Gutlé C, Salpin J-Y, Cartailler T, Tortajada J, Gaigeot M-P
Université d'Evry val d'Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement, LAMBE UMR-8587, Rue Père A. Jarland, F-91025 Evry, France.
J Phys Chem A. 2006 Oct 19;110(41):11684-94. doi: 10.1021/jp0621528.
Within the context of metal biotoxicity, electrospray ionization mass spectrometry experiments (ESIMS) have recently been performed by us on the pyrimidine nucleobases (B) uracil and thymine complexed with lead(II) [Int. J. Mass. Spectrom. 2005, 243, 279]. Among the ions detected, [Pb(B)-H]+ complexes, where the base has been deprotonated, have been identified as producing intense signals. In the same study, quantum calculations based on density functional theory (DFT) have assessed the complexation sites and energies of [Pb(B)-H]+ ions. The present DFT investigations aim at giving an understanding on the energetics and mechanisms associated with uracil's loss of a proton. We specifically assess and quantify the role of lead binding in this process. For that purpose, intra- and intermolecular proton transfers have been considered. We have found that uracil (U) 1,3-tautomerization can be exergonic when uracil is complexed with Pb2+, in opposition to the situation without lead. The corresponding intramolecular processes were nonetheless found to occur at geological time scales. In contrast, the addition of a second body to [Pb(U)]2+ complexes, namely OH- or H2O (as found in the initial water droplet of ESIMS experiments), gives exergonic and fast uracil 1,3-proton transfers. Finally, we have shown that intermolecular proton transfers in uracil-H2O, uracil-OH-, or uracil-uracil complexes are able to explain the experimentally detected [Pb(U)-H]+ ions.
在金属生物毒性的背景下，我们最近对与铅（II）络合的嘧啶核碱基（B）尿嘧啶和胸腺嘧啶进行了电喷雾电离质谱实验（ESIMS）[《国际质谱杂志》2005年，第243卷，第279页]。在检测到的离子中，已确定碱基去质子化的[Pb（B）-H]+络合物会产生强烈信号。在同一研究中，基于密度泛函理论（DFT）的量子计算评估了[Pb（B）-H]+离子的络合位点和能量。目前的DFT研究旨在理解与尿嘧啶质子损失相关的能量学和机制。我们特别评估并量化了铅结合在此过程中的作用。为此，考虑了分子内和分子间的质子转移。我们发现，当尿嘧啶与Pb2+络合时，尿嘧啶（U）的1,3-互变异构可以是放能的，这与没有铅的情况相反。然而，相应的分子内过程在地质时间尺度上发生。相比之下，向[Pb（U）]2+络合物中添加第二个物体，即OH-或H2O（如在ESIMS实验的初始水滴中发现的），会产生放能且快速的尿嘧啶1,3-质子转移。最后，我们表明尿嘧啶-H2O、尿嘧啶-OH-或尿嘧啶-尿嘧啶络合物中的分子间质子转移能够解释实验检测到的[Pb（U）-H]+离子。
