## 3 Dihydroxybenzene-Based Building Blocks (Catechol)
### Catechin  
Catechin is a representative flavonoid that is found in plants and has been overlooked during functional polyphenolic coating as a potential building block. In general, there are two methods to form polyphenols by self-assembling catechins in aqueous conditions. The first involves utilizing sodium salts that enhance the cation-\(\pi\) interaction [53], while the other involves generating radicals from catechins by irradiating with UV light for polymerization [54]. There are significant differences in the assembly mechanisms between these two methods. In general, catechol-based phenolic components (especially catecholamines) are more likely to self-polymerize under weak alkaline conditions. However, the mass spectrometry data corresponding to the poly-catechin formed in a saline buffer with a slightly basic pH [55] demonstrated that physically stacked catechins were the majority instead of covalently conjugated catechins such as dimers (or trimers). This indicates that catechin cannot be solely crosslinked under basic conditions, which is a phenomenon that may be attributed to the relatively high pKa values of catechins [56], which induce hydroxyl group protonation to inhibit quinone formation in the catechol groups. According to an existing study, the successful poly-catechin formation can be achieved by inducing the formation of non-covalent cation-\(\pi\) interactions between the catechin and sodium ions [57]. As the polyphenic layer is non-covalently crosslinked, the mechanical stability of the poly-catechin is assumed to be weak. Unfortunately, no fundamental studies on the mechanical stability of the catechin coating have yet been performed. UV irradiation is another technique that can be used for developing self-assembled catechin. Unlike sodium-mediated non-covalent self-assembly, UV irradiation-induced self-assembly involves the generation of free radicals in the molecular structure to trigger covalent cross-linking [54]. After UV irradiation, a strong signal in the higher wavelength region was observed in the UV-vis spectrum due to pigmentation, which is strong evidence of catechin polymerization.  
Catechin-derived polyphenols have been adopted as therapeutic carriers (e.g., drug delivery systems) since they have the advantage of grafting medical agents. In detail, the chemical conjugation between catechols in poly-catechin and nucleophilic functional groups in therapeutic agents can be achieved by a simple one-step functionalization process similar to other catechol-based polyphenols. However, the issue of this approach relies on the irreversible binding between the polyphenic carriers and therapeutic agents, which may reduce or even inactivate their biological activity. Numerous studies have been performed to solve the problem; grafting target biomolecules to polyphenols through reversible dynamic bonding (catechol-boronic acid interactions) is a typical breakthrough strategy [58]. As the developed system showed minimal cytotoxicity, and the therapeutic agents can be released intact, the bioactivities can be successfully conserved. Similarly, a boronate proteasome inhibitor (bortezomib) encapsulated by a poly-catechin-based nanocariser was developed, which allowed the controlled release of undamaged bortezomib at the targeted cancer site [59].