Theoretical Study Before Assembling Multicomponent Biological Nucleotides

Nucleotide is the basic unit of DNA/RNA and possesses important biochemicalfunctions, involving almost all the biochemical reactions in vivo. So, the prebioticassembly of nucleotides play an important role on revealing the chemical origins oflife and understanding the chemical nature of the biological phenomenon in molecularlevel. The mechanism of multi-component assembly of nucleotide will besystematically studied in this paper using computational chemistry. The priorselectivity and the original driven source of the self-assembled reactions will berevealed, and the control factors of regioselectivity, stereoselectivity anddiastereoselectivity of the reactions will also be clarified. Furthermore, the chemicalnature of prebiotic assembly of nucleotide will be uncovered in the micro level.The prebiotic synthesis of deoxyribonucleotide precursor C5-thiazoline has beenstudied by performing density functional theory calculations. Two possible reactionpathways are explored and the results indicate that it prefers stepwise nucleophilicaddition and ring-closure processes rather than concerted pathway. Four possiblechannels associated with four diastereoisomers have been explored in detail. Ourcalculations show that the C-C bond-forming step can be regarded as therate-determining step and thiazole addition to the Si-face of iminium represents anenergetically preferred pathway. In addition, the origin of diastereoselectivity is alsoinvestigated and the intramolecular hydrogen bond and steric hindrance areconsidered to play a very important role.On the basis of the synthesis of deoxyribonucleotide precursors C5-thiazoline,the mechanism of multicomponent assembly of purine nucleotide is studied in detail.The assembly process is composed of the synthesis of purine nucleotide precursorC5-oxazoline, cyanovinylation, the dissociative cytosine cleavage and phosphorylation.The synthesis of C5-oxazoline undergoes nucleophilic addition and ring-closure, andin the ring-closure process, the competitive6-exo-trig and5-exo-trig cyclizationexisted simultaneously. Our calculations show that the nucleophilic addition can be regarded as the rate-determining step, and also a key step in controlling thediastereoselectivity. The xylo-and lyxo-oxazolines are major products. In addition,the steric hindrance plays an important role in the formation of diastereomericproducts. Phosphate anion plays an important role by forming hydrogen bonds and asa media of proton transferring. Cyanovinylation is completed under the combinedeffect of cyanoacetylene and water. They don’t exhibit significant selectivity in theprocess of cyanovinylation, while result in a1:1mixture of products.Anhydronucleoside is formed after the separation of cytosine and intramolecularcyclization. Finally, the purine nucleoside is formed under the phosphorylation step.