Reversible immobilization of engineered molecules by Ni-NTA chelators

Electrochemical synthesis of nickel-nitrilotriacetic acid (Ni-NTA) chelators, for subsequent immobilization of (His)(6)-tagged proteins (Photosystem II (PSII) as model molecule), on Au or Au-graphite electrodes is compared to chemical synthesis. Results show: (i) higher Ni-NTA surface density, (ii) shorter treatment time (1-12 min vs. 16 h normally needed for self-assembled monolayer (SAM)), (iii) possibility of addressing the chelator to only one Au electrode, in a sensor micro-array.     

Hydro­gen‐bonded assemblages in 2,6‐bis­(hydroxy­methyl)‐4‐R‐phenol,with R = methyl,methoxy, phenoxy and 1‐(4‐methoxy­phenyl)‐1‐methyl­ethyl

Four derivatives of 2,6‐bis­(hydroxy­methyl)­phenol, with various para substituents, have been investigated; these are 2,6‐bis­(hydroxy­methyl)‐4‐methyl­phenol, C₉H₁₂O₃, (I), 2,6‐bis­(hydroxy­methyl)‐4‐methoxy­phenol, C₉H₁₂O₄, (II), 2,6‐bis­(hydroxy­methyl)‐4‐phenoxy­phenol, C₁₄H₁₄O₄, (III), and 2,6‐bis­(hydroxy­methyl)‐4‐[1‐(4‐methoxy­phenyl)‐1‐methyl­ethyl]­phenol, C₁₈H₂₂O₄, (IV). All four structures display hydrogen‐bonding networks resulting in sheets, with possible weak inter‐sheet π–π interactions in one case. In all the structures but one, the mol­ecules form centrosymmetric dimeric subunits held together by two hydrogen bonds between the hydroxy­methyl groups and, in two cases, by probable π–π interactions.     

First‐ and second‐ sphere coordination of the uranyl ion by bis­[2‐(2‐hydroxy­phenoxy)­ethoxy]­ethane

Uranyl nitrate hexahydrate reacts with bis­[2‐(2‐hydroxy­phenoxy)­ethoxy]­ethane (C₁₈H₂₂O₆), denoted LH₂ hereafter, in the presence of triethylamine to give ­triethylammonium aqua[2,2′‐(3,6‐dioxaoctane‐1,8‐diyldioxy)diphenolato‐κ²O,O′](nitrato‐κ²O,O′)dioxouranium(VI), (Et₃NH)[UO₂(H₂O)L(NO₃)], which possesses a symmetry plane. The uranyl ion is coordinated to the two phenoxide O atoms, a nitrate ion and a water mol­ecule (first sphere); the water mol­ecule is itself held in the crown ether chain by hydrogen‐bonding interactions, thus ensuring second‐sphere coordination by the ligand L.     

Theoretical study on the hydrogen migration reactions in ground state vinyl fluoride: Basis set and correlation energy effects

We performed ab initio molecular orbital (MO) calculations using Hartree—Fock SCF, and second- and fourth-order Møller—Plesset perturbation theory for hydrogen migration reactions on the singlet vinyl fluoride potential energy surface. We used different basis sets and polarization functions to obtain the stationary point geometries and activation barriers. Basis set and the polarization function extension have small effects, while the correlation energy evaluation leads to new conclusions for one of the studied reactions: the product singlet CHCH₂F is not a true local minimum on the potential energy surface.     

2,3,6,7‐Tetra­hydroxy‐9,10‐di­methyl‐9,10‐di­hydro‐9,10‐ethano­anthracene bis(1,4‐dioxane) solvate

2,3,6,7‐Tetra­hydroxy‐9,10‐di­methyl‐9,10‐di­hydro‐9,10‐ethano­anthracene crystallizes with 1,4‐dioxane to give a bis‐solvate, C₁₈H₁₈O₄·2C₄H₈O₂. The bis­(catechol) mol­ecule is located on a twofold axis and the two aromatic rings form a dihedral angle of 130.61 (4)°. Hydro­gen bonds are formed between the hydroxyl groups and either a neighbouring bis­(catechol) mol­ecule or the ether‐O atom of a dioxane mol­ecule.     

(±)‐6‐tert‐Butyl‐8‐hydroxymethyl‐2‐­phenyl‐4H‐1,3‐benzodioxin and 2,2,2′,2′,6,6′‐hexamethyl‐8,8′‐methylenebis(4H‐1,3‐benzodioxin)

Two compounds containing 1,3‐benzodioxin groups are reported, namely (±)‐6‐tert‐butyl‐8‐hydroxy­methyl‐2‐phenyl‐4H‐1,3‐benzodioxin, C₁₉H₂₂O₃, (I), and 2,2,2′,2′,6,6′‐hexamethyl‐8,8′‐methyl­enebis(4H‐1,3‐benzodioxin), C₂₃H₂₈O₄, (II).The hydroxy groups of neighbouring mol­ecules in (I) are hydrogen bonded to each other, giving rise to double‐row chains. The mol­ecule in (II) adopts a `butterfly' conformation, with the O atoms in distal positions. In both compounds, the dioxin rings are in distorted half‐chair conformations.     

Computational combinatorial ligand design: Application to human α-thrombin

Summary A new method is presented for computer-aided ligand design by combinatorial selection of fragments that bind favorably to a macromolecular target of known three-dimensional structure. Firstly, the multiple-copy simultaneous-search procedure (MCSS) is used to exhaustively search for optimal positions and orientations of functional groups on the surface of the macromolecule (enzyme or receptor fragment). The MCSS minima are then sorted according to an approximated binding free energy, whose solvation component is expressed as a sum of separate electrostatic and nonpolar contributions. The electrostatic solvation energy is calculated by the numerical solution of the linearized Poisson-Boltzmann equation, while the nonpolar contribution to the binding free energy is assumed to be proportional to the loss in solvent-accessible surface area. The program developed for computational combinatorial ligand design (CCLD) allows the fast and automatic generation of a multitude of highly diverse compounds, by connecting in a combinatorial fashion the functional groups in their minimized positions. The fragments are linked as two atoms may be either fused, or connected by a covalent bond or a small linker unit. To avoid the combinatorial explosion problem, pruning of the growing ligand is performed according to the average value of the approximated binding free energy of its fragments. The method is illustrated here by constructing candidate ligands for the active site of human -thrombin. The MCSS minima with favorable binding free energy reproduce the interaction patterns of known inhibitors. Starting from these fragments, CCLD generates a set of compounds that are closely related to high-affinity thrombin inhibitors. In addition, putative ligands with novel binding motifs are suggested. Probable implications of the MCSS-CCLD approach for the evolving scenario of drug discovery are discussed.     

Synthetic entries to 6-fluoro-7-substituted indole derivatives

Three practical synthetic entries of functionalized 6-fluoro-7-substituted indole derivatives were developed in connection with the preparation of 7-fluoro-8-substituted-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid derivatives 11 . The first route, which permits group modification about position 8 of the pyranoindole skeleton, employs 2-bromo-3-fluoroaniline ( 18 ) as a key intermediate, the preparation of which was achieved by either a novel ortho metalation of 15 or via the intermediacy of 22 . The second route utilizes 32 to append a terminally functionalized three carbon side chain onto the indole template and in addition leads to 43 from 40 . The third route to the 7-fluoro-8-substituted-pyranoindole skeleton complements route two in that the synthetic pathway exploits 32 in a nucleophilic fashion to construct a terminally functionalized two carbon appendage onto the indole nucleus.     

Hexasulfanyl analogues of cyclotriveratrylene

The synthesis of four 3,4-di(alkylsulfanyl)benzyl alcohol derivatives is described, in five steps from methyl 3,4-di(hydroxy)benzoate via a Newman–Kwart rearrangement. Incubation of these derivatives in formic acid affords 2,3,7,8,12,13-hexakis(alkylsulfanyl)-10,15-dihydro-5H-tribenzo[a,d,g]cyclononene products, which are hexa-sulfanyl analogues of the well-known supramolecular cavitand host, cyclotriveratrylene (CTV). The yield of this cyclization depends strongly on the alkylsulfanyl substituents present, in the order SMe > SEt ≈ SiPr ? SBn. A crystal structure determination of one of the cyclotrimers shows a mode of self-association that is commonly exhibited by CTV itself.     

A Bis(p-tert-butyloctahomotetraoxacalix[8]arene) Capsule with [(UO2)2(OH)2] Links and a Disordered [Rb4(H2O)4] Inner Core

p-tert-Butyloctahomotetraoxacalix[8]arene (LH⁸) reacts with uranyl nitrate hexahydrate in the presence of rubidium hydroxide to give a mixed complex that can be viewed as a tetrauranate dimer [(UO²)⁴(LH⁴)²(OH)⁴] containing four disordered rubidium ions and water molecules. Two uranyl ions are complexed in an “external” fashion by each macrocycle, each of them bound to two phenoxide groups and one ether group, as well as to two bridging hydroxide ions. The latter ensure the formation of a dimeric capsule that contains the disordered set of alkali metal ions. Apart from water molecules, the Rb⁺ ions are bound to the uranyl oxo groups directed towards the inner cavity, and to phenol and ether oxygen atoms from the macrocycle. The resulting octanuclear complex presents an unprecedented geometry evidencing the assembling potential of uranyl ions.

p-tert-Butyloctahomotetraoxacalix[8]arene (LH₈) reacts with uranyl nitrate hexahydrate in the presence of rubidium hydroxide to give a mixed complex that can be viewed as a tetrauranate dimer [(UO₂)₄(LH₄)₂(OH)₄] containing four disordered rubidium ions and water molecules. Two uranyl ions are complexed in an “external” fashion by each macrocycle, each of them bound to two phenoxide groups and one ether group, as well as to two bridging hydroxide ions. The latter ensure the formation of a dimeric capsule that contains the disordered set of alkali metal ions. Apart from water molecules, the Rb^+| ions are bound to the uranyl oxo groups directed towards the inner cavity, and to phenol and ether oxygen atoms from the macrocycle. The resulting octanuclear complex presents an unprecedented geometry evidencing the assembling potential of uranyl ions.