Electrospray ionization (ESI) has been an indispensable ion generation technique for mass spectrometric analysis of biopolymers such as intact proteins and protein digests operated at atmospheric pressure. Since its advent in 1998, atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) quickly became a popular alternative for the analysis of peptides. While AP-MALDI sources typically share the same vacuum interface and ion transmission hardware with ESI, it is generally found that ESI is superior in detection sensitivity. In this thesis, we describe a home-built AP-MALDI source coupled to a commercial 7.0 Tesla Fourier Transform Ion cyclotron Resonance Mass Spectrometer (FT ICR MS). A method based on solid-phase extraction and elution with surface-functionalized diamond nanocrystals, which we referred to as “SPEED” that not only streamlines AP-MALDI mass spectrometric analyses of peptides and other small biomolecules under typical operational conditions, but also outruns ESI in ultimate detectable concentration by at least one order of magnitude.
The application of home built AP-MALDI source coupled with FTICR-MS was used for the Collision-induced fragmentation study of L-arginine (Arg), ω-NG-monomethylarginine (MMA), ω-NG,NG-asymmetric dimethylarginine (aDMA) and ω-NG,NG’-symmetric dimethylarginine (sDMA). Admixing of nitrocellulose with the matrix reduces significantly the interfering matrix peaks in the resulting mass spectra. Tandem mass spectrometric (MS2 and MS3) methods could easily distinguish the isobaric molecules aDMA, sDMA and other intrinsic interfering molecules originating from a biological matrix. Among a total of 44 fragment ions generated from the two isomeric DMAs, 5 were uniquely produced exclusively from just one of them that allowed their differentiation. The unsurpassed advantage of high resolution and mass accuracy of FTICR MS enabled us to identify fragmentation channels that yield fragment ions differing in mass by only ~0.01 Da. The sub-ppm mass accuracies facilitated proposing chemical structures for all the fragments observed. Many hereto unreported isobaric fragments from the methylated arginines were identified for the first time.
Application of tandem mass method of distinguishing these isobaric molecules was demonstrated with human urine. Protocols were developed with commercially available solid phase extraction (SPE) products for extracting arginines and its methylated derivatives from urine samples. Without any derivatization, selected pairs of MS/MS fragment intensities were used for quantitating the relative abundances of these molecules in the urine samples. The urinary aDMA to sDMA ratio in healthy individuals was found to be 0.82 +/- 0.17, in good agreement with most reported results.

Electrospray ionization (ESI) has been an indispensable ion generation technique for mass spectrometric analysis of biopolymers such as intact proteins and protein digests operated at atmospheric pressure. Since its advent in 1998, atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) quickly became a popular alternative for the analysis of peptides. While AP-MALDI sources typically share the same vacuum interface and ion transmission hardware with ESI, it is generally found that ESI is superior in detection sensitivity. In this thesis, we describe a home-built AP-MALDI source coupled to a commercial 7.0 Tesla Fourier Transform Ion cyclotron Resonance Mass Spectrometer (FT ICR MS). A method based on solid-phase extraction and elution with surface-functionalized diamond nanocrystals, which we referred to as “SPEED” that not only streamlines AP-MALDI mass spectrometric analyses of peptides and other small biomolecules under typical operational conditions, but also outruns ESI in ultimate detectable concentration by at least one order of magnitude.
The application of home built AP-MALDI source coupled with FTICR-MS was used for the Collision-induced fragmentation study of L-arginine (Arg), ω-NG-monomethylarginine (MMA), ω-NG,NG-asymmetric dimethylarginine (aDMA) and ω-NG,NG’-symmetric dimethylarginine (sDMA). Admixing of nitrocellulose with the matrix reduces significantly the interfering matrix peaks in the resulting mass spectra. Tandem mass spectrometric (MS2 and MS3) methods could easily distinguish the isobaric molecules aDMA, sDMA and other intrinsic interfering molecules originating from a biological matrix. Among a total of 44 fragment ions generated from the two isomeric DMAs, 5 were uniquely produced exclusively from just one of them that allowed their differentiation. The unsurpassed advantage of high resolution and mass accuracy of FTICR MS enabled us to identify fragmentation channels that yield fragment ions differing in mass by only ~0.01 Da. The sub-ppm mass accuracies facilitated proposing chemical structures for all the fragments observed. Many hereto unreported isobaric fragments from the methylated arginines were identified for the first time.
Application of tandem mass method of distinguishing these isobaric molecules was demonstrated with human urine. Protocols were developed with commercially available solid phase extraction (SPE) products for extracting arginines and its methylated derivatives from urine samples. Without any derivatization, selected pairs of MS/MS fragment intensities were used for quantitating the relative abundances of these molecules in the urine samples. The urinary aDMA to sDMA ratio in healthy individuals was found to be 0.82 +/- 0.17, in good agreement with most reported results.

Chapter 1 Reference

1. J. A. Hipple, H . Sommerin, D H. A. Thomas “A precise method of determining the Faraday by magnetic resonance.” Physical Review, 1949, 76, 1877-1878
2. H. Sommer, H. A. Thomas, J. A. Hipple “The measurement of e/m by cyclotron resonance” Physical Review, 1951, 82, 697-702
3. J. W. Cooley, J. W. Tukey, Math Comp. 1965, 19, 297
4. Comisarow, M. B.; Marshall, A. G. ‘‘Fourier transform ion cyclotron resonance spectroscopy.’’ Chem. Phys. Lett.1974, 25, 282–283.
5. Comisarow, M. B.; Marshall, A. G. ‘‘Frequency-sweep Fourier transform ion cyclotron resonance spectroscopy.’’Chem. Phys. Lett. 1974, 26, 489–490.
6. Edmond de Hoffmann and Vincent Stroobant “Mass spectrometry principles and applications”
7. Lifshitz C. Kinetic shifts. Eur J Mass Spectrom 8:85-92, 2002.
8. Bowers WD, Delbert SS, Hunter RL, McIver RT. 1984. Fragmentation of oligopeptide ions using ultraviolet-laser radiation and Fourier-transform mass spectrometry. J Am Chem Soc 106:7288–7289.
9. Bowers WD, Delbert SS, McIver RT. 1986. Consecutive laser-induced photodissociation as a probe of ion structure. Anal Chem 58:969–972.
10. Williams ER, Furlong JJP, McLafferty FW. 1990. Efficiency of collisionally activated dissociation and 193-nm photodissociation of peptide ions in Fourier transform mass-spectrometry. J Am Soc Mass Spectrom 1:288–294.
11. Beu SC, SenkoMW, Quinn JP,Wampler FM, McLaffertyFW. 1993. Fourier transform electrospray instrumentation for tandem high-resolution mass spectrometry of large molecules. J Am Soc Mass Spectrom 4:557–565.
12. Lupo DW, Quack M. 1987. IR-laser photochemistry. Chem Rev 87:181–216.
13. Woodin RL, Bomse DS, Beauchamp JL. 1978. Multiphoton dissociation of molecules with low power continuous wave infrared laser radiation. J Am Chem Soc 100:3248–3250.
14. Bomse DS,Woodin RL, BeauchampJL. 1979. Molecular activation with low intensity CW infrared laser radiation. Multiphoton dissociation of ions derived from diethyl ether. J Am Chem Soc 101:5503–5512.
15. Watson CH, Baykut G, Eyler JR. 1987. Laser photodissociation of gaseous ions formed by laser desorption. Anal Chem 59:1133–1138.
16. Little DP, Speir JP, SenkoMW, O’Connor PB, McLaffertyFW. 1994. Infrared multiphoton dissociation of large multiply charged ions for biomolecule sequencing. Anal Chem 66:2809–2815.
17. Alan G. Marshall, Christopher L. Hendrickson, and George S. Jackson. Fourier transform ion cyclotron resonance mass spectrometry: a primer. Mass Spectrometry Reviews, 1998, 17, 1–35

Chapter 2 Reference

1. Karas, M.; Bachmann, D.; Hillenkamp, F. Anal. Chem. 1985, 57, 2935-2939.
2. Karas, M.; Hillenkamp, F. Anal. Chem. 1988, 60, 2299-2301
3. Hillenkamp, F.; Karas, M. Int. J. Mass spectrom. 2000, 200, 71
4. Tanaka, K.; Ido, H.; Yoshida, Y.; Yoshida, T. Proceedings of the Second Japan China Joint Symposium on Mass spectrometry, Bando Press: Osaka, Japan 1987, pp 185-187
5. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Mass Spectrum. Rev. 1990, 9, 37
6. Schriemer, D. C.; Li, L. Anal. Chem. 1996, 68, 2721-2725.
7. Renato Zenobi and Richard Knochenmuss, Mass Spectrum Rev., 1998, 17, 337–366

8. Berkenkamp, S.; Menzel, C.; Karas, M.; Hillenkamp, F. Rapid Commun Mass Spectrom 1997, 11,1399.
9. Niu, S.; Zhang, W.; Chait, B. T. J Am Soc Mass Spectrom 1998, 9, 1.
10. Overberg, A.; Karas, M.; Bahr, U.; Kaufmann, R.; Hillenkamp,F. Rapid Commun Mass Spectrom. 1990, 4, 293.
11. Berkenkamp, S.; Kirpekar, F.; Hillenkamp, F. Science 1998, 281, 260.
12. Zhang, W.; Niu, S.; Chait, B. T. J Am Soc Mass Spectrom 1998, 9, 879.
13. Chevrier, M. R.; Cotter, R. J. A Rapid Commun Mass Spectrom 1991, 5, 611.
14. Demirev, P. et al. Rapid Commun Mass Spectrom 1992, 6,187.
15. Johnson, R. E. Int J Mass Spectrom Ion Proc 1994, 139, 25.
16. Riahi, K.; Bolbach, G.; Brunot, A.; Breton, F.; Spiro, M.; Blais, J.–C. Rapid Commun
Mass Spectrom.1994, 8, 242.
17. Dreisewerd, K.; Schu‥renberg, M.; Karas, M.; Hillenkamp, F. Int J Mass Spectrom Ion
Proc 1995, 141, 127.
18. Beavis, R. C.; Chait, B. T. Rapid Commun Mass Spectrom 1989, 3, 233.
19. Spengler, B.; Kirsch, D.; Kaufmann, R. J Phys Chem 1992, 96, 9678.
20. Karas, M.; Bahr, U.; Strupat, K.; Hillenkamp, F.; Tsarbopoulos, A.; Pramanik, B. N.
Anal Chem 1995, 67, 675.
21. Karas, M.; Bahr, U.; Stah–Zeng, J. R. T. Baer; C. Y. Ng; I. Powis (Eds.); Wiley:
London,1996, 27.
22. Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. Rapid Commun Mass Spectrom 1988, 2, 151.
23. Sunner, J.; Dratz, E.; Chen, Y. Anal Chem 1995, 67, 4335.
24. Dale, M. J.; Knochenmuss, R.; Zenobi, R. Anal Chem 1996, 68, 3321.
25. Dale, M. J.; Knochenmuss, R.; Zenobi, R. Rapid Commun Mass Spectrom 1997, 11, 136.
26. Kraft, P.; Alimpiev, S.; Dratz, E.; Sunner, J. J Am Soc Mass Spectrom 1998, 9, 912.
27. Cornett, D. S.; Duncan, M. A.; Amster, I. J. Org Mass Spectrom 1992, 27, 831.
28. Cornett, D. S.; Duncan, M. A.; Amster, I. J. Anal Chem 1993, 65,2608.
29. Kolli, V. S. K.; Orlando, R. Rapid Commun Mass Spectrom 1996, 10, 923.
30. Zo‥llner, P.; Schmid, E. R.; Allmaier, G. Rapid Commun Mass Spectrom 1996, 10, 1278.
31. Zo‥llner, P.; Stu‥binger, G.; Schmid, E.; Pittenauer, E.; Allmaier, G. Int J Mass Spectrom Ion Proc 1997, 169/170, 99.
32. Kraft, P.; Alimpiev, S.; Dratz, E.; Sunner, J. J Am Soc Mass Spectrom 1998, 9, 912.
33. Sze, E. T. P.; Chan, T.–W. D.; Wang, G. J Am Soc Mass Spectrom 1998, 9, 166.
34. Becker, C. H.; Jusinski, L. E.; Moro, L. Int J Mass Spectrom Ion Proc 1990, 95, R1.
35. Berkenkamp, S.; Karas, M.; Hillenkamp, F. Proc Nat Acad Sci USA.1996, 93, 7003.
36. Hunter, J. M.; Lin, H. A.; Becker, C. H. Anal Chem 1997, 69, 3608.
37. Caldwell, K. L.; Murray, K. K. Appl Surf Sci 1998, 127–129, 242.
38. Kraft, P.; Alimpiev, S.; Dratz, E.; Sunner, J. J Am Soc Mass Spectrom 1998, 9,912.
39. Laiko, V. V.; Baldwin, M. A.; Burlingame, A. L. Anal. Chem. 2000, 72, 652-657
40 Laiko, V. V.; Burlingame, A. L. U.S. Patent 5,965,884, Oct 12, 1999.
41. Turney, K.; Drake, T. J.; Smith, J. E.; Tan, W.; Harrison, W. W. Rapid Commun. Mass
Spectrom. 2004, 18, 2367-2374.
42. Turney, K.; Harrison. W. W. Rapid Commun. Mass Spectrom. 2004, 18, 629-635
43. Ring, S.; Rudich, Y. Rapid Commun. Mass Spectrom. 14, 515–519 (2000)
44. Christopher E. Von Seggern, Ben D. Gardner, and Robert J. Cotter Anal. Chem. 2004,
76, 5887-5893
45. Christopher E. Von Seggern and Robert J. Cotter J Am Soc Mass Spectrom 2003, 14,
1158–1165
46. Comisarow, M. B.; Marshall, A. G. Chem. Phys. Lett. 1947a, 25, 282-283.
47. Marshall, A. G.; Hendrickson, C. L.; Jackson, G. S. Mass Spectrom. Rev. 1998, 17, 1
48. Castoro, J. A.; Ko‥ster, C.; Wilkins, C. L. Rapid Commun. Mass Spectrom. 1992, 6, 239.
49. Koster, C.; Castoro, J. A.; Wilkins, C. L. J. Am. Chem. Soc, 1992, 114, 7572-7574.
50. Rempel, D. L.; Gross, M. L. J. Am. Soc. Mass Spectrom. 1992, 3, 590.
51. Schweikhard, L.; Guan, S.; Marshall, A. G. Int. J. Mass Spectrom. Ion Processes 1992,
120, 71-83.
52. Shenheng Guan, Markus C. Wah1,t Troy D. Wood, and Alan G.Marshall. Anal. Chem.
1993, 65, 1753-1757.
53. Pastor, S. J.; Castoro, J. A.; Wilkins, C. L. Anal. Chem. 1995, 67, 379-384.
54. O’Connor, P. B.; Costello, C. E. Rapid Commun. Mass Spectrom. 2001, 15, 1862-1868.
55. Katherine A. Kellersberger, Phillip V. Tan, Victor V. Laiko, Vladimir M. Doroshenko,
and Daniele Fabris.Anal. Chem. 2004, 76, 3930-3934.
56. Gauthier, J. W.; Trautman, T. R.; Jacobson, D. B. Anal. Chim. Acta 1991, 246, 211–
225.

Chapter 3 Reference

1. Christine A. Miller, Donghui Yi and Patrick D. Perkins. Rapid Commun. Mass Spectrom. 2003; 17, 860-868.
2. Hutchens, T. W.; Yip, T. T. Rapid Commun. Mass Spectrom. 1993, 7, 576-580.
3. Papac, D. I.; Hoyes, J.; Tomer, K. B. Anal. Chem. 1994, 66, 2609-2613.
4. Nelson, R. W.; Krone, J. R.; Bieber, A. L.; Williams, P. Anal. Chem.1995, 67, 1153-1158.
5. Brockman, A. H.; Orlando, R. Anal. Chem. 1995, 67, 4581-4585.
6. Brockman, A. H.; Orlando, R. Rapid Commun. Mass Spectrom. 1996, 10, 1688-1692.
7. Liang, X.; Lubman, D. M.; Rossi, D. T.; Nordblom, G. D.; Barksdale, C. M. Anal. Chem. 1998, 70, 498-503.
8. Tang, N.; Tornatore, P.; Weinberger, S. R. Mass Spectrom. Rev. 2004, 23, 34-44.
9. Gevaert K, Demol H, Sklyarova T, Houthaeve T. Electrophoresis 1998; 19: 909.
10. Gevaert K, Demol H, Puype M, Broekaert D, De Boeck S, Houthaeve T, Veenstra T. Electrophoresis 1997; 18: 2950.
11. Villanueva J, Philip J, Entenberg D, Chaparr C, Tanwar M, Holland E, Tempst P. Anal. Chem. 2004; 76: 1560.
12. Yaneva M, Tempst P. Anal. Chem. 2003; 75: 6437.
13. Seyda Bucak, Deverraux A.Jones, Paul E. Laibinis, and Alan Hatton Biotechnol. Prog. 2003, 19, 477-484.
14. Xu, J.; Granger, M. C.; Chen, Q.; Strojek, J. W.; Lister, T. E.; Swain, G. M. Anal. Chem. 1997, 69, 591A.
15. Linford, M. R.; Fenter, P.; Eisenberger, P. M.; Chidsey, C. E. D. J. Am. Chem. Soc. 1995, 117, 3145.
16. Strother, T.; Cai, W.; Zhao, X.; Hamers, R. J.; Smith, L. M. J. Am. Chem. Soc. 2000, 122, 1205.
17. Strother, T.; Hamers, R. J.; Smith, L. M. Nucleic Acids Res. 2000, 28, 3535.
18. X.L. Kong, L.C.L. Huang, C.-M. Hsu, W.-H. Chen, C.-C. Han, and H.-C. Chang. Anal. Chem. 2005, 77(1), 259-265
19. Tang, L.; Tsai, C.; Gerberich, W. W.; Kruckeberg, L.; Kania, D. R. Biomaterials 1995, 16, 483.
20. Hauert, R. Diamond Relat. Mater. 2003, 12, 583.
21. Swain, G. M.; Ramesham, M. Anal. Chem. 1993, 65, 345.
22. Kawarada, H.; Araki, Y.; Sakai, T.; Ogawa, T.; Umezawa, H. Phys. Status Solidi A 2001, 185, 79.
23. Vo-Dinh, T.; Alarie, J. P.; Isola, N.; Landis, D.; Wintenberg, A. L.; Ericson, M. N. Anal. Chem. 1999, 71, 358.
24. Chen, Q. Y.; Granger, M. C.; Lister, T. E.; Swain, G. M. J. Electrochem. Soc. 1997, 144, 3806.
25. Cui, F. Z.; Li, D. J. Surf. Coat. Technol. 2000, 131, 481.
26. Wensha Yang, Orlando Auciello, James E. Butler, Wei Cai, John A. Carlisle, Jennifer E. Gerbi, Dieter M. Gruen, Tanya Knickerbocker, Tami L. Lasseter, John N. Russell Jr.3, Lloyd M. Smith and Robert J. Hamers Nature materials, 2002, 1, 253-257.
27. L.-C. L. Huang and H.-C. Chang, Langmuir 2004, 20, 5879- 5884
28. Ushizawa, K.; Sato, Y.; Mitsumori, T.; Machinami, T.; Ueda, T.; Ando, T. Chem. Phys. Lett. 2002, 351, 105-108.
29. Doucette, A.; Craft, D.; Li, L. Anal. Chem. 2000, 72, 3355-3362
30. K.A. Kellersberger, P.V. Tan, V.V. Laiko, V.M. Doroshenko, and D. Fabris, Anal. Chem. 76 (2004) 3930-3934.
31. K.A. Kellersberger, E.T. Yu, S.I. Merenbloom, and D. Fabris, J. Am. Soc. Mass. Spectrom. 16 (2005) 199-207.

Chapter 4 Reference

1. J.D. Gary, and S. Clarke, RNA and protein interactions modulated by protein arginine methylation. Progress in Nucleic Acid Research and Molecular Biology, Vol 61 (1998) 65-131.
2. A.E. McBride, and P.A. Silver, State of the Arg: Protein methylation at arginine comes of age. Cell 106 (2001) 5-8.
3. Y. Kakimoto, Y. Matsuoka, M. Miyake, and H. Konishi, Methylated Amino-Acid Residues of Proteins of Brain and Other Organs. J. Neurochem. 24 (1975) 893-902.
4. R.F. Furchgott, The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. Jama-Journal of the American Medical Association 276 (1996) 1186-1188.
5. P. Vallance, Importance of asymmetrical dimethylarginine in cardiovascular risk. Lancet 358 (2001) 2096-2097.
6. P. Vallance, A. Leone, A. Calver, J. Collier, and S. Moncada, Accumulation of an Endogenous Inhibitor of Nitric-Oxide Synthesis in Chronic-Renal-Failure. Lancet 339 (1992) 572-575.
7. R.H. Boger, S.M. Bode-Boger, A. Szuba, P.S. Tsao, J.R. Chan, O. Tangphao, T.F. Blaschke, and J.P. Cooke, Asymmetric dimethylarginine (ADMA): A novel risk factor for endothelial dysfunction - Its role in hypercholesterolemia. Circulation 98 (1998) 1842-1847.
8. T. Ogawa, M. Kimoto, H. Watanabe, and K. Sasaoka, Metabolism of Ng,Ng-Dimethylarginine and Ng,N'g-Dimethylarginine in Rats. Arch. Biochem. Biophys. 252 (1987) 526-537.
9. J. Leiper, M. Nandi, B. Torondel, J. Murray-Rust, M. Malaki, B. O'Hara, S. Rossiter, S. Anthony, M. Madhani, D. Selwood, C. Smith, B. Wojciak-Stothard, A. Rudiger, R. Stidwill, N.Q. McDonald, and P. Vallance, Disruption of methylarginine metabolism impairs vascular homeostasis. Nat. Med. 13 (2007) 198-203.
10. R.J. Nijveldt, P.A.M. van Leeuwen, C. van Guldener, C.D.A. Stehouwer, J.A. Rauwerda, and T. Teerlink, Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans. Nephrology Dialysis Transplantation 17 (2002) 1999-2002.
11. W.F. Haddon, and Mclaffer.Fw, Metastable Ion Characteristics .7. Collision-Induced Metastables. J. Am. Chem. Soc. 90 (1968) 4745-&.
12. S.A. Mcluckey, Principles of Collisional Activation in Analytical Mass-Spectrometry. J. Am. Soc. Mass Spectrom. 3 (1992) 599-614.
13. K. Biemann, and S.A. Martin, Mass-Spectrometric Determination of the Amino-Acid-Sequence of Peptides and Proteins. Mass Spectrom. Rev. 6 (1987) 1-75.
14. D.F. Hunt, J.R. Yates, J. Shabanowitz, S. Winston, and C.R. Hauer, Protein Sequencing by Tandem Mass-Spectrometry. Proc. Natl. Acad. Sci. U. S. A. 83 (1986) 6233-6237.
15. T. Yalcin, and A.G. Harrison, Ion chemistry of protonated lysine derivatives. J. Mass Spectrom. 31 (1996) 1237-1243.
16. J.J. Zwinselman, N.M.M. Nibbering, J. Vandergreef, and M.C.T. Debrauw, A N-15 Labeling, Fd and Fab Study of Ammonia Loss from Protonated Arginine Molecules. Org. Mass Spectrom. 18 (1983) 525-529.
17. N.N. Dookeran, T. Yalcin, and A.G. Harrison, Fragmentation reactions of protonated alpha-amino acids. J. Mass Spectrom. 31 (1996) 500-508.
18. P.Y.I. Shek, J. Zhao, Y. Ke, K.W.M. Siu, and A.C. Hopkinson, Fragmentations of protonated arginine, lysine and their methylated derivatives: Concomitant losses of carbon monoxide or carbon dioxide and an amine. Journal of Physical Chemistry A 110 (2006) 8282-8296.
19. K. Vishwanathan, R.L. Tackett, J.T. Stewart, and M.G. Bartlett, Determination of arginine and methylated arginines in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography B 748 (2000) 157-166.
20. P.M. Gehrig, P.E. Hunziker, S. Zahariev, and S. Pongor, Fragmentation pathways of N-G-methylated and unmodified arginine residues in peptides studied by ESI-MS/MS and MALDI-MS. J. Am. Soc. Mass Spectrom. 15 (2004) 142-149.
21. L.H. Cohen, and A.I. Gusev, Small molecule analysis by MALDI mass spectrometry. Analytical and Bioanalytical Chemistry 373 (2002) 571-586.
22. M. Donegan, A.J. Tomlinson, H. Nair, and P. Juhasz, Controlling matrix suppression for matrix-assisted laser desorption/ionization analysis of small molecules. Rapid Commun. Mass Spectrom. 18 (2004) 1885-1888.
23. P.B. Grosshans, and A.G. Marshall, Theory of Ion-Cyclotron Resonance Mass-Spectrometry - Resonant Excitation and Radial Ejection in Orthorhombic and Cylindrical Ion Traps. Int. J. Mass Spectrom. Ion Processes 100 (1990) 347-379.
24. J.W. Gauthier, T.R. Trautman, and D.B. Jacobson, Sustained Off-Resonance Irradiation for Collision-Activated Dissociation Involving Fourier-Transform Mass-Spectrometry - Collision-Activated Dissociation Technique That Emulates Infrared Multiphoton Dissociation. Anal. Chim. Acta 246 (1991) 211-225.
25. G.S. Jackson, J.D. Canterbury, S.H. Guan, and A.G. Marshall, Linearity and quadrupolarity of tetragonal and cylindrical penning traps of arbitrary length-to-width ratio. J. Am. Soc. Mass Spectrom. 8 (1997) 283-293.
26. G.S. Jackson, C.L. Hendrickson, B.B. Reinhold, and A.G. Marshall, Two-plate vs. four-plate azimuthal quadrupolar excitation for FT-ICR mass spectrometry. International Journal of Mass Spectrometry 165 (1997) 327-338.
27. A.G. Marshall, C.L. Hendrickson, and G.S. Jackson, Fourier transform ion cyclotron resonance mass spectrometry: A primer. Mass Spectrom. Rev. 17 (1998) 1-35.
28. R.R. Julian, and M.F. Jarrold, Gas-phase zwitterions in the absence of a net charge. Journal of Physical Chemistry A 108 (2004) 10861-10864.
29. I.P. Csonka, B. Paizs, and S. Suhai, Modeling of the gas-phase ion chemistry of protonated arginine. J. Mass Spectrom. 39 (2004) 1025-1035.
30. F. Rogalewicz, Y. Hoppilliard, and G. Ohanessian, Fragmentation mechanisms of alpha-amino acids protonated under electrospray ionization: a collisional activation and ab initio theoretical study. International Journal of Mass Spectrometry 196 (2000) 565-590.
31. E.P.L. Hunter, and S.G. Lias, Evaluated gas phase basicities and proton affinities of molecules: An update. J. Phys. Chem. Ref. Data 27 (1998) 413-656.
32. T. Marino, N. Russo, E. Tocci, and M. Toscano, Gas-phase acidity of proline from density functional computations. International Journal of Quantum Chemistry 84 (2001) 264-268.
33. K.J. Rosnack, K.V. Somayajula, A.G. Sharkey, N.J. Jensen, and D.M. Hercules, Determination of Water-Loss Mechanism in Amine Terminous Amino-Acids Using Laser Mass-Spectrometry. Applied Spectroscopy 43 (1989) 1087-1092.
34. C.D. Parker, and D.M. Hercules, Laser Mass-Spectra of Simple Aliphatic and Aromatic Amino-Acids. Anal. Chem. 57 (1985) 698-704.
35. B.T. Chait, W.C. Agosta, and F.H. Field, Fission Fragment Ionization (Cf-252) Mass-Spectrometry - Positive and Negative Spectra and Decomposition Mechanisms for Seven Compounds. Int. J. Mass Spectrom. Ion Processes 39 (1981) 339-366.
36. P.C. Maria, J.F. Gal, and R.W. Taft, Proton Affinities Versus Enthalpies of Complexation with Boron-Trifluoride in Solution, in the Nitrile Series - Role of the Polarizability. New Journal of Chemistry 11 (1987) 617-621.

Chapter 5 Reference

1. J.D. Gary, and S. Clarke, RNA and protein interactions modulated by protein arginine methylation. Progress in Nucleic Acid Research and Molecular Biology, Vol 61 61 (1998) 65-131.
2. A.E. McBride, and P.A. Silver, State of the Arg: Protein methylation at arginine comes of age. Cell 106 (2001) 5-8.
3. Y. Kakimoto, Y. Matsuoka, M. Miyake, and H. Konishi, Methylated Amino-Acid Residues of Proteins of Brain and Other Organs. Journal of Neurochemistry 24 (1975) 893-902.
4. R.F. Furchgott, The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. Jama-Journal of the American Medical Association 276 (1996) 1186-1188.
5. P. Vallance, Importance of asymmetrical dimethylarginine in cardiovascular risk. Lancet 358 (2001) 2096-2097.
6. R. Schnabel, S. Blankenberg, E. Lubos, K.J. Lackner, H.J. Rupprecht, C. Espinola-Klein, N. Jachmann, F. Post, D. Peetz, C. Bickel, F. Cambien, L. Tiret, and T. Munzel, Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circulation research 97 (2005) e53-9.
7. P. Vallance, A. Leone, A. Calver, J. Collier, and S. Moncada, Accumulation of an Endogenous Inhibitor of Nitric-Oxide Synthesis in Chronic-Renal-Failure. Lancet 339 (1992) 572-575.
8. R.H. Boger, S.M. Bode-Boger, A. Szuba, P.S. Tsao, J.R. Chan, O. Tangphao, T.F. Blaschke, and J.P. Cooke, Asymmetric dimethylarginine (ADMA): A novel risk factor for endothelial dysfunction - Its role in hypercholesterolemia. Circulation 98 (1998) 1842-1847.
9. T. Ogawa, M. Kimoto, H. Watanabe, and K. Sasaoka, Metabolism of Ng,Ng-Dimethylarginine and Ng,N'g-Dimethylarginine in Rats. Archives of Biochemistry and Biophysics 252 (1987) 526-537.
10. R.J. Nijveldt, P.A.M. van Leeuwen, C. van Guldener, C.D.A. Stehouwer, J.A. Rauwerda, and T. Teerlink, Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans. Nephrology Dialysis Transplantation 17 (2002) 1999-2002.
11. K.S. Park, H.W. Lee, S.Y. Hong, S. Shin, S.D. Kim, and W.K. Paik, Determination of Methylated Amino-Acids in Human-Serum by High-Performance Liquid-Chromatography. Journal of Chromatography 440 (1988) 225-230.
12. B.M. Chen, L.W. Xia, and R.Q. Zhao, Determination of N-G,N-G-dimethylarginine in human plasma by high-performance liquid chromatography. Journal of Chromatography B 692 (1997) 467-471.
13. A. Pettersson, L. Uggla, and V. Backman, Determination of dimethylated arginines in human plasma by high-performance liquid chromatography. Journal of Chromatography B 692 (1997) 257-262.
14. J. Meyer, N. Richter, and M. Hecker, High-performance liquid chromatographic determination of nitric oxide synthase-related arginine derivatives in vitro and in vivo. Analytical Biochemistry 247 (1997) 11-16.
15. J.B. Pi, Y. Kumagai, G.F. Sun, and N. Shimojo, Improved method for simultaneous determination of L-arginine and its mono- and dimethylated metabolites in biological samples by high-performance liquid chromatography. Journal of Chromatography B 742 (2000) 199-203.
16. W.Z. Zhang, and D.M. Kaye, Simultaneous determination of arginine and seven metabolites in plasma by reversed-phase liquid chromatography with a time-controlled ortho-phthaldialdehyde precolumn derivatization. Analytical Biochemistry 326 (2004) 87-92.
17. T. Teerlink, R.J. Nijveldt, S. de Jong, and P.A.M. van Leeuwen, Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Analytical Biochemistry 303 (2002) 131-137.
18. E. Causse, N. Siri, J.F. Arnal, C. Bayle, P. Malatray, P. Valdiguie, R. Salvayre, and F. Couderc, Determination of asymmetrical dimethylarginine by capillary electrophoresis-laser-induced fluorescence. Journal of Chromatography B 741 (2000) 77-83.
19. J. Albsmeier, E. Schwedhelm, F. Schulze, M. Kastner, and R.H. Boger, Determination of N-G,N-G-dimethyl-L-arginine, an endogenous NO synthase inhibitor, by gas chromatography-mass spectrometry. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 809 (2004) 59-65.
20. D. Tsikas, B. Schubert, F.M. Gutzki, J. Sandmann, and J.C. Frolich, Quantitative determination of circulating and urinary asymmetric dimethylarginine (ADMA) in humans by gas chromatography-tandem mass spectrometry as methyl ester tri(N-pentafluoropropionyl) derivative. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 798 (2003) 87-99.
21. J. Martens-Lobenhoffer, O. Krug, and S.M. Bode-Boger, Determination of arginine and asymmetric dimethylarginine (ADMAL) in human plasma by liquid chromatography/mass spectrometry with the isotope dilution technique. Journal of Mass Spectrometry 39 (2004) 1287-1294.
22. L.F. Huang, F.Q. Guo, Y.Z. Liang, B.Y. Li, and B.M. Cheng, Simultaneous determination of L-arginine and its mono- and dimethylated metabolites in human plasma by high-performance liquid chromatography-mass spectrometry. Analytical and Bioanalytical Chemistry 380 (2004) 643-649.
23. K. Vishwanathan, R.L. Tackett, J.T. Stewart, and M.G. Bartlett, Determination of arginine and methylated arginines in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography B 748 (2000) 157-166.
24. H. Kirchherr, and W.N. Kuhn-Velten, HPLC-tandem mass spectrometric method for rapid quantification of dimethylarginines in human plasma. Clinical Chemistry 51 (2005) 249-252.
25. M.J. Kang, A. Tholey, and E. Heinzle, Quantitation of low molecular mass substrates and products of enzyme catalyzed reactions using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 14 (2000) 1972-1978.
26. Y. Kim, G.B. Hurst, M.J. Doktycz, and M.V. Buchanan, Improving spot homogeneity by using polymer substrates in matrix-assisted laser desorption/ionization mass spectrometry of oligonucleotides. Analytical Chemistry 73 (2001) 2617-2624.
27. E.J. Zaluzec, D.A. Gage, J. Allison, and J.T. Watson, Direct Matrix-Assisted Laser-Desorption Ionization Mass-Spectrometric Analysis of Proteins Immobilized on Nylon-Based Membranes. Journal of the American Society for Mass Spectrometry 5 (1994) 230-237.
28. J.A. Blackledge, and A.J. Alexander, Polyethylene Membrane as a Sample Support for Direct Matrix-Assisted Laser-Desorption Ionization Mass-Spectrometric Analysis of High-Mass Proteins. Analytical Chemistry 67 (1995) 843-848.
29. S.R. Weinberger, The Laser Desorption-Ionization Mass Monitor - a Powerful Analytical Tool for Life-Science Investigations. American Laboratory 24 (1992) 54-&.
30. D.J. Harvey, P.M. Rudd, R.H. Bateman, R.S. Bordoli, K. Howes, J.B. Hoyes, and R.G. Vickers, Examination of Complex Oligosaccharides by Matrix-Assisted Laser-Desorption Ionization Mass-Spectrometry on Time-of-Flight and Magnetic-Sector Instruments. Organic Mass Spectrometry 29 (1994) 753-766.
31. A.J. Nicola, A.I. Gusev, A. Proctor, E.K. Jackson, and D.M. Hercules, Application of the Fast-Evaporation Sample Preparation Method for Improving Quantification of Angiotensin-Ii by Matrix-Assisted Laser-Desorption Ionization. Rapid Communications in Mass Spectrometry 9 (1995) 1164-1171.
32. O. Vorm, P. Roepstorff, and M. Mann, Improved Resolution and Very High-Sensitivity in Maldi Tof of Matrix Surfaces Made by Fast Evaporation. Analytical Chemistry 66 (1994) 3281-3287.
33 O. Vorm, and M. Mann, Improved Mass Accuracy in Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass-Spectrometry of Peptides. Journal of the American Society for Mass Spectrometry 5 (1994) 955-958.
34. Y.C. Ling, L.N. Lin, and Y.T. Chen, Quantitative analysis of antibiotics by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 12 (1998) 317-327.
35. R.R. Hensel, R.C. King, and K.G. Owens, Electrospray sample preparation for improved quantitation in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 11 (1997) 1785-1793.
36. J. Axelsson, A.M. Hoberg, C. Waterson, P. Myatt, G.L. Shield, J. Varney, D.M. Haddleton, and P.J. Derrick, Improved reproducibility and increased signal intensity in matrix-assisted laser desorption/ionization as a result of electrospray sample preparation. Rapid Communications in Mass Spectrometry 11 (1997) 209-213.
37. T.M. Billeci, and J.T. Stults, Tryptic Mapping of Recombinant Proteins by Matrix-Assisted Laser-Desorption Ionization Mass-Spectrometry. Analytical Chemistry 65 (1993) 1709-1716.
38. A.I. Gusev, A. Proctor, Y.I. Rabinovich, and D.M. Hercules, Thin-Layer Chromatography Combined with Matrix-Assisted Laser-Desorption Ionization Mass-Spectrometry. Analytical Chemistry 67 (1995) 1805-1814.
39. A.I. Gusev, W.R. Wilkinson, A. Proctor, and D.M. Hercules, Quantitative-Analysis of Peptides by Matrix-Assisted Laser-Desorption Ionization Time-of-Flight Mass-Spectrometry. Applied Spectroscopy 47 (1993) 1091-1092.
40. M.W. Duncan, G. Matanovic, and A. Cerpapoljak, Quantitative-Analysis of Low-Molecular-Weight Compounds of Biological Interest by Matrix-Assisted Laser-Desorption Ionization. Rapid Communications in Mass Spectrometry 7 (1993) 1090-1094.
41. D.C. Muddiman, A.I. Gusev, K. Stoppeklangner, A. Proctor, D.M. Hercules, P. Tata, R. Venkataramanan, and W. Diven, Simultaneous Quantification of Cyclosporine-a and Its Major Metabolites by Time-of-Flight Secondary-Ion Mass-Spectrometry and Matrix-Assisted Laser Desorption/Ionization Mass-Spectrometry Utilizing Data-Analysis Techniques - Comparison with High-Performance Liquid-Chromatography. Journal of Mass Spectrometry 30 (1995) 1469-1479.
42. D.C. Muddiman, A.I. Gusev, A. Proctor, D.M. Hercules, R. Venkataramanan, and W. Diven, Quantitative Measurement of Cyclosporine-a in Blood by Time-of-Flight Mass-Spectrometry. Analytical Chemistry 66 (1994) 2362-2368.
43. R.W. Nelson, M.A. Mclean, and T.W. Hutchens, Quantitative-Determination of Proteins by Matrix-Assisted Laser-Desorption Ionization Time-of-Flight Mass-Spectrometry. Analytical Chemistry 66 (1994) 1408-1415.
44. C.M. Pierce, S. Krywawych, and A.J. Petros, Elevated levels of asymmetric di-methylarginine in neonates with congenital diaphragmatic hernia. European Journal of Pediatrics 164 (2005) 248-249.
45. D. Tsikas, I. Rode, T. Becker, B. Nashan, J. Klempnauer, and J.C. Frolich, Elevated plasma and urine levels of ADMA and 15(S)-8-iso-PGF(2 alpha) in end-stage liver disease. Hepatology 38 (2003) 1063-1064.
46. F. Abbasi, T. Asagami, J.P. Cooke, C. Lamendola, T. McLaughlin, M.C. Stuehlinger, P.S. Tsao, and G.M. Reaven, Plasma concentrations of asymmetric dimethylagrinine are increased in patients with type 2 diabetes mellitus. Diabetes 50 (2001) A147-a148.
47. M. Donegan, A.J. Tomlinson, H. Nair, and P. Juhasz, Controlling matrix suppression for matrix-assisted laser desorption/ionization analysis of small molecules. Rapid Communications in Mass Spectrometry 18 (2004) 1885-1888.
48. P.Y.I. Shek, J. Zhao, Y. Ke, K.W.M. Siu, and A.C. Hopkinson, Fragmentations of protonated arginine, lysine and their methylated derivatives: Concomitant losses of carbon monoxide or carbon dioxide and an amine. Journal of Physical Chemistry A 110 (2006) 8282-8296.
49. J. Martens-Lobenhoffer, and S.M. Bode-Boger, Simultaneous detection of arginine, asymmetric dimethylarginine, symmetric dimethylarginine and citrulline in human plasma and urine applying liquid chromatography-mass spectrometry with very straightforward sample preparation. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 798 (2003) 231-239.

Chapter 6 Reference

1. a) J. H. Jensen, M. S. Gordon, J. Am. Chem. Soc. 1991, 113, 7917-7924; b) J. H. Jensen, M. S. Gordon, J. Am. Chem. Soc. 1995, 117, 8159-8170..
2. Y. Ding, K. Krogh-Jespersen, Chem. Phys. Lett. 1992, 199, 261-266.
3. C. J. Chapo, J. B. Paul, R. A. Provencal, K. Roth, R. J. Saykally, J. Am. Chem. Soc. 1998, 120, 12956-12957.
4. R. R. Julian, J. L. Beauchamp, W. A. Goddard, III, J. Phys. Chem. A 2002, 106, 32-34.
5. T. Wyttenbach, M. Witt, M. T. Bowers, J. Am. Chem. Soc. 2000, 122, 3458-3464.
6. a) M. J. Locke, R. L. Hunter, R. T. McIver, J. Am. Chem. Soc. 1979, 101, 272-273; b) M. J. Locke, R. T. McIver, J. Am. Chem. Soc. 1983, 105, 4226-4232.
7. R. R. Julian, R. Hodyss, J. L. Beauchamp, J. Am. Chem. Soc. 2001, 123, 3577-3583.
8. a) R. G. Cooks, D. Zhang, K. J Koch, F. C. Gozzo, M. N. Eberlin, Anal. Chem. 2001, 73, 3646-3655; b) Z. Takats, S. C. Nanita, R. G. Cooks, G. Schlosser, K. Vekey, Anal. Chem. 2003, 75, 1514-1523; c) Z. Takats, S. C. Nanita, R. G. Cooks, Angew. Chem. Int. Ed. 2003, 42, 3521-3523; d) S. C.; Nanita, R. G. Cooks, J. Phys. Chem. B 2005, 109, 4748-4753.
9. a) R. Hodyss, R. R. Julian, J. L. Beauchamp, Chirality 2001, 13, 703-706; b) R. R. Julian, R. Hodyss, B. Kinnear, M. F. Jarrold, J. L. Beauchamp, J. Phys. Chem. B 2002, 106, 1219-1228.
10. A. E. Counterman, D. E. Clemmer, J. Phys. Chem. B 2001, 105, 8092-8096.
11. C. A. Schalley, P. Weis, Int. J. Mass. Spectrom. 2002, 221, 9-19.
12. U. Mazurek, O. Geller, C. Lifshitz, M. A. McFarland, A. G. Marshall, B. G. Reuben, J. Phys. Chem. A 2005, 109, 2107-2112.
13. H. B. Oh, C. Lin, H. Y. Hwang, H. Zhai, K. Breuker, V. Zabrouskov, B. Y. Carpenter, F. W. McLafferty, J. Am. Chem. Soc. 2005, 127, 4076-4083.
14. F. Pollreisz, A. Gomory, G. Schlosser, K. Vekey, I. Solt, A. G. Csaszar, Chem. Eur. J. 2005, 11, 5908-5916.
15. H.-C. Chang, C.-C. Wu, J.-L. Kuo, Int. Rev. Phys. Chem. 2005, 24, 553-578.
16. D. P. Little, R. A. Chorush, J. P. Speir, M. W. Senko, N. L. Kelleher, F. W. McLafferty, J. Am. Chem. Soc. 1994, 116, 4893-4897.
17. The most stable structures suggested in ref. [14] have energies of 1 – 4 kcal/mol higher than N1 – N6 and Z1 – Z2. Very unlikely they are the global-minimum structures of the protonated serine dimer.
18. a) H.-C. Chang, J. C. Jiang, S. H. Lin, Y. T. Lee, H.-C. Chang, J. Phys. Chem. A 1999, 103, 2941-2944; b) C.-C. Wu, J. C. Jiang, D. W. Boo, S. H. Lin, Y. T. Lee, H.-C. Chang, J. Chem. Phys. 2000, 112, 176-188.
19. Y.-S. Wang, H.-C. Chang, J. C. Jiang, S. H. Lin, Y. T. Lee, H.-C. Chang, J. Am. Chem. Soc. 1998, 120, 8777-8788.
20. As previously found for other protonated molecular clusters (refs. [15,18,19,25]), the H-bonded OH and NH stretching bands are broad and congested, providing little structural information.
21. C. S. Yu, A. H. Kung, J. Opt. Soc. Am. B 1999, 16, 2233-2238.
22. The frequency of the laser was calibrated against atmospheric water with an uncertainty of ±1 cm-1.
23. S. Gronert, R. A. J. O’Hair, J. Am. Chem. Soc. 1995, 117, 2071-2081.
24. Miao, R.; Jin, C.; Yang, G.; Hong, J.; Zhao, C.; Zhu, L. J. Phys. Chem. A 2005, 109, 2340-2349.
25. a) C.-C. Wu, J. C. Jiang, I. Hahndorf, C. Chaudhuri, Y. T. Lee, H.-C. Chang, J. Phys. Chem. A 2000, 104, 9556-9565; b) C. Chaudhuri, J. C. Jiang, C.-C. Wu, X. Wang, H.-C. Chang, J. Phys. Chem. A 2001, 105, 8906-8915.
26. M. J. Frisch, et al. Gaussian 03, Revision B.01, Gaussian, Inc., 2004.
27. The research was supported by the Academia Sinica and the National Science Council (Grant No. NSC 92-3112-B-001-012-Y under the National Research Program for Genomic Medicine) of Taiwan, Republic of China. We thank Professors H. B. Oh and F. W. McLafferty for insightful discussions.
28. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the authors.

Chapter 7 Reference

1. Godovac-Zimmermann, J.; Brown, L. R. Mass Spectrom. Rev. 2001, 20, 1-57.
2. Wittke, S.; Mischak, H.; Walden, M.; Kolch, W.; Ra‥dler, T.; Wiedemann, K. Electrophoresis 2005, 26, 1476-1487.
3. Chalmers, M. J.; Mackay, C. L.; Hendrickson, C. L.; Wittke, S.; Walden, M.; Mischak, H.; Fliser, D.; Just, I.; Marshall, A. G. Anal. Chem. 2005, 77, 7163-7171.
4. Samyn, B.; Sergeant, K.; Castanheira, P.; Faro, C.; Van Beeumen, J. Nat. Methods 2005, 2, 193-200.
5. Oh, J.; Pyo, J.-H.; Jo, E.-H.; Hwang, S.-I.; Kang, S.-C.; Jung, J.-H.; Park, E.- K.; Kim, S.-Y.; Choi, J.-Y.; Lim, J. Proteomics 2004, 4, 3485-3497.
6. Wattiez, R.; Falmagne, P. J. Chromatogr., B 2005, 815, 169-178.
7. Finehout, E. J.; Franck, Z.; Lee, K. H. Electrophoresis 2004, 25, 2564- 2575.
8. Pieper, R.; Gatlin, C. L.; Makusky, A. J.; Russo, P. S.; Schatz, C. R.; Miller, S. S.; Su, Q.; McGrath, A. M.; Estock, M. A.; Parmar, P. P.; Zhao, M.; Huang, S.-T.; Zhou, J.; Wang, F.; Esquer-Blasco, R.; Anderson, N. L.; Taylor, J.; Steiner, S. Proteomics 2003, 3, 1345-1364.
9. Pieper, R.; Gatlin, C. L.; McGrath, A. M.; Makusky, A. J.; Mondal, M.; Seonarain, M.; Field, E.; Schatz, C. R.; Estock, M. A.; Ahmed, N.; Anderson, N. G.;. Steiner, S. Proteomics 2004, 4, 1159-1174.
10. Tantipaiboonwong, P.; Sinchaikul, S.; Sriyam, S.; Phutrakul, S.; Chen, S.-T. Proteomics 2005, 5, 1140-1149.
11. He, P.; He, H.-Z.; Dai, J.; Wang, Y.; Sheng, Q.-H.; Zhou, L.-P.; Zhang, Z.-S.; Sun, Y.-L.; Liu, F.; Wang, K.; Zhang, J.-S.; Wang, H.-X.; Song, Z.-M.; Zhang, H.-R.; Zeng, R.; Zhao, X.-H. Proteomics 2005, 5, 3442-3453.
12. Pang, J. X.; Ginanni, N.; Dongre, A. R.; Hefta, S. A.; Opitek, G. J. J. Proteome Res. 2002, 1, 161-169.
13. Spahr, C. S.; Davis, M. T.; McGinley, M. D.; Robinson, J. H.; Bures, E. J.; Beierle, J.; Mort, J.; Courchesne, P. L.; Chen, K.; Wahl, R. C.; Yu, W.; Luethy, R.; Patterson, S. D. Proteomics 2001, 1, 93-107.
14. Doucette, A.; Craft, D.; Li, L. Anal. Chem. 2000, 72, 3355-3362.
15. Bjo‥rhall, K.; Miliotis, T.; Davidsson, P. Proteomics 2005, 5, 307-317.
16. Chen, Y.-Y.; Lin, S.-Y.; Yeh, Y.-Y.; Hsiao, H.-H.; Wu, C.-Y.; Chen, S.-T.; Wang, A. H.-J. Electrophoresis 2005, 26, 2117-2127.
17. Cho, S. Y.; Lee, E.-Y.; Lee, J. S.; Kim, H.-Y.; Park, J. M.; Kwon, M.-S.; Park, Y.-K.; Lee, H.-J.; Kang, M.-J.; Kim, J. Y.; Yoo, J. S.; Park, S. J.; Cho, J. W.; Kim, H.-S.; Paik, Y. K. Proteomics 2005, 5, 3386-3396.
18. Ogata, Y.; Charlesworth, M. C.; Muddiman, D. C. J. Proteome Res. 2005, 4, 837-845.
19. Zolotarjova, N.; Martosella, J.; Nicol, G.; Bailey, J.; Boyes, B. E.; Barrett, W. C. Proteomics 2005, 5, 3304-3313.
20. Xu, J.; Reilly, J. P. Proceedings of INTERTECH 2003, Industrial Diamond Association of America, Columbus, OH, 2003.
21. Janecki, D. J.; Broshears, W. C.; Reilly, J. P. Anal. Chem. 2004, 76, 6643- 6650.
22. Chen, Y.-J.; Chen, S.-H.; Chien, Y.-Y.; Chang, Y.-W.; Liao, H.-K.; Chang, C.-Y.; Jan, M.-D.; Wang, K.-T.; Lin, C.-C. ChemBioChem 2005, 6, 1169-1173.
23. Jessani, N.; Niessen, S.; Wei, B. Q.; Nicolau, M.; Humphrey, M.; Ji, Y.; Han, W.; Noh, D.-Y.; Yates, J. R.; Jeffrey, S. S.; Cravatt, B. F. Nat. Methods 2005, 2, 691-697.
24. Huang, L.-C. L.; Chang, H.-C. Langmuir 2004, 20, 5879-5884.
25. Kong, X. L.; Huang, L.-C. L.; Hsu, C.-M.; Chen, W.-H.; Han, C.-C.; Chang, H.-C. Anal. Chem. 2005, 77, 259-265.
26. A 1:20 mass ratio of the total proteins to the nanodiamonds was found sufficient for effective protein adsorption, but increasing the diamond dosage to a level of 50 times the protein mass facilitates high-throughput operations due to reduced relative loss in collection of nanodiamonds after centrifugation.
27. Tsay, Y. G.; Wang, Y. H.; Chiu, C. M.; Shen, B. J.; Lee, S. C. Anal. Biochem. 2000, 287, 55-64.
28. Laemmli, U. K. Nature 1970, 227, 680-685.
29. Fung, K. Y.; Glode, L. M.; Green, S.; Duncan, M. W. Prostate 2004, 61, 171-181.
30. Smith, G.; Barratt, D.; Rowlinson, R.; Nickson, J.; Tonge, R. Proteomics 2005, 5, 2315-2318.

Chapter 8 Reference

1. J. A. Loo, Mass Spectrom. Rev. 16, 1 (1997).
2. G. Brenner-Weiss, F. Kirschhofer, B. Kuhl, M. Nusser, and U. Obst, J. Chromatogr. A 1009, 147 (2003).
3. V. Katta and B. T. Chait, J. Am. Chem. Soc. 113, 8534 (1991).
4. Y.-T. Li, Y.-L. Hsieh, J. D. Henion, and B. Ganem, J. Am. Soc. Mass Spectrom. 4, 631 (1993).
5. D. S. Gross, Y. Zhao, and E. R. Williams, J. Am. Soc. Mass Spectrom. 8, 519 (1997).
6. Y.-L. Chen, J. M. Campbell, B. A. Collings, L. Konermann, and D. J. Douglas, Rapid Commun. Mass Spectrom. 12, 1003 (1998).
7. F. He, C. L. Hendrickson, and A. G. Marshall, J. Am. Soc. Mass Spectrom. 11, 120 (2000).
8. K. R. Babu and D. J. Douglas, Biochemistry 39, 14702 (2000).
9. P. A. Chrisman, K. A. Newton, G. E. Reid, J. M. Wells, and S. A. McLuckey, Rapid Commun. Mass Spectrom. 15, 2334 (2001).
10. K. J. Mark and D. J. Douglas, Rapid Commun. Mass Spectrom. 20, 111 (2006).
11. S. Z. Hu, K. M. Vogel, and T. G. Spiro, J. Am. Chem. Soc. 116, 11187 (1994).
12. J. S. Olson and G. N. Phillips, Jr., JBIC, J. Biol. Inorg. Chem. 2, 544 (1997).
13. E. Sigfridsson and U. Ryde, JBIC, J. Biol. Inorg. Chem. 4, 99 (1999).
14. E. Antonini and M. Brunori, Hemoglobin and Myoglobin in their Reactions with Ligands _North-Holland, Amsterdam, (1971).
15. C. L. Hunter, A. G. Mauk, and D. J. Douglas, Biochemistry 36, 1018 (1997).
16. M. S. Hargrove, A. J. Wilkinson, and J. S. Olson, Biochemistry 35, 11300 (1996).
17. C. L. Hunter, E. Lloyd, L. D. Eltis, S. P. Rafferty, H. Lee, M. Smith, and A. G. Mauk, Biochemistry 36, 1010 (1997).
18. T. Solouki, L. Pasa-Tolic, G. S. Jackson, S. G. Guan, and A. G. Marshall, Anal. Chem. 68, 3718 (1996).
19. P. D. Schnier, J. C. Jurchen, and E. R. Williams, J. Phys. Chem. B 103,737 (1999).
20. J. W. Gauthier, T. R. Trautman, and D. B. Jacobson, Anal. Chim. Acta 246, 211 (1991).
21. S. K. Shin and S. J. Han, J. Am. Soc. Mass Spectrom. 8, 86 (1997).
22. S. J. Pastor and C. L. Wilkins, Int. J. Mass Spectrom. Ion Process. 175, 81 (1998).
23. M. V. Gorshkov, L. Pasa-Tolic, and R. D. Smith, J. Am. Soc. Mass Spectrom. 10, 15 (1999).
24. J. Laskin, E. Denisov, and J. H. Futrell, Int. J. Mass. Spectrom. 219, 189 (2002).
25. X. Guo, M. C. Duursma, A. Al-Khalili, and R. M. A. Heeren, Int. J. Mass. Spectrom. 225, 71 (2003).
26. J. Laskin and J. H. Futrell, Mass Spectrom. Rev. 22, 158 (2003).
27. A. G. Marshall,C. L. Hendrickson, and G. S. Jackson, Mass Spectrom. Rev. 17, 1 (1998).
28. J. Laskin and J. S. Futrell, Mass Spectrom. Rev. 24, 135 (2005).
29. R. A. Jockusch, K. Paech, and E. R. Williams, J. Phys. Chem. A 104, 3188 (2000).
30. K. Paech, R. A. Jockusch, and E. R. Williams, J. Phys. Chem. A 106, 9761 (2002).
31. M. A. Freitas, C. L. Hendrickson, and A. G. Marshall, J. Am. Chem. Soc. 122, 7768 (2000).
32. O. P. Charkin, N. M. Klimenko, P. T. Nguyen, D. O. Charkin, A. M. Mebel, S. H. Lin, Y.-S. Wang, S.-C. Wei, and H.-C. Chang, Chem. Phys. Lett. 415, 362 (2005).
33. X. L. Kong, I.-A. Tsai, S. Sabu, C.-C. Han, Y. T. Lee, H.-C. Chang, S.-Y. Tu, A. H. Kung, and C.-C. Wu, Angew. Chem., Int. Ed. 45, 4130 (2006).
34. C. S. Yu and A. H. Kung, J. Opt. Soc. Am. B 16, 2233 (1999).
35. X. Qian, T. Zhang, C. Y. Ng, A. H. Kung, and M. Ahmed, Rev. Sci. Instrum. 74, 2784 (2003).
36. H. B. Oh, K. Breuker, S. K. Sze, Y. Ge, B. K. Carpenter, and F. W. McLafferty, Proc. Natl. Acad. Sci. U.S.A. 99, 15863 (2002).
37. H. B. Oh, C. Lin, H. Y. Hwang, H. Zhai, K. Breuker, V. Zabrouskov, B. K. Carpenter, and F. W. McLafferty, J. Am. Chem. Soc. 127, 4076 (2005).
38. Y.-S. Wang, H.-C. Chang, J. C. Jiang, S. H. Lin, Y. T. Lee, and H.-C. Chang, J. Am. Chem. Soc. 120, 8777 (1998).
39. C.-C. Wu, J. C. Jiang, I. Hahndorf, C. Chaudhuri, Y. T. Lee, and H.-C. Chang, J. Phys. Chem. A 104, 9556 (2000).
40. C. Chaudhuri, J. C. Jiang, C.-C. Wu, X. Wang, and H.-C. Chang, J. Phys. Chem. A 105, 8906 (2001).
41. It was found experimentally that the ratio of ferrous versus ferric hMbn+ produced from ESI of the reducing-reagent-treated solution decreases rapidly with increasing n. At n = 11, the ratio was ~0.3, which is too low to allow accurate measurement for the dissociation rate constant of ferrous hMb11+ by IRMPD.
42. M. F. Jarrold, Acc. Chem. Res. 32, 360 (1999).
43. R. H. Austin, A. H. Xie, L. van der Meer, B. Redlich, P. A. Lindgard, H. Frauenfelder, and D. Fu, Phys. Rev. Lett. 94, 128101 (2005).
44. J. Oomens, D. T. Moore, G. von Helden, G. Meijer, and R. C. Dunbar, J. Am. Chem. Soc. 126, 724 (2004).
45. M.-S. Liao and S. Scheiner, J. Chem. Phys. 116, 3635 (2002).