Highly Efficient Synthesis of DNA-Binding Polyamides Using a Convergent Fragment-Based Approach

Two advances in the synthesis of hairpin pyrrole-imidazole polyamides (PAs) are described. First, the application of a convergent synthetic strategy is shown, involving the Boc-based solid phase synthesis of a <i>C</i>-terminal fragment and the solution phase synthesis of the <i>N</i>-terminal fragment. Second a new hybrid resin is developed that allows for the preparation of hairpin PAs lacking a C-terminal β-alanine tail. Both methods are compatible with a range of coupling reagents and provide a facile, modular route to prepare PA libraries in high yield and crude purity

Directed Assembly of DNA-Functionalized Gold Nanoparticles Using Pyrrole–Imidazole Polyamides

Traditional methods for the construction of nanoparticle arrays and lattices exploit Watson–Crick base pairing of single-stranded DNA sequences as a proxy for self-assembly. Although this approach has been utilized in a variety of applications in nanoassembly, diagnostics, and biomedicine, the diversity of this recognition lexicon could be considerably increased by developing strategies that recognize the base-pairing landscape of double-stranded DNA (dsDNA) sequences. Herein we describe the first report of programmed gold nanoparticle (GNP) aggregation directed by the recognition of dsDNA sequences using pyrrole–imidazole polyamide–GNP (PA–GNP) conjugates. We demonstrate the reversibility and selectivity of this strategy for forming GNP aggregates in the presence of fully matched dsDNA sequences relative to dsDNA sequences containing one- and two-base-pair mismatches

Sequence-Selective Detection of Double-Stranded DNA Sequences Using Pyrrole–Imidazole Polyamide Microarrays

We describe a microarray format that can detect double-stranded DNA sequences with a high degree of sequence selectivity. Cyclooctyne-derivatized pyrrole–imidazole polyamides were immobilized on azide-modified glass substrates using microcontact printing and a strain-promoted azide–alkyne cycloaddition (SPAAC) reaction. These polyamide-immobilized substrates selectively detected a seven-base-pair binding site incorporated within a double-stranded oligodeoxyribonucleotide sequence even in the presence of an excess of a sequence with a single-base-pair mismatch

Reactive Vapor-Phase Inhibitors for Area-Selective Depositions at Tunable Critical Dimensions

Area-selective depositions (ASD) take advantage of the chemical contrast between material surfaces in device fabrication, where a film can be selectively grown by chemical vapor deposition on metal versus a dielectric, for instance, and can provide a path to nontraditional device architectures as well as the potential to improve existing device fabrication schemes. While ASD can be accessed through a variety of methods, the incorporation of reactive moieties in inhibitors presents several advantages, such as increasing thermal stability and limiting precursor diffusion into the blocking layer. Alkyne-terminated small molecule inhibitors (SMIs)propargyl, dipropargyl, and tripropargylaminewere evaluated as metal-selective inhibitors. Modeling these SMIs provided insight into the binding mechanism, influence of sterics, and complex polymer network formed from the reaction between inhibitors consisting of alkene, aromatic, and network branchpoints. While a significant contrast in the binding of the SMIs on copper versus a dielectric was observed, residual amounts were detected on the dielectric surfaces, leading to variable ALD growth rates dependent on pattern-critical dimensions. This behavior can be controlled and utilized to direct film growth on patterns only above a critical threshold dimension; below this threshold, both the dielectric and metal features are protected. This method provides another design parameter for ASD processes and may extend its application to broader-ranging device fabrication schemes