Understanding Properties of Zwitterionic Materials from Their Molecular Structures

Abstract

Materials that resist nonspecific protein adsorption in complex media are important for many biological and chemical applications, such as surface coatings of biosensors, marine coatings, drug delivery, and therapeutic protein protection. Zwitterionic materials have shown unique properties for this purpose. But two critical questions about zwitterionic materials remain unsolved. First, why are zwitterionic materials different from non-ionic materials? Second, what are the differences among zwitterionic materials? This work aims to answer the two questions and design new zwitterionic materials based on the solutions. To study the differences between zwitterionic and non-ionic materials, this work investigated the effects of carboxybetaine (CB) and oligo(ethylene glycol) (OEG) moieties on protein structure and hydrophobic interactions. Non-ionic OEG moieties present amphiphilic features. They mask the hydrophobic domains of protein surfaces and impede hydrophobic associations in aqueous solutions. Zwitterionic CB moieties present superhydrophilic features. They do not influence hydrophobic substrates and hydrophobic associations. To study the differences among zwitterionic materials, this work studied hydration, ionic interactions, and self-associations of CB and sulfobetaine (SB) moieties; and the influences of carbon spacer length on hydration and ionic interactions of CB moieties. This work employed quantum mechanics, molecular dynamics simulations, free energy perturbation methods and well-tempered metadynamics simulations. Finally, properties of 12 zwitterionic moieties were studied to look for new nonfouling zwitterionic materials. The work suggests three criteria for assessing protein-resistant zwitterionic materials: strong hydration, few or moderate self-associations, and few specific interactions with proteins.