Mass spectrometric studies of potent inhibitors of farnesyl protein transferase--detection of pentameric noncovalent complexes

Farnesyl protein transferase (FPT) inhibition is an interesting and promising approach to noncytotoxic anticancer therapy. Research in this area has resulted in several orally active compounds that are in clinical trials. Electrospray ionization (ESI) time-of-flight mass spectrometry (TOF-MS) was used for the direct detection of a 95 182 Da pentameric noncovalent complex of alpha/beta subunits of FPT containing Zn, farnesyl pyrophosphate (FPP) and SCH 66336, a compound currently undergoing phase III clinical trials as an anticancer agent. It was noted that the desalting of protein samples was an important factor in the detection of the complex. This study demonstrated that the presence of FPP in the system was necessary for the detection of the FPT-inhibitor complex. No pentameric complex was detected in the spectrum when the experiment was carried out in the absence of the FPP. An indirect approach was also applied to confirm the noncovalent binding of SCH 66336 to FPT by the use of an off-line size exclusion chromatography followed by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) for the detection of the inhibitor.     

Iron(III) metallomesogen of [N2O2] donor Schiff base ligand containing 4-substituted alkoxy chains

Two new square pyramidal iron(III)-complexes of ‘salen’-type Schiff base ligands containing 4-substituted long alkoxy arms on the aromatic rings, [Fe(4-C₁₆H₃₃O)₂salcn)]Cl and [Fe(4-C₁₆H₃₃O)₂salophen)]Cl {salcn = N,N?-cyclohexanebis(salicylideneiminato) and salophen = N,N?-phenylenebis(salicylideneiminato)}, have been successfully synthesised, and their mesomorphic property investigated. The ligands and complexes were characterised by elemental analyses, UV–Vis, FT-IR, ESI–MS, ¹H and ¹³C NMR (for ligands only). The phase behaviour of the iron(III) complexes were ascertained by differential scanning calorimetry, polarising optical microscopy and variable temperature PXRD study. Ligands are non-mesomorphic, however, mesomorphism got induced upon complexation with the iron(III) centre. X-ray diffraction study revealed a layer-like arrangement of the five coordinated mesomorphic iron(III) complexes. The mesophase is stable over a wide range of temperature. The density functional theory calculations were carried out using Gaussian 09 program at B3LYP level using unrestricted 6–31G (d, p) basis set to obtain the optimised geometry of the iron(III) complexes.     

Ligand-dependent particle size control of PbSe quantum dots

Colloidal solutions of monodisperse PbSe quantum dots (QDs) were synthesized by a hot solution chemical method from a reaction mixture of lead oleate and TOPSe (TOP: tri-n-octylphosphine). The synthesis was carried out at a fixed temperature (170 degrees C) and time, while the particle sizes of the PbSe QDs were controlled by using two different kinds of organic ligands with varied chain length. It was seen that the tuning of PbSe QDs are possible by using the proper molar ratio of the co-ligands, such as acetic acid or hexanoic acid, at a fixed reaction temperature and time, verified by TEM and XRD as well as NIR absorption analysis. The effects of different organic acids were studied and the role of additional organic acids might be due to the extent of ligand exchange efficiency between the Pb oleate and acetic/hexanoic acid in the initial stage, which is caused by the steric hindrance effects of the acids.     

Glycosylated N-sulfonylamidines: highly efficient copper-catalyzed multicomponent reaction with sugar alkynes, sulfonyl azides, and amines

Copper-catalyzed multicomponent reactions with sugar alkynes, sulfonyl azides, and amines to furnish glycosylated N-sulfonylamidines are reported. The reaction is established to be general in terms of different combinations of sugar alkyne, sulfonyl azide, and amines.     

Controlled Synthesis of Nanoporous Nickel Oxide with Two‐Dimensional Shapes through Thermal Decomposition of Metal–Cyanide Hybrid Coordination Polymers

The urgent need for nanoporous metal oxides with highly crystallized frameworks is motivating scientists to try to discover new preparation methods, because of their wide use in practical applications. Recent work has demonstrated that two‐dimensional (2D) cyanide‐bridged coordination polymers (CPs) are promising materials and appropriate for this purpose (Angew. Chem. Int. Ed.­ 2013 , 52, 1235). After calcination, 2D CPs can be transformed into nanoporous metal oxides with a highly accessible surface area. Here, this strategy is adopted in order to form 2D nanoporous nickel oxide (NiO) with tunable porosity and crystallinity, using trisodium citrate dihydrate as a controlling agent. The presence of trisodium citrate dihydrate plays a key role in the formation of 2D nanoflakes by controlling the nucleation rate and the crystal growth. The size of the nanoflakes gradually increases by augmenting the amount of trisodium citrate dihydrate in the reaction. After heating the as‐prepared CPs in air at different temperatures, nanoporous NiO can be obtained. During this thermal treatment, organic units (carbon and nitrogen) are completely removed and only the metal content remains to take part in the formation of nanoporous NiO. In the case of large‐sized 2D CP nanoflakes, the original 2D flake‐shapes are almost retained, even after thermal treatment at low temperature, but they are completely destroyed at high temperature because of further crystallization in the framework. Nanoporous NiO with high surface area shows significant efficiency and interesting results for supercapacitor application.     

Seven-coordinate anion complex with a tren-based urea: binding discrepancy of hydrogen sulfate in solid and solution states

Structural characterization of a hydrogen sulfate complex with a tren-based urea suggests that the anion is coordinated with six NH···O bonds (d(N···O) = 2.857 (3) to 3.092 (3) ?) and one OH···O bond (d(O···O) = 2.57 (2) ?) from three receptors; however, in solution the anion is bound within the pseudo-cavity of one receptor.     

Solution-phase synthesis of silver nanodiscs in HPMC-matrix and simulation of UV-vis extinction spectra using DDA based method

Present investigation demonstrates a very simple seed-mediated route, using hydroxypropyl methyl cellulose (HPMC) as stabilizing agent, for the synthesis of silver nanodiscs in aqueous solution. Central to the concept of seed-mediated growth of nanoparticles is that small nanoparticle seeds serve as nucleation centres to grow nanoparticles to a desired size and shape. It is found that the additional citrate ions in the growth solution play the pivotal role in controlling the size of silver nanodiscs. Similar to the polymers in the solution, citrate ions could be likewise dynamically adsorbed on the growing silver nanoparticles and promote the two-dimensional (2D) growth of nanoparticles. Morphological, structural, and spectral changes associated with the seed-mediated growth of the nanoparticles in the presence of HPMC are characterized using UV–vis and TEM spectroscopic studies. Metal nanoparticles have received increasing attention for their peculiar capability to control local surface plasmon resonance (LSPR) when interacting with incident light waves. Extensive simulation study of the UV–vis extinction spectra of our synthesized silver nanodiscs has been carried out using discrete dipole approximation (DDA) methodology.     

DNA tetraplex structure formation from human telomeric repeat motif (TTAGGG):(CCCTAA) in nanocavity water pools of reverse micelles

In an equimolar ratio the human telomeric oligonucleotides d[AGGG(TTAGGG)(3)] and d[(CCCTAA)(3)CCCT] formed mixed structures of duplex and tetraplex in bis(2-ethylhexyl)sulfosuccinate reverse micelles; only the duplex was observed in aqueous buffer. This finding suggests that heterogeneous confined media in the cell nucleus might induce a significant fraction of the telomeric region of genomic DNA to adopt non-canonical tetraplex structure.     

An improved synthesis of pentacene: rapid access to a benchmark organic semiconductor

Pentacene is an organic semiconductor used in a variety of thin-film organic electronic devices. Although at least six separate syntheses of pentacene are known (two from dihydropentacenes, two from 6,13-pentacenedione and two from 6,13-dihydro-6,13-dihydroxypentacene), none is ideal and several utilize elevated temperatures that may facilitate the oxidation of pentacene as it is produced. Here, we present a fast (-2 min of reaction time), simple, high-yielding (≥ 90%), low temperature synthesis of pentacene from readily available 6,13-dihydro-6,13-dihydroxypentacene. Further, we discuss the mechanism of this highly efficient reaction. With this improved synthesis, researchers gain rapid, affordable access to high purity pentacene in excellent yield and without the need for a time consuming sublimation.