Applications of Small-Volume High-Sensitivity and Cryogenic NMR Probes

APPLICATIONS OF SMALL-VOLUME HIGH-SENSITIVITY AND CRYOGENIC NMR PROBES 

In 1993 shortly after 3 mm micro-probes became commercially available, an application of the use of 3 mm probe technology was reported by Hensens and coworkers at Merck.58 The enediyne antibiotic neocarzinostatin (9) is activated for duplex DNA cleavage by 1000-fold by thiol reagents. Hensens and co-workers utilized both micro-inverse and micro-dual 3 mm NMR probes to characterize the structure and stereochemistry of the novel post-activated drug (10). 

Several applications of 3 mm micro-NMR probe technology were reported in 1994. The first utilized both a 3 mm micro-inverse probe as well as a heteronuclear Nano-probe to acquire the NMR data necessary for the characterization of a 30 pg (0.07 pmol) metabolite sample.59 Following the acquisition of a 13C reference spectrum using a heteronuclear Nano-probe the 40 pL sample from the nano-cell was quantitatively transferred to a 3 mm NMR tube and diluted to a total sample 

Schwartz and co-workers, also at Merck, reported the isolation and elucidation of the structure of pramanicin (12) and a related fatty acid that were discovered during a search for novel antifungal agents.60 The authors reported using a 500 MHz 3 mm micro-inverse probe for the acquisition of the heteronuclear 2D-NMR data to characterize the molecule, including a HMQC spectrum. 

There were a several additional studies of members of the indoloquinoline family of alkaloids isolated from Cryptolepis sanguinolenta reported that utilized 3 mm micro-NMR probe capabilities reported in 1995. The elucidation of the structure of quindolinone (16) was reported next and also utilized 3 mm micro-probe technology for the acquisition of a HMQC spectrum on an 800 pg sample of the 

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Applications of Small-Volume High-Sensitivity and Cryogenic NMR Probes 31... 

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