Fe(III) Complexes as the Optical Imaging Probe for <scp>l</scp>-Arginine via the Redox Mechanism

In cell division, the function of amino acid l-arginine (Arg) is crucial, and its inappropriate level in cells is associated with several diseases including cancer cell proliferation. The Fe(III) complexes [Fe(L1)Cl3], 1 (L1 = 1-(pyren-1-yl)-N,N-bis(pyridin-2-ylmethyl)-methanamine and [Fe(L2)Cl3], 2 (L2 = 1-(anthracen-9-yl)-N,N-bis(pyridin-2-ylmethyl)-methanamine) were synthesized and characterized as optical sensor probes for Arg. The EPR spectra of Fe(III) complexes reveal the high-spin nature of the Fe(III) center (g = 8.38, 5.14, 4.21, and 2.15). The X-ray crystallography analysis of 2 showed a distorted octahedral geometry around Fe(III). The Fe(III) complexes 1 and 2 are nonfluorescent, and the pyrene-appended complex 1 showed fluorescence intensity enhancement by the interaction of Arg via the formation of a highly fluorescent Fe(II) complex through the reduction of Fe(III) in HEPES buffer at pH 7. The Arg is coordinated to the Fe(II) center via the O atom from the carboxylate group and the N atom from the deprotonated α-amino group. Similarly, His interaction with 1 showed 50% lower fluorescence intensity enhancement than Arg. However, complex 1 remained insensitive to other amino acids and was nonfluorescent. The redox studies predicted that complexes’ Fe(III)/Fe(II) redox potential is reversible; complex 1 displayed a lower redox potential (−0.358 V vs NHE) than 2 (−0.253 V vs NHE). The Fe(III)/Fe(II) redox couple of 1 (−0.358 V vs NHE) completely disappeared in cyclic voltammetry by the Arg interaction (1:1). Further, complex 1 was employed as an optical probe for imaging Arg in Henrietta Lack cervical cancer cells. The detection limit and binding constant are calculated as 0.4 μM and 4.7 × 104, respectively. However, complex 2 does not show such changes with Arg, and its Fe(III)/Fe(II) redox couple is unaffected. The Cu(II) analogues are found to be nonfluorescent and silent toward all of the amino acids.