Molecule motion at polymer brush interfaces from single‐molecule experimental perspectives

Polymer brushes have been widely used as functional surface coatings for broad applications including antifouling, energy storage, and lubrications. Understanding the molecule dynamics at polymer brush interfaces is important in unraveling the structure–property relationships in these materials and establishing a new materials design paradigm of novel functional polymer thin films with efficient interfacial transport. By applying modern fluorescence‐based single‐molecule spectroscopic and microscopic techniques, molecule dynamics at varied polymer brush interfaces have been experimentally investigated in recent years. New insights are given to the understandings of some unique and unusual materials properties of polymer brush thin films. This review summarizes some recent studies of molecular diffusion at polymer brush interfaces, highlights some new understandings of the interfacial properties of polymer brushes, and discusses future research opportunities in this field. © 2013 Wiley Periodicals, Inc. J. Polym. Sci. Part B: Polym. Phys. 2014 , 52, 85–103     

A real-time,fluorescence-based assay for Rho-associated protein kinase activity

Inhibitors of Rho-associated protein kinase (ROCK) enzymatic activity have been shown to reduce the invasive phenotype observed in metastatic hepatocellular carcinoma (HCC). We describe the design, synthesis, and evaluation of a direct probe for ROCK activity utilizing a phosphorylation-sensitive sulfonamido-oxine fluorophore, termed Sox. The Sox fluorophore undergoes an increase in fluorescence upon phosphorylation of a proximal amino acid via chelation-enhanced fluorescence (CHEF, ex. = 360 nm and em. = 485 nm), allowing for the direct visualization of the rate of phosphate addition to a peptide substrate over time. Our optimal probe design, ROCK-S1, is capable of sensitively reporting ROCK activity with a limit of detection of 10 pM and a high degree of reproducibility (Z’-factor = 0.6 at 100 pM ROCK2). As a proof-of-principle for high-throughput screening (HTS) we demonstrate the ability to rapidly assess the efficacy of a 78 member, small molecule library against ROCK2 using a robotics platform. We identify two previously unreported ROCK2 inhibitor scaffolds, PHA665752 and IKK16, with IC₅₀ values of 3.6 μM and 247 nM respectively. Lastly, we define conditions for selectively monitoring ROCK activity in the presence of potential off-target enzymes (PKCα, PKA, and PAK) with similar substrate specificities.     

Single‐Site Zeolite‐Anchored Organoiridium Carbonyl Complexes: Characterization of Structure and Reactivity by Spectroscopy and Computational Chemistry

A family of HY zeolite‐supported cationic organoiridium carbonyl complexes was formed by reaction of Ir(CO)₂(acac) (acac=acetylacetonate) to form supported Ir(CO)₂ complexes, which were treated at 298 K and 1 atm with flowing gas‐phase reactants, including C₂H₄, H₂, ¹²CO, ¹³CO, and D₂O. Mass spectrometry was used to identify effluent gases, and infrared and X‐ray absorption spectroscopies were used to characterize the supported species, with the results bolstered by DFT calculations. Because the support is crystalline and presents a nearly uniform array of bonding sites for the iridium species, these were characterized by a high degree of uniformity, which allowed a precise determination of the species involved in the replacement, for example, of one CO ligand of each Ir(CO)₂ complex with ethylene. The supported species include the following: Ir(CO)₂, Ir(CO)(C₂H₄)₂, Ir(CO)(C₂H₄), Ir(CO)(C₂H₅), and (tentatively) Ir(CO)(H). The data determine a reaction network involving all of these species.     

Capturing Transient Endoperoxide in the Singlet Oxygen Oxidation of Guanine

The chemistry of singlet O₂ toward the guanine base of DNA is highly relevant to DNA lesion, mutation, cell death, and pathological conditions. This oxidative damage is initiated by the formation of a transient endoperoxide through the Diels–Alder cycloaddition of singlet O₂ to the guanine imidazole ring. However, no endoperoxide formation was directly detected in native guanine or guanosine, even at ?100 °C. Herein, gas‐phase ion–molecule scattering mass spectrometry was utilized to capture unstable endoperoxides in the collisions of hydrated guanine ions (protonated or deprotonated) with singlet O₂ at ambient temperature. Corroborated by results from potential energy surface exploration, kinetic modeling, and dynamics simulations, various aspects of endoperoxide formation and transformation (including its dependence on guanine ionization and hydration states, as well as on collision energy) were determined. This work has pieced together reaction mechanisms, kinetics, and dynamics data concerning the early stage of singlet O₂ induced guanine oxidation, which is missing from conventional condensed‐phase studies.     

Efficient synthesis of terminal 4-methylumbelliferyl labeled 5-fluoro-2′-deoxyuridine-5′-O-tetraphosphate (Um-PPPP-FdU): a potential probe for homogenous fluorescent assay

Efficient synthesis of 5-fluoro-2′-deoxyuridine-5′-O-tetraphosphate bearing 4-methylumbelliferyl label on the terminal phosphate is reported. This compound has the potential as a promising probe molecule for homogenous fluorescent polymerase assay. This class of compounds will aid in quantification of cellular internalization and DNA incorporation of nucleotide based chemotherapeutic agents to offer mechanistic insights.     

外电场对2-氟-5-溴吡啶分子结构与电子光谱影响的研究

采用密度泛函B3LYP方法，在6-311++g(3df,3pd)基组水平上优化了不同外电场下2-氟-5-溴吡啶分子的基态稳定构型、电偶极矩和分子的总能量，在此基础上利用杂化CIS方法研究了外电场下2-氟-5-溴吡啶分子的前9个激发态的激发能、波长和振子强度受外电场的影响规律。结果表明：5C-9Br和3C-10F间键长受到X轴向外场影响最大，随着外电场的继续增加，可能最先趋于断裂；在外电场F=-0.005a.u.时总能量达到最大，而偶极矩达到最小；LUMO能级受外场影响较大，HOMO能级受外电场影响较小；激发波长、振子强度也受外电场影响，但随电场变化比较复杂。     

Assessment of the nature of interactions of cations with cycloheptatriene derivatives using change in the aromaticity: Comparison with electron density and NBO results

ABSTRACT

Interactions of cycloheptatriene derivatives, C₇H₆X, (X?=?NH, PH, AsH, O, S, Se) with the cations H⁺, CH₃⁺, Cu⁺, Al⁺, Li⁺, Na⁺, and K⁺ are studied using B3LYP functional and 6-311++G(d,p) basis set. The calculated gas-phase cation affinities (CA) and cation basicities (CB) for all molecules decrease as H⁺ > CH₃⁺ > Cu⁺ > Al⁺ > Li⁺ > Na⁺ > K⁺. We used the induced aromaticity in the 7-membered ring of C₇H₆X upon interaction with the cations, M⁺, as a measure of C₇H₆X/M⁺ interaction. Nucleus-independent chemical shift (NICS) and harmonic oscillator model of aromaticity (HOMA) were used as two indices of aromaticity. The highest and lowest induced aromaticities were observed for interactions of H⁺ and K⁺, respectively. Also, the aromaticity induced by interaction with a cation in C₇H₆AsH and C₇H₆PH was larger than that in C₇H₆NH and C₇H₆O. Hence, the aromaticity was considered as a measure of covalency for the C₇H₆X/M⁺ interactions showing a rational dependence on both the molecule and cation. The nature of the interactions was also assessed using electron density, charge distribution analysis and NBO calculations. The results of the aromaticity indices, NICS and HOMA, were compared with the electron density and NBO results.