Docking studies on NSAID/COX-2 isozyme complexes using Contact Statistics analysis

Summary The selective inhibition of COX-2 isozymes should lead to a new generation of NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex^®) and rofecoxib (Vioxx^®). To obtain inhibitors with higher selectivity it has become essential to gain additional insight into the details of the interactions between COX isozymes and NSAIDs. Although X-ray structures of COX-2 complexed with a small number of ligands are available, experimental data are missing for two well-known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results reported are controversial. We use a combination of a traditional docking procedure with a new computational tool (Contact Statistics analysis) that identifies the best orientation among a number of solutions to shed some light on this topic.     

Lead removal and recovery from battery industry wastewaters by soluble starch xanthate

Treatment, removal and recovery of lead (3 mg/L) from battery industry wastewaters have been investigated utilising a chemical precipitation process with soluble starch xanthate (SX) at pH 5-6. A reactant ratio, i.e., SX/Pb(II) = 6 mol/mol, a reaction time of 15 min., the addition of 15 mg/L of a cationic polyelectrolyte and a final filtration gave residual lead concentrations in the liquid phase less than 0.2 mg/L, well below the maximum limit established by the EU Directive. Lead was extracted from the obtained sludge by oxidation with sodium hypochlorite or hydrogen peroxide solutions. The amounts of oxidant needed were quantified as 13.5 mol NaClO/mol Pb and one order of magnitude larger, for H2O2, the latter due to the competitive disproportion reaction of the oxidant. The metal extraction was quantitative using sodium hypochlorite; when hydrogen peroxide was used, the formation of insoluble PbSO4 (Anglesite) gave a 80% metal extraction. In both cases molar ratios between sulphate and lead ions in the extracted solutions were in the range 2.1-2.2, in agreement with the stoichiometries of the reactions. Lead can be quantitatively recovered from the extracted (NaClO) solutions, for reuse, after a chemical precipitation process with 1M NaOH at pH 9-9.5, in the form of hydrocerussite [Pb3(CO3)2(OH)2].     

Conformation of microcontact-printed proteins by atomic force microscopy molecular sizing

We investigated the structural changes occurring in proteins patterned via microcontact printing. This was done by molecular sizing using atomic force microscopy to observe the structure of printed individual metalloprotein molecules in the unlabeled and untreated states. We observed that the size of the printed proteins were more than 2-fold smaller than the native shape, which indicates that some deformations take place upon the contact-assisted adsorption on silanized silicon dioxide. This can be attributed to simultaneously occurring effects, and particularly to the sandwiching between surfaces of very different hydrophilic/hydrophobic properties during contact lithography.     

On-site monitoring of trace levels of free manganese in sea water via sonoelectroanalysis using a boron-doped diamond electrode

Cathodic stripping voltammetry at a boron-doped diamond electrode utilising an insonated accumulation protocol is shown to be possible for the on-site trace detection of free manganese in seawater samples. No sample pre-treatment is required with the application of ultrasound providing a sensitive and selective protocol for the analysis of manganese. The protocol is used in the evaluation of manganese in seawater samples taken near the site of a former ferromanganese factory in the town Šibenik, Croatia.     

Intramolecular Dynamics of Tetranuclear Carbonyliridium Cluster Compounds. Part II. Disubstituted complexes with one chelating ligand. Crystal structure of [Ir4(CO)7(μ-CO)3(1,5-cyclooctadiene)]

The two complexes [Ir₄(CO)₁₀(diarsine)] (1) and [Ir₄(CO)₁₀(1,5-cyclooctadiene)] (2) bear a bidentate ligand chelating one metal atom of the basal face of the Ir₄ tetrahedron. However, they differ in fluxional behaviour as observed by 2D-exchange and variable-temperature ¹³C-NMR. The CO-site exchange with lowest activation energy proceeds via an unbridged intermediate in 2 , whereas that in 1 occurs via a concerted edge-bridging of CO's to an alternative face of the metal core. This difference is apparently related to different ground-state geometries: the basal CO's are symmetrically bridging in 2 , whereas two CO's are semi-bridging in 1 . The molecular structure of 2 was determined by single crystal X-ray diffractometry. The crystals are orthorhombic, space group Pbca, a = 11.651(4), b = 13.118(3), c = 28.64(1)Å. The idealized molecular symmetry is C_s. The diolefin chelates a basal Ir-atom replacing an axial and a radial CO group on the tetrahedral metal-atom framework.     

A reusable, insoluble polymer-bound bis(oxazoline) (IPB-box) for highly enantioselective heterogeneous cyclopropanation reactions

A reusable, insoluble polystyrene-supported bis(oxazoline) was developed, affording e.e.s > 90% in the heterogeneous enantioselective cyclopropanation of styrene and 1,1-disubstituted alkenes with ethyl diazoacetate.     

An investigation of nodal structures and the construction of trial wave functions

The factors influencing the quality of the nodal surfaces, namely, the atomic basis set, the single-particle orbitals, and the configurations included in the wave-function expansion, are examined for a few atomic and molecular systems. The following empirical rules are found: the atomic basis set must be fairly large, complete active space and natural orbitals are usually better than Hartree-Fock orbitals, multiconfiguration expansions perform better than single-determinant wave functions, but only few configurations are effective and their choice is suggested by symmetry considerations, while too long determinantal expansions spoil the nodal surfaces. These rules allow us to reduce the nodal error and to compute the best fixed node-diffusion Monte Carlo energies for a series of dimers of first-row atoms.     

Synthesis and structure of dimeric bis(isothiocyanato)tris (4-methylpyridine)nickel (II)

Summary The Ni₂(NCS)₄(4-Methylpyridine)6 complex has been prepared crystalline from methanolic solutions of Ni(NCS)2(4-Methylpyridine)4. Three dimensional x-ray diffraction data were collected by means of an automated single crystal diffractometer. The structure was solved by Patterson methods and refined to a final R value of 0.075, based on 2422 observed_ reflections. The compound crystallizes in space group P1 with one dimeric molecule in a unit cell of dimensions a = 10.57(1), 6 = 14.06(1), c = 8.66(1) Å, = 105.2(1), = 114.8(1), y = 95.6(1)°. The Ni atoms have distorted octahedral coordination with one sulfur and five nitrogen atoms - two of the four thiocyanate groups form a double bridge between the neighbouring Ni atoms.4-MePy = 4-Methylpyridine     

Reactions between or within molecular crystals

Reactions that occur within or between molecular crystals, in particular those reactions that are activated by mechanical methods, are reviewed. The focus is on processes (whether intrasolid or intersolid) that are controlled primarily by supramolecular bonding, such as template cycloadditions, formation of inclusion compounds, reactions between molecular crystals by the reassembling of noncovalent bonds, and the formation of complexes and coordination compounds. It is proposed that solvent-free mechanochemical methods, for example, cogrinding, milling, and kneading, represent viable "green" routes for the preparation of novel molecular and supramolecular solids.