Chain stretching in brushes favors sequence recognition for nucleobase-functionalized flexible precise oligomers

Abstract

Six different flexible stereocontrolled oligo(triazole-urethane)s substituted by precise sequences of nucleobases or analogs are synthesized. Molecular dynamics simulations indicate that the flexibility of the backbone leads to unspecific complexation of pairs of oligomers, irrespective of the complementarity of their sequences. This is ascribed to the existence of other interactions between pairs of oligomers, as well as to the spatial blurring of the sequence order encoded in the chemical structure of the chain due to its flexibility. The same conclusions are drawn when investigating the irreversible adsorption of different probe oligomers onto a layer of target oligomers grafted by click chemistry in a mushroom configuration on a silicon substrate. In contrast, when the target oligomers are grafted in denser brush configurations, irreversible adsorption becomes more specific, with it being twice as probable that probe chains of complementary sequence would be irreversibly-bound to the layer of target chains than those of non-complementary sequence. This is ascribed to lateral excluded volume interactions between chains in the brush, leading to partial chain stretching and increased spatial preservation of the information contained in the monomer sequence of the chains. At even higher grafting densities, however, the penetration of the probe chains in the brush becomes increasingly difficult, resulting in a loss of binding efficiency. Our work thus demonstrates the adverse role of chain flexibility in the specificity of complexation between nucleobase-functionalized oligomers and provides directions for an improvement of specificity by tuning the grafting density of target chains on a substrate.