Inc.</ref> In January 2012, BDTH₂ was designated by the [[European Commission]] as an [[orphan drug]], which guarantees CTI Science ten years of exclusive marketing rights.<ref>[http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2012/02/WC500121704.pdf EU/3/11/944] (PDF; 112&nbsp;kB) NBMI as orphan drug by the EC</ref> In April 2012, the FDA designated the compound as an orphan drug.<ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=367312|title = Enforcement Reports}}</ref>

== Potential applications ==

Like most thiols, BDTH₂ binds to mercury salts to form thiolate complexes. In principle, it could be used to remove mercury from water for industrial applications under a wide range of conditions, including the high pH and cyanide of the effluent from gold mining. In industrial use, BDTH₂ is easy to make and can be used either as-is or in the form of sodium or potassium [[salt (chemistry)|salts]] that are more soluble in water.<ref name=Blue/>

BDTH₂ binds to mercury with a strong, nonpolar covalent bond within a water-insoluble organic framework. The resulting BDT–Hg [[precipitate]] is stable, and leaches mercury only under highly acidic or basic conditions. BDTH₂ also binds to other elements, including arsenic, cadmium, copper, lead, and selenium.<ref name=Blue/> It is effective and economical for removing small traces of mercury from polluted soil, as the precipitate is inert and can be left in the soil after treatment.<ref name=Blue2008>{{cite journal |title=Low-level mercury removal from groundwater using a synthetic chelating ligand |vauthors=Blue LY, Van Aelstyn MA, Matlock M, Atwood DA |journal=Water Res |year=2008 |volume=42 |issue=8–9 |pages=2025–8 |doi=10.1016/j.watres.2007.12.010 |pmid=18207488 |bibcode=2008WatRe..42.2025B }}</ref>

== Dietary supplement and controversy ==

BDTH₂ had been marketed under the name OSR#1 as a [[dietary supplement]] for treatment of [[autism]].<ref name=Tsouderos/> The U.S. [[Food and Drug Administration]] determined that BDTH₂ is a drug rather than a supplement and issued a warning,<ref>{{Cite news

|last=Tsouderos

|first=Trine

|title=FDA warns maker of product used as alternative autism treatment

|newspaper=Chicago Tribune

|date=June 23, 2010

|url=http://www.chicagotribune.com/health/ct-met-autism-chemical-20100623,0,7088247.story

|accessdate=July 30, 2010

|archiveurl=https://web.archive.org/web/20100826065458/http://www.chicagotribune.com/health/ct-met-autism-chemical-20100623%2C0%2C7088247.story

|archivedate=August 26, 2010

|url-status=live

}}</ref><ref>{{cite web

| title = Warning Letter CIN-10-107927-14

| url = https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm216216.htm

| work = Inspections, Compliance, Enforcement, and Criminal Investigations

| publisher = U.S. Department of Health and Human Services / Food and Drug Administration

| accessdate = June 28, 2010

| date = June 17, 2010

| archiveurl = https://web.archive.org/web/20100627122411/https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm216216.htm| archivedate= 27 June 2010 | url-status= live}}</ref> resulting in its removal from the market.<ref>{{Cite news |last= Tsouderos |first= Trine |title= Controversial supplement to come off shelves |newspaper= Chicago Tribune |date= July 26, 2010 |url= https://www.chicagotribune.com/2010/07/26/controversial-supplement-to-come-off-shelves/ |access-date= July 30, 2010 | archive-url= https://web.archive.org/web/20100730071919/http://articles.chicagotribune.com/2010-07-26/health/ct-met-autism-treatment-pulled-20100726_1_cti-science-web-warning-letter-expert-in-environmental-health| archive-date= 30 July 2010 | url-status= live}}</ref> The main proponent of the compound, Dr. [[Boyd Haley]], was chairman of the department of chemistry where research is also conducted on the utility of this compound for remediation of [[Heavy metal (chemistry)|heavy metal]] pollution.<ref name=Blue/><ref name=Tsouderos/>

== See also ==

*[[Chelation therapy]]

<ref name=Blue>{{cite journal |vauthors=Blue LY, Jana P, Atwood DA |title=Aqueous mercury precipitation with the synthetic dithiolate, BDTH₂ |journal=Fuel |volume=89 |issue=6 |pages=1326–1330 |date=June 2010 |doi=10.1016/j.fuel.2009.10.031 |bibcode=2010Fuel...89.1326B }}</ref>

<ref name=Tsouderos>{{cite news |author=Tsouderos T |title=OSR#1: industrial chemical or autism treatment? |url=http://www.chicagotribune.com/health/chi-autism-chemicaljan17,0,3036818,full.story |work=Chicago Tribune |date=2010-01-17 |accessdate=2010-02-11 |archiveurl=https://web.archive.org/web/20100221055658/http://www.chicagotribune.com/health/chi-autism-chemicaljan17,0,3036818,full.story |archivedate=2010-02-21 }}</ref>

== External links ==

* [https://web.archive.org/web/20131203153631/http://www.usawaterquality.org/conferences/2009/PDF/Rural-poster/Blue09.pdf Poster: Complete Remediation of Groundwater Arsenic Using a Merloc B9, Zerovalent Iron Filtration Column] (PDF-file; 8,38&nbsp;MB)

[[Category:Benzamides]]