Fe³⁺@polyDOPA‑<i>b</i>‑polysarcosine, a T₁‑Weighted MRI Contrast Agent via Controlled NTA Polymerization

α-Amino acid <i>N</i>-thiocarboxyanhydrides (NTAs) are promising cyclic monomers to synthesize polypeptides and polypeptoids via controlled ring-opening polymerizations. Superior to <i>N</i>-carboxyanhydrides requiring protection on hydroxyl groups, NTAs are able to tolerate such nucleophiles. In this work, we report the synthesis of NTA monomers containing unprotected phenolic hydroxyl groups of 3,4-dihydroxy-l-phenylalanine (DOPA) and l-tyrosine (Tyr). Their controlled ROPs and sequential copolymerizations with polysarcosine (PSar) yield PDOPA, PTyr, and PDOPA-<i>b</i>-polysarcosine (PDOPA-<i>b</i>-PSar) products quantitatively with designable degrees of polymerization. Micellar nanoparticles of Fe³⁺@PDOPA-<i>b</i>-PSar have been prepared thanks to the strong chelation of iron­(III) cation by catechol ligands that act as T1-weighted magnetic resonance imaging (MRI) contrast agents. For instance, Fe³⁺@PDOPA₁₀-<i>b</i>-PSar₅₀ exhibits higher longitudinal relaxivity (<i>r</i>₁ = 5.6 mM^–1 s^–1) than commercial Gd³⁺-based compounds. Effective MRI contrast enhancement in vivo of nude mice with a moderate duration (150 min) and 3D magnetic resonance angiography in rabbit illustrated by using volume rendering and maximal intensity projection techniques ignite the clinical application of Fe³⁺-based polypept­(o)­ides in diagnostic radiology as Gd-free MRI contrast agents