Alkyl Chain\nAppended Fe(III) Catecholate Complex as\na Dual-Modal <i>T</i><sub>1</sub> MRI–NIR Fluorescence\nImaging Agent via Second Sphere Water Interactions

The C₁₂-alkyl chain-conjugated Fe­(III) catecholate\ncomplex\n[Fe­(C₁₂CAT)₃]^3–, <b>Fe</b>(<b>C</b>_<b>12</b><b>CAT</b>)_<b>3</b> [C₁₂CAT = <i>N</i>-(3,4-dihydroxyphenethyl)­dodecanamide],\nwas synthesized and characterized, reported as a dual-modal <i>T</i>₁-MRI and an optical imaging probe. The DFT-optimized\nstructure of <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b> reveals a distorted octahedral coordination\ngeometry around the high spin Fe­(III) center. The formation constant\n(−log K) of <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b> was calculated as 45.4. The\ncomplex exhibited <i>r</i>₁-relaxivity values\nof 2.31 ± 0.12 and 1.52 ± 0.06 mM^–1 s^–1 at 25 and 37 °C, respectively, on 1.41 T at\npH 7.3 via second-sphere water interactions. The interaction of <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b> with human serum albumin showed concomitant enhancement\nof <i>r</i>₁-relaxivity to 6.44 ± 0.15 mM^–1 s^–1. The MR phantom images are\nsignificantly brighter and directly correlate to the concentration\nof <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b>. Adding an external fluorescent marker IR780\ndye to <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b> leads to the formation of self-assembly\nby C₁₂-alkyl chains. It resulted in the fluorescence quenching\nof the dye, and its critical aggregation concentration was calculated\nas 70 μM. The aggregated matrix of <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b> and IR780\ndye is spherical, with an average hydrodynamic diameter of 189.5 nm.\nThis self-assembled supramolecular system is found to be non-fluorescent\nand was “turn-on” under acidic pH via dissociation of\naggregates. The <i>r</i>₁-relaxivity is found\nto be unchanged during the matrix aggregation and disaggregation.\nThe probe showed MRI ON and fluorescent OFF under physiological conditions\nand MRI ON and fluorescent ON under acidic pH. The cell viability\nexperiments showed that the cells are 80% viable at 1 mM probe concentration.\nFluorescence experiments and MR phantom images showed that <b>Fe­(C</b>_<b>12</b><b>CAT)</b>_<b>3</b> is a potential dual model imaging probe to visualize the acidic\npH environment of the cells.