Metal-Based Spin Labeling for Distance Determination

Long-range (nm scale) distance measurements between specific sites in biological macromolecules offer important insights into their structure and interactions. In the last decade, such distance measurements by pulse electron paramagnetic resonance (EPR) techniques have proven highly efficient on nitroxide-labeled proteins and nucleic acids. In this chapter, we introduce the idea of using spin labels that are based on paramagnetic metal ions. We review distance measurements carried out on pairs of S = 1/2 metal ions in model complexes and in intrinsic binding sites in biomacromolecules. We discuss their potential as general purpose spin labels for distance measurements based on their spectroscopic properties. Then, we present a new approach to spin labeling that is based on half-integer high-spin metal ions, mainly Gd3+, coordinated to chelating tags that are covalently attached to the molecules at specific sites. This approach is particularly suitable for high-field measurements and is attractive because of the high absolute sensitivity it offers.