DOTP versus DOTA as Ligands for Lanthanide Cations: Novel Structurally Characterized CeIV and CeIII Cyclen-Based Complexes and Clusters in Aqueous Solutions.

The coordination and redox chemistry of aqueous CeIV/III macrocyclic compounds were studied by using the ligands DOTA and DOTP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid), respectively). The hydrolysis tendency of the tetravalent cation in the presence of DOTA is shown to result in the formation of a highly ordered, fluorite-like [CeIV 6 (O)4 (OH)4 (H2 O)8 (DOTAH)4 ] oxo-hydroxo structure both in solution and in the solid state. The lifetime of the analogous species formed in the presence of DOTP was found to be much shorter. Spectroscopic measurements of the latter suggest its similarity to the former. Its gradual decomposition in solution leads to the accumulation of the in-cage complexes [CeIV DOTP] and [CeIII DOTP(H2 O)], which were crystallographically characterized in this study. The redox energetics and spectroscopic characteristics for the transition between these two in-cage complexes in aqueous solutions were studied as well. Together with the crystallographic structures of the above-mentioned species, the in-cage [CeIV DOTA(H2 O)] complex structure is presented herein for the first time. An elaborative analysis of the X-ray crystallographic structural data obtained for the in-cage complexes studied herein and similar structures published previously suggests that hard-bonding cyclen-derived ligands are, counter-intuitively, better suited for encapsulating, and perhaps kinetically stabilize softer cations than harder ones with DOTP, marked as a possible adequate chelator for the study of the aqueous properties of LnII and AcIII cations.

Oligomers Intermediates in Between Two New Distinct Homonuclear Uranium(IV) DOTP Complexes*.

Two new aqueous UIV complexes were synthesized by the interaction between the tetravalent uranium cation and the (1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTP) macrocyclic ligand. Two distinct homonuclear complexes were identified; the first was characterized by X-ray crystallography as a unique "out-of-cage", [U(DOTPH6 )2 ] complex, in which the UIV cation is octa-coordinated to 4 phosphonic arms from each ligand in a square anti-prism geometry, with a C4 symmetry. The second is the "in-cage" [U(DOTPH4 )] complex, in which the tetravalent cation is located between the macrocycle O4 and N4 planes. With the help of UV-Vis absorption, 1 H/31 P NMR, ATR-IR, and MALDI-TOFMS analytical techniques, the chemical interchange between both species is presented. It is shown that the one-way transition is governed by the formation of a multiple number of soluble oligomeric species consisting of varied stoichiometric ratios of both characterized homonuclear complexes.

On the Aqueous Chemistry of the UIV -DOTA Complex.

The 1,4,7,10-tetrazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) aqueous complex of UIV with H2 O, OH- , and F- as axial ligands was studied by using UV/Vis spectrophotometry, ESI-MS, NMR spectroscopy, X-ray crystallography, and electrochemistry. The UIV -DOTA complex with either water or fluoride as axial ligands was found to be inert to oxidation by molecular oxygen, whereas the complex with hydroxide as an axial ligand slowly hydrolyzed and was oxidized by dioxygen to a diuranate precipitate. The combined data set acquired shows that, although axial substitution of fluoride and hydroxide ligands instead of water does not seem to significantly change the aqueous DOTA complex structure, it has an important effect on the electronic configuration of the complex. The UIV /UIII redox couple was found to be quasi-reversible for the complex with both axially bonded H2 O and hydroxide, but irreversible for the complex with axially bonded fluoride. Intriguingly, binding of the axial fluoride renders the irreversible one-electron UV /UIV oxidation of the [UIV (DOTA)(H2 O)] complex quasi-reversible, which suggests the formation of the short-lived pentavalent form of the complex, an aqueous non-uranyl chelated UV cation.

Crystal structure determination of rac-11'-(1-acetyl-1H-indazol-3-yl)-11',11a'-di-hydro-10'H,17'H-spiro-[indene-2,18'-[5a,16b]methano-tri-indeno[1,2-b:1',2'-d:2'',1''-g]oxocine]-1,3,10',12',17'(10a'H)-penta-one aceto-nitrile 1.5-solvate.

The title compound, C46H26N2O7·1.5CH3CN, is the aldol condensation product of bindone with indazole-3-carbaldehyde followed by double inter-molecular cyclization. The asymmetric unit, which has monoclinic P21/c symmetry, contains two independent mol-ecules of the title compound and three aceto-nitrile mol-ecules. The title mol-ecule comprises a central eight-membered ring, which contains an enol-ester, from which five arms extend. The arms exhibit inter-molecular inter-actions within the crystal lattice between mol-ecules of the title compound and with co-crystallized solvent mol-ecules (aceto-nitrile).

Structural Basis for p53 Lys120-Acetylation-Dependent DNA-Binding Mode.

Normal cellular homeostasis depends on tight regulation of gene expression, which requires the modulation of transcription factors' DNA-binding specificity. That said, the mechanisms that allow transcription factors to distinguish between closely related response elements following different cellular signals are not fully understood. In the tumor suppressor protein p53, acetylation of loop L1 residue Lys120 within the DNA-binding domain has been shown to promote the transcription of proapoptotic genes such as bax. Here, we report the crystal structures of Lys120-acetylated p53 DNA-binding domain in complex with a consensus response element and with the natural BAX response element. Our structural analyses reveal that Lys120 acetylation expands the conformational space of loop L1 in the DNA-bound state. Loop L1 flexibility is known to increase p53's DNA-binding specificity, and Lys120-acetylation-dependent conformational changes in loop L1 enable the formation of sequence-dependent DNA-binding modes for p53. Furthermore, binding to the natural BAX response element is accompanied by global conformational changes, deformation of the DNA helical structure, and formation of an asymmetric tetrameric complex. Based on these findings, we suggest a model for p53's Lys120 acetylation-dependent DNA-binding mode.

Acridine 0.75-hydrate.

The title compound, C(13)H(9)N·0.75H(2)O was obtained during a study of the polymorphic system of acridine, by slow evaporation from an ethanol-water solution. There are two acridine mol-ecules (indicated by I and II, respectively) and one and a half water mol-ecules in the asymmetric unit. The half-mol-ecule of water is located on a crystallographic twofold axis. The crystal structure is built up from two threads of mol-ecule II sewn together with water mol-ecules through O-H⋯O and O-H⋯N hydrogen bonds from one side and with π-π inter-actions [centroid-centroid distance = 3.640 (3) and 3.7431 (3) Å] between overlapping mol-ecules II on the other side. Mol-ecule I is attached to this thread from both sides by C-H⋯O hydrogen bonds. The threads are connected to each other by π-π inter-actions [centroid-centroid distances = 3.582 (3) and 3.582 (3) Å] between the inner side of mol-ecule I and stabilized by a C-H⋯π inter-action on the other side of mol-ecule I. This thread with rows of mol-ecule I hanging on its sides is generated by translation perpendicular to the a axis.

Crystal structures of Escherichia coli KDO8P synthase complexes reveal the source of catalytic irreversibility.

The enzyme 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase (KDO8PS) catalyses the condensation of arabinose 5-phosphate (A5P) and phosphoenol pyruvate (PEP) to obtain 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P). We have elucidated initial modes of ligand binding in KDO8PS binary complexes by X-ray crystallography. Structures of the apo-enzyme and of binary complexes with the substrate PEP, the product KDO8P and the catalytically inactive 1-deoxy analog of arabinose 5-phosphate (1dA5P) were obtained. The KDO8PS active site resembles an irregular funnel with positive electrostatic potential situated at the bottom of the PEP-binding sub-site, which is the primary attractive force towards negatively charged phosphate moieties of all ligands. The structures of the ligand-free apo-KDO8PS and the binary complex with the product KDO8P visualize for the first time the role of His202 as an active-site gate. Examination of the crystal structures of KDO8PS with the KDO8P or 1dA5P shows these ligands bound to the enzyme in the PEP-binding sub-site, and not as expected to the A5P sub-site. Taken together, the structures presented here strengthen earlier evidence that this enzyme functions predominantly through positional catalysis, map out the roles of active-site residues and provide evidence that explains the total lack of catalytic reversibility.

Refined structure of c-phycocyanin from the cyanobacterium Synechococcus vulcanus at 1.6 A: insights into the role of solvent molecules in thermal stability and co-factor structure.

The crystal structure of the light-harvesting phycobiliprotein, c-phycocyanin from the thermophilic cyanobacterium Synechococcus vulcanus has been refined to 1.6 A resolution based on the previously determined lower resolution structure (PDB entry 1I7Y). The improved data was collected using synchrotron radiation at 100 K. The significantly improved crystallographic data has lead to improved calculated electron density maps, allowing the unambiguous positioning of all protein and co-factor atoms and the positioning of 377 solvent molecules. The positions of solvent molecules at specific sites important for stabilization of different levels of self-assembly of the phycobilisome structure were identified and the bonding network is described. The presence of solvent molecules in the vicinity of the co-factors and in intermolecular spaces is identified and their possible roles are suggested. All three of the phycocyanobilin co-factors bind water molecules at specific sites between the propionic acid side chains. Molecular dynamic (MD) simulations support that these special waters have a role in stabilization of this conformation. On the basis of the crystal packing reported here and in comparison to other phycobiliprotein crystal forms, we have analyzed the roles of specific sites on the formation of the phycobilisome complex.