Zhao Qiyuan, Garimella Sanjay S, Savoie Brett M
Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47906, United States.
J Am Chem Soc. 2023 Mar 22;145(11):6135-6143. doi: 10.1021/jacs.2c11857. Epub 2023 Mar 7.
The search for prebiotic chemical pathways to biologically relevant molecules is a long-standing puzzle that has generated a menagerie of competing hypotheses with limited experimental prospects for falsification. However, the advent of computational network exploration methodologies has created the opportunity to compare the kinetic plausibility of various channels and even propose new pathways. Here, the space of organic molecules that can be formed within four polar or pericyclic reactions from water and hydrogen cyanide (HCN), two established prebiotic candidates for generating biological precursors, was comprehensively explored with a state-of-the-art exploration algorithm. A surprisingly diverse reactivity landscape was revealed within just a few steps of these simple molecules. Reaction pathways to several biologically relevant molecules were discovered involving lower activation energies and fewer reaction steps compared with recently proposed alternatives. Accounting for water-catalyzed reactions qualitatively affects the interpretation of the network kinetics. The case-study also highlights omissions of simpler and lower barrier reaction pathways to certain products by other algorithms that qualitatively affect the interpretation of HCN reactivity.
寻找通往具有生物学相关性分子的益生元化学途径是一个长期存在的难题，已经产生了一系列相互竞争的假说，而用于证伪的实验前景有限。然而，计算网络探索方法的出现创造了比较各种途径动力学合理性的机会，甚至还能提出新的途径。在此，使用一种先进的探索算法全面探索了有机分子的空间，这些有机分子可由水和氰化氢（HCN）通过四个极性或周环反应形成，水和氰化氢是两种公认的用于生成生物前体的益生元候选物。在这些简单分子的几步反应内就揭示出了令人惊讶的多样反应性景观。与最近提出的替代途径相比，发现了通往几种具有生物学相关性分子的反应途径，这些途径涉及更低的活化能和更少的反应步骤。考虑水催化反应会定性地影响对网络动力学的解释。该案例研究还凸显了其他算法对某些产物遗漏了更简单、势垒更低的反应途径，这在定性上影响了对HCN反应性的解释。
