Synthesis and evaluation of derrubone and select analogues

Recently, we reported that the natural product derrubone exhibits Hsp90 inhibitory activity. Due to its unique architectural scaffold and proposed rapid assembly, the synthesis of this natural product was pursued with the aim of identifying structure--activity relationships. Synthesis of the natural product was accomplished in eight highly convergent steps, which led to a facile method for the construction of related compounds. Biological evaluation of derrubone and its analogues identified several compounds that exhibit low micromolar inhibitory activity against breast and colon cancer cell lines.     

Elucidating the Effect of Ion Exchange Protocol on the Copper Exchange Efficacy,Copper Siting,and SCR activity in Cu-SSZ-13

The influence of the copper ion exchange protocol on SCR activity of SSZ-13 is quantified. Using the same parent SSZ-13 zeolite, four exchange protocols are used to assess how exchange protocol impacts metal uptake and SCR activity. Large differences in the SCR activity, nearly 30 percentage points at 160 °C at constant copper content, are observed for different exchange protocols implying that different exchange protocols lead to different copper species. Hydrogen temperature programmed reduction on selected samples and infrared spectroscopy of CO binding corroborates this conclusion as the reactivity at 160 °C correlates with the intensity of the IR band at 2162 cm⁻¹. DFT-based calculations show that such an IR assignment is consistent with CO adsorbed on a Cu(I) cation within an eight-membered ring. This work shows that SCR activity can be influenced by the ion exchange process even when different protocols lead to the same metal loading. Perhaps most interesting, a protocol used to generate Cu-MOR for methane to methanol studies led to the most active catalyst both on a unit mass or unit mole copper basis. This points to a yet not recognized means to tailor catalyst activity as the open literature is silent on this issue.     

Dynamic self-assembly in ensembles of camphor boats

Millimeter-sized gel particles loaded with camphor and floating at the interface between water and air generate convective flows around them. These flows give rise to repulsive interparticle interactions, and mediate dynamic self-assembly of nonequilibrium particle formations. When the numbers of particles, N, are small, particle motions are uncorrelated. When, however, N exceeds a threshold value, particles organize into ordered lattices. The nature of hydrodynamic forces underlying these effects and the dynamics of the self-assembling system are modeled numerically using Navier-Stokes equations as well as analytically using scaling arguments.     

Rapid,single-step nucleic acid detection

A rapid detection method for nucleic acid based on bioluminescence resonance energy transfer (BRET) from the luminescence donor Renilla luciferase to an acceptor quantum dot upon oligonucleotide probe hybridization has been developed. Utilizing a competitive assay, we detected the target nucleic acid by correlating the BRET signal with the amount of target present in the sample. This method allows for the detection of as little as 4 pmol (20 nM) of nucleic acid in a single-step, homogeneous format both in vitro in a buffer matrix as well as in a cellular matrix. Using this method, one may perform nucleic acid detection in as little as 30 min, showing much improvement over time-consuming blotting methods and solid-phase methods which require multiple wash steps to remove unbound probe. This is the first report on the use of quantum dots as a BRET acceptor in the development of a nucleic acid hybridization assay. An erratum to this article can be found at     

Thermal desorption of hydrogen from ammonia borane: unexpected role of homopolar B-H···H-B interactions

The solid-state structure of ammonia borane is held together by an intricate N-H···H-B proton-hydride bonding network. These intermolecular interactions have long been considered to mediate the release of hydrogen from this material. Here we reveal the silent but important role played by B-H···H-B interactions in the thermal decomposition of this leading hydrogen storage candidate.     

High-precision tracking with non-blinking quantum dots resolves nanoscale vertical displacement

Novel non-blinking quantum dots (NBQDs) were utilized in three-dimensional super-localization, high-precision tracking applications under an automated scanning-angle total internal reflection fluorescence microscope (SA-TIRFM). NBQDs were randomly attached to stationary microtubules along the radial axis under gliding assay conditions. By automatically scanning through a wide range of incident angles with different evanescent-field layer thicknesses, the fluorescence intensity decay curves were obtained. Fit with theoretical decay functions, the absolute vertical positions were determined with sub-10-nm localization precision. The emission intensity profile of the NBQDs attached to kinesin-propelled microtubules was used to resolve the self-rotation of gliding microtubules within a small vertical distance of ~50 nm. We demonstrate the applicability of NBQDs in high-precision fluorescence imaging experiments.     

Effect of axially projected oligothiophene pendants and nitro-functionalized diimine ligands on the lowest excited state in cationic Ir(III) bis-cyclometalates

The novel terthiophene (3T) oligomer 6 and a series of cationic Ir(III) bis-cyclometalates [Ir(C^N)(2)(N^N)]PF(6) 9-12 were prepared. The synthesis, characterization, electrochemical, and photophysical properties are reported. The cyclometalating ligands (C^N) are 2-phenylpyridinato (ppy) or the 3T oligomer (3T-ppy), asymmetrically capped in the 5 and 5" positions with the ppy and mesityl groups. The diimine ligands (N^N) are 2,2'-bipyridine (bpy) or 4-NO(2)-bipyridine (4-NO(2)-bpy). Hybrid metal-organic complexes 11 and 12 bear 3T-pendants ligated through the ppy cap, 10 and 12 contain NO(2) functionalized diimines, whereas 9 contains neither. Structural characterization of 10 by single crystal X-ray diffraction confirms the presence of the NO(2) substituent and pseudo-octahedral coordination geometry about the Ir(III) ion. Cyclic voltammetry highlights the large electron withdrawing effect of the NO(2) substituent, providing an 850 mV shift toward lower potentials for the first diimine centered reduction of 10 and 12. Strong overlap of the intense π → π* absorptions of the 3T-pendants with Ir(III) charge transfer bands is evident in complexes of 11 and 12, precluding the possibility for selective excitation of either chromophore. Photoexcitation (λ(ex) = 400 nm) of the series affords strong luminescence from the 3T oligomer 6 and the unsubstituted 9, with φ(em) = 0.11. In stark contrast the NO(2) and 3T functionalized complexes 10-12 display near total quenching of luminescence. Computations of the ground and excited state electronic structure using density functional theory (DFT) and time-dependent DFT (TD-DFT) indicate that both the NO(2) and 3T substituents play an important role in excited state deactivation of complexes 10-12. A substantial electronic contribution of the NO(2) substituent results in stabilization of the diimine based molecular orbital (MO) and offers an efficient nonradiative decay pathway for the excited state. Spin-orbit coupling effects of the Ir(III) ion lead to efficient population of the low lying, nonluminescent, triplet states centered on the 3T-pendants.     

Quantitative analysis of the role played by poly(vinylpyrrolidone) in seed-mediated growth of Ag nanocrystals

This article presents a quantitative analysis of the role played by poly(vinylpyrrolidone) (PVP) in seed-mediated growth of Ag nanocrystals. Starting from Ag nanocubes encased by {100} facets as the seeds, the resultant nanocrystals could take different shapes depending on the concentration of PVP in the solution. If the concentration was above a critical value, the seeds simply grew into larger cubes still enclosed by {100} facets. When the concentration fell below a critical value, the seeds would evolve into cuboctahedrons enclosed by a mix of {100} and {111} facets and eventually octahedrons completely covered by {111} facets. We derived the coverage density of PVP on Ag(100) surface by combining the results from two measurements: (i) cubic seeds were followed to grow at a fixed initial concentration of PVP to find out when {111} facets started to appear on the surface, and (ii) cubic seeds were allowed to grow at reduced initial concentrations of PVP to see at which concentration {111} facets started to appear from the very beginning. We could calculate the coverage density of PVP from the differences in PVP concentration and the total surface area of Ag nanocubes between these two samples. The coverage density was found to be 140 and 30 repeating units per nm(2) for PVP of 55,000 and 10,000 g/mol in molecular weight, respectively, for cubic seeds of 40 nm in edge length. These values dropped slightly to 100 and 20 repeating units per nm(2), respectively, when 100 nm Ag cubes were used as the seeds.     

Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I of human serum albumin

Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration calorimetry (ITC). The structure of the docked warfarin anion (W-) to Site I is similar to that revealed by X-ray crystallography, with a calculated binding constant of 5.8 x 10(5) M(-1). ITC experiments (pH 7.13 and I = 0.1) carried out in three different buffers (MOPs, phosphate and Tris) reveal binding of W- is accompanied by uptake of 0.30+/-0.02 protons from the solvent. This measurement suggests that the binding of W- is stabilized by an ion-pair interaction between protonated H242 and the phenoxide group of W-.