The emerging chemical and biological threats have continued to be public health and global security issues due to their toxicity, rapid mutation, and potential for widespread impact.¹ Existing technologies often lack the adaptability and specificity needed to address these threats. Innovative strategies leveraging advancements in materials science are essential to develop scalable, programmable systems capable of effectively neutralizing chemical agents and inhibiting viral activity. Peptoids, or poly-N-substituted glycines, are sequence-defined polymers known for their ability to self-assemble into hierarchical structures, facilitating the creation of robust functional materials with programmability and predictability. ^2-3 The absence of amide hydrogen in the peptoid backbone allows them to self-assemble into crystalline nanomaterials with controlled nanostructures. Additionally, their functionality can be precisely tailored through chemical modifications of the side chains or by co-assembling peptoids with diverse functional properties.⁴ This versatility makes peptoids highly suitable for a wide range of applications, including catalysis,⁵ sensing,⁶ antiviral therapies,⁷ and mineralization.⁸ In this work, we aim to develop peptoid-based programmable materials for the degradation of chemical warfare agent (CWA) simulants and for broad-spectrum virus inhibition. To achieve these multifunctional properties, we developed active peptoid nanomembranes by incorporating active sites such as metal ions, bioactive molecules, or nanoparticles. These active sites are strategically positioned on the membrane surface with precise control over their alignment and density. This was accomplished through straightforward functionalization at the N-terminus of amphiphilic peptoids, either during solid-phase synthesis or via post-assembly modifications. Furthermore, the rotational chemistry of peptoid building blocks enables the creation of microenvironments resembling those found in natural enzymes. These nanomembranes, featuring metal complexes or nanoparticles as active sites, demonstrated the ability to neutralize CWA simulants into benign products. Simultaneously, by introducing bioactive molecules, peptoid membranes exhibited inhibition activity against various viral pathogens. In conclusion, the multifunctional nature of peptoid assemblies positions them as highly programmable materials promising for addressing chemical and biological threats.

Erika Figgins

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