Abstract
Within this PhD Dissertation, we explored the development of sustainable, biocompatible visible-light absorbing photoinitiators as alternatives to conventional [Ru(bpy)₃]²⁺ complexes for hydrogel fabrication, with implications for tissue engineering applications, and additional potential for antimicrobial and anticancer therapies. The research is structured into five interrelated chapters, as outlined below. Chapter 1 introduces the fields of tissue engineering and photocatalysis. A brief overview of photo-crosslinkable hydrogel is presented, highlighting the advantages of employing visiblelight-absorbing photocatalyst. Additionally, a brief overview on currently available photocatalysts and photosensitiser for PDT is provided, along with a discussion of their design criteria. Chapter 2 investigates water-soluble iron(II) complexes with tuneable electronic properties. A series of hetero‐ and homoleptic iron(II) polypyridyl complexes were synthesised in the form of chloride salts. Their photophysical and electrochemical properties were thoroughly investigated and correlated with their catalytic performance in initiating the crosslinking of PVA‐MA and Gel‐MA hydrogels. Notably, the complex Fe7, which exhibited the lowest oxidation potential, demonstrated efficient crosslinking via both photochemical and chemical pathways. Although Fe7 showed greater susceptibility to oxygen inhibition at low concentrations, its ability to decomplex and release bioactive iron(II) ions suggests a potential application in bone regeneration where controlled hydrogel formation and osteogenic ion release are advantageous. Chapter 3 focuses on the synthesis and characterisation of a series of water‐soluble cobalt(III) polypyridyl complexes. These complexes were prepared by oxidising the corresponding cobalt(II) polypyridyl precursors using various oxidants, including liquid bromine, air in conjunction with acid, or cerium(IV) ammonium nitrate. Despite systematic structural tuning and comprehensive characterisation, these complexes did not initiate hydrogel crosslinking under visible‐light irradiation. Factors such as interference from metal‐containing counterions, low visible‐light absorptivity and incompatibility with the macromer crosslinking mechanism v are proposed as underlying limitations, highlighting the challenges in adapting aqueoussoluble cobalt(III) systems for hydrogel photopolymerisation. Chapter 4 examines a family of hydrophobic BODIPY derivatives to establish structure–activity relationships for hydrophobic BODIPY derivatives with respect to persulfate cleavage and SO₄•– generation, processes critical for initiating methacryloyl chain-growth polymerisaiton for hydrogel fabrication. A series of previously reported BODIPY exhibiting broad visible-light absorption spanning 480–550 nm was synthesised and characterised. Owing to their intrinsic hydrophobicity, the use of organic co-solvents was necessitated to ensure compatibility with aqueous hydrogel precursor solution. Although this approach enabled preliminary evaluation of their photocatalytic performance, the incorporation of organic solvents introduced variability in the mechanical properties of the hydrogels and adversely affected biocompatibility. Controlled experiments revealed that structural modifications—specifically, 2,6-iodination to promote heavy-atom effects and the electron-donating substituents at the para position of the 8-phenyl ring—substantially enhanced crosslinking of methacryloylmodified polyvinyl alcohol (PVA-MA) macromers. These findings validate the importance of electronic tuning in optimising BODIPY-driven persulfate activation. Nonetheless, the dependence on organic solvents underscores the necessity to develop aqueous-soluble derivatives, thereby addressing biocompatibility concerns and simplifying the hydrogel fabrication process. This consideration has directed the strategic design of hydrophilic BODIPY systems, as explored in Chapter 5. Chapter 5 builds upon Chapter 4 by rationally designing and synthesising a series of second‑generation, aqueous‑soluble BODIPY derivatives. A new ethylating method was developed to yield charged, aqueous‑compatible BODIPY bromide salts. Several new aqueoussoluble neutral BODIPY structures were synthesised through thiolation. These second-generation photocatalysts were evaluated in various categories of hydrogel precursor solutions. Although some electron-rich BODIPY derivatives degraded upon irradiation, one derivative, B7Et, successfully induced hydrogel crosslinking. Moreover, derivatives B8Et and B9Et exhibited inherent antimicrobial activity, likely due to electrostatic interactions with microbial membranes, thereby offering dual functionality for wound healing and deep-tissue antimicrobial therapy. vi Collectively, this research provides insight into the development of sustainable and cost-effective alternatives to traditional [Ru(bpy)₃]²⁺ photocatalysts for hydrogel crosslinking. The promising performance of Fe7 indicates its potential for the development of bone-regenerative hydrogels, while the new BODIPY derivatives offer both photocatalytic and antimicrobial functionalities. In contrast, the limitations observed with cobalt(III) complexes underscore the necessity for further investigation to fully elucidate their potential in photoinitiated polymerisation processes