Solid-Phase Synthesis of Alkanethiols for the Preparation of Self-Assembled Monolayers

Abstract

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.

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

“…[48] The hydroxy resin was activated using thionyl chloride [49] and thiol component 5 attached to give 13. Similar to a previously reported solid-phase strategy, [41] attachment through its S atom served to protect the thiol from reaction during the solid-phase assembly. On-resin hydrazinolysis of the phthalimide revealed the amine 14.…”

“…[38][39][40][41] For the purposes of this synthesis, a solid-phase strategy is more efficient than solution-phase synthesis, because it allows excess of reagents to force high yields and simple washing steps obviates the need for purification of intermediates. Accordingly, two pegylated alkyldisulfides 1 and 2, were chosen as synthetic targets, which are more stable to oxidation and reactions with electrophiles than the corresponding thiols, but are still able to form SAMs (Scheme 1).…”

Spatial control of cell fate using synthetic surfaces to potentiate TGF-β signaling

“…To generate a surface display of peptides, we employed selfassembled monolayers (SAMs) of peptide-conjugated alkanethiols (ATs) on gold (4,(13)(14)(15)(16). ATs form defined assemblies and therefore should give rise to reproducible biological activity.…”

“…ATs form defined assemblies and therefore should give rise to reproducible biological activity. Thus, the peptide-substituted ATs were synthesized (14) and used to fabricate SAMs in an array format (13). The ability of these tailored surfaces to support the adhesion of cells expressing the TGF-β receptors was evaluated.…”

“…A linker for solid-supported synthesis of tailored ATs was assembled and loaded onto resin as described previously (14). Pep1 and Pep2 were built onto AT resin by using Fmoc solid-phase peptide synthesis.…”