Wang Ping, Ohanessian Gilles, Wesdemiotis Chrys
The Dow Chemical Company, 2301 N. Brazosport Blvd, B-1219 Freeport, TX 77541-3257, USA.
Eur J Mass Spectrom (Chichester). 2009;15(2):325-35. doi: 10.1255/ejms.987.
The unimolecular chemistry of Cu(II)AA(AA - H) complexes, composed of an intact and a deprotonated amino acid (AA) ligand, have been probed in the gas phase by tandem and multistage mass spectrometry in an electrospray ionization quadrupole ion trap mass spectrometer. The amino acids examined include Gly, Ala, Val, Leu, Ile, t-Leu and Phe. Upon collisionally-activated dissociation (CAD), the Cu(II)AA(AA - H) complexes undergo decarboxylation with simultaneous reduction of Cu(II) to Cu(I); during this process, a radical site is created at the alpha-carbon of the decarboxylated ligand (H(2)N(1) - ()C(alpha)H - C(beta)H(2) - R; R = side chain substituent). The radical site is able to move along the backbone of the decarboxylated amino acid to form two new radicals (HN(1)() - C(alpha)H(2) - C(beta)H(2) - R and H(2)N(1) - C(alpha)H(2) - (*)C(beta)H - R). From the complexes of Gly and t-Leu, only C(alpha) and N(1) radicals can be formed. The whole radical ligand can be lost to form Cu(I)AA from these three isomeric radicals. Alternatively, further radical induced dissociations can take place along the backbone of the decarboxylated amino acid ligand to yield Cu(II)AA(AA - 2H - CO(2)), Cu(I)AA((*)NH(2)), Cu(I)AA(HN = C(alpha)H(2)), or Cu(I)AA(H(2)N - C(alpha)H = C(beta)H - R' (R' = partial side chain substituent). The sodiated copper complexes, Cu(II)(AA - H + Na)(AA - H), show the same fragmentation patterns as their non-sodiated counterparts; sodium ion is retained on the intact amino acid ligand and is not involved in the CAD pathways. The amino groups of both AA units, the carbonyl group of the intact amino acid, and the deprotonated hydroxyl oxygen coordinate Cu(II) in square-planar fashion. Ab initio calculations indicate that the metal ion facilitates hydrogen atom shuttling between the N(1), C(alpha) and C(beta) atoms of the decarboxylated amino acid ligand. The dissociations of the decarboxylated radical ions unveil important insight about the so far largely unknown intrinsic chemistry of alpha-amino acid and peptide radicals, which are implicated as intermediates in numerous pathogenic biological processes.
由一个完整的氨基酸配体和一个去质子化氨基酸（AA）配体组成的[Cu(II)AA(AA - H)]⁺配合物的单分子化学，已在电喷雾电离四极杆离子阱质谱仪中通过串联和多级质谱在气相中进行了探究。所研究的氨基酸包括甘氨酸（Gly）、丙氨酸（Ala）、缬氨酸（Val）、亮氨酸（Leu）、异亮氨酸（Ile）、叔亮氨酸（t - Leu）和苯丙氨酸（Phe）。在碰撞激活解离（CAD）过程中，[Cu(II)AA(AA - H)]⁺配合物发生脱羧反应，同时Cu(II)还原为Cu(I)；在此过程中，在脱羧配体的α - 碳上产生一个自由基位点（H₂N¹ - ()CαH - CβH₂ - R；R = 侧链取代基）。该自由基位点能够沿着脱羧氨基酸的主链移动，形成两个新的自由基（HN¹() - CαH₂ - CβH₂ - R和H₂N¹ - CαH₂ - ()CβH - R）。从甘氨酸和叔亮氨酸的配合物中，只能形成Cα和N¹自由基。这三个异构自由基可导致整个自由基配体丢失，形成[Cu(I)AA]⁺。或者，沿着脱羧氨基酸配体的主链可发生进一步的自由基诱导解离，生成[Cu(II)AA(AA - 2H - CO₂)]⁺、[Cu(I)AA(()NH₂)]⁺、[Cu(I)AA(HN = CαH₂)]⁺或[Cu(I)AA(H₂N - CαH = CβH - R']⁺（R' = 部分侧链取代基）。钠化铜配合物[Cu(II)(AA - H + Na)(AA - H)]⁺显示出与非钠化对应物相同的碎裂模式；钠离子保留在完整的氨基酸配体上，不参与CAD途径。两个AA单元的氨基、完整氨基酸的羰基以及去质子化的羟基氧以平面正方形方式配位Cu(II)。从头算计算表明，金属离子促进了脱羧氨基酸配体的N¹、Cα和Cβ原子之间的氢原子穿梭。脱羧自由基离子的解离揭示了关于迄今为止在很大程度上未知的α - 氨基酸和肽自由基内在化学的重要见解，这些自由基在众多致病生物过程中作为中间体。
