This provides new understanding of the theoretical, synthetic, structural, and thermodynamic principles of molecular recognition leading to unprecedented selectivity and control of ion binding in separations such as liquid-liquid extraction and crystallization. The major line of inquiry deals with the design of fully functional ion receptors that can completely accommodate the coordination and charge-neutralization requirements for separation of ions, ion pairs, or ion aggregates, whether the recognition occurs with discrete molecular receptors or small molecular units that function by self-assembly. Three specific aims deal with computer-aided molecular design to guide the discovery of molecular structures with controlled functionality; self-assembly of small molecular units with multiple ions to form predetermined structures; and cooperativity effects in the selective separation of ions and ion pairs. Specific progress is being made with new anion-binding motifs based on new guanidinium, urea, and calixpyrrole platforms, and when these are combined with cation-binding groups, the resulting ditopic structures self-assemble with ion-pairs in high-order assemblies. Resulting transformative understanding of the theoretical, structural, and thermodynamic principles underlying ion recognition will strongly benefit DOE’s energy, environmental, and national-security missions.