Abstract
Phosphonylation and aging processes between butyrylcholinesterase with mipafox have been studied at the B3LYP/6-311G(d,p) level of theory. The calculated results indicate that the phosphonylation process employs a two-step addition-elimination mechanism with the addition (the first step) as the rate-limiting step. Two different calculation models revealed that the catalytic triad of butyrylcholinesterase plays an important role in accelerating the reaction. This is the same mechanism as the phosphonylation reaction of acetylcholinesterase by sarin reported by Wang et al. However, the energy barrier of the rate-limiting step in the present reaction is higher than that in phosphonylation reaction of acetylcholinesterase by sarin. This indicates the differences in the phosphonylation activity of sarin and mipafox. The aging process occurs through a two-step addition-elimination mechanism similar to the phosphonylation process with the addition as the rate-limiting step. The solvent effects have been evaluated by using a CPCM model and the results show that the stationary structures and the negative charges around some important atoms involved in the two processes are not significantly different. However, the energy barrier of the phosphonylation process is remarkably decreased, revealing that this process is feasible in solution.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
