Synthesis, Elemental Analysis, and Mössbauer Characterization of Copper(II), Iron(III), Zinc(II), Manganese(II), and Chromium(III) Complexes of Bisantrene and Anthracen-9-Imidazoline Hydrazone

Bisantrene (9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone]) and its monosubstituted analogue anthracen-9-imidazoline hydrazone (9-AIH) are bioactive anthracene derivatives whose antitumor activity stems from DNA intercalation and topoisomerase II inhibition. Bisantrene lacks the quinone–hydroquinone redox system responsible for anthracycline cardiotoxicity and was recently identified as a potent inhibitor of the RNA demethylase FTO, adding an epitranscriptomic dimension that has renewed interest in the scaffold. Here, we report the stepwise synthesis of 9-AIH (65%; m.p. 282 °C) and bisantrene (60%; m.p. 244 °C) by condensation of the corresponding anthracene carboxaldehydes with 2-hydrazino-2-imidazoline hydrobromide, followed by complexation with Cu(II), Fe(III), Zn(II), Mn(II), and Cr(III) chloride salts to afford ten reaction products. Product identity was confirmed by melting point, elemental analysis (C, H, N by combustion; metal content by classical volumetric titration), and qualitative ionic testing before and after acid digestion. Nine of the ten products gave elemental analyses consistent with discrete mononuclear [9-AIH·M] or binuclear [Bis·M2] coordination compounds. Eight of these nine match calculated values; the ninth, Bis·Cu, deviates by up to 3.3 percentage points (Cu content), a deviation quantitatively accounted for by a co-precipitated Cu2O impurity phase identified by XRD rather than by failure of complexation. The tenth product, from the bisantrene/FeCl3 reaction (Bis·Fe), did not match any discrete coordination formula. Room-temperature 57Fe Mössbauer spectroscopy of this material resolved two quadrupole doublets with isomer shifts and quadrupole splittings closely matching literature values for akaganeite (β-FeOOH), independently confirming, at the level of local iron coordination environment, that the isolated solid is dominated by a hydrolyzed iron oxyhydroxide phase rather than a discrete bisantrene–Fe(III) complex. FTIR and X-ray powder diffraction of the zinc(II) complexes revealed a diagnostic C=N (azomethine/hydrazone) shift upon coordination and closely related diffraction patterns, consistent with a common N,N-donor environment across both ligands. These results establish the feasibility of metal-directed functionalization of bisantrene-type ligands across a broad range of first-row transition metals and identify iron(III) as an outlier under the present conditions, opening a route to metallodrugs that combine bisantrene’s established and newly discovered pharmacophores with the enhanced bioactivity conferred by metal coordination.