1H NMR Characterization of the Product from Single Solid-Phase Resin Beads Using Capillary NMR Flow Probes

• Published in: Journal of magnetic resonance (1997) 2001-12, Vol.153 (2), p.215-222
• Main Authors: Lacey, Michael E., Sweedler, Jonathan V., Larive, Cynthia K., Pipe, Adrian J., Farrant, R.Duncan
• Format: Article
• Language: English
• ISSN: 1090-7807; 1096-0856
• DOI: 10.1006/jmre.2001.2443

A capillary NMR flow probe was designed to generate high-resolution 1H NMR spectra at 600 MHz from the cleaved product of individual 160-μm Tentagel combinatorial chemistry beads. By injecting a dissolved sample sandwiched between an immiscible, perfluorinated organic liquid directly into the probe, NMR spectra of the product cleaved from single beads were acquired in just 1 h of spectrometer time without diffusional dilution. Sample handling efficiency on the single bead scale was comparable to that obtained with a bulk sample. Using the relative intensity of the DMSO-d5H versus the analyte signals in a fully relaxed CPMG spectrum, the amount of product cleaved from a single bead was determined to be 540±170 pmol in one of the samples. Following the NMR data collection, the samples were examined with electrospray ionization mass spectrometry to provide additional structural information. By coupling with microliter-volume fluidic capabilities, the capillary flow probe described here will enable multidimensional characterization of single solid-phase resin products in an online manner.