Probing the protein–nanoparticle interface: the role of aromatic substitution pattern on affinity

A new class of cationic gold nanoparticles (NPs) has been synthesised bearing benzyl moieties featuring –NO₂ and –OMe groups to investigate the regioisomeric control of aromatic NP–protein recognition. In general, NPs bearing electron-withdrawing groups demonstrated higher binding affinities towards green fluorescent protein (GFP) than NPs bearing electron-donating groups. Significantly, a ～7.5- and ～4.3-fold increase in binding with GFP was observed for –NO₂ groups in meta-position and para-position, respectively, while ortho-substitution showed binding similar to the unsubstituted ring. These findings demonstrated that the NP–protein interaction can be controlled by tuning the spatial orientation and the relative electronic properties of the aromatic substituents. This improved biomolecular recognition provides opportunities for enhanced biosensing and functional protein delivery to the cells.