Different flavors of diffusion in paramagnetic systems: unexpected NMR signal intensity and relaxation enhancements

Abstract The NMR community is well acquainted with different kinds of diffusion but, at the same time, there are several effects that are worth a better understanding for an improved design of molecular imaging and dynamic nuclear polarization experiments. Spin diffusion and chemical diffusion are known to play important roles in determining the NMR signal and relaxation enhancements caused by the presence of paramagnetic molecules in solution. Paramagnetic complexes are used as contrast agents in magnetic resonance imaging, due to their efficacy in selectively increase the relaxation rates of solvent water protons, as well as in dynamic nuclear polarization experiments to increase the NMR signal of desired molecules through polarization transfer from unpaired electrons. In this paper we review some recent, unexpected observations in these two areas, which seem related to spin and/or chemical diffusion, and demonstrate the need for a detailed understanding of the interplay of different phenomena. A deeper understanding of spin and chemical diffusion may thus result very important for an improved design of contrast agents for magnetic resonance imaging and for the optimization of hyperpolarization experiments

Cyanide and azide behave in a similar fashion versus cuprozinc-superoxide dismutase.

The 1H NMR spectra of the cyanide adduct of Cu2Co2-superoxide dismutase have been remeasured at pH 7.5. The exchange rate of CN- is slow on the NMR time scale. The correlation with the spectrum of the unligated enzyme has been established through saturation-transfer techniques of the system in which 50% of the cyanide adduct is formed and through comparison with the spectrum of a Cu2Co2-superoxide dismutase-CN- sample in which the histidines have been deuterium labeled at the position epsilon 1. The similarities between the spectra of the CN- and N-3 derivatives are stressed, in particular with respect to the removal from copper coordination of the same histidine, assigned as His-46

NMR for sample quality assessment in metabolomics.

Abstract The EU Framework 7 project SPIDIA was the occasion for development of NMR approaches to evaluate the impact of different pre-analytical treatments on the quality of biological samples dedicated to metabolomics. Systematic simulation of different pre-analytical procedures was performed on urine and blood serum and plasma. Here we review the key aspects of these studies that have led to the development of CEN technical specifications, to be translated into ISO/IS in the course of the EU Horizon 2020 project SPIDIA4P. Inspired by the SPIDIA results, follow-up research was performed, extending the analysis to different sample types and to the different effects of long-term storage. The latter activity was in conjunction with the local European da Vinci Biobank. These results (which partially contributed to the ANNEX of CEN/TS 16945"MOLECULAR IN VITRO DIAGNOSTIC EXAMINATIONS - SPECIFICATIONS FOR PRE-EXAMINATION PROCESSES FOR METABOLOMICS IN URINE, VENOUS BLOOD SERUM AND PLASMA") are presented in detail

Solution of a Puzzle: High-Level Quantum-Chemical Treatment of Pseudocontact Chemical Shifts Confirms Classic Semiempirical Theory

A recently popularized approach for the calculation of pseudocontact shifts (PCSs) based on first-principles quantum chemistry (QC) leads to different results than the classic “semiempirical” equation involving the susceptibility tensor. Studies that attempted a comparison of theory and experiment led to conflicting conclusions with respect to the preferred theoretical approach. In this Letter, we show that after inclusion of previously neglected terms in the full Hamiltonian, one can deduce the semiempirical equations from a rigorous QC-based treatment. It also turns out that in the long-distance limit, one can approximate the complete A tensor in terms of the g tensor. By means of Kohn–Sham density functional theory calculations, we numerically confirm the long-distance expression for the A tensor and the theoretically predicted scaling behavior of the different terms. Our derivation suggests a computational strategy in which one calculates the susceptibility tensor and inserts it into the classic equation for the PCS

Theoretical analysis of the long-distance limit of NMR chemical shieldings

After some years of controversy, it was recently demonstrated how to obtain the correct long-distance limit [point-dipole approximation (PDA)] of pseudo-contact nuclear magnetic resonance chemical shifts from rigorous first-principles quantum mechanics [Lang et al., J. Phys. Chem. Lett. 11, 8735 (2020)]. This result confirmed the classical Kurland–McGarvey theory. In the present contribution, we elaborate on these results. In particular, we provide a detailed derivation of the PDA both from the Van den Heuvel–Soncini equation for the chemical shielding tensor and from a spin Hamiltonian approximation. Furthermore, we discuss in detail the PDA within the approximate density functional theory and Hartree–Fock theories. In our previous work, we assumed a relatively crude effective nuclear charge approximation for the spin–orbit coupling operator. Here, we overcome this assumption by demonstrating that the derivation is also possible within the fully relativistic Dirac equation and even without the assumption of a specific form for the Hamiltonian. Crucial ingredients for the general derivation are a Hamiltonian that respects gauge invariance, the multipolar gauge, and functional derivatives of the Hamiltonian, where it is possible to identify the first functional derivative with the electron number current density operator. The present work forms an important foundation for future extensions of the Kurland–McGarvey theory beyond the PDA, including induced magnetic quadrupole and higher moments to describe the magnetic hyperfine field

The cobalt(II)-alkaline phosphatase system at alkaline pH.

The uptake of cobalt(II) ions by apoalkaline phosphatase at pH 8 (the pH optimum for activity) has been investigated by the combined use of electronic and 1H NMR spectroscopies. The presence of fast-relaxing high spin cobalt(II) ions in the active site cavity of the protein induces sizable isotropic shifts of the 1H NMR signals of metal-coordinated protein residues, allowing us to propose a metal uptake pattern by the various metal binding sites both in the presence and in the absence of magnesium ions. In the absence of magnesium the active site is not organized in specific metal binding sites. The first equivalent of cobalt(II) ions per dimer binds in an essentially unspecific and possibly fluxional fashion, giving rise to a six-coordinated chromophore. The second and third equivalents induce the formation of increasing amounts of metal ions pairs, cooperatively arranged into the A and B sites of the same subunit with a five- and six-coordinated geometry, respectively. The fourth and fifth equivalents induce the formation of fully blocked A-B pairs in both subunits. Magnesium shows the property of organizing the metal binding sites, probably through coordination to the C sites. Electronic and 1H NMR titration with Co2+ ions show that the initial amount of fluxional cobalt is smaller than in the absence of magnesium and that A-B pairs are more readily formed. Titration of fully metalated Co4Mg2alkaline phosphatase samples with phosphate confirms binding of only one phosphate per dimer