Influence of molecular geometry on the adsorption orientation for oligophenylene-ethynylenes on Au(111)

The adsorption structures formed from a class of oligophenylene-ethynylenes on Au(111) under ultrahigh vacuum conditions is compared based on high-resolution scanning tunneling microscopy (STM) measurements. The molecules consist of three or four benzene rings connected by ethynylene spokes and are all functionalized identically with an aldehyde, a hydroxyl, and a bulky tert-butyl group. Compounds with the conjugated spokes placed in the para, meta, and threefold configurations were previously found to exclusively form molecular layers with flat-lying adsorption geometries. In contrast, the associated compound with spokes in the ortho configuration surprisingly differs in its adsorption by forming only structures with an upright adsorption orientation. The packing density for the structures formed by the compound with the ortho configuration is less dense than that in conventional self-assembled monolayers while still keeping the conducting backbone in an upright orientation. These structures are thus interesting from the perspective of performing single-molecule conduction measurements on the oligophenylene-ethynylene backbones.     

Peptide‐Directed DNA‐Templated Protein Labelling for The Assembly of a Pseudo‐IgM

The development of methods for conjugation of DNA to proteins is of high relevance for the integration of protein function and DNA structures. Here, we demonstrate that protein‐binding peptides can direct a DNA‐templated reaction, selectively furnishing DNA–protein conjugates with one DNA label. Quantitative conversion of oligonucleotides is achieved at low stoichiometries and the reaction can be performed in complex biological matrixes, such as cell lysates. Further, we have used a star‐like pentameric DNA nanostructure to assemble five DNA–Rituximab conjugates, made by our reported method, into a pseudo‐IgM antibody structure that was subsequently characterized by negative‐stain transmission electron microscopy (nsTEM) analysis.     

DNA-programmed assembly of nanostructures

DNA is a unique material for nanotechnology since it is possible to use base sequences to encode instructions for assembly in a predetermined fashion at the nanometre scale. Synthetic oligonucleotides are readily obtained by automated synthesis and numerous techniques have been developed for conjugating DNA with other materials. The exact spatial positioning of materials is crucial for the future development of complex nanodevices and the emerging field of DNA-nanotechnology is now exploring DNA-programmed processes for the assembly of organic compounds, biomolecules, and inorganic materials.     

Electrochemical properties of mixed self-assembled monolayers on gold electrodes containing mercaptooctylhydroquinone and alkylthiols

Mixed self-assembled monolayers of 2-(mercaptooctyl)hydroquinone (QH2) and alkylthiols were formed on gold electrodes in EtOH and the redox process of the hydroquinone moiety of QH2 was characterized by cyclic voltammetry (CV) in 0.1 M H(2)SO(4). The monolayers were formed at a series of QH2:alkylthiol ratios and the QH2:alkylthiol ratio in solution was compared to the electrochemical response from QH2 in the obtained monolayer. Mixed monolayers of QH2 with hexylthiol, dodecylthiol, and octadecylthiol were studied. The length of the alkylthiol is crucial for the electrochemical response from QH2 in the monolayer. The total concentration of thiols during monolayer formation and incubation times were also studied and low concentrations of < 2.5 mM and long incubation times gave rise to lower peak separation, lower peak half widths in the CVs of the mixed monolayers, and lower background current. The stability of a pure QH2 monolayer and a 1:4 QH2:hexylthiol monolayer toward high potentials of up to 1.5 V versus Ag/AgCl was also studied and it was observed that the mixed monolayer is significantly more stable than the pure QH2 monolayer.     

Density functional theory study of enantiospecific adsorption at chiral surfaces

Density functional theory calculations are carried out for the adsorption of a chiral molecule, (S)- and (R)-HSCH(2)CHNH(2)CH(2)P(CH(3))(2), on a chiral surface, Au(17 11 9)(S)(). The S-enantiomer is found to bind more strongly than the R-enantiomer by 8.8 kJ/mol, evidencing that the chiral nature of the kink sites at the Au(17 11 9) surface leads to enantiospecific binding. The adsorption of two related chiral molecules, HSCH(2)CHNH(2)COOH ("cysteine") and HSCH(2)CHNH(2)CH(2)NH(2), does not, however, lead to enantiospecific binding. The results of the density functional calculations are broken down into a local binding model in which each of the chiral molecule's three contact points with the surface provides a contribution to the overall adsorption bond strength. The enantiospecific binding is demonstrated to originate from the simultaneous optimization of these three local bonds. In the model, the deformation energy costs of both the molecule and the surface are further included. The model reveals that the molecule may undergo large deformations in the attempt to optimize the three bonds, while the surface deforms to a lesser extent. The most favorable binding configurations of each enantiomer are, however, characterized by small deformation energies only, justifying a local binding picture.     

Synthesis of dopamine and serotonin derivatives for immobilization on a solid support

The two important neurotransmitters dopamine and serotonin are synthesized with short PEG tethers and immobilized on a magnetic solid support. The tether is attached to the aromatic moiety of the neurotransmitters to conserve their original functional groups. This approach causes minimal alteration of the original structure with the aim of optimizing the immobilized neurotransmitters for aptamer selection by SELEX. For the dopamine derivative, the tether is attached to the aromatic core of a dopamine precursor by the Sonogashira reaction. For serotonin, a link to the indole core is introduced by a Claisen rearrangement from the allylated phenol moiety of serotonin. The tethers are azide-functionalized, which enables coupling to alkyne-modified magnetic beads. The coupling to the magnetic beads is quantified by UV spectroscopy using Fmoc-monitoring of the immobilized dopamine and serotonin derivatives.     

Development of a lipase-based optical assay for detection of DNA

A lipase-based assay for detection of specific DNA sequences has been developed. Lipase from Candida antarctica was conjugated to DNA and captured on magnetic beads in a sandwich assay, in which the binding was dependent on the presence of a specific target DNA. For amplification and to generate a detectable readout the captured lipase was applied to an optical assay that takes advantage of the enzymatic activity of lipase. The assay applies p-nitrophenol octanoate (NPO) as the substrate and in the presence of lipase the ester is hydrolyzed to p-nitrophenolate which has a strong absorbance at 405 nm. The method provides detection a detection limit of 200 fmol target DNA and it was able to distinguish single base mismatches from the fully complementary target.     

β-Olefination of 2-alkynoates leading to trisubstituted 1,3-dienes

A phosphine-mediated olefination of 2-alkynoates with aldehydes forming 1,3-dienes with high E-selectivity and up to 88% yield is described. Reaction conditions are optimized and reactions are demonstrated for various aryl, alkyl, and alkenyl aldehydes and for ethyl 2-alkynoates with different substituents in the δ-position. Proof of concept is shown for the generation of a β,γ-unsaturated lactone by intramolecular olefination, and furthermore the use of the generated 1,3-dienes in the Diels-Alder reaction has been demonstrated.     

Design and construction of double-decker tile as a route to three-dimensional periodic assembly of DNA

DNA is a useful material for nanoscale construction. Due to highly specific Watson-Crick base pairing, the DNA sequences can be designed to form small tiles or origami. Adjacent helices in such nanostructures are connected via Holliday junction-like crossovers. DNA tiles can have sticky ends which can then be programmed to form large one-dimensional and two-dimensional periodic lattices. Recently, a three-dimensional DNA lattice has also been constructed. Here we report the design and construction of a novel DNA cross tile, called the double-decker tile. Its arms are symmetric and have four double helices each. Using its sticky ends, large two-dimensional square lattices have been constructed which are on the order of tens of micrometers. Furthermore, it is proposed that the sticky ends of the double-decker tile can be programmed to form a three-dimensional periodic lattice with large cavities that could be used as a scaffold for precise positioning of molecules in space.     

A Nucleic Acid Dependent Chemical Photocatalysis in Live Human Cells

Only two nucleic acid directed chemical reactions that are compatible with live cells have been reported to date. Neither of these processes generate toxic species from nontoxic starting materials. Reactions of the latter type could be applied as gene‐specific drugs, for example, in the treatment of cancer. We report here the first example of a chemical reaction that generates a cytotoxic drug from a nontoxic prodrug in the presence of a specific endogeneous ribonucleic acid in live mammalian cells. In this case, the prodrug is triplet oxygen and the drug is singlet oxygen. The key component of this reaction is an inert molecule (InP–2′‐OMe‐RNA/Q–2′‐OMe‐RNA; P: photosensitizer; Q: quencher), which becomes an active photosensitizer (InP–2′‐OMe‐RNA) in the presence of single‐stranded nucleic acid targets. Upon irradiation with red light, the photosensitizer produces over 6000 equivalents of toxic singlet oxygen per nucleic acid target. This reaction is highly sequence specific. To detect the generation of singlet oxygen in live cells, we prepared a membrane‐permeable and water‐soluble fluorescent scavenger, a derivative of 2,5‐diphenylisobenzofurane. The scavenger decomposes upon reaction with singlet oxygen and this is manifested in a decrease in the fluorescence intensity. This effect can be conveniently monitored by flow cytometry.