J . Phys. Chem. 1991,95,4659-4663 Fourier transformation of the product of this with e% then yields a formal expression for the portion of the absorption intensity for the OH stretching absorption band that arises from the indirect coupling mechanism, in terms of coupling constants and absorption
4659
spectra for each low-frequency mode. In favorable casts, the latter can be experimentally a ~ a i l a b l e , ~thereby * * ~ ~ reducing the theoretical input required to describe the OH stretch spectrum in this indirect mechanism picture.
Porphyrins-Cyclodextrin. 2. Dissociation, Reduction, and Proton Relaxivfty of an Iron( I I I ) Porphyrin pox0 Dimer in Cyciodextrin Solutions S.Mosseri,* J. C.Mialocq,* B. Perly, CEA-CEN Saclay, DSM/DPhG/SCM/URA331 CNRS, F-91191 Gif-sur- Yvette Cedex. France
and P.Hambright Department of Chemistry, Howard University, Washington, D.C. 20059 (Received: September 19, 1990; In Final Form: December 21, 1990)
Spectrophotometricevidence for the dissociation of an Fe(II1) porphyrin p-oxo dimer induced by porphyrin-cyclodextrin complexation in aqueous solution is reported. Depending on the pH, the monomer may be in a diaquo monohydroxo or diaquo dihydroxo form with pK values of 6.4or 8.5,respectively. In the absence of j3-cyclodextrin (8-CD), the p-oxo dimer exists as mono- or dihydroxo species with a pK of 11.7. y- and pulse radiolysis techniques are used to study the Fe(III)/Fe(II) reduction. Fe111TSPP(H20)2 (TSPP is tetrakis(4-sulfonatopheny1)porphyrin) is reduced by hydrated electrons and CHzOH' radicals into Fe11TSPP(Hz0)2whereas Fe111TSPP(OH-)2and (H O)FeTSPP-O-FeTSPP(OH-) are both reduced to the monohydroxo Fe"TSPP(H20)(0H-) monomer. The Fe"-O-Fe tI dimer may be formed in strongly alkaline solution. Measurements of the proton (NMR) relaxivity values of this Fe(II1) porphyrin in the absence and in the presence of 8-CD indicate the possibility of using FeIIITSPP in conjunction with 8-CD as a paramagnetic contrast agent for in vivo imaging of tumors and tissue.
Introduction
With the aim of the in vivo visualization of tumors and tissues
in animals following the administration of paramagnetic contrast agents by applying magnetic resonance imaging' and relaxometry* techniques, several paramagnetic metalloporphyrins have been the subject of intense investigation.',* The relaxivity parameters (slope of the longitudinal spin-lattice relaxation rate of water protons (1 / T I )versus concentration of the agent) of the water soluble iron(111) tetrakis(4sulfonatophenyl)porphyrin (Fe'"TSPP) and iron(Il1) tetrakis(N-methyl-4pyridyl)porphyrin (FeII'TMPyP) changed from favorably high values at pH 1 to undesirably lower values at the physiological pH.* The decrease of the relaxivity at high pH has been attributed to the formation of low-moment p-oxo-bridged, antiferromagnetically coupled Fe-O-Fe dimers from their high-spin monomers, which are stable at low P H . ~ Cyclodextrin' is a polysugar that consists of a hydrophobic cavity (host) capable of enclosing an organic molecule (guest). The resulting modification of the chemical, photochemical, and photophysical properties of a large variety of guest molecules has been widely studied.s-'O Recently we showed that &cycldextrin U-CD), which possesses a cavity diameter of 7.5 A, forms a strong complex with ZnIITSPP in aqueous solution, leading to significant changes in its photochemical properties."*'* We undertook the present study of the interaction of FeIIITSPP with cyclodextrin hoping that this host would inhibit p-oxo dimerization,thus making the iron complex a more attractive imaging agent candidate. This aim was realized, and in addition, the nature of the FelI1FeIITSPP/cyclodextrin species in solution, probed by radiolytic techniques, is also reported. Experimental Section
Materials. FeII'TSPP was provided by Midcentury Chemicals. 8-cyclodextrin (Aldrich) and all the inorganic compounds were analytical grade and used as received. The pHs were adjusted Corresponding authors.
either with potassium hydroxide or perchloric acid, and water was purified by a Millipore Super-Q apparatus. Merhods. The NMR experiments were run at 300 or 500 MHz on a Bruker MSL300 or a WM 500 spectrometer for the normal spectra or relaxivity experiments, respectively. All spectra were collected at room temperature by using a 45O pulse and a 5-s recycling delay to ensure a proper relaxation of all the signals and a correct integral determination. Spin-lattice relaxation times were measured by using the inversion recovery technique at 298
K. UV-visible absorption spectra were recorded with a Beckman UV 5240 spectrophotometer. y-radiolysis experiments were performed with a 6oCosource. Pulse radiolysis was carried out with 3.6 MeV electrons from a Van de Graaff generator. The pulse duration could be varied between 0.5 and 5 ps, depending on the desired dose. The transient signals of optical absorption and conductivity were recorded and processed as described elsewhere.I3 Depending on the time scale of the recording, either (1) Patronas, N. J.; Cohen, J. S.;Knop, R. H.; Dwyer, A. J.; Colche;, D.; Lundy, J.; Mornex, F.; Hambright, P.; Sohn, M.; Myers, C. E. Cancer Treat. Rep. 1986, 70, 391. (2) Lyon, R. C.; Faustino, P. J.; Cohen, J. S.;Katz, A,; Mornex, F.; Colcher. D.; Baglin, C.; Kcenig, S.H.; Hambright, P. Magn. Reson. Med. 1987, 4, 24. (3) Helms, J. H.; ter Haar, L. W.; Hatfield, W. E.; Harris, D. L.; Jayaraj, K.; Toney, G. E.; Gold, A.; Mewborn, T. D.; Pemkrton, J. R. Inorg. Chem. 1986, 25, 2334. (4) Bendar, M. L.; Komiyama. M. Cyclodextrin Chemistry; SpringerVerlag: New York, 1978. (5) Ueno, A,; Yoshimura, H.; Saka, R.; Osa, T. J . Am. Chem. Soc. 1979, 101.2779. (6) Arad-Yellin, R.; Eaton, D. F. J. Phys. Chem. 1983, 87, 5051. (7) Schiller, R. L.; Coates, J. H.; Lincoln, S.F. J . Chem. Soc., Faraday Trans. I 1984,80. 1257. (8) Scypinski, S.;Drake, J. M. J . Phys. Chem. 1985,89, 2432. (9) Kusumoto, Y.; Shizuka, M.; Satake, 1. Chem. Len. 1986. 529. (IO) Ramamurthy, V.; Eaton, D. F. Acc. Chem. Res. 1988, 21, 300. (1 1) Mosseri, S.; Mialocq, J. C. Radiar. Phys. Chem., in press. (12) Mosseri, S.; Mialocq, J. C.; Perly, B.; Hambright, P. J. Phys. Chem. 1991, 95, 2196.
0022-3654191 12095-4659902.50/0 0 1991 American Chemical Society
Mosseri et al.
4660 The Journal of Physical Chemistry, Vol. 95, No. 12, 1991
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