113Cd NMR spectroscopy of coordination compounds and proteins

Abstract

Despite the proven utility of 113Cd NMR chemical shifts for qualitatively or, in some cases, semiquantitatively assessing the nature of ligands at metal binding sites in metalloproteins and for studying enzyme function and mechanisms, it is likely that the full potential of 113Cd spectroscopy as a metallobioprobe has yet to be realized. The development of a more quantitative relationship between structural parameters and 113Cd chemical shift has been hampered in part by the lack of suitable model compounds and chemical dynamics [6]. As described throughout this review, these challenges are currently being met through applications of solid-state and low-temperature solution NMR methods and the design and study of less labile protein model compounds. However, even for cases where dynamics and solvent or anion effects can be ruled out, it appears that ligand atom type and number, bond lengths, coordination geometry, and neighboring atoms (including other metals) all influence 113Cd shifts. Studies of coordination compounds in solution have thus far provided useful information on the influence of donor-atom type and number on isotropic Cd chemical shifts. The influence on shift of coordination geometry and CdL bond lengths will probably only be adequately evaluated using the single crystal approach pioneered by Ellis and co-workers. Studies of the Cd ion bound exclusively by O-donor ligands will likely also be only adequately addressed through solid-state NMR methods due to lability problems with these ligands. In this area, model compounds with O-donor ligands which exhibit the unusual high-field shifts found for ICaBP and HRP are lacking. 113Cd NMR chemical shift information alone is at present inadequate for unambiguous determination of structural features or structural changes at the metal binding sites of metalloproteins. In this regard, HMQC NMR spectroscopy promises to be a particularly useful tool for identifying the ligands which are coordinated to Cd. For cases where ligand exchange or nuclear relaxation rates are high (relative to 1/ J), however, this method will not work and determination of structural features may rely exclusively on chemical shift analyses. It is therefore important that both techniques be developed and utilized.