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'''Electron-capture dissociation (ECD)''' is a method of [[Fragmentation (mass spectrometry)|fragmenting]] gas phase ions for tandem mass spectrometric analysis (structural elucidation). ECD involves the direct introduction of low energy electrons to trapped gas phase ions.<ref>{{cite journal |author=Zubarev RA, Kelleher NL, McLafferty FW |title=Electron capture dissociation of multiply charged protein cations. A nonergodic process |journal=J. Am. Chem. Soc. |volume=120 | issue=13 |year=1998 |pages=3265–66 |doi=10.1021/ja973478k}}</ref><ref name=McLafferty2001>{{Cite journal | last = McLafferty | first =  F. | year = 2001 | title = Electron capture dissociation of gaseous multiply charged ions by fourier-transform ion cyclotron resonance | journal = Journal of the American Society for Mass Spectrometry | volume = 12 | pages = 245 | doi = 10.1016/S1044-0305(00)00223-3 | pmid = 11281599 | last2 = Horn | first2 = D.M. | last3 = Breuker | first3 = K. | last4 = Ge | first4 = Y. | last5 = Lewis | first5 = M.A. | last6 = Cerda | first6 = B. | last7 = Zubarev | first7 = R.A. | last8 = Carpenter | first8 = B.K. | issue = 3 }}</ref> It was developed by [[Roman Zubarev]] and [[Neil Kelleher (scientist)|Neil Kelleher]] while in [[Fred McLafferty]]'s lab at [[Cornell University]].
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== Principles ==
Electron-capture dissociation typically involves a multiply protonated molecule ''M'' interacting with a free electron to form an odd-electron ion
 
:<math>[M + nH]^{n+} + e^- \to \bigg[ [M + nH]^{(n-1)+} \bigg]^* \to fragments</math>.
 
Liberation of the [[electric potential energy]] results in fragmentation of the product ion.
 
ECD produces significantly different types of fragment ions (although primarily c- and z-type, b-ions have been identified in ECD<ref> Liu and Hakansson, JASMS 18:2007-2013, 2007; Haselmann and Schmidt, RCM 21:1003-1008, 2007; Cooper JASMS 16:1932-1940, 2005 </ref>) than other MS/MS fragmentation methods such as [[electron-detachment dissociation|electron-detachment dissociation (EDD)]] (primarily a and x type),<ref name="pmid16331920">{{cite journal |author=Anusiewicz I, Jasionowski M, Skurski P, Simons J |title=Backbone and side-chain cleavages in electron detachment dissociation (EDD) |journal=[[J Phys Chem A]] |volume=109 |issue=49 |pages=11332–7 |date=December 2005 |pmid=16331920 |doi=10.1021/jp055018g |url=}}</ref><ref name="pmid19802340">{{cite journal |author=Leach FE, Wolff JJ, Laremore TN, Linhardt RJ, Amster IJ |title=EVALUATION OF THE EXPERIMENTAL PARAMETERS WHICH CONTROL ELECTRON DETACHMENT DISSOCIATION, AND THEIR EFFECT ON THE FRAGMENTATION EFFICIENCY OF GLYCOSAMINOGLYCAN CARBOHYDRATES |journal=[[Int J Mass Spectrom]] |volume=276 |issue=2-3 |pages=110–115 |date=October 2008 |pmid=19802340 |pmc=2633944 |doi=10.1016/j.ijms.2008.05.017 |url=|bibcode = 2008IJMSp.276..110L }}</ref><ref name="pmid15672435">{{cite journal |author=Kjeldsen F, Silivra OA, Ivonin IA, Haselmann KF, Gorshkov M, Zubarev RA |title=C alpha-C backbone fragmentation dominates in electron detachment dissociation of gas-phase polypeptide polyanions |journal=[[Chemistry]] |volume=11 |issue=6 |pages=1803–12 |date=March 2005 |pmid=15672435 |doi=10.1002/chem.200400806 |url=http://www.bmms.uu.se/pubs/article030.pdf}}</ref><ref name="pmid15862776">{{cite journal |author=McFarland MA, Marshall AG, Hendrickson CL, Nilsson CL, Fredman P, Månsson JE |title=Structural characterization of the GM1 ganglioside by infrared multiphoton dissociation, electron capture dissociation, and electron detachment dissociation electrospray ionization FT-ICR MS/MS |journal=[[J. Am. Soc. Mass Spectrom.]] |volume=16 |issue=5 |pages=752–62 |date=May 2005 |pmid=15862776 |doi=10.1016/j.jasms.2005.02.001 |url=}}</ref><ref name="pmid18499037">{{cite journal |author=Wolff JJ, Laremore TN, Busch AM, Linhardt RJ, Amster IJ |title=Influence of charge state and sodium cationization on the electron detachment dissociation and infrared multiphoton dissociation of glycosaminoglycan oligosaccharides |journal=[[J. Am. Soc. Mass Spectrom.]] |volume=19 |issue=6 |pages=790–8 |date=June 2008 |pmid=18499037 |pmc=2467392 |doi=10.1016/j.jasms.2008.03.010 |url=}}</ref>  [[collision-induced dissociation]] (CID) (primarily b<ref name="pmid19338048">{{cite journal |author=Harrison AG |title=To b or not to b: the ongoing saga of peptide b ions |journal=[[Mass Spectrom Rev]] |volume=28 |issue=4 |pages=640–54 |year=2009 |pmid=19338048 |doi=10.1002/mas.20228 |url=}}</ref> and y type) and [[infrared multiphoton dissociation]]. CID and IRMPD introduce internal vibrational energy in some way or another, causing loss of post-translational modifications during fragmentation.  In ECD (and in EDD as well), fragments retain post-translational modifications such as phosphorylation<ref> Creese & Cooper, JASMS 19:1263-1274, 2008 </ref><ref> Shi et al., Anal. Chem., 73:19-22, 2001 </ref><ref> Woodling et al., JASMS 18:2137-2145, 2007 </ref> and O-glycosylation.<ref> Mirgorodskaya et al., Anal. Chem. 71:4431-4436, 1999 </ref><ref>Renfrow et al., JBC 280:19136-19145, 2005 </ref> In ECD, unique fragments (and complementary to CID) are observed<ref> Creese & Cooper JASMS 18:891-897, 2007 </ref> and the ability to fragment whole macromolecules effectively has been promising. The low fragmentation efficiencies and other experimental difficulties, which are being studied,<ref> Gorshkov et al., IJMS 234:131-136, 2004 </ref> have prevented widespread use. Although ECD is primarily used in [[Fourier transform ion cyclotron resonance]] mass spectrometry,<ref name="pmid15389856">{{cite journal |author=Cooper HJ, Håkansson K, Marshall AG |title=The role of electron capture dissociation in biomolecular analysis |journal=Mass spectrometry reviews |volume=24 |issue=2 |pages=201–22 |year=2005 |pmid=15389856 |doi=10.1002/mas.20014}}</ref> investigators have indicated that it has been successfully used in an [[quadrupole ion trap|ion trap mass spectrometer]].<ref> Baba et al., Anal. Chem., 76:4263-4266, 2004</ref><ref>Ding & Brancia, Anal. Chem. 78:1995-2000, 2006</ref><ref>Deguchi et al., Rapid Communications in Mass Spectrometry 21: 691-698, 2007 </ref>
 
ECD is a recently introduced MS/MS fragmentation technique and is still being investigated.<ref>{{cite journal |author=Syrstad EA, Turecek F |title=Toward a general mechanism of electron capture dissociation |journal=J. Am. Soc. Mass Spectrom. |volume=16 |issue=2 |pages=208–24 |year=2005 |pmid=15694771 |doi=10.1016/j.jasms.2004.11.001}}</ref><ref>{{cite journal |author=Savitski MM, Kjeldsen F, Nielsen ML, Zubarev RA |title=Complementary sequence preferences of electron-capture dissociation and vibrational excitation in fragmentation of polypeptide polycations |journal=Angew. Chem. Int. Ed. Engl. |volume=45 |issue=32 |pages=5301–3 |year=2006 |pmid=16847865 |doi=10.1002/anie.200601240}}</ref> The mechanism of ECD is still under debate but appears not to necessarily break the weakest bond and is therefore thought to be a fast process ([[Ergodic hypothesis|nonergodic]]) where energy is not free to relax intramolecularly. Suggestions have been made that radical reactions initiated by the electron may be responsible for the action of ECD.<ref>{{cite journal |author=Leymarie N, Costello CE, OConnor PB |title=Electron Capture Dissociation Initiates a Free Radical Reaction Cascade |journal=J. Am. Chem. Soc. |volume=125 |issue=29 |pages=8949–8958 |year=2003 |pmid=12862492 |doi=10.1021/ja028831n |url=http://0-pubs.acs.org.pugwash.lib.warwick.ac.uk/doi/abs/10.1021/ja028831n}}</ref>
 
In a similar MS/MS fragmentation technique called [[electron-transfer dissociation]] the electrons are transferred by collision between the analyte cations and reagent anions.<ref> Coon et al., JASMS 16:880-882, 2005</ref><ref>Zubarev et al., ''JASMS'' 19:753-761, 2008</ref><ref>Hamidane et al., JASMS 20:567-575, 2009 </ref><ref name="pmid16794768">{{cite journal |author=Bakhtiar R, Guan Z |title=Electron capture dissociation mass spectrometry in characterization of peptides and proteins |journal=Biotechnol. Lett. |volume=28 |issue=14 |pages=1047–59 |date=July 2006 |pmid=16794768 |doi=10.1007/s10529-006-9065-z |url=}}</ref>
 
== See also ==
* [[Electron capture ionization]]
* [[electron–capture mass spectrometry]]
* [[RRKM theory]]
 
== References ==
{{Reflist}}
 
{{Mass spectrometry}}
 
[[Category:Mass spectrometry fragmentation methods]]

Revision as of 04:36, 21 February 2014

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