Konstantin L. Ivanov

Level Anti-Crossings are a Key Factor for Understanding para-Hydrogen-Induced Hyperpolarization in SABRE Experiments

Various hyperpolarization methods are able to enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) by several orders of magnitude. Among these methods are para-hydrogen-induced polarization (PHIP) and signal amplification by reversible exchange (SABRE), which exploit the strong nuclear alignment of para-hydrogen. Several SABRE experiments have been reported but, so far, it has not been possible to account for the experimentally observed sign and magnetic-field dependence of substrate polarization. Herein, we present an analysis based on level anti-crossings (LACs), which provides a complete understanding of the SABRE effect. The field-dependence of both net and anti-phase polarization is measured for several ligands, which can be reproduced by the theory. The similar SABRE field-dependence for different ligands is also explained. In general, the LAC concept allows complex spin dynamics to be unraveled, and is crucial for optimizing the performance of novel hyperpolarization methods in NMR and MRI techniques.

Integral encounter theories of multistage reactions. I. Kinetic equations

The matrix kinetic equations for multi-stage reactions in liquid solutions are derived using a newly developed original method based on a many-particle master equation. The method leads to an infinite hierarchy for vector correlation patterns that can be truncated two different ways. The simplest one reproduces the conventional Integral Encounter Theory (IET), while the other allows a general modification of the kernel, resulting in the matrix formulation of so called Modified Encounter Theory (MET). Unlike IET, MET accounts for all binary contributions and correctly restores the long-time asymptotics of bimolecular reactions. The matrix MET, applied in Part II to reversible reactions of inter-molecular energy transfer, significantly improves the results obtained with other methods.

RF-SABRE: A Way to Continuous Spin Hyperpolarization at High Magnetic Fields

A new technique is developed that allows one to carry out the signal amplification by reversible exchange (SABRE) experiments at high magnetic field. SABRE is a hyperpolarization method, which utilizes transfer of spin order from para-hydrogen to the spins of a substrate in transient iridium complexes. Previously, it has been thought that such a transfer of spin order is only efficient at low magnetic fields, notably, at level anti-crossing (LAC) regions. Here it is demonstrated that LAC conditions can also be fulfilled at high fields under the action of a RF field. The high-field RF-SABRE experiment can be implemented using commercially available nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) machines and does not require technically demanding field-cycling. The achievable NMR enhancements are around 100 for several substrates as compared to their NMR signals at thermal equilibrium conditions at 4.7 T. The frequency dependence of RF-SABRE is comprised of well pronounced peaks and dips, whose position and amplitude are conditioned solely by the magnetic resonance parameters such as chemical shifts and scalar coupling of the spin system involved in the polarization transfer and by the amplitude of the RF field. Thus, the proposed method can serve as a new sensitive tool for probing transient complexes. Simulations of the dependence of magnetization transfer (i.e., NMR signal amplifications) on the frequency and amplitude of the RF field are in good agreement with the developed theoretical approach. Furthermore, the method enables continuous re-hyperpolarization of the SABRE substrate over a long period of time, giving a straightforward way to repetitive NMR experiments.

Investigation of the magnetic field dependence of CIDNP in multinuclear radical pairs. 1. Photoreaction of histidine and comparison of model calculation with experimental data

Magnetic field effects on CIDNP formed in the diamagnetic products of geminate recombination of photo-generated radical pairs are calculated at arbitrary field strength. The simulations are based on a model that uses a full quantum mechanical description of the polarized nuclei and a semiclassical account of all other nuclear spins. The results are compared with CIDNP experiments on the photoreaction between N-acetylhistidine and 2,2′-dipyridine in fields between 0 and 7 T employing field cycling between a variable field of polarization and a fixed field of detection. To allow quantitative comparison the simulation takes into account the effects of adiabatic field change and of RF excitation pulse angle on the NMR intensity. Both net and multiplet polarization as observed in two coupled spin pairs (CH2 protons in β position of histidine, and protons in H2,H4 position of its ring) are well reproduced over the whole field range. The wide applicability of the theoretical model and the possibility to extend it to larger spin systems make it particularly useful for the analysis of CIDNP in protein systems.

Transfer of SABRE-derived hyperpolarization to spin-1/2 heteronuclei

In this paper, we describe a method of hyper-polarizing “insensitive” Nuclear Magnetic Resonance (NMR) nuclei by exploiting the SABRE (Signal Amplification By Reversible Exchange) technique and transferring spin order from protons originating from parahydrogen. We demonstrate that hyperpolarization transfer is due to a coherent mechanism, which is operative at (i) very low magnetic field; (ii) geomagnetic field; (iii) high field in the presence of a suitable radiofrequency-excitation scheme. Experiments are performed using 15N-labelled pyridine as the SABRE substrate; NMR enhancements achieved for 15N nuclei are more than 1000 for free pyridine in solution and more than 20 000 for pyridine bound to the SABRE complex. High-field SABRE experiments are particularly important for enhancing the sensitivity of NMR methods: they enable strong signal enhancements and avoid technically demanding field-cycling. Furthermore, such experiments use very low power for NMR excitation and make feasible continuous re-hyperpolarization of the substrate in high-field experiments: polarization can be quickly restored to the maximal level within only 15 seconds with the result that polarization levels stay constant over several hundred experiments. The techniques outlined are applicable to hyper-polarizing spin-1/2 hetero-nuclei, such as 13C, 19F, 31P, etc. Development of such methods opens new avenues in NMR spectroscopy and imaging, which were out of reach for sensitivity reasons.

Consistent Treatment of Spin-Selective Recombination of a Radical Pair Confirms the Haberkorn Approach

In the present work, we have shown that consistent derivation of the kinetic equations describing the electron spin-selective recombination of radical pairs confirms the conventional Haberkorn approach. The derivation has been based on considering the interaction of the reactive system (radical pair and product state) with the thermal bath. The consistency of this approach has also been substantiated by numerical simulations performed for the purely quantum mechanical model of the recombining radical pair. Finally, we have shown that the quantum Zeno effect on radical pair recombination is not an exclusive feature of the approach recently proposed by Kominis, as it should be present at any rate of the singlet-triplet dephasing in the radical pair, which always accompanies the recombination process.

Transfer of Parahydrogen Induced Polarization in Scalar Coupled Systems at Variable Magnetic Field

Abstract Para-Hydrogen Induced Polarization (PHIP) experiments were performed in coupled multispin systems at variable magnetic fields. We studied the magnetic field dependence of PHIP in styrene, which is the product of hydrogenation of phenylacetylene. At low magnetic fields where the spins are coupled strongly by scalar interaction efficient polarization transfer among the interacting protons takes place. The experimentally observed spectra are in good agreement with the simulation, which takes into account eight coupled spins. We also demonstrate effects of nuclear spin level anti-crossings on the PHIP pattern. It is shown that rapid passage through the level anti-crossing enables highly efficient polarization transfer between specific spin orders. In addition, we studied PHIP transfer to 13C and 19F hetero-nuclei. It is shown that hetero-nuclei can be efficiently polarized in a wide field range; in particular, for polarizing them it is not necessary to go to ultra-low fields, which provide their strong coupling to protons. The resulting polarization is of the multiplet type and gives strong enhancements of the individual NMR lines. In general, variation of the magnetic field gives the opportunity for manipulating PHIP patterns and transferring polarization to target spins of choice.

Integral encounter theories of multistage reactions. II. Reversible inter-molecular energy transfer

The matrix Modified Encounter Theory (MET), developed in Part I of this work, is applied here to reversible inter-molecular energy transfer in liquid solutions. For fluorescence quantum yield at contact transfer the Stern–Volmer law is confirmed, but the concentration corrections to its constant are diffusion-dependent unlike those obtained earlier with Superposition Approximation. In the particular case of irreversible energy transfer, when the exact solution is available, the latter is used to discriminate between all competing approaches and establishes MET superiority. In the case of reversible energy transfer producing the long-lived or even stable products, the energy is stored there and dissipates due to backward energy transfer in re-encounters. The kinetics of this process, resulting in a delayed fluorescence, is shown to be qualitatively different in cases of short and long encounter times as compared to the excitation lifetime.

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

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 β-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.

Quantitative description of the SABRE process: rigorous consideration of spin dynamics and chemical exchange

A consistent theoretical description of the spin dynamics and chemical kinetics underlying the SABRE (Signal Amplification By Reversible Exchange) process is proposed and validated experimentally. SABRE is a promising method for Nuclear Magnetic Resonance (NMR) signal enhancement, which exploits the transfer of strong non-thermal spin order from parahydrogen (the H2 molecule in its singlet spin state) to a substrate in a transient organometallic complex. A great advantage of the SABRE method is that the substrate acquires strong nuclear spin polarization without being modified chemically, as it is only transiently bound to the complex. However, for the same reason theoretical treatment of SABRE meets difficulties because of the interplay of the spin dynamics with the association–dissociation reactions of the SABRE complex. Here we propose a quantitative model, which takes into account both the spin evolution in the SABRE complex and the substrate exchange between the free and bound forms. The model allows for the calculation of the substrate spin polarization dependency on various parameters, such as the external magnetic field strength and complex association–dissocation rates, and enables the simulation of experimental data for the SABRE time dependence. This investigation opens new insights into the SABRE process and can be generalized to treat more complex cases, such as SABRE facilitated by NMR pulses.