Quadrupolar Metal Nuclides in Bioinorganic Chemistry: Solid‐State NMR Studies

Metal ions play an important role in bioinorganic chemistry; however, following their respective chemistries is often complicated because several relevant metal ions (such as V5+, Cu1+, Zn2+, Na+, Ca2+, and Mg2+) are not always amenable to conventional UV/Vis or EPR spectroscopy. Rather, what we know of these metal sites has come from the characterization of the various compounds and proteins via X-ray crystallographic methods or from using surrogate metal probes for conventional spectroscopy. We discuss in some detail the solid-state NMR spectroscopic methods by which these metal nuclides can be investigated in biological systems. Vanadium and copper are examples of nuclides with a modest magnetic moment. Vanadium proteins can often be characterized by room temperature magic angle spinning (MAS) methods owing to their moderate quadrupole coupling constants yielding relatively narrow lines. Copper, on the other hand, often yields very broad resonances, i.e., >1 MHz, because of the large quadrupolar interaction. Owing to the small magnetic moment of nuclides (magnesium and zinc) and/or the breadth of their NMR resonances (copper), these nuclides are best characterized by utilizing cryogenic methods. This review develops the needed NMR methods that are essential to discuss the spectroscopy of the quadrupolar metal sites in biological environments. The authors further illustrate how the experimental results can be translated into meaningful biochemical conclusions. More often than not, the interpretation of these experimental results is strongly coupled to computational models of the active sites of the proteins of interest. The validity of such models is discussed. Keywords: Half–integer quadrupolar metal nuclei; Metalloproteins; Magic angle spinning; Quadrupole Carr–Purcell–Meiboom–Gill (QCPMG); Density Functional Theory; Quantum mechanics/ molecular mechanics (QM/MM) calculations