Thiol- and disulfide-modified oligonucleotide monolayer structures on polycrystalline and single-crystal Au(111) surfaces

We provide a comprehensive study of single- (ss) and double-strand (ds) oligonucleotides with either 25 or 10 bases or base pairs (bp) immobilized on polycrystalline and single-crystal Au(111) surfaces. The study is based on X-ray photoelectron spectroscopy, cyclic and differential pulse voltammetry, interfacial capacitance data, and electrochemical scanning tunnelling microscopy (in situ STM). The sequences used were the 25-bp sequence from the BRCA1 gene (25-mer), while the 10-bp oligonucleotides contained solely linear adenine and thymine sequences. The oligonucleotides were modified by the dimethoxytrityl group (DMT) via a disulfide group [DMT-S-S-ss25-mer and DMT-S-S-ds(AT)₁₀], a pure disulfide group (A₁₀-S-S-T₁₀), or a thiol group [HS-ss25-mer and HS-ds-(AT)₁₀], all via a hexamethylene linker. The overall pattern suggests strategies for controlled adsorption of DNA-based molecules and recognition of complementary strands or other molecules.     

Enhancing the effectiveness of virtual screening by fusing nearest neighbor lists: a comparison of similarity coefficients

This paper evaluates the effectiveness of various similarity coefficients for 2D similarity searching when multiple bioactive target structures are available. Similarity searches using several different activity classes within the MDL Drug Data Report and the Dictionary of Natural Products databases are performed using BCI 2D fingerprints. Using data fusion techniques to combine the resulting nearest neighbor lists we obtain group recall results which, in many cases, are a considerable improvement on standard average recall values obtained for individual structures. It is shown that the degree of improvement can be related to the structural diversity of the activity class that is searched for, the best results being found for the most diverse groups. The group recall of active compounds using subsets of the class is also investigated: for highly self-similar activity classes, the group recall improvement saturates well before the full activity class size is reached. A rough correlation is found between the relative improvement using the group recall and the square of the number of unique compounds available in all of the merged lists. The Tanimoto coefficient is found unambiguously to be the best coefficient to use for the recovery of active compounds using multiple targets. Furthermore, when using the Tanimoto coefficient, the "MAX" fusion rule is found to be more effective than the "SUM" rule for the combination of similarity searches from multiple targets. The use of group recall can lead to improved enrichment in database searches and virtual screening.     

Long-range order of organized oligonucleotide monolayers on Au(111) electrodes

Oligonucleotides modified by a hexamethylene linker group adsorb on gold electrodes via Au-S bond formation. We have obtained novel data for adsorption of thiol-modified (HS) single-strand HS-10A and double-stranded HS-10AT oligonucleotides and for analogous thiol-free 10A (A = adenine) and 10T (T = thymine) nonspecifically adsorbed as reference molecules. Mercaptohexanol has served as a second reference molecule. The data are based on cyclic and differential pulse voltammetry, interfacial capacitance data, and in situ scanning tunneling microscopy (STM) directly in an aqueous buffer solution, with electrochemical potential control of both the sample electrode and the tip. All the data are based on single-crystal, atomically planar Au(111)-electrode surfaces. The high sensitivity of such surfaces provides accurate HS-10A and HS-10AT electrode coverages on the basis of the reductive desorption of the Au-S bond. The coverage is high and in keeping with dense monolayers of adsorbed HS-10A and HS-10AT in an upright or tilted orientation, with the oligonucleotide backbone repelled from the strongly negatively charged electrode surface. Adsorbed thiol-free 10A only gives a Au(111)-reconstruction peak, while 10T shows a subtle pattern involving pronounced voltammetric adsorption peaks indicative of both nonspecific adsorption via single thymine units and potential-dependent structural reorganization in the surface layer. In situ STM supports these findings at the molecular level. In situ STM of HS-10A discloses large, highly ordered domains at strongly negative sample potentials. Reversible domain formation and disordering could, moreover, be controlled by an electrochemical potential variation in the negative and positive directions, respectively. 10A and 10T did not form ordered adsorbate domains, substantiating that domain formation rests on adsorption of thiol-modified oligonucleotide adsorption in an upright or tilted orientation. The comprehensive, high-resolution information reported may hold prospects for single-molecule electronic conduction and molecular-scale mapping of oligonucleotide hybridization.     

Langmuir monolayers of bent-core molecules

A systematic study of five different, symmetric bent-core liquid crystals in Langmuir thin films at the air/water interface is presented. Both the end chains (siloxane vs hydrocarbon) and the core (more or less amphiphilic) are varied, to allow an exploration of different possible layer structures at the interface. The characterization includes systematic surface pressure isotherms, Brewster angle microscopy, and surface potential measurements. The properties of these layers are strongly dependent on the individual type of molecule: the molecules with amphiphilic end chains lie quite flat on the surface, while the molecules with hydrophobic end chains construct multilayer structures. In both cases, the three-dimensional collapse structure is reversible.     

Simple approach to study biomolecule adsorption in polymeric microfluidic channels

Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor^®) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor^® substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor^®, and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and neutral, hydrogel-like film with polyethylene glycol (PEG) characteristics. This simple analytical approach adds to the fundamental understanding of the interaction forces in real, microfluidic systems. This method provides a straightforward and rapid way to screen surface compositions and chemistry, and relate these to their effects on the sensitivity and resistance to non-specific binding of bioassays using them. In an additional set of experiments, the surface area of the channels in this universal microfluidic chip was increased by precision milling of microscale trenches. This modified surface was then coated with APTES and tested for its potential to serve as a unique protein dilution feature.     

Post‐Grignard Reagents: Influence of the Coligands L on the Molecular Structures of Phenylcalcium Iodides [(L)nCa(R)I] and Calcium Diiodides [(L)nCaI2]

Iodide is a very soft and large anion and as such its extreme ability to be polarized leads to a flat energy surface with respect to the variation of the Ca–I distances in [(L)_nCaI₂] and [(L)_nCa(R)I]. The influence of the donor strength and the bulkiness of the neutral coligands L on the Ca–I distances is studied. The base adducts of calcium diiodide can be isolated after the addition of L to CaI₂ or from the Schlenk equilibrium after the direct synthesis of calcium powder with aryl iodides. As L the ethers diethyl ether (Et₂O), tetrahydrofuran (thf), tetrahydropyran (thp), 1,2‐dimethoxyethane (dme), 18‐crown‐6 (18C6), bis(methoxyethyl)ether (diglyme), and amines tetramethylethylenediamine (tmeda), and hexamethyltriethylenetetramine (hmteta) are studied yielding the adducts [(thp)₄Ca(Ph)I] ( 1a ), [(thf)₄Ca(Ph)I] ( 1b ), [(dme)₂(thf)Ca(Ph)I] ( 1c ), [(18C6)Ca(Ph)I] ( 1d ), and [(tmeda)₂Ca(Ph)I] ( 1e ), as well as [(thp)₄CaI₂] ( 2a ), [(thf)₄CaI₂] ( 2b ), [(Et₂O)₄CaI₂] ( 2c ), [(diglyme)(thf)₂CaI₂] ( 2d ), [(diglyme)(dme)CaI₂] ( 2e ), [(dme)₂(thf)CaI₂] ( 2f ), [(18C6)CaI₂] ( 2g ), [(tmeda)₂CaI₂] ( 2h ), and [(hmteta)CaI₂] ( 2i ). For comparison reasons, [(thf)₄Ca(Ph)Br] ( 3a ), [(thp)₄CaBr₂] ( 4a ), [(thf)₄CaBr₂] ( 4b ), and [(dme)₂(AcOH)CaBr₂] ( 4c ) with AcOH being acetic acid are included as well. The comparison shows that the coordination number of calcium itself only plays an insignificant role whereas bulkiness and donor strength of L represent the key influences.     

Adamantane-Based Tripodal Thioether Ligands Functionalized with a Redox-Active Ferrocenyl Moiety for Self-Assembled Monolayers

Self-assembled monolayers (SAMs) can decorate surfaces with `smart′ functional units possessing reversible stimulus-response behavior for optical, thermal, magnetic or redox-chemical stimuli. An independent performance of individual functional groups in such a film is desirable, which can be, in particular, ensured by fairly large lateral separations between tailgroups in the SAM. Adsorbate molecules with multiple attachment points are very promising in this context owing to their large surface footprint, which covers a surface area exceeding the lateral dimensions of the functional groups. To address these design constraints, novel tridentate long-chain tripodal thioether ligands with central adamantine units and a redox-active ferrocenyl tailgroup, 1-[4-(ferrocenylethynyl)phenyl]-3,5,7-tri[(4-n-octylsulfanyl)phenyl]adamantine (T8) and 1-[4-(ferrocenylethynyl)phenyl]-3,5,7-tri[(4-n-dodecylsulfanyl)phenyl]adamantine (T12), were synthesized and used as tripodal adsorbate molecules for the fabrication of redox-active ferrocenyl-terminated SAMs on Au(111). These SAMs were characterized by X-ray photoelectron spectroscopy, near edge X-ray absorption fine structure spectroscopy and sum frequency generation spectroscopy. The data suggest that T8 and T12 form almost contamination-free, well-aligned and fairly densely-packed SAMs on Au(111) with laterally separated ferrocenyl units. The SAMs show a homogeneous binding chemistry, an important requirement for high fidelity SAMs. SFG results indicate lateral interactions between neighboring molecules via the long-chain binding units.     

Synthesis and crystal structure of the isotypic rare earth thioborates Ce[BS3], Pr[BS3], and Nd[BS3]

The orthothioborates Ce[BS₃], Pr[BS₃] and Nd[BS₃] were prepared from mixtures of the rare earth (RE) metals together with amorphous boron and sulfur summing up to the compositions CeB₃S₆, PrB₅S₉ and NdB₃S₆. The following preparation routes were used: solid state reactions with maximum temperatures of 1323 K and high-pressure high-temperature syntheses at 1173 K and 3 GPa. Pr[BS₃] and Nd[BS₃] were also obtained from rare earth chlorides RECl₃ and sodium thioborate Na₂B₂S₅ by metathesis type reactions at maximum temperatures of 1073 K. The crystal structure of the title compounds was determined from X-ray powder diffraction data. The thioborates are isotypic and crystallize in the orthorhombic spacegroup Pna2₁ (No. 33; Z=4; Ce: , , ; Pr: , , ; Nd: , , ) . The crystal structures contain isolated [BS₃]^3‐ groups with boron in trigonal-planar coordination. The sulfur atoms form the vertices of undulated kagome nets, which are stacked along [100] according to the sequence ABAB. Within these nets every second triangle is occupied by boron and the large hexagons are centered by rare earth ions, which are surrounded by overall nine sulfur species.     

Replication of Micro- and Nanostructures on Polymer Surfaces

Summary : Via geometrical micro- and nanostructures new functionalities like controlled wetting properties, biological adhesive / dehesive properties or surface patterns for guided self assembly can be added to polymer surfaces. This is especially interesting for medical or biotechnological applications, because there is no new approval process necessary. The whole process from producing the structures via EUV-interference lithography to the injection moulding will be shown. How far the limits for the smallness of these structures on polymers are already pushed forward show the results from our latest injection moulded samples. Grooves of 18 nm width - this means world record! - could be reproduced in an industrial process and in an economical very interesting high-volume production.