# Recent Advances in Intrinsically Fluorescent
## 2 Preparation Principle  
At present, although there have been many reports on PDA applications, the formation mechanism of PDA has not yet been clarified. However, with an increasing research interest in PDA-based sensing and imaging, better chemical and physical performances are desired. There seems to be a high need to understand the basic structure-property-function relationships and to devise application for drug delivery and other fields [39]. To understand the synthesis method and mechanism of FPDA, it is necessary to clarify the mainstream PDA formation mechanism. In the early stages of this research field, the structural model of melanin plays an important guiding role in studying the self-polymerization of dopamine [40; 41; 42; 43]. DA is oxidized to dopamine quinone by dehydrogenation of catechol under alkaline aerobic conditions. The dopamine quinone is unstable and easy to cyclize to form a leucodopaminechrome yield [44]. Thereafter, leucodopaminechrome is further oxidized to dopaminergic. The oxidized heterogeneous forms 5,6-dihydroxyindole (DHI), which is easily oxidized to 5,6-indolequinone. DHI attacks dopamine quinone or other quinone oligomers to generate oligomers with mixed structures. [PERSON] et al. utilized solid state spectroscopic and crystallographic techniques to suggest the polydopamine supramolecular aggregate of monomers (consisting primarily of 5,6-dihydroxyindole and its dione derivative dopaminochrome), which are held together through a combination of charge transfer, \(\pi\)-stacking, and hydrogen-bonding interactions [19]. In parallel with these two models, [PERSON] et al. suggested that a combination of non-covalent self-assembly and covalent polymerization is the mechanism of dopamine formation [45]. Therefore, the aggregation of various unit molecules and the intra- and intermolecular coupling lead to the  
Figure 1: A brief timeline for the development of fluorescent polydopamine. low quantum yield of PDA [46]. To increase the fluorescence intensity and quantum yield of PDA, it is necessary to break the intramolecular coupling, reduce the \(\pi\)-\(\pi\) accumulation of oligomeric units in PDA nanoparticles, and form small molecule oligomers. At present, the solution oxidation method is a common way to synthesize PDA. [PERSON] et al. used hydrogen peroxide to oxidize PDA to obtain fluorescent polydopamine and open a new chapter in the preparation of FPDA by solution oxidation [22]. The increasing fluorescence intensity and quantum yield (1.2%) attributed to the hydroxyl can effectively reduce the \(\pi\)-\(\pi\) stacking of the conjugated skeleton [28]. [PERSON] et al. employed magnetic iron oxide (Fe\({}_{3}\)O\({}_{4}\)) nanoparticles as a peroxidase-mimicking enzyme to catalyze hydrogen peroxide to produce hydroxyl radicals which could prepare FPDA in mild conditions [38]. Fe\({}_{3}\)O\({}_{4}\) NPs reduce the concentration of H\({}_{2}\)O\({}_{2}\) and prevent excessive harmful free radicals from being produced, which benefits the application of FPDA. However, the synthesis of nanoscale enzymes is more complicated and technical, and a convenient way is needed to avoid the use of highly concentrated H\({}_{2}\)O\({}_{2}\) (e.g., up to 6%). [PERSON] et al. used metal ions and H\({}_{2}\)O\({}_{2}\) to synthesize water-soluble fluorescent polydopamine nanoparticles in acidic conditions [39]. The prepared PDA displayed excitation-independent emission and excellent photostability. Previous reports suggested that Cu\({}^{2+}\) ions can both oxidize the catechol groups and induce the aggregation of molecules containing catechol groups due to coordination interaction and may accelerate the polymerization of dopamine [47]. Another general method to prepare FPDA and improve quantum yield is doping with N atoms to destroy the intermolecular and intramolecular cross-linking of polydopamine [48]. In 2015, [PERSON] et al. used polyethyleneimine (PEI) and DA, stirring for 2 h at room temperature to obtain PEI-PDA particles by doping nitrogen atoms for the first time [34].