Microgram-scale testing of reaction conditions in solution using nanoliter plugs in microfluidics with detection by MALDI-MS
Abstract
This paper describes a microfluidic system to screen and optimize organic reaction conditions on a submicrogram scale. The system uses discrete droplets (plugs) as microreactors separated and transported by a continuous phase of a fluorinated carrier fluid. Previously, we demonstrated the use of a microfabricated PDMS plug-based microfluidic system to perform assays and crystallization experiments in aqueous solutions with optical detection. Here, we developed an approach that does not require microfabrication of microfluidic devices, is applicable to synthetic reactions in organic solvents, and uses detection by MALDI-MS. As a demonstration, conditions for selective deacetylation of ouabain hexaacetate were tested, and the optimum conditions for mono-, bis-, or trisdeacetylation have been identified. These conditions were validated by scale-up reactions and isolating these potentially neurotoxic products. Mono- and bisdeacetylated products are unstable intermediates in the deacetylation and were isolated for the first time. This system enables no-loss handling of submicroliter volumes containing a few micrograms of a compound of interest. It could become valuable for investigating or optimizing reactions of precious substrates (e.g., products of long synthetic sequences and natural products that can be isolated only in small quantities).
Additional Information
© 2006 American Chemical Society. Published In Issue: March 01, 2006. Received November 13, 2005. This work was supported by the NIH (R01 EB001903), NSF CRC CHE-0526693, and DuPont Young Professor Award. R.F.I. is an Alfred P. Sloan Research fellow. T.H. is a research fellow of the Japan Society for the Promotion of Science.Attached Files
Accepted Version - nihms14616.pdf
Supplemental Material - Ismagilov_SI_JACS_2006_128_2518_rxn_screen_takuji.pdf
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Additional details
- PMCID
- PMC1851926
- Eprint ID
- 40792
- DOI
- 10.1021/ja057720w
- Resolver ID
- CaltechAUTHORS:20130821-160718478
- NIH
- R01 EB001903
- NSF
- CHE-0526693
- E. I. DuPont de Nemours and Company, Inc.
- Alfred P. Sloan Foundation
- Japan Society for the Promotion of Science (JSPS)
- Created
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2013-08-27Created from EPrint's datestamp field
- Updated
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2023-06-02Created from EPrint's last_modified field