The Chemical Mechanism Of Nucleotide Formation And Repair

In the early stages of the origin of life, There is a molecular system which is composed of RNA molecules entirely. In this system, the system of information is stored by RNA and some have the function of catalytic in the transfer of information and the self-replicating RNA itself. Because this system can make information storage and copy, the system can survive and evolution. Finally, the information storage is replaced by the more stable DNA molecules, and catalytic function is replaced by protein with stronger catalytic ability, thus the system of modern life is formed. This paper adopts the computational chemistry methods study multicomponent assembly of pyrimidine and purine nucleotide prebiotic and base damage repair.Density functional theory is utilized to elucidate the detailed mechanisms of the reactions between 2-aminooxazole/2-aminothiazole and glyceraldehyde. According to our calculations, in 2-aminooxazole/glyceraldehyde system, aminooxazoline is formed via two steps including C-C formation and cyclization. C-C formation determines the reaction diastereoselectivity and ribo-aminooxazoline is the most favorable product. Although oxazole-hemiaminal is not detected in the experiment, it is deduced can be formed theoretically. In 2-aminothiazole/glyceraldehyde system, aminothiazoline is hard to be generated because of the less nucleophilic ability of 2-aminothiazole. The formation of thiazole-hemiaminal is more favorable than aminothiazoline formation in kinetics but somewhat unfavorable in thermodynamics. However, the transformation from thiazole-hemiaminal to thiazole-aminal is favorable both inkinetics and thermodynamics, which provides a driving force for the formation and transformation of thiazole-hemiaminal. Additionally, our calculations indicate that phosphate is very important in assisting proton transfer in all of the transformations.On the basis of the above research for assembly pyrimidine nucleotide precursors, we continue to study the assembly process of purine nucleotide precursors.We mainly study the formation of purine nucleotide precursors C5- oxazolines. According to the different amount of phosphate, we design the two reaction paths. Only one phosphate involved in synthesis reaction, the entire process consists of nucleophilic addition and cyclization. When two phosphates are included in reaction, the nucleophilic addition and cyclization simultaneously complete and the final step is hydrogen transfer for the synthesis of xylo configuration C5- oxazoline. The other three configuration products form through nucleophilic addition, cyclization and hydrogen transfer. The calculation results show that lyxo and ribo configuration C5- oxazolines are the main products, arabino and xylo configuration C5- oxazolines are by-products. In addition, reaction is more likely to happen, when two phosphates are included in reaction. Nucleophilic addition is the rate-determining step.Next we made some research about nucleotide repair. Organic small molecule catalyze removing formaldehyde adducts from nucleotide bases, then nucleotides get repaired. The results show that phosphanilate compound is the best catalyst. Removal process mainly includes dehydration and Transimination, in which C- N cleavage is the rate-determining step.