Spectroscopic Investigation for the Interaction of Mycophenolate Mofetil with Ferrous Ions

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The interaction of mycophenolate mofetil (MMF) with ferrous ions (Fe²⁺) in the solid state, in water, and in polar organic solvents was investigated using ¹H-NMR, ¹³C-NMR, IR, and UV-visible (Vis) spectroscopies. A red-purple colored substance was formed after grinding solid MMF and FeSO₄·7H₂O in a mortar. The IR spectrum of taken as a KBr tablet of the colored substance showed a new absorption band at 1651 cm⁻¹. Although the color disappeared when the sample was dissolved in water, it persisted in organic solvents such as MeOH or dimethyl sulfoxide (DMSO). The UV-Vis spectrum of a 0.25 mM MeOH solution of MMF showed a new absorption maximum at 507 nm in the presence of Fe²⁺ ions, while an aqueous solution of the same mixture showed no significant change from the MMF solution. All the signals in the ¹³C-NMR spectrum in DMSO-d₆ solution were unambiguously assigned. Upon the addition of 0.5 eq. of Fe²⁺ ions, all the carbon signals except those of the 2-morpholinoethyl group almost disappeared, which clearly indicated that the Fe²⁺ ions were located far away from the 2-morpholinoethyl groups in the MMF molecules. On the basis of these results, we have concluded that the MMF–Fe²⁺ complex is actually formed in the solid state as well as in polar organic solvents such as MeOH or DMSO.