Internal and external catalysis in boronic ester networks

In dynamic materials, the reversible condensation between boronic acids and diols provides adaptability, self-healing ability, and responsiveness to small molecules and pH. Recent work has shown that the thermodynamics and kinetics of bond exchange determine the mechanical properties of dynamic polymer networks. However, prior studies have focused on how structural and environmental factors influence boronic acid–diol binding affinity, and design rules for tuning the kinetics of this dynamic bond are lacking. In this work, we investigate the effects of diol (or polyol) structure and salt additives on the rate of bond exchange, binding affinity, and the mechanical properties of the corresponding polymer networks. To better mimic the environment of polymer networks in our small-molecule model systems, we incorporated proximal amide groups, which are used to conjugate diols to polymers, and included salts commonly found in buffers. Using one-dimensional selective exchange spectroscopy (1D EXSY), we find that both proximal amides and buffering anions induce significant rate acceleration consistent with internal and external catalysis, respectively. This rate acceleration is reflected in the stress relaxation of gels formed using PEG modified with different alcohols, and in the presence of salts containing acetate or phosphate. These findings contribute to the fundamental understanding of the boronic ester dynamic bond and offer new molecular strategies to tune the macromolecular properties of dynamic materials.

Identification of weak non-canonical base pairs around riboswitch-ligand recognition sites by solid-state NMR exchange spectroscopy

Base pairs are fundamental building blocks of RNA structures, and their stability and open-close equilibrium constitutes the dynamic picture. Weak base pairs, which feature the characteristics of low stability and rapid base pair opening, often play a critical role in RNA functions. However, site-specific identification of weak base pairs in RNA is challenging. Here, we report a solid-state NMR (SSNMR)-based two-dimensional proton-detected water–RNA exchange spectroscopy (WaterREXSY) to address this challenge. The approach uses the chemical exchange between hydrogen-bonded imino protons within the base pair and excited water molecules to polarize the imino protons for SSNMR observation. This process takes advantages that the imino protons within weak pairs undergo fast exchange rates with water, enabling a quick build-up and efficient detection. This method is used to characterize the weak pair in the riboA71–adenine complex (i.e., the 71nt-aptamer domain of the add adenine riboswitch from Vibrio vulnificus). We identify U47•U51, a weak non-canonical base pair that constitutes the U47•U51•(adenine-U74) base tetrad around the ligand-binding pocket. This result suggests that the breakage of U47•U51 may be the early stage in the process of ligand release.