Design of Experiment (DoE) as a Tool for the Optimization of Source Conditions in SEC-ESI-MS of Functional Synthetic Polymers Synthesized via ATRP.

Design of experiment (DoE) is applied to establish the optimum ionization conditions for analyzing synthetic polymers via coupled size exclusion chromatography electrospray ionization mass spectrometry (SEC-ESI-MS) yielding maximum ionization efficiency. The ion source conditions were optimized with regard to the ionization efficiency, the amount of fragmentation, as well as the formation of salt adducts. A D-optimal experimental design was employed for this purpose and the recorded data were evaluated by a quadratic response surface model, accounting for possible interactions between the individual source settings. It was established that the ionization efficiency can be improved by up to one order of magnitude without compromising the softness of the ionization process and that optimal ionization conditions are found at similar source settings regardless of the charge state. The present optimization exercise therefore provides a hands-on guide for the use of experimental design to determine optimum ionization conditions during the SEC-ESI-MS of functional polymers.

[1]  C. Wesdemiotis,et al.  Tandem mass spectrometry characteristics of silver-cationized polystyrenes: backbone degradation via free radical chemistry. , 2008, Analytical chemistry.

[2]  J. Scrivens,et al.  Characterisation of synthetic polymer systems , 2000 .

[3]  Ian M. Priestnall,et al.  Molecular spectroscopic characterisation of poly(methyl methacrylate) generated by means of atom transfer radical polymerisation (ATRP) , 2006 .

[4]  T. Koal,et al.  On the signal response of various pesticides in electrospray and atmospheric pressure chemical ionization depending on the flow-rate of eluent applied in liquid chromatography-tandem mass spectrometry. , 2001, Journal of chromatography. A.

[5]  O. Vitek,et al.  Statistical design of experiments as a tool in mass spectrometry. , 2005, Journal of mass spectrometry : JMS.

[6]  C. Barner‐Kowollik,et al.  Quantitative LC-MS of polymers: determining accurate molecular weight distributions by combined size exclusion chromatography and electrospray mass spectrometry with maximum entropy data processing. , 2008, Analytical chemistry.

[7]  Sébastien Perrier,et al.  Macromolecular design via réversible addition-fragmentation chain transfer (RAFT)/Xanthates (MADIX) polymerization , 2005 .

[8]  R. Cole,et al.  Some tenets pertaining to electrospray ionization mass spectrometry. , 2000, Journal of mass spectrometry : JMS.

[9]  Su Chen,et al.  Controllable synthesis of quantum dot–polymer networks with enhanced luminescence via the catalytic chain transfer polymerization (CCTP) technique , 2008 .

[10]  S. Weidner,et al.  Mass spectrometry of synthetic polymers. , 2008, Analytical chemistry.

[11]  Thomas P. Davis,et al.  Complex Macromolecular Architectures by Reversible Addition Fragmentation Chain Transfer Chemistry: Theory and Practice , 2007 .

[12]  C. Barner‐Kowollik,et al.  Probing mechanistic features of conventional, catalytic and living free radical polymerizations using soft ionization mass spectrometric techniques , 2004 .

[13]  J. Langridge,et al.  A novel precursor ion discovery method on a hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer for studying protein phosphorylation , 2002, Journal of the American Society for Mass Spectrometry.

[14]  P. Derrick,et al.  Probing the effects of cone potential in the electrospray ion source:  consequences for the determination of molecular weight distributions of synthetic polymers. , 1998, Analytical chemistry.

[15]  Christopher Barner-Kowollik,et al.  Handbook of RAFT polymerization , 2008 .

[16]  E. Harth,et al.  New polymer synthesis by nitroxide mediated living radical polymerizations. , 2001, Chemical reviews.

[17]  C. Barner‐Kowollik,et al.  Enhanced Ionization in Electrospray Ionization Mass Spectrometry of Labile End-Group-Containing Polystyrenes Using Silver(I) Tetrafluoroborate as Doping Salt , 2008 .

[18]  P. Kubisa,et al.  Studies of atom transfer radical polymerization (ATRP) of acrylates by MALDI TOF mass spectrometry , 2000 .

[19]  E. Williams,et al.  Supercharging in electrospray ionization: effects on signal and charge , 2002 .

[20]  Philipp Vana,et al.  Initiation of radical polymerization by peroxyacetates: Polymer end‐group analysis by electrospray ionization mass spectrometry , 2007 .

[21]  P. Dantigny,et al.  Application of Doehlert design to determine the combined effects of temperature, water activity and pH on conidial germination of Penicillium chrysogenum , 2001, Journal of applied microbiology.

[22]  Xulin Jiang,et al.  Mass spectrometric characterization of functional poly(methyl methacrylate) in combination with critical liquid chromatography. , 2003, Analytical chemistry.

[23]  U. Schubert,et al.  Statistical approach to understand MALDI-TOFMS matrices: discovery and evaluation of new MALDI matrices. , 2007, Analytical chemistry.

[24]  C. Barner‐Kowollik,et al.  Living Star Polymer Formation: Detailed Assessment of Poly(acrylate) Radical Reaction Pathways via ESI-MS , 2008 .

[25]  Philipp Vana,et al.  Electrospray ionization mass spectrometric end-group analysis of PMMA produced by radical polymerization using diacyl peroxide initiators , 2007 .

[26]  Koichi Tanaka,et al.  The origin of macromolecule ionization by laser irradiation (Nobel lecture). , 2003, Angewandte Chemie.

[27]  Tara M Lovestead,et al.  Mapping photolysis product radical reactivities via soft ionization mass spectrometry in acrylate, methacrylate, and itaconate systems , 2007 .

[28]  L. Prokai,et al.  Gel permeation chromatography coupled to fourier transform mass spectrometry for polymer characterization. , 1999, Analytical chemistry.

[29]  M. Stenzel.  RAFT polymerization: an avenue to functional polymeric micelles for drug delivery. , 2008, Chemical communications.

[30]  B. Gunter,et al.  Development of generic liquid chromatography-mass spectrometry methods using experimental design , 2002, Journal of the American Society for Mass Spectrometry.

[31]  S. Cherkaoui,et al.  Experimental designs to investigate capillary electrophoresis‐electrospray ionization‐mass spectrometry enantioseparation with the partial‐filling technique , 2001, Electrophoresis.

[32]  C. McEwen,et al.  Mass spectrometry of synthetic polymers. , 2004, Analytical chemistry.

[33]  W. Shou,et al.  Importance of injection solution composition for LC-MS-MS methods. , 2001, Journal of pharmaceutical and biomedical analysis.

[34]  K. Matyjaszewski,et al.  Atom transfer radical polymerization. , 2001, Chemical reviews.

[35]  D. Hercules,et al.  Polymer characterization by combining liquid chromatography with MALDI and ESI mass spectrometry , 2002, Analytical and bioanalytical chemistry.

[36]  R. Kumar,et al.  Application of Doehlert design in optimizing the determination of degraded products of nerve agents by ion-pair liquid chromatography electrospray ionization tandem mass spectrometry. , 2007, Journal of chromatography. A.

[37]  D. Irvine,et al.  Evidence for the low thermal stability of poly(methyl methacrylate) polymer produced by atom transfer radical polymerisation , 2000 .