Imperial College London
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Prof Claire S. Adjiman FREng

Faculty of Engineering, Department of Chemical Engineering

Professor of Chemical Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6638c.adjiman Website

 
 
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Location

 

608Roderic Hill BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gui:2023:10.1021/acs.iecr.2c03145,
author = {Gui, L and Adjiman, CS and Galindo, A and Sayyed, FB and Kolis, SP and Armstrong, A},
doi = {10.1021/acs.iecr.2c03145},
journal = {Industrial & Engineering Chemistry Research},
pages = {874--880},
title = {Uncovering the most kinetically influential reaction pathway driving the generation of HCN from oxyma/DIC adduct: a theoretical study},
url = {http://dx.doi.org/10.1021/acs.iecr.2c03145},
volume = {62},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The combination of ethyl (hydroxyimino)cyanoacetate (Oxyma) and diisopropylcarbodiimide (DIC) has demonstrated superior performance in amino acid activation for peptide synthesis. However, it was recently reported that Oxyma and DIC could react to generate undesired hydrogen cyanide (HCN) at 20 °C, raising safety concerns for the practical use of this activation strategy. To help minimize the risks, there is a need for a comprehensive investigation of the mechanism and kinetics of the generation of HCN. Here we show the results of the first systematic computational study of the underpinning mechanism, including comparisons with experimental data. Two pathways for the decomposition of the Oxyma/DIC adduct are derived to account for the generation of HCN and its accompanying cyclic product. These two mechanisms differ in the electrophilic carbon atom attacked by the nucleophilic sp2-nitrogen in the cyclization step and in the cyclic product generated. On the basis of computed “observed” activation energies, ΔGobs, the mechanism that proceeds via the attack of the sp2-nitrogen at the oxime carbon is identified as the most kinetically favorable one, a conclusion that is supported by closer agreement between predicted and experimental 13C NMR data. These results can provide a theoretical basis to develop a design strategy for suppressing HCN generation when using Oxyma/DIC for amino acid activation.
AU  - Gui,L
AU  - Adjiman,CS
AU  - Galindo,A
AU  - Sayyed,FB
AU  - Kolis,SP
AU  - Armstrong,A
DO  - 10.1021/acs.iecr.2c03145
EP  - 880
PY  - 2023///
SN  - 0888-5885
SP  - 874
TI  - Uncovering the most kinetically influential reaction pathway driving the generation of HCN from oxyma/DIC adduct: a theoretical study
T2  - Industrial & Engineering Chemistry Research
UR  - http://dx.doi.org/10.1021/acs.iecr.2c03145
UR  - https://pubs.acs.org/doi/10.1021/acs.iecr.2c03145
UR  - http://hdl.handle.net/10044/1/101786
VL  - 62
ER  -
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