In this scientific article published in JPCB, we establish the experimental and theoretical foundation for the use of Second Harmonic Generation (SHG) for solubility and aggregation studies in drug discovery and development. Conventional assays are either accurate but slow and resource-intensive or fast but inaccurate, limiting their usefulness. By exploiting angle-resolved second harmonic scattering, our method detects nanoscale interfacial fluctuations with high sensitivity, reducing the detection limit from ~1 μM to ~1 nM. Classical nucleation theory and nonlinear light scattering modeling reveal that changes in solvent interfacial area prior to aggregation can be precisely monitored with this approach. In additioon, the method reduces drastically the use of compounds and chemicals, reducing the environemental impacts.
Scientific Publication
