Biotin Conjugated Fe(III)‐Triscatecholate Complex as Tumour Targeting T₁ MRI Contrast Agent via Second Sphere Water Relaxation

The biotin-conjugated Fe(III) catecholate complex [Fe(BioL)₃]^3-, Fe(BioL)₃ (BioLH₂=N-(3,4-dihydroxyphenethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide) is reported as targeted magnetic resonance imaging (MRI) contrast agents (CAs) to increase the payload for early-stage imaging of tumours. The high spin state and octahedral coordination of the Fe(III) complex are confirmed by EPR spectra and DFT optimized structure, respectively. The overall formation constant (log K) of Fe(BioL)₃ is determined as 45, which is higher than the known, more stable complex [Fe(EDTA)]. The complex Fe(BioL)₃ exhibited r₁ relaxivity of 3.09±0.10 and 1.95±0.09 mM^-1 s^-1 at 25 °C and 37 °C, respectively, at 1.41 T and pH 7.35 via second-sphere water interactions as due to the absence of inner water coordination. The interaction of Fe(BioL)₃ with bovine serum albumin (BSA) and human serum albumin (HSA) displayed enhanced relaxivity of 5.16±0.15 and 10.0±0.19 mM^-1 s^-1, respectively, at 25 °C and pH 7.3 possibly via lengthening of rotational correlational time. The complex Fe(BioL)₃ uptake studies with the avidin, a biotin-binding protein pocket, showed 46 and 37 % enhancements of r₁ and r₂ relaxivities. Complex Fe(BioL)₃ showed 80 % cell viability of the human gastric adenocarcinoma (AGS) cells, and 89 % of iron has been uptaken into cells.