Periodic Reporting for period 1 - NuMagLongRx (Nuclear magnetic long-lived state relaxation)
Période du rapport: 2020-07-01 au 2022-06-30
The project aimed to develop simulation methodology and tools for understanding long-lived nuclear singlet state (LLS) relaxation. The LLS can potentially be utilized as magnetic resonance beacons (MRB) that can hold hyperpolarized nuclear spin order for long times and generate enormously enhanced nuclear magnetic resonance (NMR) signals under a specific biochemical or physicochemical stimulus. The LLS are protected against many of the mechanisms that govern relaxation occurring in the conventional nuclear magnetic resonance (NMR) experiments. In addition to the conventional mechanisms, the simulation tool developed in this project includes interactions between the nuclear spins and the internal molecular angular velocities. This new mechanism is referred to as spin nuclear motion (SNM) in this project. This mechanism has been proposed as a potential mechanism to explain LLS relaxation by the host group, and developing tools to understand this mechanism is an important motivation for this project.
The overall objectives of this project were:
1) to develop a methodology for quantum chemical calculation of the interaction parameters for the new mechanism.
2) to develop a set of tools to simulate and analyze molecular and spin dynamics in flexible molecules and extract the LLS lifetimes.
3) to synthesize and validate target molecules able to singlet state lifetimes using the model developed in this project.
The overall objectives of this project were:
1) to develop a methodology for quantum chemical calculation of the interaction parameters for the new mechanism.
2) to develop a set of tools to simulate and analyze molecular and spin dynamics in flexible molecules and extract the LLS lifetimes.
3) to synthesize and validate target molecules able to singlet state lifetimes using the model developed in this project.
Methodology and software was developed to simulate molecular dynamics and relaxation of LLS and nuclear spin states conventionally measured in NMR. Singlet relaxation mechanisms of a a maleate derivative was studied in collaborative project (article 3). Singlet relaxation mechanisms of a a maleate derivative was studied in collaborative project (article 3, recently accepted in PhysChemChemPhys). The singlet lifetime was explicable with conventional relaxation mechanisms (including coupling with paramagnetic oxygen). This article, which is now accepted for publication, describes the first successful treatment of nuclear singlet relaxation by a combination of molecular dynamics and computational chemistry, almost free from adjustable parameters, and marks the substantial achievement of the main project goals.
As part of the project, computational chemistry techniques were employed to study the interaction of a 3He atom with an encapsulating fullerene molecule. These tasks were relevant for verifying and optimizing the computational methodology involved in the relaxation calculations, and led to two high-profile publications (articles 1 and 2).
Theory and software for the calculation of the interaction parameters for the spin-nuclear-motion (SNM) relaxation mechanism was also developed. To obtain the parameters, the software post-processes spin-rotation tensor calculations (calculated by the Dalton software package). Gamma-picoline (4-methylpyridine, see attached figure) was chosen as an example system to study and understand SNM contribution to LLS relaxation. Gamma-picoline is pyridine with one of the protons replaced by the methyl group (opposed to the nitrogen atom). The methyl group is reported to have a low rotational barrier, and we, therefore, considered it to be an ideal candidate to study internal rotation coupling to nuclear spins. However, while our developed model was able to explain the lifetimes of the LLS by good approximation, it was unable to explain the relaxation of the conventional nuclear spin states. As in conventional NMR relaxation simulations, the used methodology couples classical molecular dynamics to the nuclear spins. The failure of our model may be explained by the sparsity of the accessible rotational states of the methyl group, which means that the quantum mechanical nature of the methyl rotation must be taken into account when it is coupled with the nuclear spins. It should be noted that our model explains the relaxation of the atoms of the pyridine in this system. The fellow and the host group investigated the possibility to derive theory and methodology for coupling quantum mechanical molecular dynamics of the internal motion to the nuclear spins. However, this was judged to be a very significant task which would require an entirely new approach to the problem of nuclear relaxation. This project would require several years of work and additional resources, and was not completed at the time the fellow left the project.
As part of the project, computational chemistry techniques were employed to study the interaction of a 3He atom with an encapsulating fullerene molecule. These tasks were relevant for verifying and optimizing the computational methodology involved in the relaxation calculations, and led to two high-profile publications (articles 1 and 2).
Theory and software for the calculation of the interaction parameters for the spin-nuclear-motion (SNM) relaxation mechanism was also developed. To obtain the parameters, the software post-processes spin-rotation tensor calculations (calculated by the Dalton software package). Gamma-picoline (4-methylpyridine, see attached figure) was chosen as an example system to study and understand SNM contribution to LLS relaxation. Gamma-picoline is pyridine with one of the protons replaced by the methyl group (opposed to the nitrogen atom). The methyl group is reported to have a low rotational barrier, and we, therefore, considered it to be an ideal candidate to study internal rotation coupling to nuclear spins. However, while our developed model was able to explain the lifetimes of the LLS by good approximation, it was unable to explain the relaxation of the conventional nuclear spin states. As in conventional NMR relaxation simulations, the used methodology couples classical molecular dynamics to the nuclear spins. The failure of our model may be explained by the sparsity of the accessible rotational states of the methyl group, which means that the quantum mechanical nature of the methyl rotation must be taken into account when it is coupled with the nuclear spins. It should be noted that our model explains the relaxation of the atoms of the pyridine in this system. The fellow and the host group investigated the possibility to derive theory and methodology for coupling quantum mechanical molecular dynamics of the internal motion to the nuclear spins. However, this was judged to be a very significant task which would require an entirely new approach to the problem of nuclear relaxation. This project would require several years of work and additional resources, and was not completed at the time the fellow left the project.
Theory and software was developed for the calculation of nuclear spin relaxation by a combination of molecular dynamics and computational chemistry, in the case of conventional nuclear spin relaxation mechanisms. This software was successfully validated against experimental results. This was the first time that the relaxation of nuclear long-lived states was successfully treated by such methodology. This achievement goes beyond current state of the art, and lays the groundwork for the use of such techniques for the prediction and understanding of long-lived states, for example in the context of magnetic resonance imaging applications.
Software was also developed and demonstrated for the non-bonded interactions of atoms and molecules, and validated experimentally in the case of endohedral fullerenes. The validation of such calculations by comparison with terahertz spectroscopic data and neutron scattering goes beyond the prior state of the art. The understanding and prediction of non-bonded interatomic interactions is of major significance for a wide range of materials and biomolecular sciences.
The project results are expected to have a significant direct impact on the basic science of intermolecular interactions and for hyperpolarized nuclear magnetic resonance and magnetic resonance imaging. Wider socio-economic and societal implications are longer term. Advances in materials, biochemical, and clinical sciences have a beneficial societal and socio-economic impact in the longer term.
Software was also developed and demonstrated for the non-bonded interactions of atoms and molecules, and validated experimentally in the case of endohedral fullerenes. The validation of such calculations by comparison with terahertz spectroscopic data and neutron scattering goes beyond the prior state of the art. The understanding and prediction of non-bonded interatomic interactions is of major significance for a wide range of materials and biomolecular sciences.
The project results are expected to have a significant direct impact on the basic science of intermolecular interactions and for hyperpolarized nuclear magnetic resonance and magnetic resonance imaging. Wider socio-economic and societal implications are longer term. Advances in materials, biochemical, and clinical sciences have a beneficial societal and socio-economic impact in the longer term.