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Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g −1 . Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P ( 13 C) = 25% within 8 min, through the combination of 1 H spin diffusion and 1 H →  13 C cross polarization. Solutions of 13 C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13 C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances. Hyperpolarization by dissolution dynamic nuclear polarization has brought highly sensitive magnetic resonance to reality but there still remains severe limitations. Here the authors show an approach relying on the generation of hyperpolarizing polymers that bear a dual function.

Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion. Significance Hyperpolarization by dissolution dynamic nuclear polarization can dramatically enhance signal intensities in MRI and NMR, notably for metabolic tracers for imaging and diagnosis. It is applicable to a variety of substrates for in vivo imaging and chemistry but requires the use of contaminants (glassing agents and free radicals) that may interact with cells and proteins and can have potential side effects. These contaminants can sometimes be eliminated by precipitation followed by filtration or solvent extraction, but these methods are substrate-specific, are usually time-consuming, and typically result in signal loss. Here, production of pure hyperpolarized liquids free of contaminants is shown by a simple wetting–polarization–filtration sequence for a solid silica matrix containing homogeneously distributed persistent radicals.

Cross polarization can provide significant enhancements with respect to direct polarization of low-γ nuclei such as 13 C. Substantial gains in sample throughput (shorter polarization times) can be achieved by exploiting shorter build-up times τ DNP ( 1 H) < τ DNP ( 13 C). To polarize protons rather than low-γ nuclei, nitroxide radicals with broad ESR resonances such as TEMPO are more appropriate than Trityl and similar carbon-based radicals that have narrow lines. With TEMPO as polarizing agent, the main Dynamic Nuclear Polarization (DNP) mechanism is thermal mixing (TM). Cross polarization makes it possible to attain higher polarization levels at 2.2 K than one can obtain with direct DNP of low-γ nuclei with TEMPO at 1.2 K, thus avoiding complex cryogenic technology.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g ⁻¹ . Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P( ¹³ C) = 25% within 8 min, through the combination of¹ H spin diffusion and¹ H →¹³ C cross polarization. Solutions of¹³ C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state¹³ C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR-based analysis of metabolites at natural abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such a system, who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated 13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP-enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarized NMR in metabolomics studies.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR-based analysis of metabolites at natural abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such a system, who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated 13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP-enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarized NMR in metabolomics studies.

A sensitivity increase of two orders of magnitude in proton (1H) and carbon (13C) spins via dynamic nuclear polarization (DNP) has been accomplished recently using a compact benchtop DNP polarizer operating at 1 T and 77 K. However the DNP mechanisms at play at such low magnetic field and high operating temperature are still not elucidated. A deeper understanding of the dominant polarization transfer mechanisms between electrons and 1H and 13C spins at these unconventional benchtop conditions is therefore required if one wants to devise strategies to boost sensitivity further. In this study, we found that DNP is generally dominated by solid effect for narrow electron paramagnetic resonance (EPR) line radicals (15 mM trityl OX063) and cross effect for broad EPR line radicals (50 mM TEMPOL). For both radicals, the dominant DNP mechanisms were investigated varying the microwave frequency and measuring the 1H and 13C DNP enhancement factors to obtain 1H and 13C DNP spectra. The impact of varying the microwave power on the 1H DNP buildup times and the 1H nuclear spin relaxation times were important as well to distinguish between solid effect and cross effect DNP. Finally, time-resolved electron saturation simulations under continuous microwave irradiation could replicate the experimental 1H and 13C DNP spectra at 1 T and 77 K for both radicals considering their electron relaxation properties. Only for trityl OX063, the 13C DNP spectra showed additional DNP maxima compared to the simulations. This has been attributed to methyl rotor induced 1H-13C heteronuclear cross relaxation in [1-13C] acetate present at 1 T and 77 K.

Durante los últimos 25 años el gasto educativo público real en el Perú se ha mantenido relativamente constante, aunque con fluctuaciones relacionadas con el ciclo económico. Sin embargo, en un contexto de marcado crecimiento de la matrícula, esto ha implicado una caída significativa en el gasto por alumno, en particular, en la educación básica. Como parte de este proceso se observó un aumento del número de docentes y de personal administrativo - en particular a partir de 1985 - con una caída en los ingresos reales de los mismos. El gasto por alumno así como la variabilidad del gasto educativo en el Perú es similar al promedio latinoamericano. Sin embargo, el gasto es menos de un sexto del observado en países de la OECD. El gasto público en educación alcanzó el 2.8% del PBI en 1994. Estimaciones realizadas en base a encuestas de hogares muestran que las familias que matricularon a sus hijos en instituciones educativas públicas aportaron un 0.8%. Si además, se contabiliza el gasto de las familias en instituciones privadas, el gasto total de las familias llega a 1.9%. Así, si bien la educación pública, que en el caso de la educación básica constituye el 85% de la matrícula, es gratuita, las familias peruanas en conjunto gastan en educación -a través de aportaciones extraordinarias, cuotas de padres de familia, y gastos en materiales- 2/3 de lo que gasta el Estado. La sociedad peruana en conjunto gasta al menos 4.7% del PBI en educación. Finalmente, se encuentra que, la distribución del gasto educativo por alumno no es equitativa, siendo éste mayor en aquellos departamentos donde los indicadores de pobreza son menores.

Durante los ultimos 25 anos el gasto educativo publico real en el Peru se ha mantenido relativamente constante, aunque con fluctuaciones relacionadas con el ciclo economico. Sin embargo, en un contexto de marcado crecimiento de la matricula, esto ha implicado una caida significativa en el gasto por alumno, en particular, en la educacion basica. Como parte de este proceso se observo un aumento del numero de docentes y de personal administrativo - en particular a partir de 1985 - con una caida en los ingresos reales de los mismos. El gasto por alumno asi como la variabilidad del gasto educativo en el Peru es similar al promedio latinoamericano. Sin embargo, el gasto es menos de un sexto del observado en paises de la OECD. El gasto publico en educacion alcanzo el 2.8% del PBI en 1994. Estimaciones realizadas en base a encuestas de hogares muestran que las familias que matricularon a sus hijos en instituciones educativas publicas aportaron un 0.8%. Si ademas, se contabiliza el gasto de las familias en instituciones privadas, el gasto total de las familias llega a 1.9%. Asi, si bien la educacion publica, que en el caso de la educacion basica constituye el 85% de la matricula, es gratuita, las familias peruanas en conjunto gastan en educacion -a traves de aportaciones extraordinarias, cuotas de padres de familia, y gastos en materiales- 2/3 de lo que gasta el Estado. La sociedad peruana en conjunto gasta al menos 4.7% del PBI en educacion. Finalmente, se encuentra que, la distribucion del gasto educativo por alumno no es equitativa, siendo este mayor en aquellos departamentos donde los indicadores de pobreza son menores.