Structure–Activity Studies on the Fluorescent Indicator in a Displacement Assay for the Screening of Small Molecules Binding to RNA

A series of xanthone and thioxanthone derivatives with aminoalkoxy substituents were synthesized as fluorescent indicators for a displacement assay in the study of small‐molecule–RNA interactions. The RNA‐binding properties of these molecules were investigated in terms of the improved binding selectivity to the loop region in the RNA secondary structure relative to 2,7‐bis(2‐aminoethoxy)xanthone (X2S) by fluorimetric titration and displacement assay. An 11‐mer double‐stranded RNA and a hairpin RNA mimicking the stem loop IIB of Rev response element (RRE) RNA of HIV‐1 mRNA were used. The X2S derivatives with longer aminoalkyl substituents showed a higher affinity to the double‐stranded RNA than the parent molecule. Introduction of a methyl group on the aminoethoxy moiety of X2S effectively modulated the selectivity to the RNA secondary structure. Methyl group substitution at the C1′ position suppressed the binding to the loop regions. Substitution with two methyl groups on the amino nitrogen atom resulted in reducing the affinity to the double‐stranded region by a factor of 40 %. The effect of methyl substitution on the amino nitrogen atom was also observed for a thioxanthone derivative. Titration experiments, however, suggested that thioxanthone derivatives showed a more prominent tendency of multiple binding to RNA than xanthone derivatives. The selectivity index calculated from the affinity to the double‐stranded and loop regions suggested that the N,N‐dimethyl derivative of X2S would be suitable for the screening of small molecules binding to RRE.     

Naphthyridine‐Benzoazaquinolone: Evaluation of a Tricyclic System for the Binding to (CAG)n Repeat DNA and RNA

The expansion of CAG repeats in the human genome causes the neurological disorder Huntington's disease. The small‐molecule naphthyridine‐azaquinolone NA we reported earlier bound to the CAG/CAG motif in the hairpin structure of the CAG repeat DNA. In order to investigate and improve NA ‐binding to the CAG repeat DNA and RNA, we conducted systematic structure‐binding studies of NA to CAG repeats. Among the five new NA derivatives we synthesized, surface plasmon resonance (SPR) assay showed that all of the derivatives modified from amide linkages in NA to a carbamate linkage failed to bind to CAG repeat DNA and RNA. One derivative, NBzA , modified by incorporating an additional ring to the azaquinolone was found to bind to both d(CAG)₉ and r(CAG)₉. NBzA binding to d(CAG)₉ was similar to NA binding in terms of large changes in the SPR assay and circular dichroism (CD) as well as pairwise binding, as assessed by electron spray ionization time‐of‐flight (ESI‐TOF) mass spectrometry. For the binding to r(CAG)₉, both NA and NBzA showed stepwise binding in ESI‐TOF MS, and NBzA ‐binding to r(CAG)₉ induced more extensive conformational change than NA ‐binding. The tricyclic system in NBzA did not show significant effects on the binding, selectivity, and translation, but provides a large chemical space for further modification to gain higher affinity and selectivity. These studies revealed that the linker structure in NA and NBzA was suitable for the binding to CAG DNA and RNA, and that the tricyclic benzoazaquinolone did not interfere with the binding.     

Structural Optimization of Photoswitch Ligands for Surface Attachment of α‐Chymotrypsin and Regulation of Its Surface Binding

A modified gold surface that allows photoregulated binding of α‐chymotrypsin has previously been reported. Here the development of this surface is reported, through the synthesis of a series of trifluoromethyl ketones and α‐keto esters containing the azobenzene group and a surface attachment group as photoswitch inhibitors of α‐chymotrypsin. All of the compounds are inhibitors of the enzyme, with activity that can be modulated by photoisomerization. The best photoswitch shows a reversible change in IC₅₀ inhibition constant of >5.3 times on photoisomerization. The trifluoromethyl ketone 1 exhibited excellent photoswitching and was attached to a gold surface in a two‐step procedure involving an azide–alkyne cycloaddition. The resulting modified surface bound α‐chymotrypsin to a degree that could be modulated by UV/Vis irradiation, showing “slow‐tight” enzyme binding as observed for inhibitors in solution.     

Identification and X‐ray Co‐crystal Structure of a Small‐Molecule Activator of LFA‐1‐ICAM‐1 Binding

Stabilization of protein–protein interactions by small molecules is a concept with few examples reported to date. Herein we describe the identification and X‐ray co‐crystal structure determination of IBE‐667, an ICAM‐1 binding enhancer for LFA‐1. IBE‐667 was designed based on the SAR information obtained from an on‐bead screen of tagged one‐bead one‐compound combinatorial libraries by confocal nanoscanning and bead picking (CONA). Cellular assays demonstrate the activity of IBE‐667 in promoting the binding of LFA‐1 on activated immune cells to ICAM‐1.     

Silver Nanoparticles Supported on CeO2‐SBA‐15 by Microwave Irradiation Possess Metal–Support Interactions and Enhanced Catalytic Activity

Metal–support interactions (MSIs) and particle size play important roles in catalytic reactions. For the first time, silver nanoparticles supported on CeO₂‐SBA‐15 supports are reported that possess tunable particle size and MSIs, as prepared by microwave (MW) irradiation, owing to strong charge polarization of CeO₂ clusters (i.e., MW absorption). Characterizations, including TEM, X‐ray photoelectron spectroscopy, and extended X‐ray absorption fine structure, were carried out to disclose the influence of CeO₂ contents on the Ag particle size, MSI effect between Ag nanoparticles and CeO₂‐SBA‐15 supports, and the strong MW absorption of CeO₂ clusters that contribute to the MSIs during Ag deposition. The Ag particle sizes were controllably tuned from 1.9 to 3.9 nm by changing the loading amounts of CeO₂ from 0.5 to 2.0 wt %. The Ag nanoparticle size was predominantly responsible for the high turnover frequency (TOF) of 0.41 min^?1 in ammonia borane dehydrogenation, whereas both particle size and MSIs contributed to the high TOF of 555 min^?1 in 4‐nitrophenol reduction for Ag/0.5CeO₂‐SBA‐15, which were twice as large as those of Ag/SBA‐15 without CeO₂ and Ag/CeO₂‐SBA‐15 prepared by conventional oil‐bath heating.     

Oxadiazole‐2‐thiol Adsorption on Gold Nanorods: A Joint Theoretical and Experimental Study by Using SERS,XPS, and DFT

The chemisorption of 1,3,4‐oxadiazole‐2‐thiol (ODT) on gold nanorods has been investigated by using surface‐enhanced Raman spectroscopy (SERS) and density functional theory (DFT). Although most of the SERS spectra have remarkable similarity to the normal Raman spectra of the pure analyte, the adsorption of ODT on a gold surface leads to a drastic change in its Raman spectrum and distinct vibrational features are obtained with gold nanorods and spherical nanoparticles. Simulated Raman spectra for hybrid systems that consist of an oxadiazole moiety coordinated to a Au₂₀ gold cluster provided valuable information about the coordination mode and enabled us to assign vibration modes.     

Spectroelectrochemical Evaluation of a ZnO Optically Transparent Electrode Prepared by the Spin‐spray Technique

We present a novel zinc oxide (ZnO) optically transparent electrode (OTE) prepared by the spin‐spray technique for spectroelectrochemistry. The spin‐spray technique can deposit ZnO film at a low cost, high rate deposition, and at a low temperature (<100 °C) in a single step. This new technique provides good optical transparency and electrical conductivity for ZnO. The electrochemical and spectroelectrochemical properties of the ZnO electrode were investigated for varying thicknesses of ZnO using methylene blue as a redox indicator. A ZnO OTE chip that includes three electrodes on a glass chip was developed for thin‐layer spectroelectrochemistry. Moreover, the ZnO films were successfully applied in an electrochemical‐localized surface plasmon resonance (LSPR) method for methylene blue detection by using them as a transparent conducting substrate for loading gold nanoparticles.     

Electrochemically controlled detection of adrenaline on poly(2‐aminobenzylamine) thin films by surface plasmon resonance spectroscopy and quartz crystal microbalance

In this study, we present an electrochemically controlled surface plasmon resonance (EC‐SPR) biosensor to detect adrenaline on poly(2‐aminobenzylamine) (P2ABA) thin films. The P2ABA thin films are stable and display electroactivity in a neutral PBS solution. Specific detection of adrenaline was performed on P2ABA thin films because the benzylamine groups in the P2ABA structure could specifically react with adrenalines. Adrenaline was detected in real time by EC‐SPR spectroscopy, which provides an EC‐SPR reflectivity change on the P2ABA thin film upon adrenaline injection. The measured responses were quite different from those for uric acid and ascorbic acid, which are major interferences in adrenaline detection. The electrochemically applied potential facilitates the specific detection of adrenaline. In addition, the detection of adrenaline on the P2ABA thin films was investigated by a quartz crystal microbalance technique. The detection limit for adrenaline at open circuit potential was 10 pM. The present study provides a useful information on the detection of adrenaline on the P2ABA thin films. Copyright © 2013 John Wiley & Sons, Ltd.     

Nucleation and growth of Ge nanoclusters on the Si(111)‐(7 × 7) surface studied by scanning tunneling microscopy

Nucleation and growth of two‐dimensional Ge nanoclusters on the Si(111)‐(7 × 7) surface at elevated substrate temperatures have been studied using scanning tunneling microscopy. The uniformity of the Ge nanoclusters is improved with the increase of substrate temperature, and ordered Ge nanoclusters are formed on the faulted and unfaulted halves of (7 × 7) unit cell at substrate temperature of 200 °C. It is proposed that the Ge nanoclusters consist of six Ge atoms with three on top of the center adatoms and others on the rest atoms within one half of a unit cell. Copyright © 2014 John Wiley & Sons, Ltd.     

Structural analysis of 3‐α‐acetyl‐20(29)‐lupene‐24‐oic acid,a novel pentacyclic triterpene isolated from the gum resin of Boswellia serrata,by NMR spectroscopy

3α‐Acetyl‐20(29)‐lupene‐24‐oic acid ( 1 ) was isolated from the gum resin of Boswellia serrata. Its presence evidently suggests, that the oxidosqualene triterpene pathway of Boswellia serrata closely resembles the biosynthetic route already found in other plants. Complete ¹H and ¹³C spectral assignments were derived from 1D and 2D NMR spectra. This is the first compound with the lupene backbone combining a 3α‐hydroxy or 3α‐acetyl group with the 24‐carboxyl group, a configuration which is typical of the classical boswellic acids. Copyright © 2003 John Wiley & Sons, Ltd.     

Non‐Fouling Character of Poly[2‐(methacryloyloxy)ethyl Phosphorylcholine]‐Modified Gold Surfaces Fabricated by the ‘Grafting to’ Method: Comparison of its Protein Resistance with Poly(ethylene glycol)‐Modified Gold Surfaces

Poly[2‐(methacryloyloxy)ethyl phosphorylcholine] ‐modified gold surfaces, which have been newly prepared by a ‘grafting to’ method using a series of monosulfanyl‐terminated PMPC, are characterized by protein adsorption experiments based on surface plasmon resonance spectroscopy and ellipsometry measurements. The extent of BSA adsorption on PMPC‐modified surfaces was systematically reduced for thicker PMPC layers, thus the number of MPC units on the gold surface appears to be an important factor for the excellent protein resistance offered by PMPC‐modified gold surfaces fabricated by the ‘grafting to’ method, which is sharp contrast to that of PEG tethered chains.

     

Direct versus Hydrogen‐Assisted CO Dissociation on the Fe (100) Surface: a DFT Study

CO dissociation: Three most probable pathways to CO dissociation on the Fe?(100) surface exist: a) direct, CO→C+O (-) and H-assisted b) H+CO?HCO→CH+O (-) or c) CO+H?COH→C+OH (-). Under high hydrogen pressure conditions and highly occupied surfaces the formation of HCO and subsequent dissociation to CH+O may at best compete with direct dissociation.     

Theoretical Study of Substituent Effects on Geometric and Spectroscopic Parameters (IR, 13C, 29Si NMR) and Energy Decomposition Analysis of the Bonding in Molybdenum Silylidyne Complexes CpMo(CO)2(≡Si‐para‐C6H4X)

In this study, we report the substituent effect on the structures, frontier orbital analysis, and spectroscopic properties (IR , ¹³C , ²⁹Si NMR ) in the molybdenum silylidyne complexes CpMo (CO )₂(≡Si‐para ‐C₆H₄X ) (X = H, F, Cl, CN , NO₂ , Me, OMe , NH₂ , NHMe ) using MPW1PW91 quantum chemical calculations. The calculated structural parameters and spectral parameters are compatible with the experimental values in similar complexes. The nature of the chemical bond between the [Cp(OC ) ₂Mo ]⁻ and [Si‐para ‐C₆H₄X ]⁺ fragments was explored with energy decomposition analysis (EDA ). The percentage composition in terms of the defined groups of frontier orbitals for CpMo (CO )₂(≡Si‐para ‐C₆H₄X ) complexes was investigated to explore the character of the metal–ligand bonds. The linear correlations between the properties and Hammett constants (σ _p) were illustrated. Natural bond orbital analysis (NBO ) was used to illustrate the electronic structure of the complexes.     

Biomimetic Interaction between FeII and O2: Effect of the Second Coordination Sphere on O2 Binding to FeII Complexes: Evidence of Coordination at the Metal Centre by a Dissociative Mechanism in the Formation of μ‐Oxo Diferric Complexes

We report that the formation of μ‐oxo diferric compounds from O₂ and FeCl₂ complexes within the tris(2‐pyridylmethyl)amine series (N. K. Thallaj et al. Chem. Eur. J., 2008 , 14, 6742–6753) involves coordination of O₂ to the metal centre and that this reaction occurs following initial dissociation of the bound equatorial chloride anion. We also report evidence of the formation of a reduced form of dioxygen by an inner‐sphere mechanism, thus leading to modification of the ligand. The solid‐state structures of [FeCl₂L] complexes (L¹=mono(α‐pivalamidopyridylmethyl)bis(2‐pyridylmethyl)amine, L²=mono(α‐pivalesteropyridylmethyl)bis(2‐pyridylmethyl)amine, L³=bis(α‐pivalamidopyridylmethyl)mono(2‐pyridylmethyl)amine are described, and spectroscopic data support the structural retention in solution. In [FeCl₂L³], the two amide hydrogen atoms stabilise the equatorial chloride anion in such a way that its exchange by a weak ligand is impossible: [FeCl₂L³] is perfectly oxygen‐stable. In [FeCl₂L²], the equatorial chloride anion is completely free to move and coordination of O₂ can take place. The reaction product with [FeCl₂L²] is a μ‐oxo diferric complex in which the ester function has been transformed into a phenol group. This conversion can be seen as a hydrolysis reaction in basic medium, hence supporting the initial formation of a reduced form of dioxygen in the medium. Complex [FeCl₂L¹] exhibits a very weak reactivity with O₂, in line with a semistabilised equatorial chloride counteranion.     

Study on δ‐form complex in syndiotactic polystyrene–organic molecules systems. IV. Formation of complexes with a mixture of solvents and structural changes during the sorption of solvents by syndiotactic polystyrene mesophase membranes

The syndiotactic polystyrene (sPS) δ form was crystallized from mixtures with different compositions of p‐chlorotoluene–chlorobenzene (p‐CT–CB) and p‐chlorotoluene–1,1,2‐trichloroethane (p‐CT–TCE). The presence of the δ form and TTGG helical conformation was confirmed by Fourier transform infrared and wide‐angle X‐ray diffraction (WAXD) analyses. In sPS/p‐CT–CB and sPS/p‐CT–TCE δ‐form membranes, the relative absorbance (RA) of the p‐chlorotoluene (p‐CT) solvent peak was very high even at very low concentrations of p‐CT in comparison with the RA of higher concentrations of chlorobenzene (CB) or 1,1,2‐trichloroethane (TCE) in the mixtures. However, the RAs of both CB and TCE solvent peaks decreased with decreasing concentrations of CB and TCE in the mixtures. A negligible decrease in the RA of the TTGG helical content was observed with a decreasing concentration of CB or TCE. The WAXD results showed that the 2θ peak positions of the [010] and [ 10] planes of the sPS/p‐CT–CB and sPS/p‐CT–TCE δ‐form membranes appeared in the same position and were almost equal to those of the sPS–p‐CT δ‐form membrane. The mesophases of the sPS–p‐CT [p‐CT (A‐M)] and sPS–TCE [TCE (A‐M)] membranes were used for the sorption studies with different concentrations of various solvents. The sorption amount of aromatic solvents by both p‐CT (A‐M) and TCE (A‐M) mesophase membranes was higher than that of aliphatic solvents, regardless of the size, shape, and nature of the molecular cavity. The 2θ peak of the [010] plane of the sPS membranes slowly approached the original δ‐form value when the sPS mesophase membranes were immersed in various solvents of different concentrations for 48 h. The shifting of the 2θ peak of the [010] plane to the original δ form depended on the nature and concentration of the immersion solvents. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2380–2387, 2005