生命起源前手性对映体富集与放大的数学规律与实验

01作者

朱华结 , 李志伟 ,贾云殔 , 朱王俊 , Charles U. Pittman, 

1 河北科技大学, 化学与制药工程学院, 050018, 石家庄, 中国

2 河北大学, 生命科学院, 071002, 保定, 中国

3 安徽医科大药学院, 230012, 合肥, 中国

4 密西西比州立大学化学系, Mississippi State University, Starkville, 39762, MS, US

*E-mail:[e-mail], [e-mail],[e-mail] 和 [e-mail]

DOI:10.7535/hbkd.2023yx06007

02概要

生命的诞生有三种可能。概率论强调生命来自偶然，即各种化学反应中各种偶然结合的结果；神学则相信上帝创造了生命；剩下的一个选择：生命是地球上化学反应的必然吗？即只要出现某种结构，其化学规律导致到必然的生命的起源。而科学的回答这个问题，必须在生命形成前，解决生命起源前一些化学过程中的科学问题。这包括（1）为什么L-氨基酸首先微小过量；（2）这些微量L-氨基酸的手性富集；（3）L-氨基酸与D-糖的必然关系等。本文研究的是第二个问题，即化学反应中手性富集的必然性。

生命起源前的原始海洋（池）中，并没有手性源存在，但可能存在其它不对称因素，如对称性破缺。由于这些力很弱，合成出来的手性化合物可能以极小%ee值的非外消旋（non-racemic enantiomers）存在。早期报道认为，手性分子的手性放大与富集，可能与手性放大（chiral amplification）有关或者自身催化（auto-catalysis）相关。但是后来发现了手性耗尽（asymmetric depletion）现象。因此，手性放大和手性耗尽被统称为非线性效应（non-linear effect）。目前，在生命所能存在的环境条件下，并没有发现氨基酸衍生物的反应中具有手性放大或者自身催化。因此，如何在没有手性源存在的条件下，在数学上突破手性放大原理，并在温和的实验条件下，用实验验证其数学公式的可靠性就显得尤为重要。

我们从数学理论出发，结合有机化学反应原理，推导出非外消旋体可以通过一定的反应，其较小的%ee值（%ee₁）可以富集到较大的%ee值（%ee₂）。尤其在很低%ee值的情况下，理论上其放大倍数可以随反应产物的产率增加而呈现出指数级别的增加。也就是说，即使L-氨基酸稍微过量一点，那么数学和化学的原则就保证了这些稍微过量一点的L-氨基酸能够在温和的条件下（这也是生命所需要的），其%ee值可以得到有效提高。我们进一步通过使用L-色氨酸甲酯（L-tryptophane methyl ester (L-TME)）在约1%ee值的情况下，通过有机反应，将其放大富集到3.4%（%ee₂）左右。实验表明：其单次最大放大倍数可达1.92 (6.1%的%ee₁ 到11.7%的%ee₂)；单次最大增量达到12.3% (从 44.2% (%ee₁) 提高到56.5% (%ee₂))。

最后，简单讨论一下第三个问题，即，L-氨基酸与D-糖的必然关系。已有的报道和理论计算表明：L-氨基酸能催化D-四碳糖的合成。但是缺少L-氨基酸催化D-五碳糖的研究报道。而L-氨基酸和D-糖恰恰是构成生命的最基本的两类物质。因此，生命起源的路上，有其必然规律。可以预见，虽然现在有关生命起源（手性放大/富集）中的化学部分的研究已经不再是某些杂志的热点，但是对其深入研究，挖掘其背后的必然性，在生命起源研究中发现更多的必然因素和规律，可能是化学家、物理学家和生物学家的使命之一。

(需要详细的实验、计算、HPLC分析结果等详细材料，包括投稿到Molecules所做的preprint 等，请向通讯作者索要，免费提供)

03英文版本

The mathematic rule and the experiments of chiral enhancement/amplification for enantiomers before origin of life

Huajie Zhiwei , Yunjin , Yujun Zhu ,Charles U. Pittman, Jr. 

1.Hebei University of Science and Technology, Chemical and Pharmaceutical Engineering, 050018, Shijiazhuang, China

2.Hebei University, College of Life, 071002, Baoding, China

3. Anhui Medical University, College of Pharmacy, 230012, Hefei, China

4.Mississippi State University, Department of Chemistry, Starkville, 39762, MS, US

*E-mail: [e-mail]，[e-mail]，[e-mail] 和[e-mail]: 10.7535/hbkd.2023yx06007

Abstract

The origin of life may involve three possibilities. One is the probability theory that emphasizes the origin of life by chance in various chemical reactions; the other is that the life is created by the God; the third one is that it is the natural inevitable outcome chemically. To scientifically answer the question, it is necessary to understand the following questions: (1) Why are the L-aminoacids excessed with tiny %ee values. (2) How tiny %ee values of the L-aminoacids can increase to a reasonable high value without any chiral source, and (3) What is the relationship between the L-amino acids and D-sugars. The second question was studied in this paper.In the prebiotic pool, there is no any chiral source in the earliest time, formation of chiral compounds may have tiny %ee values due to some asymmetric factors (such as symmetry breaking). In previous reports, the enhancement of the %ee values may concern with the chiral amplification phenomenon or autocatalysis. However, asymmetric depletion was observed then. Thus, non-linear effect was used to represent the chiral amplification and depletion. However, no chiral amplification or self-catalysis has been found in the reactions of amino acids derivatives under moderate reaction conditions. Thus, it is particularly important to use mathematics to understand the chiral amplification or enhancement for non-racemic compounds, including to carryout the amplification/enhancement using experiments under mild reaction conditions without any chiral source or chiral catalysts.

A general method is presented that permits enantiomers, originally present in a low enantiomeric excess , to accumulate in a high ee without a chiral source present. Importantly, the chiral enhancement factor (multiples), , depends on the one product yield of this reaction. This enrichment exhibits a nonlinear increase in enhancement as approaches . It represents a possible route by which small initial %ee values of prebiotic molecules could have been raised to high contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reacting L-tryptophane methyl ester (L-TME) samples, initially present in low enantiomeric excess , with biacetyl or oxaldehyde (model reactions) run to various yields. The experimental results showed that the largest enhancement multiples are of to of , and the maximum of the increasement of L-TME was (from to in the experiments.

The reaction model is listed below. Initially, there are moles of and moles of in the reactions with moles of bisFG (such as 2,3-dibutanone). The yield of 3 is .

Based on the mathematic deduction, the %ee2 can be computed as:

Or its relationship with %ee1 can be expressed as:

The relationship among the , the amplification multiples , enhanced ee with the are analyzed and summarized in the following Figures (A to C) using total nine yields ( ) from 10 to respectively.

The L-TME reacts with oxalaldehyde to afford two isolated compounds as the expected. The relationships for %ee1, %ee2, D%ee and the ratio of %ee2/%ee1 are obtained. The yield, p, is assumed as 90% based on the energy difference of 1.307 kcal/mol between the two compounds (dash curve). The “×” symbols represent the experimental values. The deep blue lines through the “×” symbols are the fitted experimental points. The experimental results well matches the theoretical predictions (see the following plots).Finally, it is discussed simply. It is reported that the L-amino acids can promote the formation of D- four-carbon sugar. Importantly, the L-amino acids and D-sugars are the fundamental matters for origin of life. Now, it is unknown that the L-amino acids can either catalyzing to form D-five carbon sugar or not. It can be foreseen that although the research on the origin of life using chemical methods is no longer a hot topic in some brand journals, it may be one of the missions of chemists, physicists, and biologists to conduct in-depth research, to explore the inevitability factors and laws in the origin of life.(For more details, such as the experimental results, absolute configuration assignments, computational details, HPLC analysis and others, or the preprint submitted to Molecules, please contact the corresponding author)04文章发表链接
https://xuebao.hebust.edu.cn/hbkjdx/article/pdf/b202306006

编辑：李梦晴 陈心玥

审核：冯民