A rational design of uranyl sequestering agents based on 3-hydroxy-2(1H)-pyridinone ligands has resulted in the first effective agents for mammalian uranyl decorporation. In this study crystal structures of uranyl complexes with four of these agents are compared and correlated with the chemical and biological properties. These hydroxypyridinone ligands bind the uranyl ion in the equator of a pentagonal prism; a solvent molecule fills the fifth coordination site. The tetradentate ligands are composed of two hydroxypyridonate groups connected by a diamine linker via amide coupling. The dihedral angles between two pyridinone ring planes in these complexes differ as the length of linear backbone changes, giving these molecules a ruffled shape. The physical parameters (such as NMR chemical shifts) of the uranyl complexes with tetradentate Me-3,2-HOPO ligands correlate with the length of the diamine linker, as does the in vivo activity. The ligands are amides of 3-hydroxy-N-methyl-2(1H)-4-carboxypyridone. For L-1 the amine is propane amine. For the tetradentate bis-amides the linker groups are (L-3) 1,3-diaminopropane, (L-4) 1,4-diaminobutane, (L-5) 1,5-diaminopentane. Crystal data: [UO2(L-1)(2). DMF], space group, C2/c, cell constants: a=37.430(8) Angstrom, b = 7.0808(14) Angstrom, c=26.781(5) Angstrom, beta=130.17(3)degrees, V=5424(2) Angstrom(3), Z=8. [UO2L3. DMSO], Pnma, a=8.4113(1) Angstrom, b = 16.0140(3) Angstrom, c = 16.7339(3) Angstrom, V= 2254.03(5) Angstrom(3), Z = 4. [UO2L4. DMSO]. DMSO . H2O . 0.5C(6)H(12), P2(1)/n, a = 26.7382(4) Angstrom, b = 7.4472(1) Angstrom, c = 31.4876(2) Angstrom, V = 6209.05(13) Angstrom(3), Z = 8. [UO2L5. DMSO]. DMSO, Pnma, a = 7.3808(1) Angstrom, b = 14.7403(3) Angstrom, c 23.1341(3) Angstrom, V=2516.88(8) Angstrom(3), Z= 4.