High-resolution Spectra in PHIP

R. H. ACOSTA; I. PRINA; L. BULJUBASICH

Gas Phase NMR

RSC Publishing

Año: 2016; p. 306 - 337

Nuclear Magnetic Resonance (NMR) is one of the most powerful analytical techniques used for materials characterization at a microscopic level. The application of NMR in science and technology includes chemistry, biology, food research and quality control, environmental studies of plants and soils. Determination of pore structures has a great impact in the oil industry and medicine. Additionally Magnetic Resonance Imaging (MRI) is perhaps the most powerful diagnosis technique used in medicine in modern days. Despite all the power of NMR, there is a major drawback in its application that is the poor inherent sensitivity of the signals that can be detected. This fundamental insensitivity originates from the minuscule size of nuclear magnetic moments, which results in an exceedingly small equilibrium nuclear spin polarization even in high magnetic fields. Traditionally, NMR has dealt with excitation and detection of nuclear spin angular momentum in systems in thermal equilibrium with an external static magnetic field. The intensity of the NMR signal is proportional to the population difference of quantum states, which is driven by the difference in energy levels and is given by gB0/kBT, where g is the nuclear gyromagnetic ratio, B0 is the external magnetic field intensity, T the absolute temperature and kB Boltzmann´s constant. The excess population can be described by the polarization P. For instance, for spin-1/2 nuclei, P is the population difference between the two energy states over the whole spin population. A sample of water at room temperature, placed in a magnetic field of 4.7 T has a polarization for 1H that amounts to P= 1.6 10^5. This amounts to a population difference of only 1 in 62 500 for protons. The most common strategies to overcome this small polarization are the use of higher magnetic fields or low temperature probes. However, in many applications temperature is not a variable, as for instance in physiological studies. An alternative approach is to drive the system into a metastable state where the population difference is externally increased, namely hyperpolarization. Different methods have been developed in the last years such as laser polarization (LP) of noble gases via optical pumping, [1?5] dynamic nuclear polarization (DNP), [6?8] Chemically Induced DNP (CIDNP), [9,10] or Parahydrogen Induced Polarization (PHIP), [11?14] among others. Hyperpolarization has a particular impact on gas phase NMR, where the low density of gases renders even lower signals as compared to the liquid state. LP noble gases (3He and 129Xe) are particularly suitable to be used in medical applications, mainly in human lung imaging. Helium is a perfectly inert gas that can be inhaled in large quantities without adverse effects. The solubility in blood is negligible and polarizations up to 70% have been achieved. [15,16] Xenon can be dissolved in liquids, and perfuse to enter the blood mainstream, and can be used to obtain detailed information of the tissue of the lung. [17,18] Many research and clinical applications involve the measurement of changes in relaxation times to probe local amounts of oxygen, [19,20] restricted diffusion for assessment of emphysema [21?23] or asthma, [24] among many others. [25?28] Another outstanding feature of gases is the high diffusion coefficient as compared to liquids, which is particularly useful to probe long distances in porous media. [29,30] By determination of the diffusion coefficient at short and long measurement times the surface-to-volume ratio of the system and the tortuosity, a quantity directly related to the system´s transport properties, can be respectively determined, [29,30] and information of nanotubes can be obtained by single file diffusion. [31] Hyperpolarization with PHIP involves a chemical reaction, where protons originally forming part of the parahydrogen (pH2) molecules are deposited into an unsaturated precursor before the NMR signal acquisition, resulting in a product molecule with a specific hyperpolarized site. The hydrogenation reaction can be carried out either at the same high magnetic field where the NMR experiment is performed, widely known as PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) protocol, [11] orat low magnetic fields as in the ALTADENA (Adiabatic Longitudinal Transport After Dissociation Engenders Net Alignment) protocol. [12] In this chapter we will restrict the discussion to PASADENA. The main feature of a spectrum acquired under this condition is the antiphase character of the signal, associated with the presence of longitudinal two-spin order terms which are initially present in the density operator once the chemical reactions have ceased. [32,33] As the coupling constants are in the order of a few Hz, even a slight linebroadening will result in partial peak cancellation. The effect of partial cancellation not only diminishes the signal intensity, but also introduces a deformation of a spectrum, where the separation of the antiphase peaks becomes much larger than the actual J-coupling values. Spin echoes are usually used for the refocusing of magnetic field inhomogeneities; however, evolution due to J-couplings is not affected by the refocusing 180 pulse. Spin echoes in combination with J-coupling delays have been successfully applied for PHIP-MRI [34,35] and chemical reaction monitoring with low-field time domain NMR. [36] In liquids, the application of a Carr?Purcell?Meiboom?Gill (CPMG) sequence will render a decay that is modulated by the evolution under J-couplings, namely, acquisition of a J-spectrum. [37] In this chapter we describe the performance of J-spectroscopy in PHIP. Two main aspects are considered: on one hand, partial peak cancelling is removed due to the enhanced resolution of a J-spectrum, usually in the order of 0.1 Hz; on the other hand, the evolution of the density operators steaming from PHIP under this multipulse sequence differs substantially from operators that arise from thermal polarization. This results in a frequency separation of both types of signals, even in situations where a resonance from a thermally polarized species overlaps with a hyperpolarized one. We refer to this method as parahydrogen discriminated-PHIP or PhD-PHIP. [38,39] The chapter is organized as follows: first the basic aspects of PHIP are reviewed. Then, the relevant aspects of J-spectroscopy are summarized and the particular aspects of PhD-PHIP are described. Validation of the method under different experimental situations is presented for liquids. While all the results are limited to the weak coupling regime, usually found at high magnetic fields, it must be noted that frequency separation and partial peak cancelling has also been shown at low and inhomogeneous magnetic fields (0.5 Tesla) in the strong coupling regime, [40] and could readily be applied for the study of gases. Finally, we present simulations for the performance of the method on gas phase NMR. We restrict our discussion to the most commonly used reaction of propylene into propane, which occurs upon hydrogenation with pH2. There are two main results that could render this experiment very valuable. One is the possibility to achieve highly resolved spectra for hyperpolarized gases. However, the principal result is the possibility to detect hydrogenation even in much diluted or slowly reacting systems. This can be very valuable in the field of catalyst research, where PHIP has proven to be an ideal probe. [41]