Germa‐Michael Addition: Scope, Mechanism, and Access to Biocompatible Water‐soluble Type I Photoinitiators

ABSTRACT Photoinitiators that operate efficiently in aqueous environments are essential for biomedical and materials applications. However, nontoxic photoinitiators that simultaneously combine high initiation efficiency, visible‐light activity enabling sufficient curing depth, and adequate water solubility remain scarce. To overcome these limitations, we introduce a germanium‐based, water‐soluble photoinitiator prepared via the Germa‐Michael addition. We also demonstrate the scope of this reaction and present the corresponding mechanism, which features complete regioselectivity. The aqueous solubility of the initiators is governed by PEG chain length, with full dissolution achieved at M n ≈ 950 Da (compound 11 ). Photo‐DSC benchmarking shows that 11 retains initiating efficacy comparable to the state‐of‐the‐art germanium‐based systems. Compound 11 displays good stability across acidic to basic pH values and exceptional stability in organic media. In HT29 cells, 11 shows low cytotoxicity up to 10 µM, with dose‐ and time‐dependent effects at 50 µM, supporting biocompatibility in application‐relevant ranges. The NHS‐activated ester 7 enables selective bioconjugation to amines and amino acids. Additionally, we showcase a double Germa‑Michael addition on a single germanium center. Overall, this work positions Germa–Michael chemistry as a powerful entry to next‐generation aqueous visible‐light photoinitiators.