Crystalline‐Sponge‐Based Structural Analysis of Crude Natural Product Extracts

Abstract

Characterization of complex natural product mixtures to the absolute structural level of their components often requires significant amounts of starting materials and lengthy purification process, followed by arduous structure elucidation efforts. The crystalline sponge (CS) method has demonstrated utility in the absolute structure elucidation of isolated organic compounds at miniscule quantities compared to conventional methods. In this work, we developed a new CS-based workflow that greatly expedites the in-depth structural analysis of crude natural product extracts. Using a crude extract of the red alga Laurencia pacifica, we showed that CS affinity screening prior to compound isolation enables prioritization of analytes present in the extract, and we subsequently resolved the molecular structures of six sesquiterpenes with stereochemical clarity from around 10 mg crude extract. This study demonstrates a new chemotyping workflow that can greatly accelerate natural product discovery from complex samples.

Stepwise Evolution of Molecular Nanoaggregates Inside the Pores of a Highly Flexible Metal–Organic Framework

“…[17] In the CSM, the analyte molecule is adsorbed inside the MOF pores,w hich provide al ong-range-ordered environment to the guest, making possible its structural determination via SCXRD. [18,19] This method relies on the frameworks robustness,w hich generally preserves the single-crystallinity even after significant guest loading. [20,21] Framework adaptability to guest uptake and stimuli responsiveness behavior are two of the most intriguing feature of the so-called breathing MOFs.…”

“…[27][28][29] However,i ns everal cases,t he determination of the guest species remains av ery demanding task [4] owing to the weak host-guest intermolecular interactions,mainly H-bonds, halogen-bonds,o rp-p interactions very often characterized by as ignificant positional disorder, [30] large thermal motion, and low occupancy. [4] Even though several works focusing on CSM have been presented so far, [18,19,[31][32][33] the analysis of the guest entering dynamics has not been explicitly investigated, [21,34,35] nor the formation of nanoconfined aggregates of the trapped molecules. [36,37] Recent works have shown that cutting-edge use of SCXRD allows the elucidation of inclusion processes occurring inside MOF cavities based on structural insight.…”

Stepwise Evolution of Molecular Nanoaggregates Inside the Pores of a Highly Flexible Metal–Organic Framework

“…MOFs have been largely studied as functional materials for gas separation and storage, and more recently as crystalline host, after work by Fujita on the crystalline sponge method (CSM) . In the CSM, the analyte molecule is adsorbed inside the MOF pores, which provide a long‐range‐ordered environment to the guest, making possible its structural determination via SCXRD . This method relies on the frameworks robustness, which generally preserves the single‐crystallinity even after significant guest loading .…”

“…However, in several cases, the determination of the guest species remains a very demanding task owing to the weak host–guest intermolecular interactions, mainly H‐bonds, halogen‐bonds, or π–π interactions very often characterized by a significant positional disorder, large thermal motion, and low occupancy . Even though several works focusing on CSM have been presented so far, the analysis of the guest entering dynamics has not been explicitly investigated, nor the formation of nanoconfined aggregates of the trapped molecules …”

Crystalline‐Sponge‐Based Structural Analysis of Crude Natural Product Extracts

“…The X-ray structure was crosschecked by NOESY.Key NOESY correlations are displayed. 13 Ca nd 2D NMR spectra were not obtained from this small amount of 4. Due to strong host-guest interaction, the entire host network structure was expanded and turned into non-centrosymmetric (P2 1 ).…”