Influence of Linker Geometry on Uranyl Complexation by Rigidly Linked Bis(3-hydroxy-<i>N</i>-methyl-pyridin-2-one)

A series of bis(3-hydroxy-N-methyl-pyridin-2-one) ligands was synthesized, and their respective uranyl complexes were characterized by single crystal X-ray diffraction analyses. These structures were inspected for high-energy conformations and evaluated using a series of metrics to measure co-planarity of chelating moieties with each other and the uranyl coordination plane, as well as to measure coordinative crowding about the uranyl dication. Both very short (ethyl, 3,4-thiophene and o-phenylene) and very long (α,α′-m-xylene and 1,8-fluorene) linkers provide optimal ligand geometries about the uranyl cation, resulting in planar, unstrained molecular arrangements. The planarity of the rigid linkers also suggests there is a degree of pre-organization for a planar coordination mode that is ideal for uranyl-selective ligand design. Comparison of intramolecular Namide−Ophenolate distances and 1H NMR chemical shifts of amide protons supports earlier results that short linkers provide the optimal geometry for intramolecular hydrogen bonding

Hexadentate Terephthalamide(bis-hydroxypyridinone) Ligands for Uranyl Chelation: Structural and Thermodynamic Consequences of Ligand Variation

Several linear, hexa- and tetradentate ligands incorporating a combination of 2,3-dihydroxy-terephthalamide (TAM) and hydroxypyridinone-amide (HOPO) moieties have been developed as uranyl chelating agents. Crystallographic analysis of several {UO2[TAM(HOPO)2]}2– complexes revealed a variable and crowded coordination geometry about the uranyl center. The TAM moiety dominates the bonding in hexadenate complexes, with linker rigidity dictating the equality of equatorial U–O bonding. Hexadentate TAM(HOPO)2 ligands demonstrated slow binding kinetics with uranyl affinities on average 6 orders of magnitude greater than those of similarly linked bis-HOPO ligands. Study of tetradentate TAM(HOPO) ligands revealed that the high uranyl affinity stems primarily from the presence of the TAM moiety and only marginally from increased ligand denticity. Uranyl affinities of TAM(HOPO)2 ligands were within experimental error, with TAM(o-phen-1,2-HOPO)2 exhibiting the most consistent uranyl affinity at variable pH

Hexadentate Terephthalamide(bis-hydroxypyridinone) Ligands for Uranyl Chelation: Structural and Thermodynamic Consequences of Ligand Variation

Several linear, hexa- and tetradentate ligands incorporating a combination of 2,3-dihydroxy-terephthalamide (TAM) and hydroxypyridinone-amide (HOPO) moieties have been developed as uranyl chelating agents. Crystallographic analysis of several {UO2[TAM(HOPO)2]}2– complexes revealed a variable and crowded coordination geometry about the uranyl center. The TAM moiety dominates the bonding in hexadenate complexes, with linker rigidity dictating the equality of equatorial U–O bonding. Hexadentate TAM(HOPO)2 ligands demonstrated slow binding kinetics with uranyl affinities on average 6 orders of magnitude greater than those of similarly linked bis-HOPO ligands. Study of tetradentate TAM(HOPO) ligands revealed that the high uranyl affinity stems primarily from the presence of the TAM moiety and only marginally from increased ligand denticity. Uranyl affinities of TAM(HOPO)2 ligands were within experimental error, with TAM(o-phen-1,2-HOPO)2 exhibiting the most consistent uranyl affinity at variable pH

Uranyl Sequestering Agents: Correlation of Properties and Efficacy with Structure for UO₂²⁺ Complexes of Linear Tetradentate 1-Methyl-3-hydroxy-2(1<i>H</i>)-pyridinone Ligands¹

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 L1 the amine is propane amine. For the tetradentate bis-amides the linker groups are (L3) 1,3-diaminopropane, (L4) 1,4-diaminobutane, (L5) 1,5-diaminopentane. Crystal data:  [UO2(L1)2·DMF], space group, C2/c, cell constants:  a = 37.430(8) Å, b = 7.0808(14) Å, c = 26.781(5) Å, β = 130.17(3)°, V = 5424(2) Å3, Z = 8. [UO2L3·DMSO], Pnma, a = 8.4113(1) Å, b = 16.0140(3) Å, c = 16.7339(3) Å, V = 2254.03(5) Å3, Z = 4. [UO2L4·DMSO]·DMSO·H2O·0.5C6H12, P21/n, a = 26.7382(4) Å, b = 7.4472(1) Å, c = 31.4876(2) Å, V = 6209.05(13) Å3, Z = 8. [UO2L5·DMSO]·DMSO, Pnma, a = 7.3808(1) Å, b = 14.7403(3) Å, c = 23.1341(3) Å, V = 2516.88(8) Å3, Z = 4

Designing the Ideal Uranyl Ligand: a Sterically Induced Speciation Change in Complexes with Thiophene-Bridged Bis(3-hydroxy-<i>N</i>-methylpyridin-2-one)

Structural characterization of a mononuclear uranyl complex with a tetradentate, thiophene-linked bis(3-hydroxy-N-methylpyridin-2-one) ligand reveals the most planar coordination geometry yet observed with this ligand class. The introduction of ethylsulfanyl groups onto the thiophene linker disrupts this planar, conjugated ligand arrangement, resulting in the formation of dimeric (UO2)2L2 species in which each ligand spans two uranyl centers. Relative energy calculations reveal that this tendency toward dimer formation is the result of steric interference between ethylsulfanyl substitutents and linking amides

Designing the Ideal Uranyl Ligand: a Sterically Induced Speciation Change in Complexes with Thiophene-Bridged Bis(3-hydroxy-<i>N</i>-methylpyridin-2-one)

Structural characterization of a mononuclear uranyl complex with a tetradentate, thiophene-linked bis(3-hydroxy-N-methylpyridin-2-one) ligand reveals the most planar coordination geometry yet observed with this ligand class. The introduction of ethylsulfanyl groups onto the thiophene linker disrupts this planar, conjugated ligand arrangement, resulting in the formation of dimeric (UO2)2L2 species in which each ligand spans two uranyl centers. Relative energy calculations reveal that this tendency toward dimer formation is the result of steric interference between ethylsulfanyl substitutents and linking amides

Untangling the Diverse Interior and Multiple Exterior Guest Interactions of a Supramolecular Host by the Simultaneous Analysis of Complementary Observables

The entropic and enthalpic driving forces for encapsulation versus sequential exterior guest binding to the [Ga₄L₆]^12– supramolecular host in solution are very different, which significantly complicates the determination of these thermodynamic parameters. The simultaneous use of complementary techniques, such as NMR, UV–vis, and isothermal titration calorimetry, enables the disentanglement of such multiple host–guest interactions. Indeed, data collected by each technique measure different components of the host–guest equilibria and together provide a complete picture of the solution thermodynamics. Unfortunately, commercially available programs do not allow for global analysis of different physical observables. We thus resorted to a novel procedure for the simultaneous refinement of multiple parameters (Δ<i>G</i>°, Δ<i>H</i>°, and Δ<i>S</i>°) by treating different observables through a weighted nonlinear least-squares analysis of a constrained model. The refinement procedure is discussed for the multiple binding of the Et₄N⁺ guest, but it is broadly applicable to the deconvolution of other intricate host–guest equilibria

Coordination Chemistry of the Amonabactins, Bis(catecholate) Siderophores from <i>Aeromonas </i><i>hydrophila</i>¹

The amonabactins are a series of four bis(catecholate) siderophores isolated from the pathogenic organism, Aeromonas hydrophila. As tetradentate ligands, they cannot singly satisfy the octahedral coordination sphere of iron. The solution coordination chemistry of the amonabactins has been elucidated using potentiometric and spectrophotometric titrations, circular dichroism, and mass spectroscopy. They form 2:3 metal:ligand complexes at high pH and excess ligand. Their complexation behavior is essentially identical to one another, with log β230 = 86.3. At lower pH, they preferentially form a 1:1 bis(catecholato)bis(aqua) iron(III) species, with log β110 = 34.3. The 2:3 complexes show a very slight Δ preference in chirality at the metal center, while the 1:1 complexes are achiral. The biological implications of these properties are discussed

Influence of Linker Geometry on Uranyl Complexation by Rigidly Linked Bis(3-hydroxy-<i>N</i>-methyl-pyridin-2-one)

A series of bis(3-hydroxy-N-methyl-pyridin-2-one) ligands was synthesized, and their respective uranyl complexes were characterized by single crystal X-ray diffraction analyses. These structures were inspected for high-energy conformations and evaluated using a series of metrics to measure co-planarity of chelating moieties with each other and the uranyl coordination plane, as well as to measure coordinative crowding about the uranyl dication. Both very short (ethyl, 3,4-thiophene and o-phenylene) and very long (α,α′-m-xylene and 1,8-fluorene) linkers provide optimal ligand geometries about the uranyl cation, resulting in planar, unstrained molecular arrangements. The planarity of the rigid linkers also suggests there is a degree of pre-organization for a planar coordination mode that is ideal for uranyl-selective ligand design. Comparison of intramolecular Namide−Ophenolate distances and 1H NMR chemical shifts of amide protons supports earlier results that short linkers provide the optimal geometry for intramolecular hydrogen bonding

The Self-Assembly of a [Ga₄<b>L</b>₆]^12- Tetrahedral Cluster<i> Thermodynamically</i> Driven by Host−Guest Interactions^†

The guest-induced synthesis of a [Ga4L6]12- tetrahedral metal−ligand cluster resulting from a predictive design strategy is described. Each of the six dicatecholamide ligands spans an edge of the molecular tetrahedron with four Ga(III) ions at the vertices. Small cationic species not only were found to occupy the large void volume (ca. 300−400 Å3) inside this cluster but also are necessary thermodynamically to drive cluster assembly via formation of a host−guest complex. NMe4+, NEt4+, and NPr4+ all suit this purpose, and in addition the cluster exhibits a preference in the binding of these three guests:  NEt4+ is bound 300 times more strongly than NPr4+, which is in turn bound 4 times more strongly than NMe4+, as determined by 1H NMR spectroscopy. The K6(NEt4)6[Ga4L6] cluster was characterized by NMR spectroscopy, high- (Fourier transform ion cyclotron resonance, FT-ICR) and low-resolution electrospray ionization (ESI) mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. The binding of the NEt4+ guest molecule was confirmed in the solid state structure, which reveals that the molecule contains large channels in the solid state. As this result exemplifies, it is suggested that guest molecules will play an increasing role in the formation of larger, predesigned metal−ligand clusters