Polymerization mechanism of dopamine resolved: A story of strong π stacking

The polymerisation mechanism of dopamine in aqueous solutions has puzzled the scientific community for a couple of decades.1–4 After the initial cyclisation, dopamine undergoes a rapid polymerization by forming a black precipitate called polydopamine (PDA) found to be insoluble in all organic solvents.5 This has prevented the resolution of polydopamine’s structure as solid-state characterization techniques have not been conclusive in their findings. Interest in polydopamine originates from its ability to exhibit strong antimicrobial and adhesive properties, making it a versatile coating material for corrosion prevention, implanted medical devices and even drug delivery.4,6,7 Recently, select ionic liquids (ILs) were discovered to dissolve polydopamine, thus enabling the use of liquid-phase characterization techniques to decipher its structure.8,9 In this study we identify the mechanism of dopamine polymerisation in a series of ionic liquids using in-situ solution-phase 1H NMR spectroscopy. We show that after the 5,6-dihydroxyindole (DHI) monomer is formed with the aid of basic IL anions, it undergoes rapid dimerization via the 2-2′, 2-4′and 2-7′ routes on the indole ring forming covalently bonded dimers. The dimers were observed to aggregate via strong 𝜋 stacking interactions forming cylindrical shapes of 36 Å in length supported by ab initio calculations, FTIR and SAXS measurements. These findings conclusively confirm that covalently bonded dimers of DHI are the essential building blocks of PDA. The previously proposed models of PDA’s structure can be ruled out, suggesting that unique adhesive properties of PDA stem from strong 𝜋 stacking forces of the indole moiety. Ionic liquids containing basic anions have demonstrated their ability to initiate and slow down the polymerization of dopamine, thus opening a new chapter for discovery of polymerisation pathways of catecholamines enabling the synthesis of organic surface coatings with superior properties.