Mechanistic Understanding and Nanomechanics of Multiple Hydrogen-Bonding Interactions in Aqueous Environment

Hydrogen-bonding interaction is one of the most developed approaches for generating supramolecular polymers, and self-assemblies solely based on hydrogen bonds are generally unstable in water. Although considerable efforts have been made to improve the stability of the hydrogen-bonded arrays by other interactions such as hydrophobic interactions, it still remains a challenge to elucidate the effects of surrounding environment on hydrogen bonding at the single-molecular level, which is crucial for developing desired hydrogen-bonded structures. In this work, for the first time, single-molecule force spectroscopy was employed to characterize the binding strength and dynamics of hydrogen-bonded 2-ureido-4[1H]-pyrimidinone (UPy) dimers in water in combination with molecular dynamics (MD) simulations, and the hydrophobic effect was investigated by tethering alkylene spacers of different lengths to the hydrogen binding moieties. The rupture force and unbinding energy of self-complementary UPy-UPy dimers were found to be remarkably enhanced with increasing spacer length, which reveals cooperative effect between hydrogen bonding and hydrophobic interactions. In good agreement, the MD simulations on interactions of UPy-UPy dimers also indicate higher structural stability with longer hydrophobic spacers. Our results provide quantitative information and fundamental insights into the understanding of the multiple hydrogen-bonding interactions in aqueous environment, with important implications on the design of hydrogen-bonded assemblies for various bioengineering and engineering applications, such as functional molecular machines, novel self-organized structures, and advanced soft materials.