Orzeł Ł, Waś J, Kania A, Susz A, Rutkowska-Zbik D, Staroń J, Witko M, Stochel G, Fiedor L
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060, Kraków, Poland.
Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
J Biol Inorg Chem. 2017 Aug;22(6):941-952. doi: 10.1007/s00775-017-1472-1. Epub 2017 Jun 21.
In this study, we evaluate the factors which determine the reactivity of divalent metal ions in the spontaneous formation of metallochlorophylls, using experimental and computational approaches. Kinetic studies were carried out using pheophytin a in reactions with various divalent metal ions combined with non- or weakly-coordinative counter ions in a series of organic solvents. To obtain detailed insights into the solvent effect, the metalations with the whole set of cations were investigated in three solvents and with Zn in seven solvents. The reactions were monitored using electronic absorption spectroscopy and the stopped-flow technique. DFT calculations were employed to shed light on the role of solvent in activating the metal ions towards porphyrinoids. This experimental and computational analysis gives detailed information regarding how the solvent and the counter ion assist/hinder the metalation reaction as activators/inhibitors. The metalation course is dictated to a large extent by the reaction medium, via either the activation or deactivation of the incoming metal ion. The solvent may affect the metalation in several ways, mainly via H-bonding with pyrrolenine nitrogens and the activation/deactivation of the incoming cation. It also seems to affect the activation enthalpy by causing slight conformational changes in the macrocyclic ligand. These new mechanistic insights contribute to a better understanding of the "metal-counterion-solvent" interplay in the metalation of porphyrinoids. In addition, they are highly relevant to the mechanisms of metalation reactions catalyzed by chelatases and explain the differences between the insertion of Mg and other divalent cations.
在本研究中，我们采用实验和计算方法，评估了在金属叶绿素自发形成过程中决定二价金属离子反应活性的因素。动力学研究是使用脱镁叶绿素a与各种二价金属离子在一系列有机溶剂中反应进行的，这些二价金属离子结合了非配位或弱配位抗衡离子。为了深入了解溶剂效应，我们在三种溶剂中研究了与所有阳离子的金属化反应，并在七种溶剂中研究了与锌的金属化反应。反应通过电子吸收光谱和停流技术进行监测。采用密度泛函理论（DFT）计算来阐明溶剂在激活金属离子与卟啉类化合物反应中的作用。这种实验和计算分析提供了关于溶剂和抗衡离子如何作为活化剂/抑制剂协助/阻碍金属化反应的详细信息。金属化过程在很大程度上由反应介质决定，这是通过对进入的金属离子的活化或失活来实现的。溶剂可能通过多种方式影响金属化反应，主要是通过与吡咯啉氮形成氢键以及对进入阳离子的活化/失活。它似乎还通过引起大环配体的轻微构象变化来影响活化焓。这些新的机理见解有助于更好地理解卟啉类化合物金属化过程中的“金属 - 抗衡离子 - 溶剂”相互作用。此外，它们与螯合酶催化的金属化反应机制高度相关，并解释了镁和其他二价阳离子插入反应之间的差异。
