title: Spectroscopic investigation for the interaction of mycophenolate mofetil with ferrous ions.
abstract: The interaction of mycophenolate mofetil (MMF) with ferrous ions (Fe(2+)) in the solid state, in water, and in polar organic solvents was investigated using (1)H-NMR, (13)C-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 Fe(2+) ions, while an aqueous solution of the same mixture showed no significant change from the MMF solution. All the signals in the (13)C-NMR spectrum in DMSO-d6 solution were unambiguously assigned. Upon the addition of 0.5 eq. of Fe(2+) ions, all the carbon signals except those of the 2-morpholinoethyl group almost disappeared, which clearly indicated that the Fe(2+) 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-Fe(2+) complex is actually formed in the solid state as well as in polar organic solvents such as MeOH or DMSO.
authors.affiliation: Department of Pharmacy, Toho University Omori Hospital.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yasuoki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Hikawa
authors.forename: Isao
authors.initials: I
authors.lastname: Azumaya
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakakoshi
authors.forename: Yuusaku
authors.initials: Y
authors.lastname: Yokoyama
mesh_terms: D002413:Cations, Divalent / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002413:Cations, Divalent; D005296:Ferrous Compounds; D007166:Immunosuppressive Agents; D012997:Solvents; D009173:Mycophenolic Acid; D000432:Methanol; D004121:Dimethyl Sulfoxide