NMR Spectroscopy and Metal Ions in Life Sciences

Abstract

Metal ions play important structural and functional roles in many biological systems. The NMR spectroscopic characterization of biomolecules not only had to deal with the need of taking them into account, but also successfully exploited the characteristics of the paramagnetic metals to obtain structural information. The latter proved so important that diamagnetic proteins are in several cases made paramagnetic through substitution of a diamagnetic metal ion with a paramagnetic one or attachment of a paramagnetic tag. NMR studies of metal ions are also important for biomedical applications. Examples are provided here in the field of drug discovery and the development of contrast agents for MRI. More recently, paramagnetic metals proved useful also for improving the NMR sensitivity by dynamic nuclear polarization. Finally, NMR metabolomics studies are emerging for the identification and quantification of metal ions present in biological fluids.

Inhibition of toxic metal-alpha synuclein interactions by human serum albumin

“…1a). 14,62,63 When unlabeled fatty-acid free HSA (rHSA) was titrated into the equimolar solution of Ac-aSyn and Cu(II) ions, we observed a progressive recovery of intensities at both His-50 and Asp-121 sites (Fig. 2b-e), indicating that rHSA removes Cu(II) from Ac-aSyn.…”

Halogen Bonding Tripodal Metallo‐Receptors for Phosphate Recognition and Sensing in Aqueous‐Containing Organic Media

“…A TPMA complexed Zn II cation along the C 3 ‐axis gives rise to a tetrahedral XB binding pocket and provides the additional Lewis acidic metal coordinative interaction commensurate with the design strategy (Figure 1). Our choice of metal cation was based upon the well‐documented high affinity of Zn II for phosphate oxoanions; [24–28] the diamagnetic property of the metal also allowed for anion binding studies to be conducted by 1 H NMR spectroscopy [29] …”

“…Our choice of metal cation was based upon the well-documented high affinity of Zn II for phosphate oxoanions; [24][25][26][27][28] the diamagnetic property of the metal also allowed for anion binding studies to be conducted by 1 H NMR spectroscopy. [29] A multi-step synthetic route was undertaken to afford XB tripodal ligand 5I (Scheme 1). The known compound 6-azidomethyl pyridyl methanol 2, [30] was reacted with 1-decyne via a one-pot "iodo-click" copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) reaction protocol [31] to give the XB synthon 3I in 71 % yield after purification.…”

Studying Peptide-Metal Ion Complex Structures by Solution-State NMR

“…Analyses of protein-metal complexes by NMR are always challenging because the position of complexation within the protein needs to be determined by other means, however their prevalence in nature requires their study and many excellent reviews have been written on the subject [24][25][26][27]. In cases of paramagnetic metal ions, the region around the iron is effectively erased from the NMR spectrum due to paramagnetic linebroadening from fast relaxation.…”