Center: CCI Phase I: NSF Center for the Creation of Abiotic Replicating Materials and Assemblies (CARMA)

University Of Texas At Austin, Austin TX

Investigators

Abstract

The NSF Center for the Creation of Abiotic Replicating Materials and Assemblies (CARMA) is supported by the Centers for Chemical Innovation (CCI) Program of the Division of Chemistry. One hallmark of terrestrial life is that it is both driven by sequence-specific replication and subject to self-sustaining Darwinian evolution. CARMA will demonstrate an entirely new chemistry-based system of molecular building blocks comprised of non-biological components, but still capable of self-replication and evolution. Establishment of these molecular replicating systems will have numerous societal benefits, including materials that can self-heal in a self-sustaining manner, repairing themselves akin to how a body heals wounds or become stronger with stress, as do muscles. Activities within this Center will include a public facing website to transfer all technology developed to the broader community, and week-long annual workshops that diversify graduate experiences. CARMA will integrate high school students into university laboratories, and expand an outreach program that sparks scientific excitement in K-6 age children and their families within the Spanish speaking community (“Supper and Science”). Sequence defined chemical chains or polymers and their hybridization will be demonstrated using a set of four chemical “pairs” that have physicochemical properties which both mimic the Watson:Crick isosteres, while simultaneously being very different. CARMA will build upon previously demonstrated TORC (Tunable, Orthogonal, Reversible, Covalent) bonding pairs which associate via dynamic covalent bonding rather than hydrogen bonding. Four classes of reactions are embodied by the TORC pairs: thiol conjugate additions, boronic acid/diol condensations, metal chelation, and amine/carbonyl condensations. Sequence-specific hybridization and subsequent dissociation of polymers containing TORC pairs will be investigated by balancing between the kinetics of association/dissociation and the valency of individual pairs. Distinct combinations of molecular design properties—including different backbone chemistries (e.g., phospho-ribose, peptide, peptoid, urethane), spacing between the TORC pairs, and the number and identity of specific TORC pairs—will enable dynamic and tunable sequence-specific hybridization. Modeling will play a critical role in judiciously guiding and informing synthetic efforts, including the structural characteristics (rigidity) of short sequence motifs across different backbone chemistries, the type of linkages to append the TORC pairs to the backbones, and optimization of regiochemistry. CARMA will explore how TORC bonds and architecture influence the hybridization and ultimate copolymer replication, thereby unlocking strategies for improving the precision of selection and evolution. This will begin with probing the hybridization of ‘perfect’ complementary oligomers to block copolymer templates, followed by examining the impact of dispersity in duplex assembly. CARMA’s investigations will enable critical understanding of the necessary limits on block size and proper TORC pairs to achieve hybridization selection that will set the stage for multiple cycles of hybridization and replication in the future. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.