Backbone and side chain-linker tunability among dithiocarbamate, ester and amide in sequence-defined oligomers: synthesis and structure–property–function relationship

Abstract

Structural diversity and tunable properties achieved by a defined monomeric sequence are the trademarks of a sequence-defined polymer (SDP). Herein, we report a modular synthetic platform where, in addition to the provision of changing the side chain, the backbone functional groups of the SDP can also be tuned among three key functional groups, namely dithiocarbamate (DTC), ester and amide. An efficient synthetic strategy has been developed to incorporate DTC into the SDP backbone without the need for separate design of the monomer. This unique strategy with the potential to vary both the backbone as well as the side chain is, to the best of our knowledge, the first report in the field of man-made SDPs. Three different classes of sequence-defined oligomers (SDOs) have been synthesized: (i) SDO1 with DTC alone in the backbone; (ii) SDO2 with DTC and ester in the backbone; and (iii) SDO3 with DTC and ester in the backbone and amide in the side-chain linkage. The structure–activity relationships of the three SDOs were investigated, which is important for their biomedical and material applications. This led to the conclusion that SDO1 with DTC functionality was stable under conditions of hydrolysis, heat and acid treatment, whereas SDO2 (DTC and ester) and SDO3 (DTC, ester and amide) are not stable under those conditions. On the other hand, for applications related to toxic Hg²⁺ removal, SDO3, which contained all three functional groups (DTC, ester and amide), was the most efficient, followed by SDO2 (DTC and ester) with medium efficiency and SDO1 (DTC) with the lowest efficiency. The investigation of the protein binding affinity with serum albumin concluded that all three SDOs are transportable via serum proteins. Taken together, this is a proof-of-concept to explore SDOs with tunable backbones and side-chains to modulate their properties and employ the best suited SDO for any given application.