An Unusual Determinant Of Chirality. Unique Solution Chemistry And Novel Nmr Spectroscopic Changes In Fluxional Re(V)=O Complexes With Rearranging Meso N2s2 Ligands

The nature of metal species in aqueous solution is often ambiguous since the two processes, OH- coordination and ligand deprotonation, have the same pH profile. This problem plagues the assessment of the form of some radiopharmaceuticals present at physiological pH. Representative M(V)=O(N2S2) (M = Tc-99m, Re) radiopharmaceuticals include ReO(ECH3) complexes (ECH3 = thrice deprotonated ethylene di(cysteine), ECH6). We found that syn-ReO(DL-ECH3) (1) (meso-ECH3, formed from DL-cysteine) and the tetramethyl analog, syn-ReO(DL-TMECH3) (2, TMECH6 = ethylene di(penicillamine)), have uniquely informative spectral properties. Two equivalents of OK-convert 1 and 2 to the dianionic form. This form of 2 has only one set of three penicillamine (pen) H-1 NMR signals near pH 6. However, these signals underwent major changes from pH 6 to 10 as follows: they broadened and collapsed; two equal sets of three signals emerged; these then broadened and collapsed; and the original set of three signals reemerged. Combined with the Raman data given below, these results require that one form is present from pH 6 to 10 and that this form be chiral and both conformationally and configurationally fluxional; one N is protonated and the other N bears a lone pair (Lp). The determinant of chirality of this NH/NLp, form is the site of the NH group. The magnetic equivalence leading to one set of pen signals observed at the low and high ends of the pH range demonstrates the occurrence of fast exchange of the NH site between the two N's. This exchange leads to rapid inversion of complex chirality through symmetric intermediates, an NH/NH monoanion and an NLp/ NLp trianion, in the acid-and base-catalyzed processes, respectively. At neutral pH, the H+ = and OH- concentrations are low; as a result, the inversion of chirality is slow compared to the NMR time scale, and the two halves of the ligand are magnetically inequivalent. The two Re=O bands found in a fixed ratio in the resonance Raman spectra of 2 between pH 6 and 10 indicate that two major NH/NLp conformers are present throughout the range, including physiological pH. Two conformers of a form axially ligated by OH- cannot explain the two equal sets of pen NMR signals. However, two NH/NLp conformers differing only in NLp orientation and in rapid interchange via NLp inversion explain all the spectral results. Thus, the use of fast and slow time scale spectroscopies eliminates the ligation/deprotonation ambiguity in this case.