2,4-二硝基苯酚

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|   ImageFileR1 = 2,4-Dinitrophenol 3D.png
|   ImageSizeR1 = 120px
|   IUPACName = 2,4-dinitrophenol
|   OtherNames = Solfo Black
| Section1 = {{Chembox Identifiers
|   KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C02496
| InChI = 1/C6H4N2O5/c9-6-2-1-4(7(10)11)3-5(6)8(12)13/h1-3,9H
| InChIKey = UFBJCMHMOXMLKC-UHFFFAOYAV
| SMILES1 = c1cc(c(cc1[N+](=O)[O-])[N+](=O)[O-])O
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 273386
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H4N2O5/c9-6-2-1-4(7(10)11)3-5(6)8(12)13/h1-3,9H
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UFBJCMHMOXMLKC-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
|   CASNo = 51-28-5
|   PubChem = 1493
|   UNNumber = [[List of UN Numbers 0001 to 0100|0076]], [[List of UN Numbers 1301 to 1400|1320]]
|   ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 42017
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| UNII = Q13SKS21MN
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| DrugBank = DB04528
| SMILES = O=[N+]([O-])c1cc(ccc1O)[N+]([O-])=O
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| ChemSpiderID = 1448
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| Section2 = {{Chembox Properties
|   Formula = C<sub>6</sub>H<sub>4</sub>N<sub>2</sub>O<sub>5</sub>
|   MolarMass = 184.106
|   Appearance =
|   Density = 1.683 g/cm3
|   MeltingPtC = 108
|   BoilingPtC = 113
|   Solubility =
|   pKa = 4.114
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| Section7 = {{Chembox Hazards
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|   FlashPt = 135 °C
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|  LD50 = 30mg·kg<sup>-1</sup>
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'''2,4-二硝基苯酚'''（{{lang-en|'''2,4-Dinitrophenol'''}}，簡(jiǎn)稱'''DNP'''），分子式C<sub>6</sub>H<sub>4</sub>N<sub>2</sub>O<sub>5</sub>，是一種[[細(xì)胞]][[代謝]][[毒素]]。DNP能夠通過運(yùn)送質(zhì)子通過[[線粒體]]膜使[[氧化磷酸化]][[解偶聯(lián)蛋白|解偶聯(lián)化]]，使得能量被大量消耗卻不被用來制造[[ATP]]。

二硝基酚這類[[化合物]]包含了六種人工合成的非天然有機(jī)物。

==化學(xué)性質(zhì)==

2,4-二硝基苯酚常[[溫下]]為黃色固態(tài)結(jié)晶，具有香甜的[[發(fā)霉]]氣味。緩慢加熱時(shí)升華，并有[[揮發(fā)性]]。DNP溶于[[乙酸乙酯]]、[[丙酮]]、[[氯仿]]、[[吡啶]]、[[四氯化碳]]、[[甲苯]]、[[乙醇]]、苯和堿的水溶液。<ref>Budavari, Susan(ed); O'Neil, Maryadele J(ed); Heckelman, Patricia E(red). "The merck index an encyclopedia of chemical, drugs, and biologicals / The merck index an encyclopedia of chemical, drugs, and biologicals." Rahway, NJ; [[默克藥廠]]; 1989. [1900] p. </ref> 它的鈉[[鹽溶]]于水。DNP與堿或氨反應(yīng)生成爆炸性的鹽；加熱DNP使其分解會(huì)產(chǎn)生有毒的[[氮氧化物]]。<ref>{{cite book |last=Sax |first=N.Irving |coauthors= Bruce, Robert D |title= Dangerous properties of industrial materials |publisher= [[約翰威立]] | edition = 7th |volume=3 |year= 1989 |isbn= 0-442-27368-1}}</ref> 它不與重金屬及重金屬鹽反應(yīng)。

==用途==

DNP目前主要用于科學(xué)研究和工業(yè)生產(chǎn)。DNP有時(shí)被用來制造染料，合成其他有機(jī)物，以及木材的[[防腐]]。它同時(shí)還被用作顯影劑、炸藥和[[殺蟲劑]]的中間體。

==[[藥理學(xué)]]==

在活[[體細(xì)胞]]中，DNP是一種{{link-en|離子載體|ionophore}}（即可以運(yùn)送質(zhì)子穿過生物膜）。它能夠消除線粒體和[[葉綠體]]的部分跨膜質(zhì)子濃度梯度，而由于質(zhì)子濃度梯度是絕大部分制造ATP的能量來源，這因而防礙了ATP的產(chǎn)生。這其中浪費(fèi)的大量能量隨即以熱量的方式散失。

DNP在[[生物化學(xué)]]研究上常被用來幫助探究[[化學(xué)滲透]]和其他{{link-en|膜輸送|Membrane transport}}的{{link-en|生物能量學(xué)|Bioenergetics}}原理。

==[[減肥]]用藥==

自從斯坦福大學(xué)的Cutting和Tainter發(fā)表他們第一份關(guān)于DNP能夠極大程度地增加代謝速率的報(bào)告之后，從1933年到1938年，這種藥物被人們廣泛用作[[減肥藥]]。<ref>{{cite journal| author = Cutting WC, Mehrtens HG, Tainter ML | title = Actions and uses of dinitrophenol: Promising metabolic applications | journal = [[美國(guó)醫(yī)學(xué)會(huì)雜志]] | year = 1933 | volume = 101 | pages =  193–195}}</ref><ref>{{cite journal| author = Tainter ML, Stockton AB, Cutting WC | title = Use of dinitrophenol in obesity and related conditions: a progress report | journal = [[美國(guó)醫(yī)學(xué)會(huì)雜志]] | year = 1933 | volume = 101 | pages =  1472–1475}}</ref> 僅僅當(dāng)DNP進(jìn)入市場(chǎng)一年之后，Tainter估計(jì)在美國(guó)已經(jīng)有至少大概10萬(wàn)人使用了該藥，而還不包括眾多的海外使用者。<ref>{{cite journal | doi = 10.2105/AJPH.24.10.1045 | author = Tainter ML, Cutting WC, Stockton AB | title = Use of Dinitrophenol in Nutritional Disorders : A Critical Survey of Clinical Results | journal = [[美國(guó)公共衛(wèi)生雜志]] | pmc = 1558869 | year = 1934 | volume = 24 | issue = 10 | pages =  1045–1053 | pmid=18014064}}</ref> DNP在人體內(nèi)是一種質(zhì)子載體，能夠使質(zhì)子進(jìn)入[[線粒體內(nèi)膜]]而跳過[[三磷酸腺苷合酶]]。 這使得ATP的合成效率變低——實(shí)際上，[[細(xì)胞呼吸]]產(chǎn)生的部分用來合成ATP的能量以熱量的形式散失了。ATP的合成效率與DNP的攝入量成反比，因此，隨著DNP用量的增加，細(xì)胞為了提供人體足夠能量與補(bǔ)充ATP，代謝速率也隨之大幅度增加，從而使得更多的[[脂肪]]被消耗。DNP或許是最著名的一種“[[解偶聯(lián)劑]]”，因?yàn)樗淖饔迷砭褪墙獬糠终[呼吸鏈]]中應(yīng)有的[[電子傳遞]]與[[磷酸化]]兩者之間[[偶聯(lián)]]關(guān)系，即氧化磷酸化的“[[解偶聯(lián)]]”。有趣的是，DNP用量的限制不是由于人體ATP的不足，而是因?yàn)榻馀悸?lián)過程中產(chǎn)生的大量熱量及隨之的[[體溫]]大幅度升高。因此，DNP的過量使用會(huì)導(dǎo)致致命的[[中暑]]。為了解決這個(gè)問題，醫(yī)生通常會(huì)建議減肥者根據(jù)個(gè)人藥物耐受度（不同人可能有十分大的區(qū)別）逐漸增加DNP用量。<ref>{{cite journal | author = Simkins S. | title = Dinitrophenol and desiccated thyroid in the treatment of obesity: a comprehensive clinical and laboratory study | journal = [[美國(guó)醫(yī)學(xué)會(huì)雜志]] | year = 1937 | volume = 108 | pages = 2110–2117}}</ref> 有案例報(bào)告對(duì)于人類20–50mg/kg的一次性用量可導(dǎo)致死亡。<ref name="pmid16035205">{{cite journal |author=Hsiao AL, Santucci KA, Seo-Mayer P, ''et al.'' |title=Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement" |journal=Clin Toxicol (Phila) |volume=43 |issue=4 |pages=281–285 |year=2005 |pmid=16035205 |doi= |url=}}</ref> 由于對(duì)許多危險(xiǎn)的[[副作用]]（除高體溫引起的[[抽搐]]、[[昏迷]]之外，還有迅速發(fā)展的[[白內(nèi)障]]癥狀）的擔(dān)憂，在1938年末，DNP被迫從美國(guó)市場(chǎng)上下架。然而DNP仍然被一些[[健美]]人士和運(yùn)動(dòng)員用來快速減少身體脂肪含量。過量導(dǎo)致的死亡比較罕見，不過有時(shí)還是有報(bào)告。這其中包括的案例有意外接觸、<ref name="pmid7058360">{{cite journal |author=Leftwich RB, Floro JF, Neal RA, Wood AJ |title=Dinitrophenol poisoning: a diagnosis to consider in undiagnosed fever |journal=South. Med. J. |volume=75 |issue=2 |pages=182–184 |year=1982 |month=February |pmid=7058360 |doi= 10.1097/00007611-198202000-00016|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0038-4348&volume=75&issue=2&spage=182}}</ref> 自殺<ref name="pmid16035205" /><ref name="GermanDeath">A. Hahn, K. Begemann, R. Burger, J. Hillebrand, H. Meyer, K. Preu?ner: "Cases of Poisoning Reported by Physicians in 2006", page 40. BfR Press and Public Relations Office, 2006.</ref><ref name="pmid20156878">{{cite journal |author=Bartlett J, Brunner M, Gough K |title=Deliberate poisoning with dinitrophenol (DNP): an unlicensed weight loss pill |journal=Emerg Med J |volume=27 |issue=2 |pages=159–160 |year=2010 |month=February |pmid=20156878 |doi=10.1136/emj.2008.069401 |url=}}</ref> 和普通減肥使用。<ref name="GermanDeath" /><ref name="pmid15487646">{{cite journal |author=McFee RB, Caraccio TR, McGuigan MA, Reynolds SA, Bellanger P |title=Dying to be thin: a dinitrophenol related fatality |journal=Veterinary and human toxicology |volume=46 |issue=5 |pages=251–254 |year=2004 |pmid=15487646 |doi = }}</ref><ref name="pmid16803658">{{cite journal |author=Miranda EJ, McIntyre IM, Parker DR, Gary RD, Logan BK |title=Two deaths attributed to the use of 2,4-dinitrophenol |journal=Journal of analytical toxicology |volume=30 |issue=3 |pages=219–222 |year=2006 |pmid=16803658 |doi = }}</ref>

目前科學(xué)家掌握的DNP的[[藥代動(dòng)力學(xué)]]數(shù)據(jù)仍然有限，并且一部分相互矛盾。美國(guó)國(guó)家環(huán)境保護(hù)局（EPA）的有關(guān)資料為“未能找到[[二硝基苯酚]]的代謝動(dòng)力學(xué)或代謝產(chǎn)物數(shù)據(jù)”。<ref>{{cite web | publisher = [[美國(guó)國(guó)家環(huán)境保護(hù)局]] | title = Ambient water quality criteria for nitrophenols, 440/5-80-063 | url = http://www.epa.gov/ost/pc/ambientwqc/nitrophenols80.pdf |format=PDF| year = 1980}}</ref> 美國(guó)[[毒物]]和疾病登記署（ATSDR）的資料為“沒有關(guān)于口服2,4-DNP后該物質(zhì)在人體內(nèi)的分布的研究；動(dòng)物口服后的資料則是有限的”。但是ATSDR也說明了“DNP的代謝速率似乎很快，除了在[[肝功能]]不足的情況下”。<ref>{{cite web | author = Harris, M. O., and Cocoran, J. J. | year = 1995 | title = Toxicological Profile for Dinitrophenols | publisher = [[美國(guó)毒物和疾病登記署]] | url =  http://www.atsdr.cdc.gov/toxprofiles/tp64.html}}</ref> 這一點(diǎn)和新英格蘭醫(yī)學(xué)雜志上有關(guān)2,4-二硝基苯酚生物活性的一篇論文相符合：這篇論文上說“從代謝過程上來說，DNP能在3至4日之內(nèi)被完全代謝；在肝或[[腎損傷]]的情況下該藥物則會(huì)在體內(nèi)停留更久”。<ref>{{cite journal | doi = 10.1056/NEJM193408302110901 | author = Edsall, G. | year = 1934 | title = Biological actions of dinitrophenol and related compounds: a review | journal = [[新英格蘭醫(yī)學(xué)雜志]] | volume = 211 | pages =  385–390 | issue = 9}}</ref> 奇怪的是，更新的一些研究卻給出了不同藥物半衰期——從3個(gè)小時(shí)<ref name="pmid16045446">{{cite journal |author=Korde AS, Pettigrew LC, Craddock SD, Maragos WF |title=The mitochondrial uncoupler 2,4-dinitrophenol attenuates tissue damage and improves mitochondrial homeostasis following transient focal cerebral ischemia |journal=J. Neurochem. |volume=94 |issue=6 |pages=1676–1684 |year=2005 |month=September |pmid=16045446 |doi=10.1111/j.1471-4159.2005.03328.x }}</ref> 到5–14天。<ref name="pmid16035205" /> 最近的一些其他研究則保持人體半衰期未知的觀點(diǎn)。<ref name="GermanDeath" />

有案例報(bào)告稱成功用{{link-en|丹曲林|dantrolene}}治愈二硝基酚引起的體溫過高，雖然這份報(bào)告仍需要進(jìn)一步調(diào)查。<ref>Kumar S, Barker K, Seger D. Dinitrophenol-Induced Hyperthermia Resolving With Dantrolene Administration. Abstracts of the North American Congress of Clinical Toxicology. Clin Toxicol 2002; 40:599–673.</ref> DNP解偶聯(lián)作用的時(shí)候會(huì)使得線粒體儲(chǔ)存的鈣被釋放出來并且阻止了鈣的[[重吸收]]。這會(huì)導(dǎo)致細(xì)胞內(nèi)自由鈣離子濃度升高，引起[[肌肉收縮]]和體溫升高。而[[丹曲林]]能夠阻止[[內(nèi)質(zhì)網(wǎng)|肌質(zhì)網(wǎng)]]釋放鈣離子從而降低細(xì)胞內(nèi)的鈣離子濃度，從而使[[肌肉]]放松，熱量釋放。因?yàn)榈で值母弊饔檬稚?，并且能夠某種程度上有效地減少解偶聯(lián)劑引起的體溫過高，所以盡早使用丹曲林可以取得更好的搶救效果。<ref name="pmid16749560">{{cite journal |author=Barker K, Seger D, Kumar S |title=Comment on "Pediatric fatality following ingestion of Dinitrophenol: postmortem identification of a 'dietary supplement'" |journal=Clin Toxicol (Phila) |volume=44 |issue=3 |pages=351 |year=2006 |pmid=16749560 |doi= 10.1080/15563650600584709|url=}}</ref>

盡管許多人覺得DNP對(duì)于人體來說太過于危險(xiǎn)，它本身的高效作用原理仍被認(rèn)為有待研究，以尋求潛在的治療[[肥胖癥]]的藥物。<ref name="pmid12119996">{{cite journal |author=Harper JA, Dickinson K, Brand MD |title=Mitochondrial uncoupling as a target for drug development for the treatment of obesity |journal=Obesity reviews : an official journal of the International Association for the Study of Obesity |volume=2 |issue=4 |pages=255–265 |year=2001 |pmid=12119996 |doi =10.1046/j.1467-789X.2001.00043.x }}</ref> 目前，有關(guān)研究主要關(guān)注于人體內(nèi)自然存在的[[解偶聯(lián)蛋白]]。

==環(huán)境[[毒性]]==

DNP被美國(guó)國(guó)家環(huán)境保護(hù)局認(rèn)為是一種較嚴(yán)重的環(huán)境污染物。它可以通過機(jī)動(dòng)車廢氣、工業(yè)垃圾燃燒以及空氣中氮?dú)夂推渌鸞[化學(xué)]]物質(zhì)反應(yīng)進(jìn)入大氣。

DNP主要在土壤中由微生物降解。然而，它對(duì)[[厭氧生物|厭氧]][[微生物]]的影響仍然未知；有研究指出DNP對(duì)這些微生物可能具有毒性，能夠減少它們產(chǎn)生甲烷的量。

==參考資料==

{{reflist|2}}

==擴(kuò)展閱讀==
* {{cite press release | publisher = Food Standards Agency | date = June 17, 2003 | url = http://www.food.gov.uk/news/pressreleases/2003/jun/fatburnpress | title = Food Standards Agency issues urgent advice on consumption of 'fat burner' capsules containing DNP | accessdate = 2007-09-30}}

==外部鏈接（英文）==
* {{Cite web | publisher =美國(guó)毒物和疾病登記署 | month = September | year = 1996 | url = http://www.atsdr.cdc.gov/tfacts64.html | title = 二硝基酚毒性FAQ | accessdate = 2005-07-17}}
* [http://www.scorecard.org/chemical-profiles/html/24dinitrophenol.html 2,4-二硝基苯酚的通用資料]

{{抗肥胖制劑}}

[[Category:撤回藥物]]

[[Category:抗肥胖藥]] [[Category:毒理學(xué)]] [[Category:硝基苯]] [[Category:酚]] [[Category:離子載體]] [[Category:毒物]]
==參考來源==
*[http://zh.wikipedia.org/wiki/2%2C4-%E4%BA%8C%E7%A1%9D%E5%9F%BA%E8%8B%AF%E9%85%9A 維基百科-2,4-二硝基苯酚]