Molecular Duplexes with Encoded Sequences and Stabilities

Abstract

Through specific molecular shapes and repeating polymeric sequences, biomacromolecules encode information about both structure and function. Inspired by DNA molecules, we have conceived a strategy to encode linear molecular strands with sequences that specify intermolecular association, and we and our collaborators have supported this idea through our experimental work. This Account summarizes the design and development of a class of molecular duplexes with programmable hydrogen-bonding sequences and adjustable stabilities. The specific system involves oligoamide strands synthesized from readily available monomeric modules based on standard amide (peptide) chemistry. By covalently linking three types of basic building blocks in different orders, we create oligoamide strands with various arrangements of amide O and H atoms that provide arrays of hydrogen bonding sequences. Because one of the two edges of these molecules presents the sequences of hydrogen-bond donors and acceptors, these oligoamide strands associate via their hydrogen-bonding edges into double-stranded pairs or duplexes. Systematic studies have demonstrated the strict sequence specificity and tunable stability of this system. These structurally simple duplexes exhibit many features associated with DNA sequences such as programmable sequence specificity, shape and hydrogen-bonding complementarity, and cooperativity of multipoint interactions. Capable of specifying intermolecular associations, these duplexes have formed supramolecular structures such as β-sheets and non-covalent block copolymers and have templated chemical reactions. The incorporation of dynamic covalent interactions into these H-bonded duplexes has created association units that undergo sequence-specific association and covalent ligation in both nonpolar solvents and polar media including water. These new association units may facilitate the development of new dynamic covalent structures, and new properties are emerging from these structures. For example, we discovered hydrogen-bonded duplexes that could gelate different organic solvents, and we could tune the gelatinization by adjusting the multiple side chains attached to the duplexes. In addition, we have recently designed duplexes whose formation and dissociation are controlled by changes in external stimuli such as acidity. With their programmable specificity and tunable stability, these molecular duplexes have provided a systematic approach for the association of different structural units. Further development of this system could facilitate the creation of many supramolecular and dynamic covalent structures. Because these duplexes are easily modifiable and information is easily encoded and retrieved, this system may address some of the remaining challenges facing information-storing molecules including self-replication.