Computer Vision as a New Paradigm for Monitoring of Solution and Solid Phase Peptide Synthesis

10 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


We report a strategy for the direct, non-contact colorimetric reaction monitoring of amide bond formation, mediated by coupling reagents, from video footage. For amide bond formation in solution phase, investigation of reactions mediated by HATU, PyAOP, and DIC/Oxyma revealed correlations between color parameters extracted from video data and the extent of conversion to amide product measured by off-line HPLC analysis of concentration. These correlations, supported by mutual information analysis, were further investigated using video recordings of solid phase peptide synthesis (SPPS), co-analyzed by off-line HPLC to track remaining unreacted substrate in solution. An optimization method of coupling time in SPPS was derived from E (a measurement of color contrast), giving comparable isolated peptide quality at 65 – 95% reduced overall reaction time. The same color data enabled data-rich monitoring of reaction rate attenuation, consisted with computationally-derived measures of amino acid steric bulk. These findings evidence the promise of camera technologies towards a fully automated and online mechanistic profiling of SPPS.


amino acid
solid phase peptide synthesis
computer vision
reaction monitoring

Supplementary materials

Supporting Information
Key details of experimental set-ups, video analyses, DFT calculations, and associated references.
Machine readable supporting information
Datasets and code


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