**3. Dopamine Polymerization**

The self-assembly of polymer molecules has gained significant research attention in research and development because of the versatility of the process, its practicability, and its ability to form products with a broad range of morphologies, including hierarchical assemblies, cylinders, vesicles, and micelles [52]. Polydopamine is a versatile organic molecule that can be deposited onto any substrate at the nanoscale; this means that the material might act as a suitable coat or primer [52–54]. The versatile chemistry of polydopamine is linked to the molecule's ability to form strong covalent bonds [54], physical interactions associated with π-interactions, hydrogen bonding, presence of different surface functional groups including amines, and thiols [54]. However, surface functionalization in isolation does not explain the broad commercial application of dopamine and polydopamine; the material exhibits appropriate antibacterial activities through gelation [54].

The extensive conjugation influences the application of polydopamine coatings in polymers, ceramics, and metals [53]. The extended application of polydopamine in the coating is augmented by extended bio-conjugation, which is integral in the bio-adhesion of protein molecules, adsorption-resistant surfaces, drug delivery systems, contrast agents, and bioadhesives. The adhesion properties of polydopamine are also vital in cardiovascular, diagnostic, and neurotechnology applications [53]. In other cases, the polydopamine

coatings have been proven useful in the surface functionalization at the nanoscale to enhance the chemical and electronic properties [55].

The oxidative polymerization of dopamine primarily occurs in the presence of aminoethyl and catechol groups, which are catalysts for oxidative polymerization [56]—a process that is integral to the formation of PDA nano-coatings and polydopamine coatings [57] through the formation of the aromatic rings of dopamine. Recently, there has been a growing demand for nano-coatings developed using dopamine polymerization techniques; this could be attributed to the capability for secondary modification, generalizability, and simplicity of the synthetic process relative to other techniques [57].

Other unique applications of dopamine polymerization include the electrochemical analysis of dopamine, uric acid, and ascorbic acid using hollow nitrogen-doped carbon microspheres (HNCMS)-based glassy electrodes [58]. The application of dopamine polymerization in biosensors and bioelectronics documented by Xiao et al. [58] was corroborated by Kalimuthu and John [59], who reported successful electrochemical determination of xanthine, ascorbic acid, dopamine, and uric acid using 2-amino-1, 3, 4-thiadiazole (p-ATD) modified glassy carbon electrodes.

The application of dopamine polymerization in biosensors and bioelectronics and the development of the desired products in manufacturing applications depends on a broad array of factors such as size control of polydopamine nodules and chemical composition of the precursors (carboxylic acid-containing compounds) [60]. The carboxylic-acid-containing compounds introduce an acidic environment, which yields products with unique chemical characteristics compared to dopamine polymerization under basic conditions.

Even though the findings reported by Chen et al. [61] seem to favor acidic dopamine polymerization, basic polymerization techniques have yielded stable products through the customization of the synthesis process. Du et al. [57] observed that the challenges associated with dopamine polymerization under basic environments could be offset by light-triggered regulation of light initiation and termination of dopamine polymerization; this was achieved through the incorporation of small quantities of antioxidant Vitamin C (sodium ascorbate). Vitamin C contributed to the inhibition of the polymerization process under basic conditions—a process that has remained a challenge in traditional synthesis. Du et al. [57] attributed the superior performance to Vitamin C's ability to delay/inhibit dopamine polymerization and reduce the reactive dopamine quinone. The inhibition process can be halted through UV irradiation. Once vitamin C is exposed to UV radiation, instantaneous dopamine polymerization is achieved. The customization of the process using a natural antioxidant and UV radiation helps to explain why it was feasible to attain optimal dopamine polymerization under basic conditions through a facile, scalable, and environmentally benign process.

Fichman and Schneider [54] reported a facile synthetic route for dopamine polymerization under basic conditions in the absence of Vitamin C. Optimal polymerization was achieved in this case through gelation of 1 wt% MAX1 peptide; this experiment was conducted in the presence of 10 mM dopamine at neutral pH [54], and molecular oxygen. The process resulted in the spontaneous polymerization of dopamine. The temperature was adjusted to room temperature to trigger a hydrophobic effect, which was instrumental in promoting MAX1 assembly. Considering that the final product exhibited a 66-fold improvement in mechanical rigidity relative to other materials synthesized using alternative synthetic routes [54], sodium ascorbate is not a prerequisite.

The reports of the positive synthesis of polydopamine and dopamine under basic and acidic conditions by Chen et al. [61], Du et al. [57], Fichman and Schneider [54], Kwon and Bettinger [53], and Qui et al. [52] do not address other emergent challenges such as the relationship between film thickness and solution pH, dopamine concentration and self-polymerization time optimization. The critical requirements for the process underscore the need to select a suitable pH range for the controlled synthesis of materials with the desired film thickness, mechanical rigidity, and industrial/biological performance.
