Session MOA. There are 6 abstracts in this session.

Session: Small Molecules 1, time: 10:45am-11:05am

Ultrafast multiple-quantum and diffusion-ordered NMR spectroscopy

Corentin Jacquemmoz1, 2; Maria Grazia Concilio2; Jean-Nicolas Dumez1, 2
1CEISAM – CNRS, Nantes, France; 2ICSN - CNRS, Gif-Sur-Yvette, France
We describe the “ultrafast” implementation of two classes of experiments that are particularly useful for mixture analysis: 2D maximum quantum (MaxQ) and 3D diffusion ordered (DOSY) NMR. We show how multiple quantum (MQ) coherences can be encoded spatially, as validated by numerical simulation. With this approach, 2D MQ-SQ correlation spectra are collected in a single scan of less than one second, instead of several minutes.We then show how spatial encoding of the chemical shift can accelerate 3D DOSY experiments. With an ultrafast acquisition of 2D correlation spectra for each gradient increment, experiments lasts less than 5 min instead of several hours.These accelerated experiments will be particularly relevant for the monitoring of time-evolving and/or hyperpolarized solution mixtures.

Session: Small Molecules 1, time: 11:05am-11:25am

Understanding hydrogen-bonding of molecular crystals by electron- and NMR-nanocrystallography

Candelaria Guzmán-Afonso1; Youlee Hong1, 2; Henri Colaux1; Hirofumi IIjima3; Akihiro Saitow3; Takuma Fukumura3; Yoshitaka Aoyama3; Souhei Motoki3; Tetsuo Oikawa4; Toshio Yamazaki5, 7; Koji Yonekura6; Yusuke Nishiyama1, 8
1RIKEN-JEOL Collaboration Center, Kanagawa, Japan; 2WPI-iCeMS and ChEM-OIL, Kyoto University, Kyoto, Japan; 3JEOL Ltd., Tokyo, Japan; 4JEOL ASIA Pte. Ltd, Corporation Road, Singapore; 5RIKEN SPring-8 Center, Kanagawa, Japan; 6RIKEN SPring-8 Center, Hyogo, Japan; 7RIKEN-JEOL Collaboration Center, Hyogo, Japan; 8JEOL RESONANCE Inc., Tokyo, Japan
X-ray diffraction (XRD) requires large (>10 μm) single-crystals or large amount (>1mg) of pure micro-crystalline powders. In addition, XRD poorly locates hydrogens. Thus, it is still a big challenge to solve the structure, especially hydrogen-bonding structure, of nano- to micro-sized molecular crystals. Recently, it is shown that electron diffraction (ED) can solve the structure using nano-sized molecular crystals. However, ED fails to distinguish carbon, nitrogen, and oxygen, and also to locate hydrogen position precisely. On the other hand, SSNMR directly observes carbon, nitrogen and hydrogen, providing complementary information to ED. Here, we present a combined approach of ED, SSNMR and GIPAW computation based on NMR-crystallography approach. Cimetidine form B, whose structure has been unknown, is successfully solved from a micro-crystal.

Session: Small Molecules 1, time: 11:25am-11:45am

Discovery of Extreme NMR Chemical Shifts: How to Predict, Measure and Analyze Nuclei Directly Bound to a Paramagnetic Metal Center

Jonas Ott; Lutz Gade; Markus Enders
Universität Heidelberg, Heidelberg, Germany
Small paramagnetic metal complexes are increasingly important in catalysis, molecular magnetism and for Magnetic Resonance Imaging. The widespread use of NMR as an analytical tool for such compounds is hindered by a number of difficulties arising from the influence of the unpaired electrons. NMR of paramagnetic molecules (pNMR) can be extremely useful, if the spectra are interpreted reliably. This is nowadays possible by the help of quantum chemistry.
Here we report, pNMR analysis of Fe-complexes where we were able to determine the NMR shifts of directly bound atoms. In agreement with DFT modelling chemical shifts in the range of several thousands of ppm have been measured and were analyzed comprehensively.

Session: Small Molecules 1, time: 11:45am-12:05pm

Small molecules-based targeting of p8(TTD-A) dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy

Virginie Gervais
Institute of Pharmacology and Structural Biology, Toulouse, France
The TFIIH transcription factor is composed of 10 subunits that form an intricate network of protein–protein interactions critical for regulating its transcriptional and DNA repair activities. The smallest subunit (TTD-A/p8) displays dimerization properties allowing to shift from a homodimeric state, in the absence of a functional partner, to a heterodimeric structure with the p52 TFIIH subunit, enabling dynamic binding to TFIIH.
            We identified small-molecule compounds that bind to the dimerization interface of p8 and provoke its destabilization, as assessed by NMR and biophysical studies. Using quantitative imaging, we found that these molecules reduce the intracellular concentration of TFIIH and its transcriptional activity, demonstrating the utility of small molecules for targeting p8 dimerization and down-regulating transcription in cancer cells.

Session: Small Molecules 1, time: 12:05pm-12:25pm

Continuous Flow Hyperpolarisation in a Microfluidic Chip

William Hale; James Eills; Sylwia Ostrowska; Manvendra Sharma; Malcolm Levitt; Marcel Utz
University of Southampton, Southampton, United Kingdom
NMR is an ideal tool to follow chemical and biochemical processes in microfluidic lab-on-a-chip (LoC) devices due to its non-invasive properties and its generality and specificity. In spite of this, NMR is rarely used in the context of LoC systems due to limited sensitivity. Hyperpolarisation techniques such as parahydrogen induced polarisation (PHIP) may overcome this limitation. In this work, we demonstrate the integration of PHIP on a flexible microfluidic platform. The combination of hyperpolarisation with a highly optimised transmission line NMR probe leads to exceptionally good sensitivity. Moreover, the integrated system allows operation under continuous flow enabling detailed kinetic studies of the hydrogenation, polarisation transfer, and relaxation processes.

Session: Small Molecules 1, time: 12:25pm-12:45pm

Structure and Dynamics of a Stereoselective Brønsted Acid Catalyst using RDC, NOE Distances and Chemical Shifts as MD Constraints

Ulrich Sternberg1; Christophe Farès2
1Research partner of KIT, Karlsruhe, Germany; 2Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany
The catalyst consists of two S-BINOL groups that are connected by the IDPi motif formed by a -SO2-N=PO2-N=PO2-NH-SO2- group. This compound activates olefins in reactions to chiral products. We performed MD simulations that are driven by 12 C-F and 88 C-H RDC (MDOC). It turned out that the rotations around central P-N-P bonds are possible with maxima at about 150°. The chiral character of the two S-BINOL groups leads to an asymmetry in the surrounding of the central P-N-P system. 2000 MD snapshots were geometry-optimized using C-13 chemical shifts as constraints. The structure with the best fit of calculated and experimental chemical shifts proved to be optimal for docking the substrate to a structure called intermediate I.