Thionizing Solution Stability via Aromatic Mediators
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Solution Overview
Problem
Existing thiolation solutions for nucleic acid synthesis, particularly those containing ADTT, suffer from instability, which affects the quality and yield of nucleic acid molecules.
Innovation Solution
A thiolation solution with high stability is achieved by combining an aromatic heterocyclic compound, such as pyridine, with an aromatic hydrocarbon compound, such as toluene, and a thiolating agent represented by ADTT, maintaining the ADTT concentration between 0.001 to 0.3 M.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ADTT is used as a thiolating agent in solution state, then thiolation reaction can be performed, but the stability of the solution deteriorates
Solution Approach 1:
The patent introduces an aromatic heterocyclic compound as an intermediary substance that mediates between ADTT and the reaction environment. This intermediary compound stabilizes ADTT in solution state, preventing its decomposition while maintaining its thiolating activity. The aromatic heterocyclic compound acts as a protective mediator that allows ADTT to function effectively without suffering from its inherent instability in solution.
2Productivity
If thiolation solution is used for nucleic acid synthesis, then phosphite triester can be converted to thiophosphate triester, but the instability of existing solutions reduces production efficiency
Solution Approach 1:
The patent changes the chemical parameters of the thiolation solution by introducing an aromatic heterocyclic compound and controlling the concentration ratio between ADTT and the aromatic heterocyclic compound. This parameter change transforms the solution from unstable to stable, enabling it to maintain its thiolating function throughout the nucleic acid synthesis process without degradation, thereby improving productivity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The stable thiolation solution improves the stability and purity of nucleic acid molecules produced by the amidite method, enhancing the overall efficiency of nucleic acid synthesis.
Implementation Method 1
a thiolation solution containing a compound represented by formula (3), an aromatic heterocyclic compound, and an aromatic hydrocarbon compound
Implementation Method 2
a step of converting a phosphite triester bond to a thiophosphate triester bond using the composition
Data Source
Figure 1
AI summary
The present invention provides a thiolation solution with high stability, which contains a compound represented by formula (3) as a thiolating agent, and a production method of a nucleic acid molecule by the amidite method using the thiolation solution. The present invention also provides a composition which comprises an aromatic heterocyclic compound represented by formula (1) (wherein, X1 to X5 are identical to or different from each other and each independently represents a hydrogen atom or the like.), an aromatic hydrocarbon compound represented by formula (2) (wherein, Y1 to Y6 are identical to or different from each other and each independently represents a hydrogen atom, a C1-C5 alkyl group, or a halogen atom.), and a thiolating agent represented by formula (3).