Screening reactions in one-second DESI-MS droplets
Desorption electrospray ionization mass spectrometry reads amine alkylation and Suzuki hits from nanoliter spots in about a second.
Source
High throughput reaction screening using desorption electrospray ionization mass spectrometry
What they did
Authors spotted nanoliter reaction mixtures on porous PTFE, analyzed them by DESI-MS/MS, and screened N-alkylations plus Pd-catalyzed Suzuki couplings across multi-thousand-spot plates.
What they found
Product ions appear within about 1 s per droplet. Benzyl bromide alkylated 7 of 8 amines versus 3 of 8 for 2-(bromoethyl)benzene. Peak analysis reached 6004 reactions per hour at 6144-well density, using less than 0.5 μg of each reagent in 50 nL spots.
The limits
What it doesn't show
Qualitative reproducibility falls at the highest speeds, and translating every DESI hit to optimized continuous-flow yield is not completed in this paper.
Key terms
- DESI-MS
- Desorption electrospray ionization mass spectrometry of spots on a surface, here reaction droplets.
- N-alkylation
- Reaction of amines with alkyl bromides to form C–N products.
- Suzuki coupling
- Pd-catalyzed C–C coupling of boronic acids with aryl halides.
- PTFE plate
- Porous Teflon substrate that holds nanoliter reaction spots for DESI.
- Conversion rate (CR)
- MS-based estimate of how complete a spotted reaction is.
Flashcards
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Quiz yourself
Each DESI droplet analysis takes about:
Common questions
How fast is each DESI analysis?
About 1 second per reaction droplet.
Which alkyl bromide worked better?
Benzyl bromide (7/8 amines) beat 2-(bromoethyl)benzene (3/8).
What Pd catalyst was screened for Suzuki?
Commercial XPhos Pd G3.
How much reagent per spot?
50 nL mixtures with less than 0.5 μg of each reagent.
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