Rhenium(V) and Technetium(V) Oxo Complexes of an N₂N‘S Peptidic Chelator:  Evidence of Interconversion between the Syn and Anti Conformations

Neutral Re(V) and Tc(V) oxo complexes of the peptide dimethylglycyl-l-seryl-l-cysteinylglycinamide (RP294) were prepared and characterized by HPLC, spectroscopic techniques, and X-ray crystallographic analysis. The peptide was prepared as a single peptide chain using solid phase methods and characterized by HPLC and various spectroscopic techniques. The water-soluble Re(V) oxo complex of dimethylglycyl-l-seryl-l-cysteinylglycinamide [ReO(RP294)] was prepared from the reaction of the peptide with either [ReO₂(en)₂]Cl or ReOCl₃(PPh₃)₂ in the presence of base. The complex exists as two isomers, the serine CH₂OH group being in the syn or anti conformation with respect to the Re−oxo bond. The ratio of the isomers at room temperature is 1:1.1. The isomers were separated by reverse-phase HPLC, but the isolation of each isomer was complicated by their rapid interconversion in aqueous solution at room temperature. The molecular structure of the syn isomer of the Re complex was determined by X-ray crystallography. Crystals of syn-[ReO(RP294)] (C₁₂H₂₀N₆O₅ReS) are orthorhombic, of space group P2₁2₁2₁, with a = 6.954(1) Å, b = 8.0472(1) Å, c = 32.9183(4) Å, and Z = 4. The structure was solved by direct methods and was refined by full-matrix least-squares procedures to R = 0.0327 (R_w = 0.0838) for 10 447 reflections with I > 2σ(I). The Re metal was coordinated in a distorted square pyramidal geometry with the oxo moiety in the apical position. The peptide coordinated to ReO³⁺ via the N_amine atom of dimethylglycine, the S_thiolate atom of cysteine, and the two N_amide atoms of serine and cysteine (an N₂N‘S donor atom set). The Re atom lies ∼0.74 Å above the distorted plane formed by the N₂N‘S donor atom set. Variable-pH ¹H NMR spectral data showed the Re complex was stable from pH 5 to 8.5. The reaction of ⁹⁹TcO₄^- with SnCl₂, sodium gluconate, and RP294 produced the ⁹⁹Tc(V) oxo RP294 complex, [⁹⁹TcO(RP294)]. Like the [ReO(RP294)] complex, [⁹⁹TcO(RP294)] also exists in the syn and anti conformations in a ratio of approximately 1:1. The ^99mTc complex of RP294 was prepared at the tracer level from the reaction of Na[^99mTcO₄] with excess SnCl₂, sodium gluconate, and RP294. The ^99mTc and Re RP294 complexes behaved similarly under identical HPLC conditions.