Novel approaches to absolute structure

Katja Desiree Pedersen

Research output: Book/ReportPh.D. thesis

133 Downloads (Pure)


The function, activity and specificity of natural- and other organic compounds are decided by their 3D structure in solution, and accurate characterization methods are of great value in e.g. drug discovery. Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique in structure elucidation of organic compounds and have been used to identify countless compounds as well as their interactions. This thesis covers work related to expanding the applicability of NMR structural analysis towards compounds, whose 3D structure still represent a challenge for the structure elucidation process.

As an example of the structure elucidation process based on conventional NMR analysis, the 3D structure of the lasso peptide triculamin was elucidated using internuclear distances derived from NOE data. The analysis resulted in a structural ensemble, which displays both the conformational stability of the macrolactam ring and the flexibility of the tail region.

Graphene oxide (GO) has risen as a novel material with numerous attractive properties and potential applications. GO spontaneously forms liquid crystals in aqueous solution, which induces a degree of order for dissolved compounds, when placed in a magnetic field. This makes GO applicable as alignment media for acquisition of NMR spectra under anisotropic conditions. Additional structural information can be extracted from these spectra and used in structure elucidation of organic compounds. The alignment properties of GO were explored by measuring residual dipolar couplings (RDCs) of model compounds, resulting in many observations for sample preparation and stability of GO solutions, among these discussions related to the effects of GO concentration and solvent composition for the degree of alignment.

Multiple methods of GO functionalization was pursued to expand its applicability toward a broader range of compounds and enable enantiodiscrimination. Synthesis strategies based on amide coupling and increasing the amount of carboxylic acids on the GO sheets were carried out, producing modified GO materials that preserved the alignment properties. The synthesized materials were analyzed using AFM, IR and 13C MAS NMR spectroscopy. However, the analysis could not unambiguously prove the covalent functionalization, when compared to a control sample. The results highlight the need for a critical approach when characterizing functionalized GO materials.

An alternative approach based on click (CuAAC) chemistry was pursued. Azide groups were successfully introduced on the GO sheets, and subsequent reactions strived to further functionalize GO by coupling with a small alkyne. The functionalized products obtained from initial testing revealed incomplete reaction by the continued presence of azides, thus future effort will focus on finding optimal reaction conditions and accurate characterization methods.
Original languageEnglish
Place of PublicationKgs. Lyngby
PublisherDTU Chemistry
Number of pages157
Publication statusPublished - 2021


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