A novel nano-electrospray emitter has been developed containing two separated channels running throughout the length of the emitter. The emitters have been fabricated from “theta-shaped” borosilicate capillaries. Loading of different solutions into the two different channels opens up the possibility to study short timescale interactions within a Taylor cone common to both channels. The common Taylor cone constitutes an extremely small “mixing volume” of the order of femtolitres. The products of electrospray from the dual-channel emitters have been analysed by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Results are presented for interactions of vancomycin with diacetyl-l-lysyl-d-alanyl-d-alanine and interactions of vancomycin with deuterated vancomycin. On the basis of these results, it is concluded that, during electrospray, specific non-covalent adducts have been formed and that there have been exchange reactions involving making and breaking of covalent bonds.
TangK.TolmachevA.V.NikolaevE.ZhangR.BelovM.E.UdsethH.R. and SmithR.D., “Independent control of ion transmission in a jet disrupter dual-channel ion funnel electrospray ionization MS interface”, Anal. Chem.74, 5431 (2002). doi: 10.1021/ac0202583
2.
BelovM.E.AndersonG.A.WingerdM.A.UdsethH.R.TangK.PriorD.C.SwansonK.R.BuschbachM.A.StrittmatterE.F.MooreR.J. and SmithR.D., “An automated high performance capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometer for high-throughput proteomics”, J. Am. Soc. Mass Spectrom.15, 212 (2004). doi: 10.1016/j.jasms.2003.09.008
3.
KellyR.T.TolmachevA.V.PageJ.S.TangK. and SmithR.D., “The ion funnel: Theory, implementations, and applications”, Mass Spectrom. Rev.29, 294 (2010). doi: 10.1002/mas.20232
4.
ShafferS.A.TolmachevA.PriorD.C.AndersonG.A.UdsethH.R. and SmithR.D., “Characterization of an improved electrodynamic ion funnel interface for electro spray ionization mass spectrometry”, Anal. Chem.71, 2957 (1999). doi: 10.1021/ac990346w
5.
DerrickP.J.ColburnA.W. and GiannakopulosA., “An ion focussing and conveying device and a method of focussing and conveying ions”, UK Patents 2373630, 2408384 and 2408385, Priority date 23-11-2000.
6.
ColburnA. W.GiannakopulosA. E. and DerrickP. J., “The ion conveyor. An ion focussing and conveying device”, Eur. J. Mass Spectrom.10, 149 (2004). doi: 10.1255/ejms.630
7.
FloraJ.W.NullA.P. and MuddimanD.C., “Dual-micro-ESI source for precise mass determination on a quadrupole time-of-flight mass spectrometer for genomic and proteomic applications”, Anal. Bioanal. Chem.373, 538 (2002). doi: 10.1007/s00216-002-1357-0
8.
ErbW.J. and OwensK.G., “Development of a dual-spray electrospray deposition system for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry”, Rapid Commun. Mass Spectrom.22, 1168 (2008). doi: 10.1002/rcm.3492
9.
DandavinoS.AtamanC.SheaH.RyanC. and StarkJ., “Microfabrication of capillary electrospray emitters and ToF characterization of the emitted beam,” in Proceedings of The 32nd International Electric Propulsion Conference, Wiesbaden, Germany, September 11–15, (2011).
10.
BonvinG.VeutheyJ-L.RudazS. and SchapplerJ., “Evaluation of a sheathless nanospray interface based on a porous tip sprayer for CE-ESI-MS coupling”, Electrophoresis33, 552 (2012). doi: 10.1002/elps.201100461
11.
SikanenT.FranssilaS.KauppilaT.J.KostiainenR.KotiahoT. and KetolaR.A., “Microchip technology in mass spectrometry”, Mass Spectrom. Rev.29, 351 (2010). doi: 10.1002/mas.20238
12.
ChenC. and HahnJ.H., “Dual-channel method for interference-free in-channel amperometric detection in microchip capillary electrophoresis”, Anal. Chem.79, 7182 (2007). doi: 10.1021/ac070721h
13.
YangL.ZhuS.HangW.WuL. and YanX., “Development of an ultrasensitive dual-channel flow cytometer for the individual analysis of nanosized particles and biomolecules”, Anal. Chem.81, 2555 (2009). doi: 10.1021/ac802464a
14.
LeeC. and ShieaJ., “Gas chromatography connected to multiple channel electrospray ionization mass spectrometry for the detection of volatile organic compounds”, Anal. Chem.70, 2757 (1998). doi: 10.1021/ac971325+
15.
ChangD-Y.LeeC-C. and ShieaJ., “Detecting large biomolecules from high-salt solutions by fused-droplet electrospray ionization mass spectrometry”, Anal. Chem.74, 2465 (2002). doi: 10.1021/ac010788j
16.
ShieaJ.ChangD.LinC. and JiangS., “Generating multiply charged protein ions by ultrasonic nebulization/multiple channel-electrospray ionization mass spectrometry”, Anal. Chem.73, 4983 (2001). doi: 10.1021/ac0101609
17.
ShiehI.LeeC. and ShieaJ., “Eliminating the interferences from TRIS buffer and SDS in protein analysis by fused-droplet electrospray ionization mass spectrometry”, J. Protein Res.4, 606 (2005). doi: 10.1021/pr049765m
18.
ChenH.VenterA. and CooksR.G., “Extractive electrospray ionization for direct analysis of undiluted urine, milk and other complex mixtures without sample preparation”, Chem. Commun.2042 (2006). doi: 10.1039/b602614a
19.
LawW.S.ChenH.W.DingJ.H.YangS.P.ZhuL.GomezG.ChinginK.RenY.L. and ZenobiR., “Rapid characterization of complex viscous liquids at the molecular level”, Angew. Chem. Int. Ed.48, 8277 (2009). doi: 10.1002/anie.200902360
20.
PengI.X.LooOgorzalek R.R.MargalithE.LittleM.W. and LooJ.A., “Electrospray-assisted laser desorption ionization mass spectrometry (ELDI-MS) with an infrared laser for characterising peptides and proteins”, Analyst135, 769 (2010). doi: 10.1039/b923303b
21.
SampsonJ.S.HawkridgeA.M. and MuddimanD.C., “Generation and detection of multiply-charged peptides and proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) Fourier transform ion cyclotron resonance mass spectrometry”, J. Am. Soc. Mass Spectrom.17, 1712 (2006). doi: 10.1016/j.jasms.2006.08.003
22.
MeierL.BerchtoldC.SchmidS. and ZenobiR., “Extractive electrospray ionization mass spectrometry-enhanced sensitivity using an ion funnel”, Anal. Chem.84, 2076 (2012). doi: 10.1021/ac203022x
23.
MeestersG.M.H.VercoulenP.H.W.MarijnissenJ.C.M. and ScarlettB., “Generation of micron-sized droplets from the Taylor cone”, J. Aerosol Sci.23, 37 (1992). doi: 10.1016/0021-8502(92)90316-N
24.
de la MoraFernandez J., “The fluid dynamics of Taylor cones”, Annu. Rev. Fluid Mechanics39, 217 (2007). doi: 10.1146/annurev.fluid.39.050905.110159
25.
TaylorG.I., “Disintegration of water drops in an electric field”, Proc. Roy. Soc.A280, 383 (1964).
26.
LeutholdL.A.ReymondF.RossierJ.S.VaresisE. and HopfgartnerG., “Multi-track single- and dual-channel plastic microchips for electrospray mass spectrometry”, Eur. J. Mass Spectrom.16, 47 (2010). doi: 10.1255/ejms.1043
FennJ.B.MannM.MengC.K.WongS.F. and WhitehouseC.M., “Electrospray ionization for mass spectrometry of large biomolecules”, Science246, 64 (1989). doi: 10.1126/science.2675315
29.
SobottF. and RobinsonC.V., “Protein complexes gain momentum”, Curr. Opin. Struct. Biol.12, 729 (2002). doi: 10.1016/S0959–440X(02)00400–1
30.
HillT.J.LafitteD.WallaceJ.I.CooperH.J.TsvetkovP.O. and DerrickP.J., “Calmodulin-peptide interactions: Apocalmodulin binding to the myosin light chain kinase target-site”Biochemistry39, 7284 (2000). doi: 10.1021/bi000139m
31.
SharonM. and RobinsonC.V., “The role of mass spectrometry in structure elucidation of dynamic protein complexes”, Annu. Rev. Biochem.76, 167 (2007). doi: 10.1146/annurev.biochem.76.061005.090816
32.
MorozO.V.BurkittW.WittkowskiH.HeW.IanoulA.NovitskayaV.XieJ.PolyakovaO.LednevI.K.ShekhtmanA.DerrickP.J.BjoerkP.FoellD. and BronsteinI.B., “Both Ca2+ and Zn2+ are essential for S100A12 protein-oligomerization and function”, BMC Biochem.10, 1471 (2009). doi: 10.1186/1471-2091-10-11
33.
HernándezH. and RobinsonC.V., “Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry”, Nature Protocols2, 715 (2007). doi: 10.1038/nprot.2007.73
34.
LorenzenK.VanniniA.CramerP. and HeckA.J.R., “Structural biology of RNA polymerase III: Mass spectrometry elucidates subcomplex architecture”, Structure15, 1237 (2007). doi: 10.1016/j.str.2007.07.016
35.
DoleM.MackL.L.HinesR.L.MobleyR.C.FergusonL.D. and AliceM.B., “Molecular beams of macroions”, J. Chem. Phys.49, 2240 (1968). doi: 10.1063/1.1670391
36.
Schmelzeisen-ResekerG.BütferingL. and RöllgenF.W., “Desolvation of ions and molecules in thermospray mass spectrometry”, Int. J. Mass Spectrom. Ion Proc.90, 139 (1989). doi: 10.1016/0168-1176(89)85004–9
37.
KebarleP. and TangL., “From ions in solution to ions in the gas phase”, Anal. Chem.65, 972A (1993).
38.
ThomsonB.A. and IribarneJ.V., “Field induced ion evaporation from liquid surfaces at atmospheric pressure”, J. Chem. Phys.71, 4451 (1979). doi: 10.1063/1.438198
39.
DavisS.C.NatoliV.NeumannG.M. and DerrickP.J., “A model of ion evaporation tested through field desorption experiments on glucose mixed with alkali metal salts”, Int. J. Mass Spectrom. Ion Proc.78, 17 (1987). doi: 10.1016/0168-1176(87)87039–8
40.
GillM., “A dual-channelled nano-electrospray source for mass spectrometry”, M. Chem. Project Report, Department of Chemistry, University of Warwick, (2005).
41.
ZampronioC.G.GiannakopulosA.E.ZellerM.BitziouE.MacphersonJ.V. and DerrickP.J., “Production and properties of nanoelectrospray emitters used in Fourier transform ion cyclotron resonance mass spectrometry: Implications for determination of association constants for noncovalent complexes”, Anal. Chem.76, 5172 (2004). doi: 10.1021/ac049569z
42.
WilmM. and MannM., “Analytical properties of the nanoelectrospray ion source”, Anal. Chem.68, 1 (1996). doi: 10.1021/ac9509519
43.
SchmidtA.KarasM. and DülcksT.J., “Effect of different solution flow rates on analyte ion signals in nano-ESI MS, or: When does ESI turn into nano-ESI?”, J. Am. Soc. Mass Spectrom.14, 492 (2003). doi: 10.1016/S1044–0305(03)00128–4
44.
RobT. and WilsonD.J., “A versatile microfluidic chip for millisecond time-scale kinetic studies by electrospray mass spectrometry”, J. Am. Soc. Mass Spectrum.1, 124 (2009). doi: 10.1016/j.jasms.2008.09.005
45.
WilsonD.J. and KonermanL.A., “Analytical properties of the nanoelectrospray ion source”, Anal. Chem.75, 6408 (2003). doi: 10.1021/ac0346757
46.
HeckA.J.R.JorgensenT.D.O'SullivanM.von RaumerM. and DerrickP.J., “Gas-phase noncovalent interactions between vancomycin-group antibiotics and bacterial cell-wall precursor peptides probed by hydrogen/deuterium exchange”, J. Am. Soc. Mass Spectrom.9, 1255 (1998). doi: 10.1016/S1044–0305(98)00110-X
47.
GaleE.F.CundliffeE.ReynoldsP.RichmondM.H. and WaringM.J., The Molecular Basis of Antibiotic Action2nd Edn.Wiley-Interscience, New York, USA (1981).
48.
KannanR.HarrisC.M.HarrisT.M.WalthoJ.P.SkeltonN.J. and WilliamsD.H., “Function of the amino sugar and N-terminal amino acid of the antibiotic vancomycin in its complexation with cell wall peptides”, J. Am. Chem. Soc.110, 2946 (1988). doi: 10.1021/ja00217a042
49.
CohenM.L., “Epidemiology of drug resistance: Implications for a post-antimicrobial ear”, Science257, 1050 (1992). doi: 10.1126/science.257.5073.1050
50.
NietoM. and PerkinsH.R., “Physicochemical properties of vancomycin and iodovancomycin and their complexes with diacetyl-L-lysyl-D-alanyl-D-alanine”, Biochem. J.123, 773 (1971). doi: 10.1021/ja00189a017
51.
WalthoJ.P. and WilliamsD.H., “Aspects of molecular recognition: Solvent exclusion and dimerization of the antibiotic ristocetin when bound to a model bacterial cell-wall precursor”, J. Am. Chem. Soc.111, 2475 (1989). doi: 10.1021/ja00189a017
52.
BattaG.SztaricskaiF.KoverK.E.RuedelC. and BerdnikovaT.F., “An NMR study of eremomycin and its derivatives. Full 1H and 13C assignment, motional behavior, dimerization and complexation with Ac-D-Ala-D-Ala”, J. Antibiotics44, 1208 (1991). doi: 10.7164/antibiotics.44.1208
53.
MackayJ.P.GerhardU.BeauregardD.A.WilliamsD.H.WestwellM.S. and SearleM.S., “Glycopeptide antibiotic activity and the possible role of dimerization: A model for biological signaling”, J. Am. Chem. Soc.116, 4581 (1994). doi: 10.1021/ja00090a006
54.
MarkL., “Carbon nanotubes and other highly curved surfaces for field emission and field-pronated ionisation”, PhD Thesis, University of Warwick (2009).
55.
MacphersonJ.V. and UnwinP.R., “Radial flow microring electrode: Development and characterization”, Anal. Chem.70, 2914 (1998). doi: 10.1021/ac9801667
56.
PalmbladM.HåkanssonK.HåkanssonP.FengX.CooperH.J.GianakopulosA.E.GreenP.S. and DerrickP.J., “A 9.4 T Fourier transform ion cyclotron resonance mass spectrometer: Description and performance”, Eur. J. Mass Spectrum.6, 267 (2000). doi: 10.1255/ejms.348
57.
MarshallA.G.HendricksonC.L. and JacksonG.S., “Fourier transform ion cyclotron resonance mass spectrometry: A primer”, Mass Spectrom. Rev.17, 1 (1998). doi: 10.1002/(SICI)1098–2787(1998)17:1<1::AID-MAS1>3.0.CO;2-K
