Effect of Metals in Biomimetic Dimetal Complexes on Affinity and Gas-Phase Protection of Phosphate Esters

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• 作者：Simon Svane ; Thomas J. D. J酶rgensen ; Christine J. McKenzie ; Frank Kjeldsen
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：July 21, 2015
• 年：2015
• 卷：87
• 期：14
• 页码：7060-7068
• 全文大小：457K
• ISSN：1520-6882

文摘

Although the biomimetic dimetal complex [LGa₂(OH)₂(H₂O)₂]³⁺ [L = 2,6-bis((N,N鈥?bis(2-picolyl)amino)methyl)-4-tertbutylphenolate] provides efficient protection against phosphate loss in phosphopeptides upon collision-induced dissociation tandem mass spectrometry (CID MS/MS), the underlying mechanism remains unknown. Here, we explored the mechanism in detail and investigated the selective binding to phosphate groups in solution. Dimetal complexes containing combinations of Ga³⁺, In³⁺, Fe³⁺, Co³⁺, Zn²⁺, Cu²⁺, and V²⁺ were reacted with HPO₄^{2鈥?/sup>, phosphoserine, and a phosphopeptide (FQpSEEQQQTEDELQDK, abbreviated 鈥溛瞔as鈥? and studied with isothermal titration calorimetry (ITC), CID MS/MS, and density functional theory (DFT). K_a for HPO₄2鈥?/sup> binding scaled with the metal charge and was 35-fold larger for [LGa₂(OH)₂(H₂O)₂]3+ (3.08 卤 0.31 脳 106 M鈥?) than for [LZn₂(HCOO)₂]+. CID MS/MS of [LGa₂(尾cas)]n+ revealed protection against phosphate detachment (<3% of the total ion intensity). Phosphate detachment from 尾cas was 22鈥?0% and increased to 42鈥?1% when bound to dimetal complexes of lower charge than {LGa₂}5+. CID data suggests that facile metal鈥損hosphate dissociation is associated with proton transfer from the intermediate oxazoline ring formed in the phosphopeptide to the metal鈥損hosphate complex. The observed phosphate stabilization was attributed to a significant reduction in the gas-phase basicity (GB) of the phosphate group when bound to {LGa₂}5+/{LIn₂}5+ complex cores. Absence of proton transfer results in formation of an ion鈥搝witterion intermediate with a greater dissociation threshold. This hypothesis is supported by DFT calculations for [LGa₂(PO₄)]2+, [LGaZn(PO₄)]+, [LZn₂(PO₄)], and 2,4-dimethyl-3-oxazoline showing that [LGa₂(PO₄)]2+ is the only compound with a substantial lower GB (321 kJ/mol less) than 2,4-dimethyl-3-oxazoline.}