Thermodynamic Insights into Protein Adsorption on Supramolecular Assemblies of π-Amphiphiles.

Nonspecific adsorption of proteins on the surface of nanocarriers plays a critical role in their cellular uptake and other biological functions. This article reports vesicular assemblies of two π-amphiphiles (NDI-1 and NDI-2) and thermodynamic aspects of their interaction with bovine serum albumin (BSA). Both contain a hydrophobic naphthalene-diimide (NDI) core and two oligo-oxyethylene (OE) wedges but differ by the presence of the hydrazide group in NDI-1. NDI-2 exhibits a constricted π-stacking and enthalpy-driven adsorption of BSA. In contrast, NDI-1 exhibits a stronger interaction due to enhanced entropy contribution. It is postulated that a tight packing of NDI chromophores in NDI-2 results in an inadequate space in the corona, leading to the dehydration of OE chains, which contributes to the observed enthalpy-driven binding. On the other hand, due to H-bonding along the direction of π-stacking in NDI-1, an enhanced interchromophoric distance provides more space in the shell, resulting in less dehydration of the OE chains, which results in an entropy gain from the BSA binding-induced release of water from the OE chains. Intercalation of an electron-rich pyrene in the electron-deficient NDI-1 stack further reduces the grafting density of the OE chains, resulting in negligible BSA adsorption, similar to a stealth polymer. A correlation can be seen between the thermodynamic landscape of the protein adsorption and the trend of their lower critical solution temperature (LCST), which follows the order NDI-1 + Py < NDI-1 < NDI-2.