Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal (15)N2-diazirine molecular tags.
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2016-03
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Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize (15)N2 magnetization and long-lived (15)N2 singlet spin order, with signal decay time constants of 5.8 and 23 minutes, respectively. We find >10,000-fold enhancements generating detectable nuclear MR signals that last for over an hour. (15)N2-diazirines represent a class of particularly promising and versatile molecular tags, and can be incorporated into a wide range of biomolecules without significantly altering molecular function.
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Theis, T, GX Ortiz, AWJ Logan, KE Claytor, Y Feng, WP Huhn, V Blum, SJ Malcolmson, et al. (2016). Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal (15)N2-diazirine molecular tags. Sci Adv, 2(3). p. e1501438. 10.1126/sciadv.1501438 Retrieved from https://hdl.handle.net/10161/11770.
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Scholars@Duke
Volker Blum
Volker Blum heads the "Ab initio materials simulations" group at Duke University. Dr. Blum's research focuses on first-principles computational materials science: using the fundamental laws of quantum mechanics to predict the properties of real materials from the atomic scale on upwards.
Specific focus areas are interface and nanoscale systems with electronic and energy applications, as well as work on molecular structure and spectroscopy. He is actively working on novel semiconductor materials, including hybrid organic-inorganic perovskites and complex chalcogenide materials. Both groups of materials hold promise as absorbers for photovoltaics (i.e., solar cells), as materials for spin-based electronics and optoelectronics, and other semiconductor applications.
Dr. Blum is the coordinator of a major computer package for computational materials and molecular science based on electronic structure theory, FHI-aims. Work in his group is interdisciplinary (touching areas of physics and chemistry in addition to materials science), with opportunities for international collaboration and exchange.
Steven Malcolmson
The discovery of catalysts is of great importance to the practice of modern synthetic chemistry, both to improve upon the existing catalog of chemical transformations and to generate new modes of reactivity. Research in the Malcolmson lab focuses on the discovery of novel methods for the efficient and selective synthesis of small molecule scaffolds through the design and development of new catalysts. In these transformations, we seek to realize new synthetic bond disconnections while also controlling some aspect of selectivity (e.g., enantio-, and/or site selectivity). The catalysts and methods developed in the group are being applied to the synthesis of biologically active molecules to drive the development of new chemistry as well as help to address problems in human health.
Qiu Wang
Research in the Wang group aims to answer fundamental questions that lie at the interface of chemistry and biology. In particular, we are interested in developing small-molecule based probes and methods to understand the cause of disease with an emphasis on identifying potential therapeutic agents towards cancer and neurodegenerative disorders.
- Bioactive molecules as probes in human biology and disease. Starting from naturally occurring molecules that possess unique anti-cancer activity or neuroprotective/neurotrophic activities, our research incorporates synthetic chemistry and biological efforts to expedite discovery of novel bioactive molecules and to facilitate the study of their biological properties. Chemistry efforts will emphasize the development of modular approaches to target molecules and new methodologies to maximize synthetic efficiency. Biological studies will focus on profiling the activities of selected compounds and identifying their mode of action.
- Epigenetic modifying enzymes as novel therapeutic targets. We are interested in developing small-molecule regulators of epigenetics modifications, the new frontier in understanding and treatment of disease. For example, research will be directed towards identifying small-molecule modulators of arginine methylation and uncovering their regulatory pathways. Discovery of such molecules will provide powerful tools to interrogate the physiological roles of arginine methylation and offer potential lead molecules for novel therapies to contribute to a new era of epigenetic-based drugs.
- New chemical tools for biomolecule labeling and target identification. Our research also involves the development of new chemical tools to enable selective detection of the temporal and spatial small-molecule ligand-biomolecule interactions in vitro and in vivo. Towards this end, we will design and synthesize photoaffinity cross-linking tools to label methyltransferases, their substrates, and their binding partners.
Overall, the research in the Wang group involves the interplay of these three complementary areas and integrates the principles of synthetic chemistry, assay development, molecular and cell biology, genetics, and proteomics. Through this interdisciplinary approach, we will create a small-molecule toolbox for studying genes and pathways of importance to cancer and neurodegenerative disorders.
Warren S. Warren
Our work focuses on the design and application of what might best be called novel pulsed techniques, using controlled radiation fields to alter dynamics. The heart of the work is chemical physics, and most of what we do is ultrafast laser spectroscopy or nuclear magnetic resonance. It generally involves an intimate mixture of theory and experiment: recent publications are roughly an equal mix of pencil- and-paper theory, computer calculations with our workstations, and experiments. Collaborations also play an important role, particularly for medical applications.
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