High-affinity tamoxifen analogues retain extensive positional disorder when bound to calmodulin

Using a combination of NMR and fluorescence measurements, we have investigated the structure and dynamics of the complexes formed between calcium-loaded calmodulin (CaM) and the potent breast cancer inhibitor idoxifene, a derivative of tamoxifen. High-affinity binding (Kd∼300 nM) saturates with a 2:1 idoxifene:CaM complex. The complex is an ensemble where each idoxifene molecule is predominantly in the vicinity of one of the two hydrophobic patches of CaM but, in contrast with the lower-affinity antagonists TFP, J-8, and W-7, does not substantially occupy the hydrophobic pocket. At least four idoxifene orientations per domain of CaM are necessary to satisfy the intermolecular nuclear Overhauser effect (NOE) restraints, and this requires that the idoxifene molecules switch rapidly between positions. The CaM molecule is predominantly in the form where the N and C-terminal domains are in close proximity, allowing for the idoxifene molecules to contact both domains simultaneously. Hence, the 2:1 idoxifene:CaM complex illustrates how high-affinity binding occurs without the loss of extensive positional dynamics.

Crystal structure and computational study of an oxo-bridged bis-titanium(III) complex

The solid-state structure of the new compound μ-oxido-bis[dichloridotris(tetrahydrofuran-κO)titanium(III)], [Ti2Cl4O(C4H8O)6], at 150 K has been determined. The crystal has monoclinic (C2/c) symmetry and the complex features C 2 symmetry about the bridging O atom. Positional disorder is evident in one of the three tetrahydrofuran environments. A post-Hartree–Fock computational analysis indicates that the complex has nearly degenerate triplet and singlet spin states, with the former favoured slightly by ca 2 kJ mol−1.

High Affinity Tamoxifen Analogues Retain Extensive Positional Disorder when Bound to Calmodulin

Using a combination of NMR and fluorescence measurements we have investigated the structure and dynamics of the complexes formed between calcium loaded calmodulin (CaM) and the potent breast cancer inhibitor idoxifene, a derivative of tamoxifen. High affinity binding (Kd ~ 300 nM) saturates with a 2:1 idoxifene:CaM complex. The complex is an ensemble where each idoxifene molecule is predominantly in the vicinity of one of the two hydrophobic patches of CaM but, in contrast with the lower affinity antagonists TFP, J-8 and W-7, does not substantially occupy the hydrophobic pocket. At least four idoxifene orientations per domain of CaM are necessary to satisfy the intermolecular NOE restraints, and this requires that the idoxifene molecules switch rapidly between positions. The CaM molecule is predominantly in the form where the N and C-terminal domains are in close proximity allowing for the idoxifene molecules to contact both domains simultaneously. Hence, the 2:1 idoxifene:CaM complex illustrates how high affinity binding occurs without the loss of extensive positional dynamics.

Rerefinement of poly[diaquabis(μ3-2-methylpropanoato-κ4 O:O,O′:O′)bis(μ3-2-methylpropanoato-κ3 O:O:O)(μ2-2-methylpropanoato-κ3 O:O,O′)(2-methylpropanoato-κ2 O,O′)trilead(II)]

The crystal structure of the title complex, [Pb3(C4H7O2)6(H2O)2] n , was redetermined on basis of modern CCD-based single-crystal X-ray data at 120 K. The current study basically confirms the previous report [Fallon et al. (1997). Polyhedron, 16, 19–23] at 190 K, but with higher accuracy and precision. In particular, positional disorder of one of the 2-methylpropanoate anions over two sets of sites was resolved, showing a refined ratio of the disorder components of 0.535 (9):0.465 (9). The three independent cations in the structure have coordination numbers of [7 + 1], [6 + 1], and [5 + 3], with O atoms belonging either to carboxylate groups or water molecules. This arrangement leads to the formation of sheets parallel to (\overline{1}01), whereby the hydrophobic 2-methylpropanyl groups of the anions are oriented above and below the hydrophilic sheets to form a layered structure. Within a sheet, hydrogen bonds of the type Owater—H...O are formed, whereas the hydrophobic groups between adjacent layers interact through van der Waals forces.

Crystal structures of catena-poly[[μ-aqua-diaqua(μ3-2-methylpropanoato-κ4 O:O,O′:O′)calcium] 2-methylpropanoate dihydrate], catena-poly[[μ-aqua-diaqua(μ3-2-methylpropanoato-κ4 O:O,O′:O′)strontium] 2-methylpropanoate dihydrate] and catena-poly[[μ-aqua-diaqua(μ3-2-methylpropanoato-κ4 O:O,O′:O′)(calcium/strontium)] 2-methylpropanoate dihydrate]

The crystal structures of catena-poly[[μ-aqua-diaqua(μ3-2-methylpropanoato-κ4 O:O,O′:O′)calcium] 2-methylpropanoate dihydrate], {[Ca(C4H7O2)(H2O)3](C4H7O2)·2H2O} n , (I), catena-poly[[μ-aqua-diaqua(μ3-2-methylpropanoato-κ4 O:O,O′:O′)strontium] 2-methylpropanoate dihydrate], {[Sr(C4H7O2)(H2O)3](C4H7O2)·2H2O} n , (II), and catena-poly[[μ-aqua-diaqua(μ3-2-methylpropanoato-κ4 O:O,O′:O′)(calcium/strontium)] 2-methylpropanoate dihydrate], {[(Ca,Sr)(C4H7O2)(H2O)3](C4H7O2)·2H2O} n , (III), are related. (III) can be considered as an Sr-containing solid solution of (I), with Ca2+ and Sr2+ occupationally disordered in the ratio 0.7936 (16):0.2064 (16). (I)/(III) and (II) are homeotypic with different space groups of Pbca and Cmce, respectively. All the title crystal structures are composed of hydrophilic sheets containing the cations, carboxylate groups as well as water molecules. The hydrophobic layers, which consist of 2-methylpropanoate chains, surround the hydrophilic sheets from both sides, thus forming a sandwich-like structure extending parallel to (001). The cohesion forces within these sheets are the cation–oxygen bonds and O—H...O hydrogen bonds of moderate strength. Stacking of these sandwiches along [001] is consolidated by van der Waals forces. The structures contain columns defined by the cation–oxygen interactions in which just one symmetry-independent 2-methylpropanoate anion is included, together with three water molecules. These molecules participate in an irregular coordination polyhedron composed of eight O atoms around the cation. Additional water molecules as well as the second 2-methylpropanoate anion are not part of the coordination sphere. These molecules are connected to the above-mentioned columns by O—H...O hydrogen bonds of moderate strength. In (II), the Sr2+ cation, two of the coordinating water molecules and both anions are situated on a mirror plane with a concomitant positional disorder of the 2-methylpropyl groups; the non-coordinating water molecule also shows positional disorder of its hydrogen atom.

Layered alkali propanoates M +(C2H5COO)−; M + = Na+, K+, Rb+, Cs+

The title alkali propanoates poly[(μ5-propanoato)alkali(I)], M +(C2H5COO)−, with alkali/M + = Na+, K+, Rb+ and Cs+, show close structural similarity, which is manifested by the coordination of the cations by six oxygen atoms in a chessboard motif, forming a bilayer. This bilayer is situated between hydrophobic layers composed of dangling ethyl chains from the carboxylate groups. Stacking of these two-dimensional sandwiches, which are parallel to (001), forms the title structures. Each metal cation is coordinated by six O atoms in the form of a distorted trigonal prism. One pair of these oxygen atoms belongs to a bridging, bidentately coordinating carboxylate anion, while each of the other four oxygen atoms belongs to different carboxylate groups, which are in a bridging monodentate mode. Despite the close similarity, each of the studied alkali propanoates crystallizes in a different space group. The atoms are in general positions, except for the cation in K+(C2H5COO)−, which is situated on a mirror plane. Positional disorder of the methyl groups that are disordered over two positions is present in the Na+ and K+ propanoates, in contrast to the Rb+ and Cs+ propanoates. In the Na+ compound, the occupational parameters of the disordered methyl groups are different compared to the K+ compound where they are equal. This difference results in doubling of the a unit-cell parameter of the Na+ compound with respect to that of the K+ compound, otherwise the structures are homeotypic. In Cs+ propanoate, a disorder of the methyl H atoms is observed.

Synthesis and crystallographic studies of two new 1,3,5-triazines

The synthesis and characterization of two new 1,3,5-triazines containing 2-(aminomethyl)-1H-benzimidazole hydrochloride as a substituent are reported, namely, 2-{[(4,6-dichloro-1,3,5-triazin-2-yl)amino]methyl}-1H-benzimidazol-3-ium chloride, C11H9Cl2N6 +·Cl− (1), and bis(2,2′-{[(6-chloro-1,3,5-triazine-2,4-diyl)bis(azanediyl)]bis(methylene)}bis(1H-benzimidazol-3-ium)) tetrachloride heptahydrate, 2C19H18ClN9 2+·4Cl−·7H2O (2). Both salts were characterized using single-crystal X-ray diffraction analysis and IR spectroscopy. Moreover, the NMR (1H and 13C) spectra of 1 were obtained. Salts 1 and 2 have triclinic symmetry (space group P-1) and their supramolecular structures are stabilized by hydrogen bonding and offset π–π interactions. In hydrated salt 2, the noncovalent interactions yield pseudo-nanotubes filled with chloride anions and water molecules, which were modelled in the refinement with substitutional and positional disorder.

Rb9– x Ag3+x Sc2(WO4)9: a new glaserite-related structure type, rubidium disorder, ionic conductivity

A new triple tungstate Rb9−x Ag3+x Sc2(WO4)9 (0 ≤ x ≤ 0.15) synthesized by solid state reactions and spontaneous crystallization from melts presents a new structure type related to those of Cs7Na5Yb2(MoO4)9 and Na13Sr2Ta2(PO4)9. The title compound in centrosymmetric space group Cmcm contains dimers of two ScO6 octahedra sharing corners with three bridging WO4 tetrahedra. Three pairs of opposite terminal WO4 tetrahedra are additionally linked by AgO2 dumbbells to form {Ag3[Sc2(WO4)9]}9− groups, which together with some rubidium ions are packed in pseudohexagonal glaserite-like layers parallel to (001), but stacking of the layers is different in these three structures. In the title structure, the layers stack with a shift along the b axis and their interlayer space contains disordered Rb+ cations partially substituted by Ag+ ions. Almost linear chains of incompletely filled close Rb3a–Rb3d positions (the shortest distances Rb–Rb are 0.46 to 0.64 Å) are found to locate approximately along the b axis. This positional disorder and the presence of wide common quadrangular faces of Rb2 and Rb3a–Rb3d coordination polyhedra favor two-dimensional ionic conductivity in the (001) plane with Rb+ and Ag+ carriers, which was confirmed with bond valence sum (BVS) maps. Electrical conductivity measurements on Rb9Ag3Sc2(WO4)9 ceramics revealed a first-order superionic phase transition at 570 K with a sharp increase in the electrical conductivity. The conductivity σi = 1.8 × 10−3 S cm−1 at 690 K is comparable with the value of 1.0 × 10−3 S cm−1 (500 K) observed earlier for rubidium-ion transport in pyrochlore-like ferroelectric RbNbWO6.