Dynamic Residual Complexity of Natural Products by qHNMR: Solution Stability of Desmethylxanthohumol

Abstract

The use of chromatographic assays to assess the residual complexity of materials that are purified from natural sources by chromatographic means is, in a sense, a case of the fox watching the henhouse. Beside their static residual complexity, which is intrinsic to their metabolic origin, biologically active natural materials can also be involved in chemical reactions that lead to dynamic residual complexity. The present study examines the dynamics of the hop prenylphenol, desmethylxanthohumol (DMX), by means of quantitative ¹H-NMR (qHNMR) in a setting that mimics in vitro and physiological conditions. The experiments provide a comprehensive, time-resolved, and mechanistic picture of the spontaneous isomerization of DMX into congeneric flavanones, including their ¹H/²D isotopomers. Formation of the potent phytoestrogen, 8-prenylnaringenin (8PN), suggests that measurable estrogenic activity even of high-purity DMX is an artifact. Together with previously established qHNMR assays including purity activity relationships (PARs), dynamic qHNMR assays complement important steps of the post-isolation evaluation of natural products. Thus, qHNMR allows assessment of several unexpected effects that potentially break the assumed linkage between a single chemical entity (SCE) and biological endpoints.

Abbreviations

6PN:6-prenylnaringenin

8PN:8-prenylnaringenin

DMX:desmethylxanthohumol

qHNMR:quantitative ¹H NMR

SCE:single chemical entity

Key words

Humulus lupulus - Cannabaceae - residual complexity - isomerization - dynamics - qHNMR - prenylchalcones

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