The coordination chemistry of lanthionine (LANH(2)) and cystathionine (CSTH2) dipeptides, which respectively consist of two cysteines and one cysteine and one homocysteine linked by a thioether bridge, is almost unstudied. Recently for fac-[Tc-99m(CO)(3)(LAN)](-) isomers, the first small Tc-99m(CO)(3) agents evaluated in humans were found to give excellent renal images and to have a high specificity for renal excretion. Herein we report the synthesis and characterization of Re complexes useful for interpreting the nature of tracer Tc-99m radiopharmaceuticals. Treatment of [Re(CO)(3)(H2O)(3)]OTf with commercially available LANH(2) (a mixture of meso (D,L) and chiral (DD,LL) isomers) gave three HPLC peaks, 1A, 1B, and 1C, but treatment with CSTH2 (L,L isomer) gave one major product, Re(CO)(3)(CSTH) (2). Crystalline Re(CO)(3)(LANH) products were best obtained with synthetic LANH(2), richer in meso or chiral isomers. X-ray crystallography showed that these dipeptides coordinate as tridentate N2S-bound ligands with two dangling carboxyls. The LANH ligand is meso in 1A and 1C and chiral in 1B. While 1A (kinetically favored) is stable at ambient temperature for days, it converted into 1C (thermodynamically favored) at 100 degrees C; after 6 h, equilibrium was reached at a 1A:1C ratio of 1:2 at pH 8. The structures provide a rationale for this behavior and for the fact that 1A and 1C have simple NMR spectra. This simplicity results from fluxional interchange between an enantiomer with both chelate rings having the same delta pucker and an enantiomer with both chelate rings having the same lambda pucker. Agents with the {Tc-99m(CO)(3)}(+) core and N2S ligands show promise of becoming an important class of Tc-99m radiopharmaceuticals. The chemistry of Re analogues with these ligands, such as the LAN(2-) complexes reported here, provides a useful background for designing new small agents and also tagged large agents because two uncoordinated carboxyl groups are available for conjugation with biological molecules such as proteins.