Solid-phase synthesis of alkanethiols for the preparation of self-assembled monolayers

Self-assembled monolayers (SAMs) of alkanethiols (ATs) on gold can be used to fabricate surfaces for nanoscience and biology. The chemical structure of the interface can be tailored simply by modifying the AT headgroup. To streamline access to different precursor ATs, we developed a general solid-phase synthetic route. A key feature of this route is the use of a modified resin containing an AT linker ("AT resin") because it minimizes purification steps. The precursor to the AT resin was prepared in five steps, and all of the synthetic intermediates are stable solids that can be purified by crystallization. Accordingly, the AT resin can be prepared on a multigram scale. The utility of the AT resin was evaluated by using it to generate a variety of ATs. For example, ATs presenting different types of integrin-binding ligands (linear and cyclic RGD derivatives) were prepared and used to form arrays of SAMs that support cell adhesion. Additionally, the AT resin also provides a starting point for the synthesis of ATs presenting reactive groups (e.g., an amine-reactive AT or a maleimide-containing alkanedisulfide) or protein immobilization tags (e.g., biotin-AT). Thus, our synthetic strategy provides a convenient and flexible means for the synthesis of the necessary building blocks for custom SAMs and SAM arrays.     

A tetrafluorophenyl activated ester self-assembled monolayer for the immobilization of amine-modified oligonucleotides

A tetrafluorophenyl (TFP) ester-terminated self-assembled monolayer (SAM) for the fabrication of DNA arrays on gold surfaces is described. Activated ester SAMs are desirable for biomolecule array fabrication because they readily react with amine-containing molecules to form a stable amide linkage. N-Hydroxysuccinimide (NHS) ester SAMs are commonly used for this purpose but are subject to a competing hydrolysis side reaction, limiting their effectiveness under basic conditions. TFP was evaluated here as an alternative activated ester leaving group with a potentially greater stability under basic conditions. It is shown that TFP SAMs are much more stable to basic pH than their NHS analogs and are also more hydrophobic, which is an advantage in the fabrication of high-density spotted arrays. DNA arrays prepared on TFP SAMs at pH 10 have a 5-fold greater surface density of DNA molecules, reduced fluorescence background, and smaller spot radii than those prepared on NHS SAM analogs.     

Expedient generation of patterned surface aldehydes by microfluidic oxidation for chemoselective immobilization of ligands and cells

An expedient and inexpensive method to generate patterned aldehydes on self-assembled monolayers (SAMs) of alkanethiolates on gold with control of density for subsequent chemoselective immobilization from commercially available starting materials has been developed. Utilizing microfluidic cassettes, primary alcohol oxidation of tetra(ethylene glycol) undecane thiol and 11-mercapto-1-undecanol SAMs was performed directly on the surface generating patterned aldehyde groups with pyridinium chlorochromate. The precise density of surface aldehydes generated can be controlled and characterized by electrochemistry. For biological applications, fibroblast cells were seeded on patterned surfaces presenting biospecifc cell adhesive (Arg-Glyc-Asp) RGD peptides.     

Tripodal Binding Units for Self-Assembled Monolayers on Gold: A Comparison of Thiol and Thioether Headgroups

Whereas thiols and thioethers are frequently used as binding units of oligodentate precursor molecules to fabricate self-assembled monolayers (SAMs) on coinage metal and semiconductor surfaces, their use for tridentate bonding configuration is still questionable. Against this background, novel tridentate thiol ligands, PhSi(CH(2)SH)(3) (PTT) and p-Ph-C(6)H(4)Si(CH(2)SH)(3) (BPTT), were synthesized and used as tripodal adsorbate molecules for the fabrication of SAMs on Au(111). These SAMs were characterized by X-ray photoelectron spectroscopy (XPS) and near edge X-ray absorption fine structure (NEXAFS) spectroscopy. The PTT and BPTT films were compared with the analogous systems comprised of same tripodal ligands with thioether instead of thiol binding units (anchors). XPS and NEXAFS data suggest that the binding uniformity, packing density, and molecular alignment of the thiol-based ligands in the respective SAMs is superior to their thioether counterparts. In addition, the thiol-based films showed significantly lower levels of contamination. Significantly, the quality of the PTT SAMs on Au(111) was found to be even higher than that of the films formed from the respective monodentate counterpart, benzenethiol. The results obtained allow for making some general conclusions on the specific character of molecular self-assembly in the case of tridentate ligands.     

Nanoscale Biomolecular Structures on Self‐Assembled Monolayers Generated from Modular Pegylated Disulfides

A solid‐phase synthetic strategy was developed that uses modular building blocks to prepare symmetric oligo(ethylene glycol)‐terminated disulfides with a variety of lengths and terminal functionalities. The modular disulfides, composed of alkyl amino groups linked by an amide group to oligoethylene chains were used to generate self‐assembled monolayers (SAMs), which were characterised to determine their applicability for biomolecular applications. X‐ray photoelectron spectroscopy (XPS) of the SAMs obtained from these molecules demonstrated improved stability towards displacement by 16‐hexadecanethiol, while surface plasmon resonance (SPR) analyses of SAMs prepared with the hydroxy‐terminated oligoethylene disulfide showed equal resistance to non‐specific protein adsorption in comparison to 11‐mercaptoundecyl tri(ethylene glycol). SAMs made from these adsorbates were amenable to nanoscale patterning by scanning near‐field photolithography (SNP), facilitating the fabrication of nanopatterned, protein‐functionalised surfaces. Such SAMs may be further developed for bionanotechnology applications such as the fabrication of nanoscale biological arrays and sensor devices.     

Fabrication of microarrays on fused silica plates using the laser-induced backside wet etching method

A novel approach in the fabrication of microarrays of dye and protein on fused silica plates using the laser-induced backside wet etching (LIBWE) technique is described. The surface of fused silica plates was initially precoated using trimethoxysilane self-assembled monolayers (SAMs) and then etched using the LIBWE method to obtain the desired microstructures on the plate surface. Using this technique, the SAMs on the nonirradiated areas were able to survive the LIBWE process and were used as templates for the subsequent deposition of dye molecules or proteins via chemical bonding or physical adsorption. In the case of fused silica plates precoated with fluorinated SAMs, the LIBWE method is used to remove the SAMs to expose the etched silica surfaces, on which a thin layer of pyranine molecules can be site-selectively deposited using an aqueous solution of pyranine. In another application, an ethanol solution of rhodamine 6G was preferentially deposited onto the nonirradiated areas. In yet another application, bovine serum albumin was preferentially deposited onto the laser-irradiated areas; in this case, the fused silica plates were precoated with poly(ethylene oxide) SAMs. Interestingly, when an aqueous suspension of polystyrene (PS) microbeads was cast onto the fused silica precoated with the fluorinated SAMs, hexagonally close-packed PS microbeads were deposited into the etched cavities. Depositions of the dye, protein, and microbeads were confirmed by visualization using a fluorescence microscope and scanning electron microscope.     

Well-ordered self-assembled monolayer surfaces can be used to enhance the growth of protein crystals

A series of hydrophobic self-assembled monolayers (SAMs) was generated by the adsorption of undecanethiol, dodecanethiol, and octadecanethiol onto transparent gold-coated glass microscope slides. Protein crystallization trials using droplets deposited on the surfaces of the optically transparent SAMs were compared to those for which the droplets were deposited on the surfaces of conventional silanized glass microscope slides. For the five distinct proteins examined in the crystallization trials (i.e., lysozyme, alpha-lactalbumin, hemoglobin, thaumatin, and catalase), the SAMs generally afforded, (1) a faster rate of crystallization, (2) a larger crystal size; and (3) a broader range of crystallization conditions than that afforded by silanized glass. The greatest enhancements were observed with the highly ordered SAMs derived from octadecanethiol, which are evaluated here for the first time.     

Microfluidic lithography of SAMs on gold to create dynamic surfaces for directed cell migration and contiguous cell cocultures

A straightforward, flexible, and inexpensive method to create patterned self-assembled monolayers (SAMs) on gold using microfluidics-microfluidic lithography-has been developed. Using a microfluidic cassette, alkanethiols were rapidly patterned on gold surfaces to generate monolayers and mixed monolayers. The patterning methodology is flexible and, by controlling the solvent conditions and thiol concentration, permeation of alkanethiols into the surrounding PDMS microfluidic cassette can be advantageously used to create different patterned feature sizes and to generate well-defined SAM surface gradients with a single microfluidic chip. To demonstrate the utility of microfluidic lithography, multiple cell experiments were conducted. By patterning cell adhesive regions in an inert background, a combination of selective masking of the surface and centrifugation achieved spatial and temporal control of patterned cells, enabling the design of both dynamic surfaces for directed cell migration and contiguous cocultures. Cellular division and motility resulted in directed, dynamic migration, while the centrifugation-aided seeding of a second cell line produced contiguous cocultures with multiple sites for heterogeneous cell-cell interactions.     

In situ Raman monitoring triazole formation from self-assembled monolayers of 1,4-diethynylbenzene on Ag and Au surfaces via "click" cyclization

We prepared acetylenyl-terminated aromatic self-assembled monolayers (SAMs) of 1,4-diethynylbenzene on silver and gold. After the fabrication of pendent acetylenyl SAMs, the formation of triazoles was performed via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition "click" chemistry. A density functional theory (DFT) calculation of Raman frequencies showed good agreement with our experimental data to provide evidence of the formation of the triazole molecule. Our results indicated that "click" chemistry could be successfully applied to simple aromatic SAMs proximate (<1 nm) to roughened gold surfaces. The reaction process could be monitored in real time by measuring intensity changes of the nu(CC)(free) band in surface-enhanced Raman scattering (SERS) spectra.     

Synthesis and surface structure of thymine-functionalized, self-assembled monolayer-protected gold nanoparticles

Thymine-functionalized SAM-protected gold nanoparticles with diameters of 2.2 +/- 0.3 nm and 7.0 +/- 1.0 nm were prepared via a modified two-phase transfer method. UV-vis spectra showed that particle size and solvent type, as well as surface charge, influenced the gold surface plasmon band absorption, along with the interaction between thymine terminal groups in the solution. Although the bulky thymine end groups interacted strongly on the particle surface, a well-ordered monolayer of thyminethiol derivatives with a long hydrocarbon chain was formed on the particle surface, exhibiting an ordered, all-trans conformation of the methylene backbone, similar to those of corresponding self-assembled monolayers (SAMs) generated from normal alkanethiols. A larger particle size and a longer reaction time facilitated the formation of more ordered thymine-terminated thiol SAMs. Thermal analysis indicated that reorientation of the SAMs during heat treatment occurred by two processes, caused possibly by the separate recrystallization of the hydrocarbon long chains and thymine units. More ordered SAMs with a higher thermal stability were formed on the larger particle surfaces when compared with those on the smaller ones. A greater density of molecular packing was found on the smaller particle surfaces. However, SAMs formed on the larger gold particles resembled 2D SAMs on the smooth, flat gold surfaces. XPS results confirmed the thymine structure as well as the chemical bond between gold and sulfur. One type of adsorbed sulfur species was observed for the smaller particles and two for the larger ones, but a slightly higher binding energy of thiolate was found for the smaller ones.     

Self-assembled monolayers of 2-(thienyl)hexylphosphonic acid on native oxide surface of silicon fabricated by air-liquid interface-assisted method

A simple, fast, and low-compound-consuming procedure based on the air-liquid interface-assisted method for preparing self-assembled monolayers (SAMs) of organic molecules with phosphonic acid head groups on the native oxide surface of silicon was demonstrated. The SAMs thus prepared were characterized by contact angle measurement, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and atomic force microscopy (AFM). This approach enabled the fabrication of ordered SAMs in a large-area substrate.     

Controlled amine functionality in self-assembled monolayers via the hidden amine route: chemical and electronic tunability

A synthetic strategy for fabricating a dense amine functionalized self-assembled monolayer (SAM) on hydroxylated surfaces is presented. The assembly steps are monitored by X-ray photoelectron spectroscopy, Fourier transform infrared- attenuated total reflection, atomic force microscopy, variable angle spectroscopic ellipsometry, UV-vis surface spectroscopy, contact angle wettability, and contact potential difference measurements. The method applies alkylbromide-trichlorosilane for the fabrication of the SAM followed by surface transformation of the bromine moiety to amine by a two-step procedure: S(N)2 reaction that introduces the hidden amine, phthalimide, followed by the removal of the protecting group and exposing the free amine. The use of phthalimide moiety in the process enabled monitoring the substitution reaction rate on the surface (by absorption spectroscopy) and showed first-order kinetics. The simplicity of the process, nonharsh reagents, and short reaction time allow the use of such SAMs in molecular nanoelectronics applications, where complete control of the used SAM is needed. The different molecular dipole of each step of the process, which is verified by DFT calculations, supports the use of these SAMs as means to tune the electronic properties of semiconductors and for better synergism between SAMs and standard microelectronics processes and devices.     

Electrochemically controlled self-assembled monolayers characterized with molecular and sub-molecular resolution

Self-assembled organization of functional molecules on solid surfaces has developed into a powerful and sophisticated tool for surface chemistry and nanotechnology. A number of reviews on the topic have been available since the mid 1990s. This perspective article aims to focus on recent development in the investigations of electronic structures and assembling dynamics of electrochemically controlled self-assembled monolayers (SAMs) of thiol containing molecules on gold surfaces. A brief introduction is first given and particularly illustrated by a Table summarizing the molecules studied, the surface lattice structures and the experimental operating conditions. This is followed by discussion of two major high-resolution experimental methods, scanning tunnelling microscopy (STM) and single-crystal electrochemistry. In Section 3, we briefly address choice of supporting electrolytes and substrate surfaces, and their effects on the SAM structures. Section 4 constitutes the major body of the article by offering some details of recent studies for the selected cases, including in situ monitoring of assembling dynamics, molecular electronic structures, and the key external factors determining the SAM packing. In Section 5, we give examples of what can be offered by theoretical computations for the detailed understanding of the SAM electronic structures revealed by STM images. A brief summary of the current applications of SAMs in wiring metalloproteins, design and fabrication of sensors, and single-molecule electronics is described in Section 6. In the final two sections (7 and 8), we discuss the current status in understanding of electronic structures and properties of SAMs in electrochemical environments and what could be expected for future perspectives.     

One-dimensional SAMs of (12-pyrrol-1-yl-dodecyl)-phosphonic acid templated by polyelectrolyte molecules

We present a novel method for the fabrication of one-dimensional (1-D) self-assembled monolayers and multilayers (SAMs) of (12-pyrrol-1-yl-dodecyl)-phosphonic acid (Py-DPA) on various polar surfaces using polyelectrolyte nanostructures as positive templates. Particularly, we demonstrate that (i) patterns of aligned 1-D polycation structures on a poly(dimethylsiloxane) stamp can be prepared by moving a droplet of polycation solution along the surface; (ii) these patterns can be used as templates for the ordered assembly of Py-DPA in water where Py-DPA carries a charge opposite to the charge of the template; and (iii) Py-DPA SAMs can then be transferred onto mica or silicon wafers by a printing process. These nanostructures with a polymerizable pyrrole headgroup might be useful for the creation of electrically conductive patterns of conjugated polymers.     

Partial Air Wetting on Solvophobic Surfaces in Polar Liquids

The properties of solvophobic surfaces in polar liquids are studied by sedimentation experiments as well as by force measurements using a scanning force microscope (SFM). Depending on whether the polar liquid contacts the solvophobic surface under normal air pressure or under vacuum the experimental results are different. Sedimentation velocities of vacuum-contacted solvophobic surfaces are similar to those of solvophilic vacuum- or air-contacted ones. However, for the air-contacted solvophobic surfaces there is a slip boundary condition of the hydrodynamic flow causing a change of the sedimentation velocity of about 20%, and a long-range attraction varying with the polarity of the liquid molecule is observed between them. These effects can be explained by an incomplete air dewetting of the solvophobic surface when brought into contact with the polar liquid at normal air pressure. Copyright 1999 Academic Press.     

Zinc oxide growth morphology on self-assembled monolayer modified silver surfaces

Using organic molecules to direct inorganic crystal growth has opened up new avenues for controlled synthesis on surfaces. Combined with soft lithography to form patterned templates, self-assembled monolayers (SAMs) have been shown to be a powerful approach for the assembly of inorganic nanostructures. In this work, we show that the surface free energy of SAM-modified silver, which depends on end groups and deposition method of SAMs, has a dramatic effect on the nucleation and growth of crystalline ZnO, a technologically important material, from supersaturated solutions. For SAMs with inert methyl end groups, ZnO nucleation is inhibited. For SAMs with chemically active (carboxylic or thiol) end groups, the ZnO morphology is found to be three-dimensional nanorods on low-surface-energy surfaces and two-dimensional thin films on high-energy surfaces.     

Investigation into pH-responsive self-assembled monolayers of acylated anthranilate-terminated alkanethiol on a gold surface

This article describes the preparation of pH-responsive self-assembled monolayers (SAMs) of acylated anthranilate-terminated alkanethiol. These monolayers are formed by chemisorption of the alkanethiol molecules onto a gold surface, resulting in different wetting properties of the surfaces depending upon the pH. By using various characterization techniques (e.g., infrared spectroscopy, cyclic voltammetry, contact angle measurements, and surface energy analysis), we have found that the changes in the wetting properties originate from the different surface structures of the monolayers in different pH environments. From surface energy analysis, we found that the disperse components of the surface energy on such SAMs predominate after treatment with pH 1 water, whereas the polar components of the surface energy on such SAMs predominate after treatment with pH 13 water. It is greatly anticipated that this line of research will provide new insight into the mechanism behind pH-responsive properties, facilitating the design and synthesis of new surface-active molecules for the fabrication of pH-responsive functional surfaces.     

Organic surfaces exposed by self-assembled organothiol monolayers: Preparation, characterization, and application

Organic surfaces play a major role in materials science. Most surfaces that we touch in our daily lives are made from organic materials, e.g., vegetables, fruit, skin, wood, and textiles made from natural fibers. In the context of biology, organic surfaces play a prominent role too, proteins docking onto cell surfaces are a good example. To better understand the characteristics of organic surfaces, including physico-chemical properties like wettability or chemical reactivities and physical properties like friction and lubrication, a structurally well-defined model system that can be investigated with numerous analytical techniques is desirable. In the last two decades, one particular system, self-assembled monolayers or SAMs, have demonstrated their suitability for this purpose. In particular, organothiols consisting of an organic molecule with an attached SH-group are well suited to fabricating structurally well-defined adlayers of monolayer thickness on gold substrates using a simple preparation procedure. These ultrathin monolayers expose an organic surface with properties that can be tailored by varying the type of organothiol employed. After a short introduction into the preparation of SAMs, this article provides an overview of the possibilities and limitations of organic surfaces exposed by Au-thiolate SAMs. Applications are as diverse as the metallization of organic surfaces, a fundamental problem in materials science, and the fabrication of surfaces that resist the adsorption of proteins. In addition to a number of different case studies, we will also discuss the most powerful analytical techniques needed to characterize these important model systems.     

Molecular dynamics simulations of low-ordered alzheimer β-amyloid oligomers from dimer to hexamer on self-assembled monolayers

Accumulation of small soluble oligomers of amyloid-β (Aβ) in the human brain is thought to play an important pathological role in Alzheimer's disease. The interaction of these Aβ oligomers with cell membrane and other artificial surfaces is important for the understanding of Aβ aggregation and toxicity mechanisms. Here, we present a series of exploratory molecular dynamics (MD) simulations to study the early adsorption and conformational change of Aβ oligomers from dimer to hexamer on three different self-assembled monolayers (SAMs) terminated with CH(3), OH, and COOH groups. Within the time scale of MD simulations, the conformation, orientation, and adsorption of Aβ oligomers on the SAMs is determined by complex interplay among the size of Aβ oligomers, the surface chemistry of the SAMs, and the structure and dynamics of interfacial waters. Energetic analysis of Aβ adsorption on the SAMs reveals that Aβ adsorption on the SAMs is a net outcome of different competitions between dominant hydrophobic Aβ-CH(3)-SAM interactions and weak CH(3)-SAM-water interactions, between dominant electrostatic Aβ-COOH-SAM interactions and strong COOH-SAM-water interactions, and between comparable hydrophobic and electrostatic Aβ-OH-SAM interactions and strong OH-SAM-water interactions. Atomic force microscopy images also confirm that all of three SAMs can induce the adsorption and polymerization of Aβ oligomers. Structural analysis of Aβ oligomers on the SAMs shows a dramatic increase in structural stability and β-sheet content from dimer to trimer, suggesting that Aβ trimer could act as seeds for Aβ polymerization on the SAMs. This work provides atomic-level understanding of Aβ peptides at interface.     

Magnetic nanoparticle assembly on surfaces using click chemistry

Controlled assembly of ferromagnetic nanoparticles on surfaces is of crucial importance for a range of spintronic and data storage applications. Here, we present a novel method for assembling monolayers of ferromagnetic FePt nanoparticles on silicon oxide substrates using "click chemistry". Reaction of alkyne-functionalized FePt nanoparticles with azide-terminated self-assembled monolayers (SAMs), on silicon oxide, leads to the irreversible attachment of magnetic nanoparticles to the surface via triazole linkers. Based on this covalent interaction, well-packed monolayers of FePt nanoparticles were prepared and nanoparticle patterns are generated on surfaces via microcontact printing (μCP).