Designing new ligands: asymmetric cyclopropanation by Cu(i) complexes based on functionalised pyridine-containing macrocyclic ligands

The synthesis and characterisation of copper(i) complexes, including two crystal structures of the new chiral pyridine-containing macrocyclic ligands (PC-type), and their use as catalysts in asymmetric cyclopropanation reactions are reported.     

A cation-directed switch of intermolecular spin-spin interaction of guanosine derivatives functionalized with open-shell units

The guanosine derivative 1 functionalized with the persistent radical unit 4-carbonyl-2,2,6,6-tetramethylpiperidin-1-oxyl in solution has no particular intermolecular spin-spin interactions; however, in the presence of potassium ions this compound can form a D4-symmetric octameric assembly [1(8)K]+ in which the nitroxyl moieties show a weak electron spin-spin exchange interaction. Since the relative geometry of the radicals is the outcome of K+-directed self-assembly, the spin-spin interaction can be suppressed by removing the alkaline ion.     

Threading, growth, and aggregation of pseudopolyrotaxanes

The formation of supramolecular inclusion compounds (pseudopolyrotaxanes) produced by cyclodextrins and polymers can be monitored through turbidimetry. In this paper, we studied the kinetics of the threading of linear poly(ethylene glycol) chains of different molecular weights and of a four-arm star-like polymer as a function of temperature. The main thermodynamic parameters are extracted. The aggregation and precipitation of pseudopolyrotaxanes are described in terms of the Avrami-Erofe'ev model, which provides relevant information on the mechanism of these processes. SAXS and TGA experiments confirm the structure and hydration of the final products obtained from the different polymers. A new hypothesis for the interaction between pseudopolyrotaxanes that leads to aggregation and precipitation, based on the spatial dielectric anisotropy, is proposed.     

Iodine Activation of Coordinated White Phosphorus: Formation and Transformation of 1,3-Dihydride-2-iodidecyclotetraphosphane

Double stabilization: Previously unknown polyphosphorus compounds are obtained by activation of white phosphorus (P(4) ) coordinated between two CpRu(PPh(3) )(2) moieties with iodine, and subsequent hydrolysis. The polyphosphorus compounds (P(4) H(2) I, P(4) H(2) , P(3) H(5) ; see scheme, Cp=cyclopentadienyl) are all stabilized by coordination to two ruthenium centers.     

Insights into the conformational switching mechanism of the human vascular endothelial growth factor receptor type 2 kinase domain

Human vascular endothelial growth factor receptor type 2 (h-VEFGR2) is a receptor tyrosine kinase involved in the angiogenesis process and regarded as an interesting target for the design of anticancer drugs. Its activation/inactivation mechanism is related to conformational changes in its cytoplasmatic kinase domain, involving first among all the αC-helix in N-lobe and the A-loop in C-lobe. Affinity of inhibitors for the active or inactive kinase form could dictate the open or closed conformation of the A-loop, thus making the different conformations of the kinase domain receptor (KDR) domain different drug targets in drug discovery. In this view, a detailed knowledge of the conformational landscape of KDR domain is of central relevance to rationalize the efficiency and selectivity of kinase inhibitors. Here, molecular dynamics simulations were used to gain insight into the conformational switching activity of the KDR domain and to identify intermediate conformations between the two limiting active and inactive conformations. Specific energy barriers have been selectively removed to induce, and hence highlight at the atomistic level, the regulation mechanism of the A-loop opening. The proposed strategy allowed to repeatedly observe the escape of the KDR domain from the DFG-out free energy basin and to identify rare intermediate conformations between the DFG-out and the DFG-in structures to be employed in a structure-based drug discovery process.     

PEGylation of Nanosubstrates (Titania) with Multifunctional Reagents: At the Crossroads between Nanoparticles and Nanocomposites

Titania (anatase) nanoparticles were successfully PEGylated through the use of catechol (dopamine)-terminated PEG derivatives. The resulting materials were characterized by excellent stability at neutral pH and extremely low toxicity (phagocytic and nonphagocytic cell lines). In particular, we focused on the comparison between mono- and bis-catechol PEGs. Due to the double terminal anchorage on the titania surface, bis-catechol ligands can produce chains differing from classical monoanchored PEG in conformation (horseshoe-shaped vs brush) and thus the possibility of interactions with biomolecules. At the same time, less than quantitative catechol binding may lead to the presence of dangling chains with unbound catechols which can polymerize and eventually produce PEG/titania nanocomposite colloids. Our results on double-functional PEG2000 show the latter to be the case. Pluronic F127 was also used as a bifunctional ligand, leading to nanocomposite aggregates with an even larger organic content.     

Inclusion compound based approach to arrays of artificial dipolar molecular rotors. A surface inclusion

We describe an approach to regular triangular arrays of dipolar molecular rotors based on insertion of dipolar rotator carrying shafts as guests into channels of a host, tris(o-phenylenedioxy)cyclotriphosphazene (TPP). The rotor guests can either enter the bulk of the host or stay at or near the surface, if a suitable stopper is installed at the end of the shaft. Differential scanning calorimetry, solid-state NMR, and powder X-ray diffraction were used to examine the insertion of a dipolar rotor synthesized for the purpose, 1-n-hexadecyl-12-(2,3-dichlorophenyl)-p-dicarba-closo-dodecaborane, and it was found that it forms a surface inclusion compound. Rotational barriers from 1.2 to 9 kcal/mol were found by dielectric spectroscopy and were attributed to rotors inserted into the surface to different degrees, some rubbing the surface as they turn.     

Analysis of selected pharmaceuticals in fish and the fresh water bodies directly affected by reclaimed water using liquid chromatography-tandem mass spectrometry

A comprehensive method for the analysis of 11 target pharmaceuticals representing multiple commonly used therapeutic classes was developed for biological tissues (fish), reclaimed water, and the surface water directly affected by irrigation with reclaimed water. One gram of fish tissue homogenate was extracted by accelerated solvent extraction with methylene chloride followed by mixed-mode cation exchange solid phase extraction (SPE) cleanup and analyzed by liquid chromatography-tandem mass spectrometry. Compared to previously reported methods, the protocol produces cleaner extracts resulting in lower method detection limits. Similarly, an SPE method based on Oasis HLB cartridges was used to concentrate and cleanup reclaimed and surface water samples. Among the 11 target compounds analyzed, trimethoprim, caffeine, sulfamethoxazole, diphenhydramine, diltiazem, carbamazepine, erythromycin, and fluoxetine were consistently detected in reclaimed water. Caffeine, diphenhydramine, and carbamazepine were consistently detected in fish and surface water samples. Bioaccumulation factors for caffeine, diphenhydramine, and carbamazepine in mosquito fish (Gambusia holbrooki) were calculated at 29?±?26, 821?±?422, and 108?±?144, respectively. This is the first report of potential accumulation of caffeine in fish from a water body directly influenced by reclaimed water.