Alkyl Chain Appended Fe(III) Catecholate Complex as a Dual-Modal T₁MRI-NIR Fluorescence Imaging Agent via Second Sphere Water Interactions

The C₁₂-alkyl chain-conjugated Fe(III) catecholate complex [Fe(C₁₂CAT)₃]^3-, Fe(C₁₂CAT)₃[C₁₂CAT = N-(3,4-dihydroxyphenethyl)dodecanamide], was synthesized and characterized, reported as a dual-modal T₁-MRI and an optical imaging probe. The DFT-optimized structure of Fe(C₁₂CAT)₃reveals a distorted octahedral coordination geometry around the high spin Fe(III) center. The formation constant (-log K) of Fe(C₁₂CAT)₃was calculated as 45.4. The complex exhibited r₁-relaxivity values of 2.31 ± 0.12 and 1.52 ± 0.06 mM^-1s^-1at 25 and 37 °C, respectively, on 1.41 T at pH 7.3 via second-sphere water interactions. The interaction of Fe(C₁₂CAT)₃with human serum albumin showed concomitant enhancement of r₁-relaxivity to 6.44 ± 0.15 mM^-1s^-1. The MR phantom images are significantly brighter and directly correlate to the concentration of Fe(C₁₂CAT)₃. Adding an external fluorescent marker IR780 dye to Fe(C₁₂CAT)₃leads to the formation of self-assembly by C₁₂-alkyl chains. It resulted in the fluorescence quenching of the dye, and its critical aggregation concentration was calculated as 70 μM. The aggregated matrix of Fe(C₁₂CAT)₃and IR780 dye is spherical, with an average hydrodynamic diameter of 189.5 nm. This self-assembled supramolecular system is found to be non-fluorescent and was "turn-on" under acidic pH via dissociation of aggregates. The r₁-relaxivity is found to be unchanged during the matrix aggregation and disaggregation. The probe showed MRI ON and fluorescent OFF under physiological conditions and MRI ON and fluorescent ON under acidic pH. The cell viability experiments showed that the cells are 80% viable at 1 mM probe concentration. Fluorescence experiments and MR phantom images showed that Fe(C₁₂CAT)₃is a potential dual model imaging probe to visualize the acidic pH environment of the cells.