(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholino-carbenium Hexafluorophosphate

Easy parallel screening of reagent stability, quality control, and metrology in solid phase peptide synthesis (SPPS) and peptide couplings for microarrays

“…Oxyma, the leaving group of COMU, was also stable at ~23 °C in solid form and its solutions in DMF and NMP were stable for several weeks . Likewise, COMU in solid state was reported to be stable for several months when stored refrigerated and its solutions in DMF were found to be 100% stable for one day and retained 93% stability for two days . A stability of 85% was reported using NMR, after COMU solution in DMF was stored for 23 h in a closed vial, whereas COMU was almost completely hydrolyzed (8% residual COMU) after 5 h in an open vial .…”

“…It was first reported that COMU dissolved in DMF and stored in an open container retained 100% hydrolytic stability up to 24 h and 93% at 48 h along with >95% stability in closed container as determined by proton nuclear magnetic resonance ( 1 H‐NMR) . Oxyma, the leaving group of COMU, was also stable at ~23 °C in solid form and its solutions in DMF and NMP were stable for several weeks . Likewise, COMU in solid state was reported to be stable for several months when stored refrigerated and its solutions in DMF were found to be 100% stable for one day and retained 93% stability for two days .…”

“…In general, closed vial was favored to confer stability by acting as a barrier to moisture permeation, a culprit in reagent instability during SPPS . The presence of oxygen atom in the carbon skeleton and the polar morpholine group in COMU contributed to the factors impacting solubility and stability . Vendors listed COMU stability in DMF as 100% (5 and 24 h) and 93% (48 h) in their product datasheet.…”

“…In open containers, degradation after 2 days was 86%, whereas in closed containers, after 7 and 14 days, 46 and 36% residual stabilities of COMU were retained . COMU was cautioned to be ‘sensitive to hydrolysis’ although in solid state it was stable for several months at 4 °C .…”

“…Clearly, there were uncertainties regarding COMU stabiilty with a broad range of lifetimes being reported ( vide supra ). Because COMU was used in microwave peptide synthesis involving heating up to 80 °C and 10 min , such elevated temperature conditions could accelerate COMU degradation, affecting peptide synthesis, purity, and yield. The screening data of COMU stability (Figure ) was supported by Tofteng et al who found that COMU dissolved in DMF and stored in open vials had a half life of 3 h, and after 24 h no peptide synthesis would occur.…”