Dipolar Order Saves the Day: Sensitivity Enhancement under Static and MAS Conditions

Sensitivity enhancement of unreceptive nuclei is a major goal of solid-state NMR. This tutorial will focus on methods to enhance the sensitivity of dilute and unreceptive nuclei under static and magic-angle-spinning (MAS) conditions using dipolar order, the theoretical framework to understand them, and practical considerations when performing them.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Long-loved nuclear singlet spin order and its applications

Nuclear singlet spin order is the population difference between the singlet and triplet states in a system of two coupled spin-1/2 nuclei. This form of order is long-lived, silent and accessible on demand. For almost two decades, my research activities were focused at exploiting these three main properties of nuclear spin order to develop new applications in NMR and MRI.  

            In this talk, I will introduce the concept and the main features of singlet order as well as the tools developed for its manipulations.

            I will then show how we are using this form of order to enhance several NMR and MRI techniques for the long-term storage of hyperpolarisation, to obtain a new form of contrast in MRI, for the measurements of slow diffusion and flow, or for the determination of structural features of porous media such as tortuosity and structural anisotropy through singlet-assisted diffusion NMR.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Hyperpolarized Xenon NMR for Exploring Molecular Host Cavities and Advancing MR Imaging

The large chemical shift range of Xe-129 NMR makes this nucleus a valuable probe in spectroscopy and biomedical imaging. Hyperpolarized Xe can be used also as dissolved noble gas to provide 10’000-fold improved sensitivity over extended periods of time. In combination with saturation transfer techniques, reversibly bound hyperpolarized xenon gives insights into exchange kinetics of various host-guest complexes. This talk will give an overview of studies investigating the affinity of dissolved Xe for various hosts like biogenic hollow protein structures with attoliter volumes or synthetic hosts for trapping individual Xe atoms. Both strategies find applications in the spectroscopic investigation of exchange kinetics of host-guest systems and in the design of ultra-sensitive magnetic resonance imaging agents.

9:00 AM California or 12:00 PM Boston or 5:00 PM Paris or 9:30 PM Delhi

The Application of NMR Metabolomics to Drug Discovery and Disease Diagnosis

NMR-based metabolomics has benefited a variety of fields including drug discovery and disease diagnosis. Metabolomics is technically very challenging and requires expertise in a diversity of scientific areas. In this regard, this tutorial will discuss best practices for sample preparation and handling, data collection and analysis, and statistical modeling and interpretation to achieve biologically and clinically significant results.

8:00 AM California or 11:00 AM Boston or 4:00 PM Paris or 8:30 PM Delhi

Title to Be Announced

Abstract to be announced.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

Why Is DOSY So Different From COSY?

Peaks in COSY, NOESY, ROESY and HSQC 2D spectra either appear where they should, or not at all. In DOSY spectra, it is all too common to see peaks at incorrect positions in the diffusion domain. This tutorial will explore why this happens, what we can do about it, and how to avoid being misled by DOSY spectra.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

Challenges in the characterization of polymeric materials for drug delivery and tissue engineering applications

NMR spectroscopy is sensitive to subtle changes in local environment and dynamics over multiple length and time scales making it a versatile technique to study polymeric materials and incorporated molecules. Challenges, which will be discussed in this presentation arise from the size (distribution), rigidity and intrinsic disorder of the samples.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

Single Chip Dynamic Nuclear Polarization Microsystems

Dynamic nuclear polarization (DNP) is one of the most powerful and versatile hyperpolarization methods to enhance nuclear magnetic resonance (NMR) signals. A major drawback of DNP is the cost and complexity of the required microwave hardware, especially at high magnetic fields and low temperatures. To overcome this drawback and with the focus on the study of nanoliter and subnanoliter samples, I will present single chip DNP microsystems where the microwave excitation and detection are performed locally on chip without the need of external microwave generators and transmission lines.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

NMR Strategies for Examining Interactions Between Small Molecules and Nanoparticle Surfaces

Interactions between small molecules and the surface of nanoparticles are important in a variety of fields, from drug delivery to the fate of nanoparticles in the environment. In this talk, I will discuss several NMR techniques that can be used to gain structural and dynamic information about these interactions, with a focus on saturation-transfer difference (STD)-NMR.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

Solution and Solid-state NMR Applications in Pharmaceutical Sciences

Advancements in drug delivery systems and therapeutic modalities have driven the growth of modern medicine, while also increasing molecular complexity. NMR spectroscopy is a pivotal tool in understanding the structural attributes that contribute to overcoming physiological and physicochemical barriers, thereby providing scientific rationales for drug development. This presentation will highlight the structure-related challenges in the development of pharmaceutical drug products and the role that solution and solid-state NMR techniques play in addressing them, with examples from both chemical and biological therapies.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

High-dimensional spectroscopy and other tools to tackle complexity in biological solid-state NMR

Fast (> 60 kHz) magic-angle spinning provides high sensitivity and narrowed 1H linewidths, however, spectral analysis of large proteins are often severely hampered by peak overlap and/or ambiguity, depending on system size and sample quality. In this tutorial lecture, I will discuss several experimental techniques to address this, namely high-dimensional (4D, 5D) spectroscopy with non-uniform sampling, projection spectroscopy and time-shared acquisition. Additionally, I will explore selected tools for automation of resonance assignment and present early data on protein dynamics measurement as pseudo-4D series. 

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

Scaling Analyses of Hyperpolarization Transfer in Solids and Across Interfaces

Classical scaling analyses, with analogies to heat conduction and mass transfer, quantitatively describe the propagation and dissipation of non-Boltzmann spin polarization in heterogeneous solids. The analyses yield general design criteria for predicting, analyzing, and optimizing polarization transfer within solids and across interfaces between dissimilar materials.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 9:30 PM Delhi

Inside an NMR Spectrometer

Let us take a brief look at what is happening inside an NMR spectrometer when we operate it, running pulse sequences and acquiring NMR signals. In particular, I will focus on open-resource, home-built NMR spectrometers we routinely use in our lab, and show how we apply them in the conventional and unconventional NMR experiments.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Title to Be Announced

Abstract to be announced.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

NMR Pulse Sequence Basics and Design Principles

NMR is commonly used for studying structure and dynamics of molecules, and many NMR
experiments have been developed for different purposes. In each NMR experiment it is necessary to choose the most suitable NMR pulse sequence to obtain optimal results, which requires understanding about the basic theory. During NMR pulse sequence the studied system is evolved under different types of interactions, which can be represented by density matrix or product operator. The basic syntax for NMR pulse sequence programming will be briefly introduced together with several examples, which helps to understand how NMR pulse sequences work and make further optimization.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Nano- and microscale magnetic resonance spectroscopy using spin defects in diamond

Nuclear magnetic resonance (NMR), one of the most powerful analytical techniques in chemistry and life sciences, is typically limited to macroscopic volumes due to its inherent low sensitivity. This excludes NMR spectroscopy from the analysis of microscopic sample sizes, such as in single-cell biology or microfluidic applications. In recent years, it has been shown that NMR signals from nano- to microscale volumes can be detected by a new class of sensors - quantum sensors based on defects in the diamond lattice - the nitrogen vacancy (NV) centre. In this talk, I will first introduce NV centres and explain how these atom-sized sensors can be used to detect NMR signals. In the second part, I will provide an overview of this rapidly developing technology and discuss potential applications ranging from surface and materials science to lab-on-a-chip applications.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Measuring Dynamics Using Anisotropic Interactions in MAS-NMR

 Solid-state MAS NMR gives direct access to anisotropic interactions such as CSA, dipole-dipole and quadrupolar couplings. The precise measurement of these interactions, in addition to providing structural features,  also gives access to dynamics via their partial averaging due to molecular motion. This tutorial will explore various techniques that are available to extract details of molecular motion via the measurement of these anisotropic interactions, with a particular focus on the measurement of dipole-dipole couplings.

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Title to Be Announced

Abstract to be announced

8:00 AM California or 11:00 AM Boston or 5:00 PM Paris or 8:30 PM Delhi

Triplet Dynamic Nuclear Polarization: New Polarizing Agents and Targets"

Triplet dynamic nuclear polarization (triplet-DNP), which utilizes the
polarized electron spins of the photo-excited triplet, is an excellent
method to obtain large nuclear spin polarization even under mild
conditions below 1 T near room temperature. This talk will highlight
the potential of triplet-DNP and the exciting new possibilities that
have emerged with recent advancements in polarizing agents and
targets. Specifically, I will cover the following topics:
1. Mechanism of triplet-DNP as an introduction
2. Expanding the targets using supramolecular polarizing agents
3. Improving air stability and solubility with non-pentacene polarizing agents
4. Challenging polarization transfer with the use of nanomaterials.

7:00 AM California or 10:00 AM Boston or 4:00 PM Paris or 7:30 PM Delhi

NMR Chemical Shifts Beyond Numbers: Understanding Electronic Structures to a Reactivity Descriptor

NMR chemical shift is successfully used to identify the structure of molecules (and materials) making NMR an invaluable tool of characterizations. Because of its power to elucidate molecular structure, NMR interpretation is taught at an early stage, often in laboratory courses, even before one understands the fundamentals of spectroscopy and their selection rules. This lecture will concentrate on developing a detailed understanding of the origin of NMR chemical shift, and show how it can be used to reconstruct the electronic structure of molecules, particular organometallic intermediates. This lecture will illustrate why the symmetry of the angular momentum operator makes NMR a privileged spectroscopic descriptor of reactivity.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 8:30 PM Delhi

NMR crystallography: integrative foundations and applications to materials chemistry and structural biology

NMR crystallography – the integrated application of solid-state NMR, X-ray diffraction, and first-principles computational chemistry – is rapidly developing as an atomic-resolution probe of structure and function across the molecular sciences.  Here, I will discuss critical aspects in the integration of these three techniques, including the need for a priori determination of linear rescaling parameters and rigorous methods of statistical analysis. I will present two recent examples from my group's work that highlight these factors. The first is to photomechanical materials, connecting the molecular-level structural rearrangement to the experimentally-observed macroscopic response. The second is to integrative structural biology, revealing chemically-detailed structure and dynamics in the enzyme active site of tryptophan synthase, and how this has changed our understanding of its mechanism and inhibition.

9:00AM California or 12:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

The Basics of Ultra-Wideline Solid-State NMR Spectroscopy

This tutorial will cover the basic concepts surrounding the acquisition of ultra-wideline solid-state NMR spectra, including the use of WURST pulses for direct excitation and broadband cross polarization, new methods for indirect detection, and applications to a wide range of nuclides from elements across the Periodic Table.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Chemical Exchange Saturation Transfer (CEST) MRI: from basic principles to potential clinical applications

Novel MRI methods are focusing on imaging events and structures at the molecular level. One of the methods gaining popularity is Chemical Exchange Saturation Transfer (CEST). Here we will discuss basic physical principles of this approach, followed by potential applications and challenges associated with the translation to in-vivo and human imaging.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Solid-state NMR for investigating crystallization from solution

Crystallization underpins essential processes in our everyday life, creating exceptional materials. Yet, fundamental understanding of the mechanisms underlying crystallization processes is still lacking because of the scarcity of experimental approaches allowing atomic-level investigation of the sequence of intermediate phases formed during crystallization as a function of time.
After introducing the basic principles of crystallization and the associated experimental challenges and current analytical approaches, I will discuss how NMR, coupled with hyperpolarization methods, can contribute to solve longstanding questions on crystallization, with particular attention to organic polymorphic compounds. Current limitations and possible future directions will be discussed.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Microfluidic Systems and Magnetic Resonance

Microfluidic technology has rapidly advanced over the last two decades, and is increasingly transforming the practice of life science research, as well as (arguably more slowly) medical diagnostics. In particular, microfluidic assays are ideal platforms for the culture of cells, cell aggregates, and tissue slices, and form the basis of increasingly predictive disease models. Nuclear magnetic resonance, due to its non-invasive nature and ability to provide rich and detailed information on biological systems, is ideally suited to follow life processes in such microfluidic culture devices. However, the integration of high-performance NMR spectroscopy with microfluidic lab-on-a-chip devices is technically challenging due to the small sample volumes involved. Recent advances in hyperpolarization and alternative detection approaches offer important opportunities in this field. In this talk, I will give an overview of the opportunities and challenges in microfluidic NMR, and present some recent examples.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Title to Be Announced

Abstract to be announced

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Room Temperature DNP via Substitutional-Nitrogen (P1) Centers in Diamond

Electron spins in diamond have long coherence and relaxation times at room temperature, making them an exciting platform for EPR and DNP experiments under ambient conditions. In this talk I will describe our recent W-band DNP experiments using the substitutional nitrogen (or P1) defect to hyperpolarize the 13C spins in both single crystal and diamond powders. The DNP spectra measured in these samples show signatures of multiple mechanisms including the solid effect, the cross effect, the truncated cross effect and the Overhauser effect. I will discuss how variations in the microscopic environments of the spins could lead to these observations.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Integrating EPR Distance Distribution Restraints with NMR Data in Protein Models

This zoominar will start with a short explanation of in silico spin labelling, which is useful for planning paramagnetic relaxation enhancement (PRE) NMR experiments as well as DEER EPR experiments for measuring distance distributions. I will continue with a primer on converting DEER data into distance distributions. The zoominar concludes with an example of using distance distributions in modelling a weakly structured low-complexity domain of an RNA-binding protein.

8:00AM California or 11:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi

Using Deep Learning to Transform and Analyse NMR Data

It will be shown how deep neural networks (DNNs) can be trained for reconstruction of sparsely sampled NMR spectra and for virtual homonuclear decoupling. Another area covered in the talk will be autonomous analysis of chemical exchange saturation transfer (CEST) data, where the Trained DNN accurately predicts both the chemical shifts and the uncertainties associated with these.

9:00AM California or 12:00 am Boston or 5:00 PM Paris or 9:30 PM Delhi