The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with (211)At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different (211)At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of (211)At(-) and *I(-) (*I = (131)I or (125)I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I(-) anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with (211)At. Four complexes Rh[16aneS4-diol]*I/(211)At and Ir[16aneS4-diol]*I/(211)At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0-4.0. Syntheses required heating for 1-1.5 h at 75-80 degrees C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS4-diol](131)I and Ir[16aneS4-diol](131)I complexes were obtained after only 20 min exposure of the reaction mixtures to microwave radiation. In conclusion, this study has shown that it is possible to attach an astatide anion to soft metal cations in a simple and fast one-step procedure, with high yields. These complexes will be evaluated as reagents for labeling biomolecules.