A Chiral Self‐Assembled Monolayer Derived from a Resolving Agent and its Performance as a Crystallization Template for an Organic Compound from Organic Solvents

A new chiral nonracemic thiol derived from a popular acidic resolving agent that incorporates a cyclic disubstituted phosphate group (phencyphos) has been prepared in enantiomerically pure form. The stereochemistry and absolute configuration were established by performing a single‐crystal X‐ray structural analysis of a synthetic intermediate. The thiol compound was used for the preparation of self‐assembled monolayers (SAMs) on both monocrystalline and polycrystalline metallic gold, which have very different surface roughness. The monolayers were used to promote the nucleation and growth of crystals from nonaqueous solutions of an organic molecule (the parent phencyphos) of similar structure to the compound present in the monolayer. The template layers influence the nucleation and growth of the phencyphos crystals despite the lack of two‐dimensional order in the surfaces. Heterogeneous nucleation of phencyphos takes place upon evaporation of either CHCl₃ or isopropanol solutions of the compound on the SAM surfaces, where the evaporation rate merely influences the size and homogeneity of the crystals. The roughness of the surface also plays an important role; the polycrystalline gold produces more homogeneous samples because of the greater number of nucleation sites. Clear evidence for nucleation and growth on the surfaces is shown by scanning electron microscopy. The variation in crystal form achieved by using different surfaces and solvents suggests that the layers are applicable for the preparation of organic crystals from organic solutions.     

An original electrochemical method for assembling multilayers of terpyridine-based metallic complexes on a gold surface

A new method based on the electrochemical oxidation of thiols was used to easily generate multilayer assemblies of coordination complexes on a gold surface. For this purpose, two complexes bearing two anchoring groups for surface attachment have been prepared: [Ru(tpySH)(2)](2+) (1) and [Fe(tpySH)(2)](2+) (2) (tpySH = 4'-(2-(p-phenoxy)ethanethiol)-2,2':6',2″-terpyridine). Cyclic voltammetry of 1 in CH(3)CN exhibits two successive oxidation processes. The first is irreversible and attributed to the oxidation of the thiol substituents, whereas the second is reversible and corresponds to the 1 e(-) metal-centered oxidation. In the case of 2 both processes are superimposed. Monolayers of 1 or 2 have been formed on gold electrodes by spontaneous adsorption from micromolar solutions of the complexes in CH(3)CN. SAMs (self-assembled monolayers) exhibit redox behavior similar to the complexes in solution. The high surface coverage value obtained (Γ = 6 × 10(-10) and 4 × 10(-10) mol cm(-2) for 1 and 2, respectively) is consistent with a vertical orientation for the complexes; thus, one thiol is bound to the gold electrode, with the second unreacted thiol moiety exposed to the outer surface. Successive cyclic voltammetry induced a layer-by-layer nanostructural growth at the surface of the SAMs, and this is presumably due to the electrochemical formation of disulfide bonds, where the thiol moieties play a double role of both an anchoring group and an electroactive coupling agent. The conditions of the deposition are studied in detail. Modified electrodes containing both 1 and 2 alternatively can be easily prepared following this new approach. The film proved to be stable, displaying a similar current/voltage response for more than 10 repeating cycles in oxidation up to 0.97 V vs Ag/AgNO(3) (10(-2) M).     

Reactive hydrogels grafted on gold surfaces

Three different strategies for the fixation of stable hydrogel coatings on gold surfaces, by the grafting‐to and grafting‐from techniques, are described. Monomeric or polymeric disulfide initiators are employed to start the photopolymerization of N‐[tris(hydroxy‐methyl)methyl]acrylamide 1 via decomposition of azo compounds or via a photoredox system. Different approaches, based on the post functionalization of the poly(1) films or on copolymerization of reactive monomers with 1 , are employed to bind potential receptor molecules bearing amino or thiol groups as anchor to the hydrogel. Thus, the functionalized coatings should allow the selective binding of particular analyzates. The overall goal is focused on hydrogel films for the preparation of biochips used in analytical devices such as Surface Plasmon Resonance (SPR), though our approach seems to be generally useful for related purposes.     

Critical review of bio/nano sensors for arsenic detection

Detection of arsenic is a long-standing challenge in environmental analytical chemistry. In recent years, using biomolecules and nanomaterials for sensing arsenic has been growingly reported. In this article, this field is critically reviewed based on some recent fundamental understandings including interactions between arsenic and gold, thiol, and DNA aptamers. First, taking advantage of the adsorption of As(III) on noble metal surfaces such as silver and gold, sensors were developed based on surface enhanced Raman spectroscopy, electrochemistry and colorimetry. In addition, by functionalizing metal nanoparticles with thiol containing molecules, As(III) induced aggregation of the particles based on As(III)/thiol interactions. As(V) interacts with metal oxides strongly and competitive sensors were developed by displacing pre-adsorbed DNA oligonucleotides. A DNA aptamer was selected for As(III) and many sensors were reported based on this aptamer, although careful binding measurements indicated that the sequence has no affinity towards As(III). Overall, bio/nano systems are promising for the detection of arsenic. Future work on fundamental studies, searching for more specific arsenic binding materials and aptamers, incorporation of sensors into portable devices, and more systematic test of sensors in real samples could be interesting and useful research topics.     

Alkanephosphonates on hafnium-modified gold: a new class of self-assembled organic monolayers

A new method for assembling organic monolayers on gold is reported that employs hafnium ions as linkers between a phosphonate headgroup and the gold surface. Monolayers of octadecylphosphonic acid (ODPA) formed on gold substrates that had been pretreated with hafnium oxychloride are representative of this new class of organic thin films. The monolayers are dense enough to completely block assembly of alkanethiols and resist displacement by alkanethiols. The composition and structure of the monolayers were investigated by contact angle goniometry, XPS, PM-IRRAS, and TOF-SIMS. From these studies, it was determined that this assembly strategy leads to the formation of ODPA monolayers similar in quality to those typically formed on metal oxide substrates. The assembly method allows for the ready generation of patterned surfaces that can be easily prepared by first patterning hafnium on the gold surface followed by alkanephosphonate assembly. Using the bifunctional (thiol-phosphonate) 2-mercaptoethylphosphonic acid (2-MEPA), we show that this new assembly chemistry is compatible with gold-thiol chemistry and use TOF-SIMS to show that the molecule attaches through the phosphonate functionality in the patterned region and through the thiol in the bare gold regions. These results demonstrate the possibility of functionalizing metal substrates with monolayers typically formed on metal oxide surfaces and show that hafnium-gold chemistry is complementary and orthogonal to well-established gold-thiol assembly strategies.     

Oriented immobilization of antibodies and their fragments on modified silicon for the production of nanosensors

Different methods for the covalent immobilization of specific antibodies and their fragments on a silicon surface with the subsequent formation of immune complexes that consist of an immobilized monoclonal antibody, an antigen molecule, and a molecule of a second monoclonal antibody labeled with gold nanoparticles have been studied. Prostate-specific antigen (PSA), which is a molecular biomarker for prostate cancer, was used as an antigen. A covalent conjugate of the fragments of PSA-specific antibodies with gold nanoparticles has been obtained using the thiol groups of the antibodies. Scanning electron microscopy (SEM) was used for the registration of immune complexes on the surface. The high resolution of the method made it possible to detect individual immune complexes by the presence of gold nanoparticles and to calculate their number. A new method for the chemical modification of silicon by 3-aminopropyltrimetoxysilane (APTMS) and a bifunctional reagent 1,4-phenylene diisothiocyanate (PDITC) has been developed. This method provides a uniform distribution of antigen-binding centers and their availability for the formation of immune complexes. The developed immobilization method is promising for the formation of a biospecific biosensor layer based on silicon nanowires.     

Fabrication of immunosensor microwell arrays from gold compact discs for detection of cancer biomarker proteins

A simple method is reported to fabricate gold arrays featuring microwells surrounding 8-electrodes from gold compact discs (CDs) for less than $0.2 per chip. Integration of these disposable gold CD array chips with microfluidics provided inexpensive immunoarrays that were used to measure a cancer biomarker protein quickly at high sensitivity. The gold CD sensor arrays were fabricated using thermal transfer of laserjet toner from a computer-printed pattern followed by selective chemical etching. Sensor elements had an electrochemically addressable surface area of 0.42 mm(2) with RSD <2%. For a proof-of-concept application, the arrays were integrated into a simple microfluidic device for electrochemical detection of cancer biomarker interleukin-6 (IL-6) in diluted serum. Capture antibodies of IL-6 were chemically linked onto the electrode arrays and a sandwich immunoassay protocol was developed. A biotinylated detection antibody with polymerized horseradish peroxidase labels was used for signal amplification. The detection limit of IL-6 in diluted serum was remarkably low at 10 fg mL(-1) (385 aM) with a linear response with log of IL-6 concentration from 10 to 1300 fg mL(-1). These easily fabricated, ultrasensitive, microfluidic immunosensors should be readily adapted for sensitive detection of multiple biomarkers for cancer diagnostics.     

Spontaneous assembly of organic thiocyanates on gold sufaces. Alternative precursors for gold thiolate assemblies

Thiolate self-assembly on gold has proven to be a valuable technique for assembling monolayers on a wide variety of substrates. However, the oxidative instability of the thiols, especially aromatic thiols and alpha,omega-dithiols, presents several difficulties. Shown here is that thiocyanates, easily synthesized stable thiol derivatives, can be directly assembled on gold surfaces with no auxiliary reagents required. Assembly is complete in 24 h and leaves a similar gold thiolate structure as seen in typical thiol self-assembled monolayers.     

Microstructuring of phospholipid bilayers on gold surfaces by micromolding in capillaries

Microstructuring of lipid bilayers on gold surfaces was achieved by micromolding in capillaries employing chemically modified polydimethylsiloxane (PDMS). Microfluidic networks of PDMS were prepared by micromolding and functionalized with thiol end-groups using 3-mercaptopropyltrimethoxysilane. The PDMS stamps were firmly attached to the gold substrate via quasi-covalent linkage providing a tight seal, a prerequisite for establishing individual addressable capillaries. Bilayers composed of POPC/POPG were subsequently prepared on microstructured self assembly monolayers of 11-amino-1-undecanethiol via strong electrostatic interactions. This way it is possible to generate individually addressable lipid bilayers on gold surfaces, a procedure, which is of widespread interest for investigating protein lipid interactions with microscopic techniques.     

A zinc carboxylate network containing metal sites with low coordination numbers

A bifunctional m-terphenyl, 2,6-diphenyl-1,4-dibenzoic acid (Ph2BDC), was synthesized and used in the preparation of a 2-D metal-organic coordination polymer. The steric hindrance of the bulky bifunctional linker forces low coordination at the Lewis-acidic zinc center. A zinc carboxylate dimer was prepared as a model compound to examine the unusual tricoordinate geometry at the metal site.     

A New Porphyrin for the Preparation of Functionalized Water-Soluble Gold Nanoparticles with Low Intrinsic Toxicity

A potential new photosensitizer based on a dissymmetric porphyrin derivative bearing a thiol group was synthesized. 5-[4-(11-Mercaptoundecyloxy)-phenyl-10,15,20-triphenylporphyrin (PR-SH) was used to functionalize gold nanoparticles in order to obtain a potential drug delivery system. Water-soluble multifunctional gold nanoparticles GNP-PR/PEG were prepared using the Brust–Schiffrin methodology, by immobilization of both a thiolated polyethylene glycol (PEG) and the porphyrin thiol compound (PR-SH). The nanoparticles were fully characterized by transmission electron microscopy and ¹H nuclear magnetic resonance spectroscopy, UV/Vis absorption spectroscopy, and X-ray photoelectron spectroscopy. Furthermore, the ability of GNP-PR/PEGs to induce singlet oxygen production was analyzed to demonstrate the activity of the photosensitizer. Cytotoxicity experiments showed the nanoparticles are nontoxic. Finally, cellular uptake experiments demonstrated that the functionalized gold nanoparticles are internalized. Therefore, this colloid can be considered to be a novel nanosystem that could potentially be suitable as an intracellular drug delivery system of photosensitizers for photodynamic therapy.     

Preparation of stable micropatterns of gold oncell-adhesion-resistant hydrogels assisted by ahetero-bifunctional macromonomer linker

Surface patterning is very useful in biomaterial studies, yet it is not easy to prepare a micropattern with cell-adhesion contrast that is stable in a wet environment. Recently, a platform technique of transfer photolithography was invented to fabricate stable metal microarrays on the surface of a cell-adhesion resistant and mechanically biomimetic poly(ethylene glycol) hydrogel; the linker is the key chemical in such a transfer strategy. This article reports the design and synthesis of a hetero-bifunctional macromonomer linker with a thiol group at one end and an acryloyl group at the other end. The bifunctional linker was characterized by GPC and ¹H NMR, and the average number of thiol groups in the bifunctional linker was detected by Ellman’s reagent. The regent stability under wet conditions was also confirmed by the model reactants. The resultant micropatterned surfaces are meaningful for future studies of cell behaviors on mechanically biomimetic matrixes.     

4-Fluoropyrrolidine-2-carbonyl fluorides: useful synthons and their facile preparation with 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride

4-Fluoropyrrolidine derivatives are useful in medicinal chemistry applications such as dipeptidyl peptidase IV inhibitors. As attractive synthons for these, N-protected (2S,4S)-4-fluoropyrrolidine-2-carbonyl fluorides were synthesized in high yield by double fluorination of N-protected (2S,4R)-4-hydroxyproline with 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead). The 4-fluoropyrrolidine-2-carbonyl fluorides were converted to useful intermediates such as 4-fluoropyrrolidine-2-carboxamides, -N-methoxy-N-methylcarboxamide (Weinreb amide), -carboxylate methyl esters, and -carbonitriles in excellent yields. The crystalline N-Fmoc-cis-4-fluoropyrrolidine-2-carbonyl fluoride 2a is a particularly useful synthon due to its high yield of preparation and easy isolation as an enantiomerically pure compound by crystallization. Thus, the methodology using the synthons prepared by the stereospecific double fluorination has enabled a significant decrease in the synthetic steps needed for the preparation of the 4-fluoropyrrolidine derivatives useful for medicinal applications.     

Transferable potentials for phase equilibria. 8. United-atom description for thiols, sulfides, disulfides, and thiophene

An extension of the transferable potentials for phase equilibria united-atom (TraPPE-UA) force field to thiol, sulfide, and disulfide functionalities and thiophene is presented. In the TraPPE-UA force field, nonbonded interactions are governed by a Lennard-Jones plus fixed point charge functional form. Partial charges are determined through a CHELPG analysis of electrostatic potential energy surfaces derived from ab initio calculations at the HF/6-31g+(d,p) level. The Lennard-Jones well depth and size parameters for four new interaction sites, S (thiols), S(sulfides), S(disulfides), and S(thiophene), were determined by fitting simulation data to pure-component vapor-equilibrium data for methanethiol, dimethyl sulfide, dimethyl disulfide, and thiophene, respectively. Configurational-bias Monte Carlo simulations in the grand canonical ensemble combined with histogram-reweighting methods were used to calculate the vapor-liquid coexistence curves for methanethiol, ethanethiol, 2-methyl-1-propanethiol, 2-methyl-2-propanethiol, 2-butanethiol, pentanethiol, octanethiol, dimethyl sulfide, diethyl sulfide, ethylmethyl sulfide, dimethyl disulfide, diethyl disulfide, and thiophene. Excellent agreement with experiment is achieved, with unsigned errors of less than 1% for saturated liquid densities and less than 3% for critical temperatures. The normal boiling points were predicted to within 1% of experiment in most cases, although for certain molecules (pentanethiol) deviations as large as 5% were found. Additional calculations were performed to determine the pressure-composition behavior of ethanethiol+n-butane at 373.15 K and the temperature-composition behavior of 1-propanethiol+n-hexane at 1.01 bar. In each case, a good reproduction of experimental vapor-liquid equilibrium separation factors is achieved; both of the coexistence curves are somewhat shifted because of overprediction of the pure-component vapor pressures.     

Solid-state bonding technique for template-stripped ultraflat gold substrates

A simple procedure using gold diffusion bonding for the preparation of template-stripped gold (TSG) surfaces is described. TSG surfaces are useful for surface studies because a very consistent flat gold surface with few defects can be easily prepared. We have developed a method of producing TSG surfaces that relies only on gold diffusion bonding rather than epoxies. The resulting substrates are free from concerns of solvent compatibility, heat stability, and impurities. Bonding of centimeter-sized substrates is performed at 300 degrees C for 2 h using a vise and aluminum foil.     

AFM force measurements between SAM-modified tip and SAM-modified substrate in alkaline solution

The reversible desorption and adsorption of ethanethiol (ET) and hexadecane thiol (HDT) self-assembled monolayers (SAMs) on gold substrates are addressed with potential-dependent AFM force measurements where both tip and substrate potentials are controlled independently. For HDT-modified tip and substrate, the potential dependence of the force curve corresponds to the observed voltammetric features. The adhesion interaction between HDT-modified tip and substrate exhibits a large adhesion, whereas the adhesion is reduced to one-quarter of its original value after HDT on the substrate is removed. The presence of both attractive features on the approach curve and large adhesion on retraction after thiol desorption are ascribed to micelle formation from the desorbed, insoluble, thiols above the Au surface. For the ET-modified tip and substrate, the force curve evinces time-dependent recovery after the thiol adsorption peak which arises from the finite time of diffusion of the desorbed thiol back to the substrate. However, the force curves exhibit little potential dependence when the ET-desorbed tip is interacted with ET-modified substrate.     

Carboranethiol-modified gold surfaces. A study and comparison of modified cluster and flat surfaces

Four different carboranethiol derivatives were used to modify the surfaces of gold nanoparticles and flat gold films. The novel materials engendered from these modifications are extraordinarily stable species with surfaces that support self-assembled monolayers of 1-(HS)-1,2-C2B10H11, 1,2-(HS)2-1,2-C2B10H10, 1,12-(HS)2-1,12-C2B10H10, and 9,12-(HS)2-1,2-C2B10H10, respectively. Surprisingly, characterization of these materials revealed that a number of molecules of the carboranethiol derivatives are incorporated inside the nanoparticles. This structural feature was studied using a number of techniques, including X-ray photoelectron spectroscopy (XPS), UV-vis, and IR spectroscopies. Thermal desorption experiments show that carborane molecules detach and leave the nanoparticle surface mostly as 1,2-C2B10H10 isotopic clusters, leaving sulfur atoms bound to the gold surface. The surfaces of both the gold nanoparticles and the flat gold films are densely packed with carboranethiolate units. One carborane cluster molecule occupies an area of six to seven surface gold atoms of the nanoparticle and eight surface gold atoms of the flat film. XPS data showed that molecules of 1,12-(HS)2-1,12-C2B10H10 bind to the flat gold surface with only half of the thiol groups due to the steric demands of the icosahedral carborane skeleton. Electrochemical measurements indicate complete coverage of the modified gold surfaces with the carboranethiol molecules.     

Theoretical Study of Ethanethiol Adsorption on HZSM-5 Zeolite

The density functional theory and the cluster model methods have been employed to investigate the interactions between ethanethiol and HZSM-5 zeolites. Molecular complexes formed by the adsorption of ethanethiol on silanol H3SiOH with two coordination forms, model Bronsted acid sites of zeolite cluster H3Si(OH)Al(OH)2SiH3 interaction with ethanethiol, aluminum species adsorbed ethanethiol have been comparatively studied. Full optimization and frequency analysis of all cluster models have been carried out using B3LYP hybrid method at 3-21G basis level for hydrogen atoms and 6-31G(d) basis set level for silicon, aluminum, oxygen, carbon, and sulfur atoms. The structures and energy changes of different coordination forms of H3Si(OH)Al(OH)2SiH3-ethanethiol, silanol-ethanethiol and Al(OH)3-ethanethiol have been studied. The calculated results showed the nature of interactions was van der Waals force as exhibited by not much change in geometric structures and properties. The preference order of ethanethiol adsorbed on HZSM-5 zeolite may be residual aluminum species, bridging hydroxyl groups and silanol OH groups from the adsorption heat. The adsorbed models of protonized ethanethiol on bridging hydroxyl OH groups and linear hydrogen bonded ethanethiol on bridging OH groups suggested in literature might not exist as revealed by this theoretical calculation. Possible adsorption models were obtained for the first time.     

An Experimental and Theoretical Approach to Investigate the Effect of Chain Length on Aminothiol Adsorption and Assembly on Gold

Despite the numerous studies on the self‐assembled monolayers (SAMs) of alkylthiols on gold, the mechanisms involved, especially the nature and influence of the thiol–gold interface are still under debate. In this work the adsorption of aminothiols on Au(111) surfaces has been studied by using surface IR and X‐ray photoelectron spectroscopy (XPS) as well as by density functional theory (DFT) modeling. Two aminothiols were used, cysteamine (CEA) and mercaptoundecylamine (MUAM), which contain two and eleven carbon atoms, respectively. By combining experimental and theoretical methods, it was possible to draw a molecular picture of the thiol–gold interface. The long‐chain aminothiol produced better ordered SAMs, but, interestingly, the XPS data showed different sulfur binding environments depending on the alkyl chain length; an additional peak at low binding energy was observed upon CEA adsorption, which indicates the presence of sulfur in a different environment. DFT modeling showed that the positions of the sulfur atoms in the SAMs on gold with similar unit cells [(2√3×2√3)R30°] depended on the length of the alkyl chain. Short‐chain alkylthiol SAMs were adsorbed more strongly than long‐chain thiol SAMs and were shown to induce surface reconstruction by extracting atoms from the surface, possibly forming adatom/vacancy combinations that lead to the additional XPS peak. In the case of short alkylthiols, the thiol–gold interface governs the layer, CEA adsorbs strongly, and the mechanism is closer to single‐molecule adsorption than self‐assembly, whereas for long chains, interactions between alkyl chains drive the system to self‐assembly, leading to a higher level of SAM organization and restricting the influence of the sulfur–gold interface.     

Real-time monitoring of nanomolar binding to a cyclodextrin monolayer immobilized on a Si/SiO2/novolac surface using white light reflectance spectroscopy: the case of triclosan

The monitoring of the antibacterial agent triclosan binding at nanomolar concentration from an aqueous solution by employing a well-packed monolayer with a predetermined single orientation made of specifically synthesized 2,3-dimethyl-6-(undec-10-enamide)-6-deoxy-β-cyclodextrin (DMBUA) on a silicon wafer (Si/SiO(2)) coated with a novolac resin is reported. A white light reflectance spectroscopy (WLRS) setup was used for the real-time monitoring of the DMBUA deposition and triclosan binding processes. Film thicknesses obtained by WLRS were in very good agreement with the ones measured by X-ray reflectivity (XRR) experiments. Triclosan binds strongly to the DMBUA monolayer (logK(assoc)=6.68). NMR studies in aqueous solution indicated that the chlorophenolyl ring rather than the dichlorophenyl ring is preferentially inserted into DMBUA cups. The current detecting system that requires no tedious surface chemistry, no thiolated cyclodextrins, no gold surfaces, and no expensive equipment may be useful in capturing small molecules and may permit various applications, e.g., preparation of antimicrobial surfaces.