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Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate
Tsukasa Sano1, Keiichi Shimada2, Yohei Aoki3
1Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan. tsukasano8.24@gmail.com.
Abstract:
Thionitrates (R-SNO₂) have been proposed as key intermediates in the biotransformation of organic nitrates that have been used for the clinical treatment of angina pectoris for over 100 years. It has been proposed and widely accepted that a thiol would react with an organic nitrate to afford a thionitrate intermediate. However, there has been no example of an experimental demonstration of this elementary chemical process in organic systems. Herein, we report that aryl- and primary-alkyl-substituted thionitrates were successfully synthesized by the reaction of the corresponding lithium thiolates with organic nitrates by taking advantage of cavity-shaped substituents. The structure of a primary-alkyl-substituted thionitrate was unambiguously established by X-ray crystallographic analysis.
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Rate-Determining Steps
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...

