Friday, August 31, 2012

Water-Soluble Narrow-Line Radicals for Dynamic Nuclear Polarization

Haze, O., et al., Water-Soluble Narrow-Line Radicals for Dynamic Nuclear Polarization. J. Am. Chem. Soc., 2012.


The synthesis of air-stable, highly water-soluble organic radicals containing a 1,3-bis(diphenylene)-2-phenylallyl (BDPA) core is reported. A sulfonated derivative, SA-BDPA, retains the narrow electron paramagnetic resonance linewidth (<30 MHz at 5 T) of the parent BDPA in highly concentrated glycerol/water solutions (40 mM), which enables its use as polarizing agent for solid effect dynamic nuclear polarization (SE DNP). A sensitivity enhancement of 110 was obtained in high-field magic-angle-spinning (MAS) NMR experiments. The ease of synthesis and high maximum enhancements obtained with the BDPA-based radicals constitute a major advance over the trityl-type narrow-line polarization agents.

Wednesday, August 29, 2012

Para-hydrogen induced polarization of Si-29 NMR resonances as a potentially useful tool for analytical applications

Ellena, S., et al., Para-hydrogen induced polarization of Si-29 NMR resonances as a potentially useful tool for analytical applications. Magn. Reson. Chem., 2012. 50(8): p. 529-533.


Para-hydrogen–induced polarization effects have been observed in the 29Si NMR spectra of trimethylsilyl para-hydrogenated molecules. The high signal enhancements and the long T1 values observed for the 29Si hyperpolarized resonances point toward the possibility of using 29Si for hyperpolarization applications. A method for the discrimination of multiple compounds and/or complex mixtures of hydroxylic compounds (such as steroids), consisting of the silylization of alcoholic functionalities with an unsaturated silylalkyl moiety and subsequent reaction with para-H2, is proposed. 

Monday, August 27, 2012

Solid effect in magic angle spinning dynamic nuclear polarization

Corzilius, B., A.A. Smith, and R.G. Griffin, Solid effect in magic angle spinning dynamic nuclear polarization. J. Chem. Phys., 2012. 137(5): p. 054201-12.


For over five decades, the solid effect (SE) has been heavily utilized as a mechanism for performing dynamic nuclear polarization (DNP). Nevertheless, it has not found widespread application in contemporary, high magnetic field DNP experiments because SE enhancements display an omega(0) (-2) field dependence. In particular, for nominally forbidden zero and double quantum SE transitions to be partially allowed, it is necessary for mixing of adjacent nuclear spin states to occur, and this leads to the observed field dependence. However, recently we have improved our instrumentation and report here an enhancement of varepsilon = 91 obtained with the organic radical trityl (OX063) in magic angle spinning experiments performed at 5 T and 80 K. This is a factor of 6-7 higher than previous values in the literature under similar conditions. Because the solid effect depends strongly on the microwave field strength, we attribute this large enhancement to larger microwave field strengths inside the sample volume, achieved with more efficient coupling of the gyrotron to the sample chamber. In addition, we develop a theoretical model to explain the dependence of the buildup rate of enhanced nuclear polarization and the steady-state enhancement on the microwave power. Buildup times and enhancements were measured as a function of (1)H concentration for both trityl and Gd-DOTA. Comparison of the results indicates that for trityl the initial polarization step is the slower, rate-determining step. However, for Gd-DOTA the spread of nuclear polarization via homonuclear (1)H spin diffusion is rate-limiting. Finally, we discuss the applicability of the solid effect at fields > 5 T and the requirements to address the unfavorable field dependence of the solid effect.

Thursday, August 23, 2012

Formal Theory of Spin-Lattice Relaxation

Besides transferring electron polarization to the nuclei, spin lattice relaxation is a very important process for DNP. Many papers and books have been published about this topic, but I recently came across a very nice paper by Maurice Goldman that describes the different formal descriptions of spin lattice relaxation process in glorious details. If you are a theory junky, this article is for you, with very detailed mathematical description of the processes.

Goldman, M., Formal Theory of Spin–Lattice Relaxation. J. Magn. Reson., 2001. 149(2): p. 160-187.


Tuesday, August 21, 2012

Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods

Lloyd, L.S., et al., Utilization of SABRE-Derived Hyperpolarization To Detect Low-Concentration Analytes via 1D and 2D NMR Methods. J. Am. Chem. Soc., 2012. 134(31): p. 12904-12907.


The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of 13C, 13C{1H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established.

Sunday, August 19, 2012

Dynamic nuclear polarization-enhanced 1H–13C double resonance NMR in static samples below 20 K

Potapov, A., et al., Dynamic nuclear polarization-enhanced 1H–13C double resonance NMR in static samples below 20 K. J. Magn. Reson., 2012. 221(0): p. 32-40.


We demonstrate the feasibility of one-dimensional and two-dimensional 1H–13C double resonance NMR experiments with dynamic nuclear polarization (DNP) at 9.4 T and temperatures below 20 K, including both 1H–13C cross-polarization and 1H decoupling, and discuss the effects of polarizing agent type, polarizing agent concentration, temperature, and solvent deuteration. We describe a two-channel low-temperature DNP/NMR probe, capable of carrying the radio-frequency power load required for 1H–13C cross-polarization and high-power proton decoupling. Experiments at 8 K and 16 K reveal a significant T2 relaxation of 13C, induced by electron spin flips. Carr–Purcell experiments and numerical simulations of Carr–Purcell dephasing curves allow us to determine the effective correlation time of electron flips under our experimental conditions. The dependence of the DNP signal enhancement on electron spin concentration shows a maximum near 80 mM. Although no significant difference in the absolute DNP enhancements for triradical (DOTOPA-TEMPO) and biradical (TOTAPOL) dopants was found, the triradical produced greater DNP build-up rates, which are advantageous for DNP experiments. Additionally the feasibility of structural measurements on 13C-labeled biomolecules was demonstrated with a two-dimensional 13C–13C exchange spectrum of selectively 13C-labeled β-amyloid fibrils.

Friday, August 17, 2012

A 250 GHz gyrotron with a 3 GHz tuning bandwidth for dynamic nuclear polarization

Barnes, A.B., et al., A 250 GHz gyrotron with a 3 GHz tuning bandwidth for dynamic nuclear polarization. J. Magn. Reson., 2012. 221(0): p. 147-153.


We describe the design and implementation of a novel tunable 250 GHz gyrotron oscillator with > 10 W output power over most of a 3 GHz band and > 35 W peak power. The tuning bandwidth and power are sufficient to generate a > 1 MHz nutation frequency across the entire nitroxide EPR lineshape for cross effect DNP, as well as to excite solid effect transitions utilizing other radicals, without the need for sweeping the NMR magnetic field. Substantially improved tunability is achieved by implementing a long (23 mm) interaction cavity that can excite higher order axial modes by changing either the magnetic field of the gyrotron or the cathode potential. This interaction cavity excites the rotating TE5,2,q mode, and an internal mode converter outputs a high-quality microwave beam with &gt;94% Gaussian content. The gyrotron was integrated into a DNP spectrometer, resulting in a measured DNP enhancement of 54 on the membrane protein bacteriorhodopsin.

Thursday, August 16, 2012

DNP - Historical Overview

Check out the recent post that I wrote for Agilent's Spinsights blog that gives a historical overview and timeline for DNP spectroscopy.



DNP is not a new technique and is almost as old as the first EPR or NMR experiments. However, with it's recent gain of interest in the structural biology or material science community it is often forgotten that DNP was and still is extensively used in particle physics (polarized targets). Even polarizing agents based on nitroxides were already used back in the 1960's. So, check out the DNP timeline that I put together and let me know if I missed an important milestone contribution in DNP.

Wednesday, August 15, 2012

A large volume double channel 1H–X RF probe for hyperpolarized magnetic resonance at 0.0475 T

Coffey, A.M., et al., A large volume double channel 1H–X RF probe for hyperpolarized magnetic resonance at 0.0475 T. J. Magn. Reson., 2012. 220(0): p. 94-101.


In this work we describe a large volume 340 mL 1H-X magnetic resonance (MR) probe for studies of hyperpolarized compounds at 0.0475 T. 1H/13C and 1H/15N probe configurations are demonstrated with the potential for extension to 1H/129Xe. The primary applications of this probe are preparation and quality assurance of 13C and 15N hyperpolarized contrast agents using PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) and other parahydrogen-based methods of hyperpolarization. The probe is efficient and permits 62&#xa0;μs 13C excitation pulses at 5.3 W, making it suitable for portable operation. The sensitivity and detection limits of this probe, tuned to 13C, are compared with a commercial radio frequency (RF) coil operating at 4.7 T. We demonstrate that low field MR of hyperpolarized contrast agents could be as sensitive as conventional high field detection and outline potential improvements and optimization of the probe design for preclinical in vivo MRI. PASADENA application of this low-power probe is exemplified with 13C hyperpolarized 2-hydroxyethyl propionate-1-13C,2,3,3-d3.

Inductively coupled NMR probe for versatile dynamic nuclear polarization operation at 7 T: Observation of 61 +/- 2% 1H polarization at 4K

Siaw, T.A., et al., Inductively coupled NMR probe for versatile dynamic nuclear polarization operation at 7 T: Observation of 61 +/- 2% 1H polarization at 4K. J. Magn. Reson., 2012. 221(0): p. 5-10.


We have performed dynamic nuclear polarization (DNP) experiments at liquid helium temperatures using a low-power (<70 mW) solid-state diode microwave source at 200 GHz—the electron paramagnetic resonance frequency of stable radicals at 7 T. We employed a home-built Alderman–Grant probe for the detection of 1H NMR signal at 300 MHz, as such coils are well suited for higher frequency NMR detection. The Alderman–Grant coil is inductively coupled to the rest of the radiofrequency (rf) circuit, whose design allows probe components to be placed away from the sample area, and also enables easy switching of coils with different diameters and resonance frequencies. We have tested our DNP instrument on a frozen nitroxide model system consisting of 4-Amino TEMPO dissolved in a glycerol:water mixture. The largest nuclear spin polarization observed was 61 ± 2% with a sample containing 20 mM 4-Amino TEMPO dissolved in deuterated glycerol (d-glycerol):D2O:H2O (50:40:10), amounting to record polarization measured to date at an easily amenable temperature of 4 K.

Monday, August 13, 2012

Thermoresponsive Spin-Labeled Hydrogels as Separable DNP Polarizing Agents Assessing the Functional Structure of Molecular Transporters by EPR Spectroscopy

J.N.Junk, M. and M.J.N. Junk, Thermoresponsive Spin-Labeled Hydrogels as Separable DNP Polarizing Agents Assessing the Functional Structure of Molecular Transporters by EPR Spectroscopy. 2012: p. 133-148.

http://dx.doi.org/10.1007/978-3-642-25135-1_6

Dynamic nuclear polarization (DNP) is a commonly applied NMR hyperpolarization technique, which is based on the polarization transfer from electron spins to nuclear spins. While DNP allows a significant enhancement of NMR signals by several orders of magnitude, major drawbacks of the method include enhanced nuclear relaxation times due to the presence of unpaired electrons and the toxicity of radicals, which is the limiting factor for in vivo applications in magnetic resonance imaging. Thus, an efficient separation of the polarization agent is a key requirement for possible applications in medicine. In this chapter, the application of spin-labeled thermoresponsive hydrogels as polarizing agents for dynamic nuclear polarization is explored.

NIH Funds Development of Solution-State DNP-NMR Probe

Press Release

NIH Funds Development of Solution-State DNP-NMR Probe 
Second SBIR Grant Awarded to Bridge12 for Dynamic Nuclear Polarization 



Framingham, Mass. – August 13th, 2012 – Bridge12 Technologies, a leading provider of terahertz (THz) technology for applications in science, medicine, security, and defense, announces it has received the National Institute of Health’s first small business innovation research (SBIR) grant for the development and commercialization of a solution-state DNP-NMR probe.

Saturday, August 11, 2012

15N Magnetic Resonance Hyperpolarization via the Reaction of Parahydrogen with 15N-Propargylcholine

Reineri, F., et al., 15N Magnetic Resonance Hyperpolarization via the Reaction of Parahydrogen with 15N-Propargylcholine. J. Am. Chem. Soc., 2012. 134(27): p. 11146-11152.


15N-Propargylcholine has been synthesized and hydrogenated with para-H2. Through the application of a field cycling procedure, parahydrogen spin order is transferred to the 15N resonance. Among the different isomers formed upon hydrogenation of 15N-propargylcholine, only the nontransposed derivative contributes to the observed N-15 enhanced emission signal. The parahydrogen-induced polarization factor is about 3000. The precise identification of the isomer responsible for the observed 15N enhancement has been attained through a retro-INEPT (15N-1H) experiment. T1 of the hyperpolarized 15N resonance has been estimated to be ca. 150 s, i.e., similar to that reported for the parent propargylcholine (144 s). Experimental results are accompanied by theoretical calculations that stress the role of scalar coupling constants (JHN and JHH) and of the field dependence in the formation of the observed 15N polarized signal. Insights into the good cellular uptake of the compound have been gained.



Thursday, August 9, 2012

Dynamic Nuclear Polarization of Oxygen-17

Michaelis, V.K., et al., Dynamic Nuclear Polarization of Oxygen-17. The Journal of Physical Chemistry Letters, 2012: p. 2030-2034.


Oxygen-17-detected DNP NMR of a water/glycerol glass enabled an 80-fold enhancement of signal intensity at 82 K, using the biradical TOTAPOL. The >6000-fold savings in acquisition time enable 17O?1H distance measurements and heteronuclear correlation experiments. These experiments are the initial demonstration of the feasibility of DNP NMR on quadrupolar 17O.



Tuesday, August 7, 2012

4th International DNP Symposium

The 4th International Meeting on Dynamic Nuclear Polarization will be held August 2013, in Copenhagen, Denmark, following the highly successful meetings in Nottingham (2007), Koenigstein (2009) and Lausanne (2011).

An array of key players of this emerging field will assess the present state of the art while participants will be encouraged to reveal and discuss the current issues and new trends in DNP, including the developments in Overhauser effect, dissolution DNP, gyrotrons, magic angle spinning, low temperature DNP, radical chemistry, and hyperpolarized imaging.

Registration will open January 2013 and closes June 1st, 2013.

For more information visit: http://www.dnpsymposium.org/

Creating Long-Lived Spin States at Variable Magnetic Field by Means of Photochemically Induced Dynamic Nuclear Polarization

Kiryutin, A.S., et al., Creating Long-Lived Spin States at Variable Magnetic Field by Means of Photochemically Induced Dynamic Nuclear Polarization. The Journal of Physical Chemistry Letters, 2012. 3(13): p. 1814-1819.


We have shown that long-lived spin states (LLS) can be selectively populated by photogenerated chemically induced dynamic nuclear polarization (CIDNP) over a wide range of magnetic fields. Relaxation times of LLS of the beta-CH2 protons in N-acetyl histidine and partially deuterated histidine have been measured. Our experiments demonstrate that CIDNP enables creating LLS in the amino acid in a field range of up to a few Tesla and that their lifetimes can be 45 times longer than T1. The advantage of the method is thus two-fold: it allows one to accumulate high levels of spin hyperpolarization and to preserve them for periods of time far exceeding T1. Therefore, photo-CIDNP is a technique suitable for creating long-lived spin order in biologically relevant molecules.



Pulsed Dynamic Nuclear Polarization

High-field, solid-state DNP experiments typically rely on a cw mechanism such as the cross-effect, thermal mixing or the solid effect. However, there are some examples in the literature about pulsed DNP experiments. Most of the experiments are performed at low magnetic field strenghts (0.35 T up to 3.3 T) but there are some rare examples of high-field pulsed DNP experiments such as this one. It is a fairly old paper but still a very interesting one:

Un, S., et al., Pulsed dynamic nuclear polarization at 5 T. Chem. Phys. Lett., 1992. 189(1): p. 54-59.


A new dynamic nuclear polarization (DNP) technique utilizing high frequency, pulsed microwaves is described and demonstrated with observation of an Overhauser enhanced, 13C magic angle spinning nuclear magnetic resonance spectrum of a powdered sample of the organic conductor, fluoranthenyl hexafluorophosphate ((FA)2PF6). The spectrum was obtained at room temperature in a 5 T magnetic field, where the conduction electron spin resonance frequency is 140 GHz. A simple theory that accounts for the salient aspects of this pulsed DNP technique is presented. In systems where Overhauser mechanisms dominate the DNP, this new pulsed method can produce enhancements which are comparable to or greater than those obtained with conventional cw irradiation techniques, with lower average microwaves powers.

Monday, August 6, 2012

Quantum Mechanical Simulation of Cross Effect DNP Using Krylov–Bogolyubov Averaging

Karabanov, A., G. Kwiatkowski, and W. Köckenberger, Quantum Mechanical Simulation of Cross Effect DNP Using Krylov–Bogolyubov Averaging. Appl. Magn. Reson., 2012. 43(1): p. 43-58.


Krylov–Bogolyubov averaging is applied to reduce the dimension in quantum mechanical simulations of the cross effect dynamic nuclear polarization experiment. The exact form of the averaged master equation, describing the polarization dynamics of individual nuclear spins, is provided. The relevant relaxation superoperator is derived in the conventional product basis avoiding the diagonalization of the Hamiltonian for the purpose of finding its eigenbasis. Furthermore, we show that it is sufficient to retain the relaxation terms arising from the full set of electron Zeeman states and the terms arising from paramagnetic relaxation of the nuclear spins for deriving the relaxation superoperator. The subspace of the Liouville space to which the spin dynamics can be confined by the averaging procedure is identified. In addition, it is demonstrated that the state space can be truncated at a low spin correlation order, thus reducing the dimensions even further. Numerical results, illustrating the theory, are presented.



Saturday, August 4, 2012

Fast Dissolution Dynamic Nuclear Polarization NMR of 13C-Enriched 89Y-DOTA Complex: Experimental and Theoretical Considerations

Lumata, L., et al., Fast Dissolution Dynamic Nuclear Polarization NMR of 13C-Enriched 89Y-DOTA Complex: Experimental and Theoretical Considerations. Appl. Magn. Reson., 2012. 43(1): p. 69-79.


The yttrium complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(1′- 13 C-acetic acid) [ 13 C]DOTA was synthesized. Fast dissolution dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) studies revealed that the 89 Y, 13 C, and 15 N nuclei present in the complex could be co-polarized at the same optimum microwave irradiation frequency. The liquid-state spin–lattice relaxation time T 1 of these nuclei were found to be reasonably long to preserve some or most of the DNP-enhanced polarization after dissolution. The hyperpolarized 13 C and 89 Y NMR signals were optimized in different glassing mixtures. The overall results are discussed in light of the thermal mixing model of DNP.



Thursday, August 2, 2012

Fully MR-Compatible Syringe Pump for the Controllable Injection of Hyperpolarized Substrate in Animals

Reynolds, S., et al., Fully MR-Compatible Syringe Pump for the Controllable Injection of Hyperpolarized Substrate in Animals. Appl. Magn. Reson., 2012. 43(1): p. 263-273.


A major application of dynamic nuclear polarization has been in the study of the conversion of hyperpolarized 13 C 1 -pyruvate to lactate in various disease models. In a typical experimental protocol, hyperpolarized pyruvate is converted from solid to liquid state with superheated fluid and collected in a receiving vessel. The hyperpolarized solution is then rapidly transferred by hand from the polarizer to the imaging magnet, where it is manually injected through an intravenous cannula into the test subject by an experienced operator. Such a procedure leads to inconsistencies in timing, injection rate and volume, all of which can influence the time resolved signal as the pyruvate is metabolized. We have developed a fully magnetic-resonance-compatible withdraw/infuse syringe pump made entirely of plastic so that it can be operated within the bore of an unshielded 7 T (310 mm) magnet. The injector can be programed for variable injection volumes and rates to permit the rapid and reproducible injection of hyperpolarized material without human intervention. The injector was designed for use with 1 ml or 3 ml syringes with a maximum delivery volume of 2.4 ml. The standard deviation of delivered volume from the desired volume was found to be 0.7 % across a volume range of 0.6–2.4 ml.