Session TOE. There are 5 abstracts in this session.



Session: SMALL MOLECULES 1, time: 10:45 - 11:10 am

Defeating Complexity: New NMR Methods for Mixture Analysis


Laura Castanar Acedo
University of Manchester, Manchester, United Kingdom

NMR spectroscopy is a powerful and versatile tool for analysing mixtures in solution due to its ability to identify and determine structures of unknowns without physical separation. However, in complex mixtures, signal overlap increases massively, making spectral analysis extremely difficult. In this talk several novel NMR methods to solving some of the most challenging problems encountered in mixture analysis will be presented: REST (Relaxation-Encoded Selective TOCSY), SCALPEL (Spectral Component Acquisition by Localized PARAFAC Extraction of Linear components), and FESTA (Fluorine-Edited Selective TOCSY Acquisition). The usefulness of these methods will be demonstrated on carbohydrate mixtures, fermented beverage (beer) and mixtures containing fluorinated pharmaceuticals. All of our pulse sequences and processing tools are free and can be downloaded from our webpage: https://nmr.chemistry.manchester.ac.uk.


Session: SMALL MOLECULES 1, time: 11:10 - 11:35 am

Novel NMR Methodologies for Addressing the Challenges in the Analysis of NMR spectra in Isotropic and Anisotropic Media


Suryaprakash Nagarajarao
Indian Institute of Science, Bangalore, India
Novel techniques have been designed for the simplification of NMR spectral complexity both in isotropic and weak chiral aligning media, enhancement of sensitivity of detection, unravelling of overlap and the facile extraction of isotropic and partially averaged anisotropic parameters. The manipulation of spin dynamics prevented evolution of unwanted couplings, eradicated axial peaks, in addition to enhancing the resolution. The discovery of several water compatible weak chiral aligning medium with physical parameter dependent tunability of its degree of order, sustainability of the mesophase over a broad range of temperature and the concentration of ingredients also circumvented the inherent challenges and rendered first order analysis of spectra.

Session: SMALL MOLECULES 1, time: 11:35 - 11:50 am

19F-NMR screening of RNA for fragment-based drug discovery using an accessible small molecule library 


Albrecht Völklein1; Oliver Binas1; Tom Landgraf1; Christian Richter2; Sridhar Sreeramulu2; Marcel Blommers3; Harald Schwalbe1
1Goethe University Frankfurt, Frankfurt Am Main, Germany; 2Center for Biomolecular Magnetic Resonance, Frankfurt, N/A; 3Saverna, Basel, Switzerland

Drug discovery through fragment-based screenings yields lead-structures that can be interlinked or grown into strong binders. This methodology has so far only rarely been applied to highly structured RNAs and these studies focused on single targets. Using 19F-detected relaxation experiments on 106 fluorinated fragments in multicomponent mixtures and 8 different RNA targets found multiple hits ranging from general RNA binders to single target specific. Hits were confirmed using single fragment titrations, TOCSY, HMQC or through ITC measurements. These findings prove the viability of the library for the search of target-specific RNA binders and the targetability of highly structure RNAs. The applied iNEXT fragment library is intended for research driven access and can easily be applied to more biological targets.


Session: SMALL MOLECULES 1, time: 11:50 - 12:05

Hyperpolarization of Long-lived Nuclear Spin States on Universal 15N Labeled Molecular Tags at Low Field


Guannan Zhang1; Thomas Glachet2; Raul Laasner1; Junu Bae1; Hyejin Park1; Qiu Wang1; Volker Blum1; Vincent Reboul2; Thomas Theis3; Warren Warren1
1Duke University, Durham, NC; 2ENSICAEN Université de Caen, Caen, France; 3NC State University, Raleigh, NC

A very common motif in molecular imaging is insertion of a chemically inert tag which is capable of giving a strong signal (most commonly, fluorescence). Hyperpolarization methods now make it possible to instead tag molecules with long-lived polarization, and transfer to magnetization then allows a sensitive readout. Signal amplification by reversible exchange (SABRE) is a cost-effective and simple hyperpolarization technique which significantly enhances an NMR signal by several orders of magnitude. Here, we discuss SABRE induced singlet order on 15N2 labeled diazirine moieties (-CH15N2), its ability to sustain long-lived hyperpolarized spin state at low field. We will further discuss a strategy using 15N3-azide tags (-15N=15N=15N) to create long-lived hyperpolarization in biomolecules.


Session: SMALL MOLECULES 1, time: 12:05 - 12:20 pm

Magnetically Induced Alignment of Natural Products for Determination of Configuration via NMR Specifically Robust for Large Conformational Fluctuations


Niels Karschin1; Klaus Wolkenstein2; Christian Griesinger1
1MPI for Biophysical Chemistry, Goettingen, Germany; 2Department of Geobiology, GAU, Goettingen, Germany

Anisotropic NMR has gained increasing popularity to determine the configuration of small flexible, non-crystallizable molecules. It suffers from the necessity to dissolve the analyte in special media such as liquid crystals or polymer gels. Small degrees of alignment are caused by the interaction of the magnetic field with aromatic moieties. A key feature of this mechanism is that the alignment can be predicted via DFT. We show that both RDC and RCSA can be acquired from natural products without special sample preparation using magnetically induced alignment. On the examples of a novel natural product with a large aromatic system and strychnine featuring a single aromatic ring these data, together with the predicted alignment, yield the correct configuration with high certainty.