Bythell Benjamin J, Harrison Alex G
Department of Chemistry and Biochemistry, University of Missouri-St. Louis, St. Louis, MO, 63131, USA,
J Am Soc Mass Spectrom. 2015 May;26(5):774-81. doi: 10.1007/s13361-015-1080-7. Epub 2015 Mar 26.
It is well-known that oxazolone b2 ions fragment extensively by elimination of CO to form a2 ions, which often fragment further to form a1 ions. Less well-known is that some oxazolone b2 ions may fragment directly to form a1 ions. The present study uses energy-resolved collision-induced dissociation experiments to explore the occurrence of the direct b2→a1 fragmentation reaction. The experimental results show that the direct b2→a1 reaction is generally observed when Gly is the C-terminal residue of the oxazolone. When the C-terminal residue is more complex, it is able to provide increased stability of the a2 product in the b2→a2 fragmentation pathway. Our computational studies of the relative critical reaction energies for the b2→a2 reaction compared with those for the b2→a1 reaction provide support that the critical reaction energies are similar for the two pathways when the C-terminal residue of the oxazolone is Gly. By contrast, when the nitrogen of the oxazolone ring in the b2 ion does not bear a hydrogen, as in the Ala-Sar and Tyr-Sar (Sar = N-methylglycine) oxazolone b2 ions, a1 ions are not formed but rather neutral imine elimination from the N-terminus of the b2 ion becomes a dominant fragmentation reaction. The M06-2X/6-31+G(d,p) density functional theory calculations are in general agreement with the experimental data for both types of reaction. In contrast, the B3LYP/6-31+G(d,p) model systematically underestimates the barriers of these SN2-like b2→a1 reaction. The difference between the two methods of barrier calculation are highly significant (P < 0.001) for the b2→a1 reaction, but only marginally significant (P = 0.05) for the b2→a2 reaction. The computations provide further evidence of the limitations of the B3LYP functional when describing SN2-like reactions.
众所周知,恶唑酮b2离子通过消除CO而广泛裂解形成a2离子,而a2离子常常会进一步裂解形成a1离子。不太为人所知的是,一些恶唑酮b2离子可能直接裂解形成a1离子。本研究利用能量分辨碰撞诱导解离实验来探究直接b2→a1裂解反应的发生情况。实验结果表明,当甘氨酸是恶唑酮的C端残基时,通常会观察到直接b2→a1反应。当C端残基更为复杂时,它能够在b2→a2裂解途径中提高a2产物的稳定性。我们对b2→a2反应与b2→a1反应的相对临界反应能进行的计算研究支持了这样的观点:当恶唑酮的C端残基是甘氨酸时,这两条途径的临界反应能相似。相比之下,当b2离子中恶唑酮环的氮不带有氢时,如在丙氨酸-肌氨酸和酪氨酸-肌氨酸(肌氨酸=N-甲基甘氨酸)恶唑酮b2离子中,不会形成a1离子,而是从b2离子的N端消除中性亚胺成为主要的裂解反应。M06-2X/6-31+G(d,p)密度泛函理论计算结果与这两种反应类型的实验数据总体上一致。相比之下,B3LYP/6-31+G(d,p)模型系统性地低估了这些类SN2的b2→a1反应的势垒。对于b2→a1反应,两种势垒计算方法之间的差异非常显著(P<0.001),但对于b2→a2反应,差异仅略微显著(P=0.05)。这些计算进一步证明了B3LYP泛函在描述类SN2反应时的局限性。