Filtering the NMR Spectra of Mixtures by Coordination to Paramagnetic Cu²

The paramagnetic spin relaxation (PSR) filter allows the selective NMR signal suppression of components in mixtures according to their complexation ability to a paramagnetic ion. It relies on the faster relaxation of nuclei in paramagnetic environments and thus is complementary to classical diffusion and relaxation filters. So far, the PSR filter has established Gd³⁺ as the sole PSR agent, restricting the paramagnetic filtering repertoire. Herein, we present Cu²⁺ as a robust PSR agent with characteristic filtering properties. While Gd³⁺ depends on unspecific ion-pair interactions with anionic components, Cu²⁺ stands out for filtering species via ordered coordination complexes. An evaluation of the paramagnetic effect of Cu²⁺ over more than 50 small molecules and polymers has unveiled different sensitivities to Cu²⁺ (especially high for pyridines, diamines, polyamines, and amino alcohols) and precise filtering conditions for mixtures (¹H, COSY, and HMQC) that were challenged with a test bed of commercial drugs. The advantage of integrating Cu²⁺ and Gd³⁺ for the stepwise PSR filtering of complex mixtures is also shown.