Fragmentation Reaction of Complexes of Alkali Metal Cations with Tripeptides in Gas Phase†

doi:10.7503/cjcu20160447

Abstract

Abstract:

For exploring effects of side chain R groups on dissociations of complexes of alkali metal ions with peptides in gas phase, the complexes of Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺ and the tripeptides Glycyl-glycyl-glycine(GGG), Glycyl-phenylalanyl-glycine(GFG) and Glycyl-glycyl-phenylalanine(GGF) were chosen to probe the fragmentation reaction process by electrospray ionization mass spectrometry. The experimental results demonstrated that Li⁺, Na⁺ or K⁺and GGG, GFG or GGF can form complexes in a coordination ratio of 1∶1 or 2∶1, respectively. The mass spectra for competition reactions of GGG, GFG or GGF with Li⁺, Na⁺ or K⁺showed peak intensity of alkali metallated-tripeptide complexes decrease in the order of Li⁺, Na⁺, K⁺ similarly, indicating that the binding strength of complexes descend with the ascend of the radii of alkali metal ion. Collision-induced dissociation(CID) results showed the center of mass frame collision energy E(CM)₅₀ values were 1.94, 1.76 and 1.63 eV for the precursor of [GGG+Na]⁺, [GGF+Na]⁺ and [GFG+Na]⁺, respectively. The mass spectrometric titrations determined the lg $K a 1$ values were 5.30, 5.25 and 5.17, respectively. Quantitative analyses of mass spectra further confirmed the stability order [GGG+Na]⁺ >[GGF+Na]⁺>[GFG+Na]⁺, indicating binding strength of complexes GFG or GGF with R side chain(benzyl group) were weaker than GGG with R side chain(only hydrogen atom) due to effects of steric hindrance. The tandem mass spectrometric analysis revealed that dissociation of soliated GGG produces most abundant soliated a₂, b_n, y_n ion series, while soliated GGF or GFG ion gives abundant soliated y_n and b_n ions, but rarely soliated a_n. Moreover, doubly alkali meallated GGF tends to dissociate to more metallated y ion series. The breakdown graph for the complex [GGF+Na]⁺ showed the percentage of fragment ion [b₂+Na+OH]⁺ will go up greatly upon the increasing of collision energy. According to Siu’s fragmentation mechanisms of protonated tripeptide, it is inferred that soliated GFG will fragment to [b₂+Na]⁺ ion with an incipient oxazolone. Then [b₂+Na]⁺ will continue to fragment to [a₂+Na]⁺ with a cyclic protonted 4-imidazolidone.

Key words: Electrospray ionization mass spectrometry, Alkali metal ion, Tripeptide, Complex, Fragmentation reaction

CLC Number:

O657.6

TrendMD:

WU Ruofei, CHU Yanqiu, XU Chongsheng, LIU Zhipan, DING Chuanfan. Fragmentation Reaction of Complexes of Alkali Metal Cations with Tripeptides in Gas Phase^†[J]. Chem. J. Chinese Universities, 2016, 37(12): 2150.

Figures/Tables 10

Fig.1 Nomenclature used for fragments of tripeptidesGGG: R1=R2=R3=H; GFG: R1=R3=H, R2=—CH2—C6H5; GGF: R1=R2=H, R3=—CH2—C6H5.

Fig.2 Mass spectra for competition reaction of tripeptides with alkali metal ions(A) GGG with Li+, Na+, K+, Rb+ and Cs+ in a molar ratio of 1∶1∶1∶1∶1∶1; (B) GFG with Li+, Na+ and K+ in a molar ratio of 1∶1∶1∶1; (C) GGF with Li+, Na+ and K+ in a molar ratio of 1∶1∶1∶1.

Fig.3 Normalized percentages of the intact complexes plotted against collision energy of mass frame(A) GGG with a proton or an alkali ion; (B) GGG, GFG or GGF with a Na+; (C) GGG with one or two Na+.

Table 1 lg K a 1 values of GGG,GFG or GGF with Li+, Na+ or K+

Complex	lg $K a 1 a$	SD^b	RSD(%)^c	Complex	lg $K a 1 a$	SD^b	RSD(%)^c
[GGG+Li]⁺	5.32	0.20	3.4	[GFG+K]⁺	5.10	0.02	0.3
[GGG+Na]⁺	5.30	0.07	1.3	[GGF+Li]⁺	5.25	0.13	2.6
[GGG+K]⁺	5.14	0.12	2.3	[GGF+Na]⁺	5.17	0.19	3.8
[GFG+Li]⁺	5.20	0.10	2.0	[GGF+K]⁺	5.11	0.06	1.1
[GFG+Na]⁺	5.15	0.04	0.7

Table 1 lg K a 1 values of GGG,GFG or GGF with Li+, Na+ or K+

Complex	lg $K a 1 a$	SD^b	RSD(%)^c	Complex	lg $K a 1 a$	SD^b	RSD(%)^c
[GGG+Li]⁺	5.32	0.20	3.4	[GFG+K]⁺	5.10	0.02	0.3
[GGG+Na]⁺	5.30	0.07	1.3	[GGF+Li]⁺	5.25	0.13	2.6
[GGG+K]⁺	5.14	0.12	2.3	[GGF+Na]⁺	5.17	0.19	3.8
[GFG+Li]⁺	5.20	0.10	2.0	[GGF+K]⁺	5.11	0.06	1.1
[GFG+Na]⁺	5.15	0.04	0.7

Fig.4 Collision-induced dissociation(CID) spectra for complexes at collision energy of 32 eV(A) [GGF+Na]+; (B) [GGF+2Na-H]+.

Table 2 CID fragment ions formed from protonated or alkali metallated triglycine complexes

Precursor ion(#)	a_n/ $a n $ / $a n *$	b_n/ $b n $ / $b n *$	y_n/ $y n $ / $y n *$	Other
[G3+H]⁺	a₂	b₁, b₂	y₁, y₂	[#-H₂O]⁺
[G3+Li]⁺	a₂, $a 2 *$	$b 1 $ , $b 2 $ , [b₁+OH+Li]⁺, [b₂+OH+Li]⁺	$y 1 $ , $y 2 $ , $y 1 $ -H₂O, $y 2 $ -H₂O	[#-H₂O]⁺, [#-NH₃-H₂O]⁺
[G3+Na]⁺	$a 2 *$	$b 2 *$ , [b₁+OH+Na]⁺, [b₂+OH+Na]⁺	$y 1 $ , $y 2 $ , $y 2 *$ -H₂O	[#-H₂O]⁺, [#-NH₃]⁺
[G3+K]⁺	$a 2 *$			K⁺
[G3+2Li-H]⁺	a₂, $a 2 **$	$b 2 **$	$y 2 $ , $y 2 $ -H₂O, $y 1 **$	[#-H₂O]⁺ , [#-NH₃]⁺ , [#-NH₃- H₂O]⁺
[G3+2Na-H]⁺	$a 2 **$	$b 1 **$	$y 1 **$	[#-H₂O]⁺
[G3+2K-H]⁺		$b 2 **$		K⁺

Table 2 CID fragment ions formed from protonated or alkali metallated triglycine complexes

Precursor ion(#)	a_n/ $a n $ / $a n *$	b_n/ $b n $ / $b n *$	y_n/ $y n $ / $y n *$	Other
[G3+H]⁺	a₂	b₁, b₂	y₁, y₂	[#-H₂O]⁺
[G3+Li]⁺	a₂, $a 2 *$	$b 1 $ , $b 2 $ , [b₁+OH+Li]⁺, [b₂+OH+Li]⁺	$y 1 $ , $y 2 $ , $y 1 $ -H₂O, $y 2 $ -H₂O	[#-H₂O]⁺, [#-NH₃-H₂O]⁺
[G3+Na]⁺	$a 2 *$	$b 2 *$ , [b₁+OH+Na]⁺, [b₂+OH+Na]⁺	$y 1 $ , $y 2 $ , $y 2 *$ -H₂O	[#-H₂O]⁺, [#-NH₃]⁺
[G3+K]⁺	$a 2 *$			K⁺
[G3+2Li-H]⁺	a₂, $a 2 **$	$b 2 **$	$y 2 $ , $y 2 $ -H₂O, $y 1 **$	[#-H₂O]⁺ , [#-NH₃]⁺ , [#-NH₃- H₂O]⁺
[G3+2Na-H]⁺	$a 2 **$	$b 1 **$	$y 1 **$	[#-H₂O]⁺
[G3+2K-H]⁺		$b 2 **$		K⁺

Table 3 CID fragment ions formed from protonated or alkali metallated GFG complexes

Precursor ion(#)	a_n/ $a n $ / $a n *$	b_n/ $b n $ / $b n *$	y_n/ $y n $ / $y n *$	Other
[GFG+H]⁺	a₂	b₂	y₂, y₂-H₂O
[GFG+Li]⁺	a_2*	[b₁+OH+Li]⁺, [b₂+OH+Li]⁺ , $b 1 $ , $b 2 $	$y 1 $ , $y 2 $ , $y 2 $ -H₂O, $y 1 $ -H₂O, $y 1 *$ -H₂O-C₇H₇	[#-H₂O]⁺,[#-C₇H₇]⁺ , [#-H₂O-NH₃]⁺ , [#-H₂O-C₇H₇]⁺
[GFG+Na]⁺	$a 2 *$	[b₂+OH+Na]⁺, [b₁+OH+Na]⁺ ,b_2*	$y 1 $ , $y 2 $ -H₂O, $y 2 *$	[#-H₂O]⁺
[GFG+K]⁺	$a 2 *$			[#-H₂O]⁺ , K⁺
[GFG+2Li-H]⁺	$a 2 **$	$b 2 **$	$y 2 $ -H₂O, $y 1 $ , $y 2 $ , $y 2 $ -C₇H₇	[#-H₂O]⁺, [#-H₂O-C₇H₇]⁺, [#-C₇H₇]⁺
[GFG+2Na-H]⁺		$b 2 **$	$y 2 $ , $y 1 $ , $y 2 $ -H₂O, $y 2 $ -C₇H₇	[#-H₂O]⁺ , [#-NH₃-H₂O]⁺, [#-C₇H₇]⁺

Table 3 CID fragment ions formed from protonated or alkali metallated GFG complexes

Precursor ion(#)	a_n/ $a n $ / $a n *$	b_n/ $b n $ / $b n *$	y_n/ $y n $ / $y n *$	Other
[GFG+H]⁺	a₂	b₂	y₂, y₂-H₂O
[GFG+Li]⁺	a_2*	[b₁+OH+Li]⁺, [b₂+OH+Li]⁺ , $b 1 $ , $b 2 $	$y 1 $ , $y 2 $ , $y 2 $ -H₂O, $y 1 $ -H₂O, $y 1 *$ -H₂O-C₇H₇	[#-H₂O]⁺,[#-C₇H₇]⁺ , [#-H₂O-NH₃]⁺ , [#-H₂O-C₇H₇]⁺
[GFG+Na]⁺	$a 2 *$	[b₂+OH+Na]⁺, [b₁+OH+Na]⁺ ,b_2*	$y 1 $ , $y 2 $ -H₂O, $y 2 *$	[#-H₂O]⁺
[GFG+K]⁺	$a 2 *$			[#-H₂O]⁺ , K⁺
[GFG+2Li-H]⁺	$a 2 **$	$b 2 **$	$y 2 $ -H₂O, $y 1 $ , $y 2 $ , $y 2 $ -C₇H₇	[#-H₂O]⁺, [#-H₂O-C₇H₇]⁺, [#-C₇H₇]⁺
[GFG+2Na-H]⁺		$b 2 **$	$y 2 $ , $y 1 $ , $y 2 $ -H₂O, $y 2 $ -C₇H₇	[#-H₂O]⁺ , [#-NH₃-H₂O]⁺, [#-C₇H₇]⁺

Table 4 CID fragment ions formed from protonated or alkali metallated GFG complexes

Precursor ion(#)	a_n/ $a n $ / $a n *$	b_n/ $b n $ / $b n *$	y_n/ $y n $ / $y n *$	Other
[GGF+H]⁺			y₂-H₂O
[GGF+Li]⁺	$a 2 *$	[b₂+OH+Li]⁺, [b₁+OH+Li]⁺	$y 1 $ , $y 2 $ , $y 2 $ -H₂O, $y 2 $ -H₂O-C₇H₇	[#-H₂O]⁺, [#-NH₃- H₂O]⁺ , [#-H₂O-C₇H₇]⁺ , [#-C₇H₇]⁺
[GGF+Na]⁺		$b 1 *$ , [b₁+OH+Na] ⁺, [b₂+OH+Na]⁺	$y 1 $ , $y 2 $ , $y 2 *$ -H₂O	[#-H₂O]⁺ , [#-NH₃-H₂O]⁺ , [#-C₇H₇]⁺
[GGF+K]⁺				[#-H₂O]⁺ , K⁺
[GGF+2Li-H]⁺	$a 2 *$	$b 1 $ , $b 2 $	$y 1 $ -H₂O, $y 1 $ -C₇H₇, $y 2 $ , $y 2 *$ -C₇H₇	[#-H₂O]⁺, [#-NH₃]⁺ , [#-NH₃-H₂O]⁺ , [#-H₂O-C₇H₇]⁺ , [#-C₇H₇]⁺
[GGF+2Na-H]⁺		$b 1 $ , $b 2 $	$y 2 $ , $y 1 $ , $y 2 $ -H₂O, $y 1 $ -C₇H₇, $y 2 **$ -C₇H₇	[#-H₂O]⁺ , [#-NH₃-H₂O]⁺ , [#-C₇H₇]⁺

Table 4 CID fragment ions formed from protonated or alkali metallated GFG complexes

Precursor ion(#)	a_n/ $a n $ / $a n *$	b_n/ $b n $ / $b n *$	y_n/ $y n $ / $y n *$	Other
[GGF+H]⁺			y₂-H₂O
[GGF+Li]⁺	$a 2 *$	[b₂+OH+Li]⁺, [b₁+OH+Li]⁺	$y 1 $ , $y 2 $ , $y 2 $ -H₂O, $y 2 $ -H₂O-C₇H₇	[#-H₂O]⁺, [#-NH₃- H₂O]⁺ , [#-H₂O-C₇H₇]⁺ , [#-C₇H₇]⁺
[GGF+Na]⁺		$b 1 *$ , [b₁+OH+Na] ⁺, [b₂+OH+Na]⁺	$y 1 $ , $y 2 $ , $y 2 *$ -H₂O	[#-H₂O]⁺ , [#-NH₃-H₂O]⁺ , [#-C₇H₇]⁺
[GGF+K]⁺				[#-H₂O]⁺ , K⁺
[GGF+2Li-H]⁺	$a 2 *$	$b 1 $ , $b 2 $	$y 1 $ -H₂O, $y 1 $ -C₇H₇, $y 2 $ , $y 2 *$ -C₇H₇	[#-H₂O]⁺, [#-NH₃]⁺ , [#-NH₃-H₂O]⁺ , [#-H₂O-C₇H₇]⁺ , [#-C₇H₇]⁺
[GGF+2Na-H]⁺		$b 1 $ , $b 2 $	$y 2 $ , $y 1 $ , $y 2 $ -H₂O, $y 1 $ -C₇H₇, $y 2 **$ -C₇H₇	[#-H₂O]⁺ , [#-NH₃-H₂O]⁺ , [#-C₇H₇]⁺

Scheme 1 Fragmentation paths of [GFG+Na]+

Fig.5 Breakdown graph for precursor [GGF+Na]+

References 30

[1]	Xu B. F., Yang S., Zhu J. M., Ma Y. D., Zhao G., Guo Y., Xu L., Chem. Res. Chinese Universities, 2014, 30(1), 103—107
[2]	Li W. Z., Meng W., Tian P., Chem. Res. Chinese Universities, 2015, 31(1), 149—155
[3]	Chen C., Chu Y. Q., Dai X. H., Fang X., Ding C. F., J. Acta Phys.-Chim. Sin., 2013, 29(6), 1336—1343
	(陈琛, 储艳秋, 戴新华, 方向, 丁传凡. 物理化学学报,2013, 29(6), 1336—1343)
[4]	Dongre A. R., Jones J. L., Somogyi A., Wysocki V. H., J. Am. Chem. Soc., 1996, 118(35), 8365—8374
[5]	Paizs B., Suhai S., Mass Spectrom. Rev., 2005, 24(4), 508—548
[6]	Watson H. M., Vincent J. B., Cassady C. J., J. Mass Spectrom., 2011, 46(11), 1099—1107
[7]	Rozman M., Gaskell S. J., J. Mass Spectrom., 2010, 45(12), 1049—1415
[8]	Dunbar R. C., Polfer N. C., Berden G., Oomens J., Int. J. Mass Spectrom., 2012, 330, 71—77
[9]	Tang X., Ens W., Standing K. G., Westmore J. B., Anal. Chem., 1988, 60(17), 1791—1799
[10]	Teesch L. M., Orlando R. C., Adam J., J. Am. Chem. Soc., 1991, 113(10), 3668—3675
[11]	Teesch L. M., Adams J., J. Am. Chem. Soc., 1990, 112(11), 4110—4120
[12]	Feng W. Y., Gronert C., Fletcher K. A., Warres A., Lebrilla C. B., Int. J. Mass Spectrom., 2003, 222(1—3), 117—134
[13]	Wang Q., Chu Y. Q., Zhang K., Dai X. H., Fang X., Ding C. F., J. Acta Phys.-Chim. Sin., 2012, 28(4), 971—977
	(王青, 储艳秋, 张开, 戴新华, 方向, 丁传凡. 物理化学学报,2012, 28(4), 971—977)
[14]	Chen X. F., Liu G. Q., Wong Y. L. E., Chan T. W. D., Rapid Commun. Mass Spectrom., 2016, 30(6), 705—710
[15]	Asakawa D., de Pauw E., J. Am. Soc. Mass Spectrom., 2016, 27(7), 1165—1175
[16]	El A. H., Rodriquez C. F., Almeida D. R. P., Siu K. W. M., J. Am. Chem. Soc., 2003, 125(30), 9229—9236
[17]	Bythell B. J., Hernandez O., Steinmetz V., Paizs B., Int. J. Mass Spectrom., 2012, 316, 227—234
[18]	Wang H. X., Wang B., Wei Z. L., Zhang H., Guo X. H., J. Mass Spectrom., 2015, 50(1), 212—219
[19]	Wang B., Yu J. Y., Wang H. X., Wei Z. L., Guo X. H., J. Am. Soc. Mass Spectrom., 2014, 25(12), 2116—2124
[20]	Chen Y. J.,Yue L., Li Z. H., Ding X. L., Ding C. F., Anal. Methods, 2015, 7(13), 5551—5556
[21]	Qin Y. J., Wei S. G., Wang X. L., Yang F., Wang B., Guo X. H., Chem. J. Chinese Universities, 2011, 32(8), 2748—2751
	(秦玉娇, 魏士刚, 王晓录, 杨帆, 汪兵, 国新华. 高等学校化学学报,2011, 32(8), 2748—2751)
[22]	Biemann K., J. Methods Enzymol., 1990, 193, 455—479
[23]	Morishetti K. K., Russell S. C., Zhao X. N., Robinson D. B., Ren J. H., Int. J. Mass Spectrom., 2011, 308(1), 98—108
[24]	Chu Y. Q., Dai X. H., Jiang D., Fang X., Ding C. F., J. Rapid Commun. Mass Spectrom., 2010, 24(15), 2255—2261
[25]	Zhang H. R., Chen G., Wang L., Ding L., Jin W. J., Int. J. Mass Spectrom., 2006, 252(1), 1—10
[26]	Bligh S. W. A., Haley T., Lowe P. N., J. Mol. Recognit., 2003, 16(3), 139—147
[27]	Schmidt A. C., Mickein K., J. Mass Spectrom., 2012, 47(8), 949—961
[28]	He X. D., Wei W. H., Chu Y. Q., Liu Z. P., Ding C. F., Chin. J. Chem. Phys., 2013, 26(3), 287—294
[29]	Dai Z. Y., Chu Y. Q., Wu B., Wu L., Ding C. F., Acta Pharmacol. Sin., 2008, 29(6), 759—771
[30]	Powell K. D., Ghaemmaghami S., Wang M. Z., Ma L., Oas T. G., Fitzgerald M. C., J. Am. Chem. Soc., 2002, 124(35), 10256—10257