Chirality and concentration govern polycatecholamine self-assembly: a comparative study of dopamine, levodopa, and norepinephrine

Polycatecholamines (pCAs), including poly(dopamine) (pDA), poly(levodopa) (pLD) and poly(norepinephrine) (pNE), hold enormous potential in biomaterials science in the form of functional coatings and particles due to their adhesive and versatile physicochemical properties. However, while pDA has been extensively studied, the potential of pLD and pNE has yet to be fully explored. To bridge this gap, this study provides a comparative analysis of dopamine (DA), levodopa (LD), L-norepinephrine (L-NE), and racemic norepinephrine (rac-NE), focusing on how precursor chemistry, concentration (0.5 <i>vs.</i> 2.0 mg mL^-1), and NE chirality influence polymerization kinetics and particle formation. By employing dual-wavelength absorbance (450 nm, <i>A</i>₄₅₀; 600 nm, <i>A</i>₆₀₀) measurements, we revealed distinct concentration-dependent effects, with higher concentrations accelerating monomer-to-intermediate transitions and inducing saturation kinetics. Dynamic light scattering (DLS) highlighted particle size evolution, showing how the zwitterionic character of pLD and chirality in pNE affect stability and size distribution. Additionally, we introduced the polymer dispersion ratio (PDR), a novel metric mapping spatial and temporal aggregate distribution, identifying distinct aggregation and sedimentation patterns. Results from this study underscore the critical role of precursor concentration and chirality in shaping the properties of pCA coatings, namely the temporal evolution of the surface-deposited polymer. Ultimately, this framework informs the synthesis and selection of pCAs for biomedical applications, including functional (<i>e.g.</i>, cell-instructive, antibacterial) coatings with tailored topography for implantable devices, drug-eluting platforms, and bioadhesive technologies, while also translating to broader research areas which could benefit from these findings, such as energy storage and environmental remediation, among others.