Direct-injection NMR (DI-NMR): A flow NMR technique for the analysis of combinatorial chemistry libraries

A new tool for analyzing compound libraries by NMR has been developed. Aliquots of solution-state samples (between 120 and 350 mu L) are directly injected, using a standard liquids handler, into an NMR (LC-NMR) flow probe. Automated NMR software tracks-and suppresses-intense signals arising from the nondeuterated solvents used (if any) and acquires high-sensitivity one-dimensional H-1 NMR spectra. An 88-member combinatorial library, dissolved in DMSO and stored in a 96-well microtiter plate, has been analyzed a number of ways using this technique. This nondestructive technique, which we call direct-injection NMR (DI-NMR) and which is embodied in our versatile automated sample changer (VAST) hardware, has proven to be both routine and robust. Our success in automatically acquiring the NMR data for entire plates of library compounds (within 4-8 h) has caused us to develop new ways to display and analyze the resulting NMR data, as will be shown here.