The RNA world hypothesis assumes that RNA was the first informational polymer that originated from prebiotic chemical soup. However, since the reaction of D-ribose with canonical nucleobases (A, C, G and U) fails to yield ribonucleosides (rNs) in substantial amounts, the spontaneous origin of rNs and the subsequent synthesis of RNA remains an unsolved mystery. To this end, it has been suggested that RNA may have evolved from primitive genetic material (preRNA) composed of simpler prebiotic heterocycles that spontaneously form glycosidic bonds with ribose. As an effort toward evaluating this hypothesis, the present study uses density functional theory (DFT) to assess the suitability of barbituric acid (BA) and melamine (MM) to act as prebiotic nucleobases, both of which have recently been shown to spontaneously form a glycosidic bond with ribose and organize into supramolecular assemblies in solution. The significant strength of hydrogen bonds involving BA and MM indicates that such interactions may have played a crucial role in their preferential selection over competing heterocycles that interact solely through stacking interactions from the primordial soup during the early phase of evolution. However, the greater stability of stacked dimers involving BA or MM and the canonical nucleobases compared to those consisting solely of BA and/or MM points towards the possible evolution of intermediate informational polymers consisting of prebiotic and canonical nucleobases, which could have eventually evolved into RNA. Analysis of the associated rNs reveals an anti conformational preference for the biologically-relevant β-anomer of both BA and MM rNs, which will allow complementary WC-like hydrogen bonding that can stabilize preRNA polymers. Large calculated deglycosylation barriers suggest BA rNs containing C–C glycosidic bonds are relevant in challenging prebiotic environments such as volcanic geotherms, while lower barriers indicate the MM rNs containing C–N–C glycosidic linkages may have been more likely synthesized from simple precursors such as urea-ice in icy (polar) regions. Together, our quantum chemical data clarifies the physicochemical interactions and stability of potential prebiotically-relevant constituents of BA and MM polymeric assemblies, and complements information from previous experimental studies to bolster the candidature of these heterocycles as prebiotic nucleobases.

中文翻译：

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巴比妥酸和含三聚氰胺的核糖核苷作为益生元RNA可能的组成部分的结构和电子性质：对益生元自组装的影响

RNA世界假说假设RNA是最早源自益生元化学汤的信息聚合物。但是，由于D的反应具有典型核碱基（A，C，G和U）的核糖无法大量产生核糖核苷（rNs），rNs的自发起源以及随后的RNA合成仍然是一个未解之谜。为此，已经提出RNA可能已经由原始遗传物质（preRNA）进化而来，该原始遗传物质由更简单的益生元杂环组成，这些益生元杂环与核糖自发形成糖苷键。为了评估这一假设，本研究使用密度泛函理论（DFT）评估了巴比妥酸（BA）和三聚氰胺（MM）充当益生元核酸碱基的适用性，最近两者均被证明可以自发形成核糖核酸。与核糖形成糖苷键，并在溶液中组织成超分子组装体。涉及BA和MM的氢键的显着强度表明，这种相互作用可能在它们的优先选择中起着至关重要的作用，而不是竞争的杂环，后者仅在进化的早期仅通过来自原始汤的堆叠相互作用而相互作用。但是，与仅由BA和/或MM组成的堆叠二聚体相比，仅由BA和/或MM构成的堆叠二聚体具有更大的稳定性，这表明可能存在由益生元和规范核碱基组成的中间信息聚合物的进化，而这些信息聚合物最终可能会进化为RNA 。对相关rNs的分析显示 与仅由BA和/或MM组成的堆叠二聚体相比，由BA或MM和典型核碱基组成的堆叠二聚体具有更大的稳定性，这表明可能存在由益生元和规范核碱基组成的中间信息聚合物的进化，而这些信息聚合物最终可能会进化为RNA。对相关rNs的分析显示 与仅由BA和/或MM组成的堆叠二聚体相比，由BA或MM和典型核碱基组成的堆叠二聚体具有更大的稳定性，这表明可能存在由益生元和规范核碱基组成的中间信息聚合物的进化，而这些信息聚合物最终可能会进化为RNA。对相关rNs的分析显示反对BA和MM rNs具有生物学相关性的β-异头物的构象偏爱，这将允许WC样互补氢键结合，从而稳定preRNA聚合物。较大的计算出的去糖基化障碍表明，含有C–C糖苷键的BA rNs在具有挑战性的益生元环境（如火山地热）中具有相关性，而较低的障碍则表明含有C–N–C糖苷键的MM rNs可能更可能是由简单的前体合成的，例如冰（极性）区域中的尿素冰。总之，我们的量子化学数据阐明了BA和MM聚合物装配体中潜在的与益生元相关的成分的物理化学相互作用和稳定性，并补充了来自先前实验研究的信息，以增强这些杂环作为益生元核碱基的候选资格。