| Abstract
| - By using a new strategy for preparing solutions of the fac-[Re(CO)3(H2O)3]+ precursor analogous to the solutions for preparing 99mTc radiopharmaceuticals, we have synthesized Re(CO)3 complexes with tridentately coordinated α-amino acids bearing a thioether group. The latter generates an asymmetric center, and NMR and X-ray methods provided evidence for the formation of both possible diastereoisomers, which interchange rapidly in solution except when the thioether has an appended acetate group.
- Parallel studies of the preparation of Re and 99mTc agents aid in interpreting the nature of tracer 99mTcradiopharmaceuticals. Aqueous solutions of the fac-[99mTc(CO)3(H2O)3]+ cation are gaining wide use and are readilyprepared, but such solutions of the fac-[Re(CO)3(H2O)3]+ cation (1) are not so easily accessible. Herein we describea new, reliable, and straightforward preparation of aqueous solutions of 1, characterized by HPLC and ESI-MS.Treatment of solutions of 1 with thioether-bearing amino acids, AAH = S-methyl-l-cysteine (MECYSH), S-propyl-l-cysteine (PRCYSH), and methionine (METH), gave high yields of fac-Re(CO)3AA complexes. X-ray crystallographicand NMR analyses indicated that MECYS-, PRCYS-, and MET- were bound in fac-Re(CO)3AA complexes astridentate monoanionic ligands through amino, thioether, and α-carboxyl groups. In CD3OD, 1H NMR spectra havebroad signals but have two sets of signals at −10 °C, consistent with two isomers with different configurations atthe pyramidal sulfur; these interconvert slowly on the NMR time scale at low temperatures. Indeed, the crystalstructure of the fac-Re(CO)3(PRCYS) reveals a mixture of the two possible diastereoisomers. S-(Carboxymethyl)-l-cysteine (CCMH2) and 1 gave two products, 5A (kinetically favored) and 5B (thermodynamically favored). X-raycrystallographic analyses of a crystal of 5B and of a 1:1 cocrystal of 5A and 5B showed that 5A and 5B arediastereoisomers with the CCMH- α-carboxyl group dangling. In addition to the amino and thioether groups, theS-(carboxymethyl) carboxyl group is coordinated, a feature that slows interconversion of diastereoisomers relativeto the other fac-Re(CO)3AA complexes because interconversion can now occur only after the rupture of Re−ligandbonds. These N, O, and S tridentate adducts are quite stable, and the grouping has promise in 99mTc(CO)3 tracerdevelopment.
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