Online monitoring of dopamine particle formation via continuous light scattering intensity measurement

Abstract Using time resolved total intensity light scattering a two phase process was found in the conversion of 2-(3,4-dihyroxyphenyl)ethylamine, dopamine (DP), into microparticles. Phase 1 appears to involve oxidation of the DP, and may also include oligomerization below the light scattering threshold of detectability. After a certain lag time, the ‘Phase 1 Period’ (P1P), dependent upon reaction conditions, the light scattering increases sharply, heralding the onset of Phase 2. Precipitating particles are eventually formed in latter Phase 2. The solution goes through a series of color changes throughout Phase 1 and 2, starting as pink in Phase 1, and culminating in black particles in Phase 2. The reaction proceeds under virtually any conditions; purged with O 2 or N 2 , unpurged, stirred or unstirred, under different pH conditions, etc. Stirring, increasing temperature, and adding potassium persulfate (KPS), all accelerate the reaction. P1P varied over nearly four orders of magnitude, from 10 s (pH initial  = 9.5) to 8 × 10 4  s (T = 25 °C, no pH control). Arrhenius behavior is found for P1P with low activation energies in the range of 10–25 Kcal/Mole. The precipitating particulates rapidly formed in Phase 2 suggest that they may involve non-covalent associations of oligomers formed in Phase 1, possibly due to loss of oligomeric solubility, in addition to possibly involving covalent polymer branching and cross-linking. Non-covalent aggregation of oligomers formed in Phase 1 seems most likely.