J. Am. Chem. Soc. 2000, 122, 8289-8298
8289
Influence of Large Metal Cations on the Photophysical Properties of Texaphyrin, a Rigid Aromatic Chromophore Dirk M. Guldi,*,† Tarak D. Mody,‡ Nikolay N. Gerasimchuk,‡ Darren Magda,‡ and Jonathan L. Sessler*,§ Contribution from the Radiation Laboratory, UniVersity of Notre Dame, Notre Dame, Indiana 46556, Pharmacyclics, Inc., 995 East Arques AVenue, SunnyVale, California 94086, and Department of Chemistry and Biochemistry, UniVersity of Texas at Austin, Austin, Texas 78712 ReceiVed May 8, 2000. ReVised Manuscript ReceiVed June 16, 2000
Abstract: The excited-state properties, including singlet oxygen quantum yields, of a series of metallotexaphyrins (M-Tex), containing coordinated paramagnetic and also diamagnetic lanthanide(III) and other cations, are reported as are the solution-phase magnetic susceptibilities of the paramagnetic species. It is found that the singlet (1.593-1.638 eV) and triplet excited-state (1.478-1.498 eV) energies are only marginally affected by the choice of coordinated metal species. By contrast, photophysical parameters that are directly associated with the intrinsic decay rates of, for example, the singlet excited state, such as fluorescence lifetimes, reveal a strong dependence on the nature of the coordinated metal species. In particular, for the series of diamagnetic metals including Y-Tex, In-Tex, Lu-Tex, and Cd-Tex, an increase in atomic number leads to notably shorter lifetimes (τfluorescence(Y-Tex) ) 1298 ps, τfluorescence(Lu-Tex) ) 414 ps), a result that is interpreted as a heavy atom effect. The paramagnetic species, as a general rule, give rise to much shorter fluorescence lifetimes (τfluorescence ) 99-515 ps) as compared to their diamagnetic analogues and are seen to fluoresce weakly, with fluorescence quantum yields (ΦF ) 0.0002-0.0028) that are at least 1 order of magnitude smaller than those found for the corresponding diamagnetic species (ΦF ) 0.015-0.04). Similar trends were also noted for the intersystem crossing rates and the triplet lifetimes, a finding that is interpreted in terms of an enhanced coupling between the singlet excited and triplet states or triplet excited and singlet ground states, respectively. The magnetic moments of the paramagnetic lanthanide(III) texaphyrin complexes were found to correlate well with the fluorescence lifetimes and the intersystem crossing rates, an observation that, along with other findings, including analyses of diamagnetic texaphyrin complexes, is considered consistent with the presence of covalent interactions between the texaphyrin ligand and the various coordinated metal centers.
Introduction The investigation of metal complexes provides an experimental basis for understanding the effect of metal cations on the photophysical properties of coordinating ligands. In the specific case of the trivalent lanthanides, a class of cations made interesting by their obvious internal congruence in terms of charge (albeit not ionic radius or magnetic moment), such studies have been almost entirely limited to porphyrin-based complexes due to a generalized lack of ligands that provide 1:1 complexes of high kinetic stability.1-6 The recent advent of metallotexaphyrins (M-Tex) is now changing this latter situation; these systems contain five nearly coplanar nitrogen donor atoms (cf. Figure 1) and form nonlabile 1:1 complexes with lanthanide(III) cations that are far superior to the corresponding porphyrin †
University of Notre Dame. Pharmacyclics, Inc. § University of Texas at Austin. (1) Gouterman, M.; Schumaker, C. D.; Srivastava, T. S.; Yonetani, T. Chem. Phys. Lett. 1976, 40, 456-461. (2) Tsvirko, M. P.; Stelmakh, G. F.; Pyatosin, V. E.; Solovyov, K. N.; Kachura, T. F.; Piskarskas, A. S.; Gadonas, R. A. Chem. Phys. 1986, 106, 467-476. (3) Aaviksoo, J.; Freiberg, A.; Savikhin, S.; Stelmakh, G. F.; Tsvirko, M. P. Chem. Phys. Lett. 1984, 111, 275-278. (4) Tsvirko, M. P.; Stelmakh, G. F.; Pyatosin, V. E.; Solovyov, K. N.; Kachura, T. F. Chem. Phys. Lett. 1980, 73, 80-83. (5) Martarano, L. A.; Wong, C.-P.; Horrocks, W. D.; Goncalves, A. M. P. J. Phys. Chem. 1976, 80, 2389-2393. ‡
systems in terms of their kinetic stability.7-10 In this paper, we report a detailed photophysical analysis of various metallotexaphyrins, including those of the lanthanide(III) series.11 Briefly, in the case of the paramagnetic complexes derived from Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III), Tm(III), and Yb(III), the triplet lifetimes and intersystem crossing rates are found to depend on the magnitude of the magnetic moment of the metal cation. In the case of the (6) A considerable body of work has been devoted to exploring the “opposite problem”, namely the effects of ligands on the absorption and luminescent properties of the lanthanide cations themselves. For a leading reference, see: Balzani, V.; Scandola, F. Supramolecular Photochemistry; Ellis Horwood: New York, 1991; pp 326-330. See also: Beitz, J. V. Similarities and Differences in Trivalent Lanthanide- and Actinide-ion Solution Absorption Spectra and Luminescence Studies. In Handbook on the Physics and Chemistry of Rare Earths, Vol. 18sLanthanides/Actinides: Chemistry; Gschneider, K. A., Jr., Eyring, L., Choppin, G. R., Lander, G. H., Eds.; Elsevier Science BV: Amsterdam, 1994; pp 159195. (7) Sessler, J. L.; Mody, T. D.; Hemmi, G. W.; Lynch, V. Inorg. Chem. 1993, 32, 3175-3187. (8) Sessler, J. L.; Hemmi, G.; Mody, T. D.; Murai, T.; Burrell, A.; Young, S. W. Acc. Chem. Res. 1994, 27, 43-50. (9) Mody, T. D.; Sessler, J. L. Porphyrin and Expanded Porphyrin Based Diagnostic and Therapeutic Agents. In Supramolecular Materials and Technologies; Reinhoudt, D. N., Ed.; Wiley: New York, 1999; pp 245294. (10) Mody, T. D.; Fu, L.; Sessler, J. L. Prog. Inorg. Chem., in press. (11) For the results of an early preliminary study, see: Harriman, A.; Maiya, B. G.; Murai, T.; Hemmi, G.; Sessler, J. L.; Mallouk, T. E. J. Chem. Soc., Chem. Commun. 1989, 314-316.
10.1021/ja001578b CCC: $19.00 © 2000 American Chemical Society Published on Web 08/06/2000
8290 J. Am. Chem. Soc., Vol. 122, No. 34, 2000
Figure 1. Compounds used in this study. For Cd-Tex, M ) Cd and n ) 1. For all other metallotexaphyrins complexes, Y-Tex, In-Tex, LuTex, Nd-Tex, Sm-Tex, Eu-Tex, Gd-Tex, Tb-Tex, Dy-Tex, Ho-Tex, ErTex, Tm-Tex, Yb-Tex, n ) 2 and M ) Y, In, Lu, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb, respectively.
diamagnetic Y(III), In(III), and Lu(III) complexes, the singlet lifetime, triplet lifetime, and intersystem crossing rate are found to correlate with the atomic number of the cation. We interpret these findings as evidence of covalency in the metal-texaphyrin bonding interactions. While bearing important analogy to the porphyrins, the texaphyrins differ from these prototypical aromatic ligands in several important ways.7-10 First, as noted above, they contain five, not four, nitrogen donor atoms. Second, they possess cores that are roughly 20% larger than those of the porphyrins and generally coordinate cations that are bigger. Third, they act as monoanionic, rather than dianionic, ligands when complexed to cationic metal centers. Finally, incorporating a Hu¨ckel aromatic periphery of 22 π-electrons (instead of 18 π-electrons), they possess a greater degree of aromatic delocalization and display spectral features, such as absorption and emission bands, that are substantially red-shifted compared to those of the porphyrins. The lowest energy or Q-band maximum of texaphyrin complexes typically occurs around 730 nm,7-10,12-15 a region where human tissues are relatively transparent.16 This property has led to the development of the Lu(III) texaphyrin complex (Lu-Tex, motexafin lutetium; CAS Registry No. (provided by the author) 156436-90-7) as a photosensitizer for photodynamic therapy (PDT) of cancer, cardiovascular disease, and age-related (12) Young, S. W.; Woodburn, K. W.; Wright, M.; Mody, T. D.; Fan, Q.; Sessler, J. L.; Dow, W. C.; Miller, R. A. Photochem. Photobiol. 1996, 63, 892-897. (13) Woodburn, K. W.; Fan, Q.; Miles, D. R.; Kessel, D.; Luo, Y.; Young, S. W. Photochem. Photobiol. 1997, 65, 410-415. (14) Sessler, J. L.; Dow, W. C.; O’Connor, D.; Harriman, A.; Hemmi, G.; Mody, T. D.; Miller, R. A.; Qing, F.; Springs, S.; Woodburn, K.; Young, S. W. J. Alloys Compd. 1997, 249, 146-152. (15) Woodburn, K. W.; Fan, Q.; Kessel, D.; Wright, M.; Mody, T. D.; Hemmi, G.; Magda, D.; Sessler, J. L.; Dow, W. C.; Miller, R. A.; Young, S. W. J. Clin. Laser Med., Surg. 1996, 14, 343-348. (16) Wan, S.; Parrish, J. A.; Anderson, R. R.; Madden, M. Photochem. Photobiol. 1981, 34, 679-681.
Guldi et al. macular degeneration.9,10,12-15,17,18 The paramagnetic gadolinium(III) texaphyrin (Gd-Tex, motexafin gadolinium; CAS Registry No. (provided by the author) 156436-89-4), on the other hand, displayed no photodynamic activity in preclinical studies19 and is currently in Phase III testing as a radiation therapy enhancer.9,10,17,20 This observation provided the impetus for the current study, namely to understand the impact of the heavy metal atom and its associated spin state on the photophysical properties of the metallotexaphyrins. To this end, texaphyrin compounds, including most of the trivalent lanthanide series, as well as several analogous complexes, were examined using steady-state and fast kinetic techniques. Of major interest was the effect of the metal cation on the singlet excited-state lifetime, intersystem crossing, and triplet excited-state lifetime, insofar as these parameters largely determine the quantum yield of singlet oxygen formation in oxygenated systems. While the large core size of the texaphyrins makes them ideally suited for the coordination of trivalent lanthanides, the inorganic chemistry of texaphyrins is not limited to this class of cations. For example, cadmium(II), yttrium(III), and indium(III) all form stable, well-characterized complexes and these species were thus included in this study. On the other hand, in marked contrast to the porphyrins, cation-free (so-called “freebase”) texaphyrins appear to undergo rapid hydrolysis under protic conditions and therefore could not be subject to photophysical analysis. Experimental Section Synthesis. The Y(III), In(III), Lu(III), Eu(III), Gd(III), Dy(III), Tm(III), Yb(III), and Cd(II) complexes used in this study (Figure 1) have been described previously.12,21 The syntheses of the Nd(III), Sm(III), Tb(III), Er(III), and Ho(III) complexes are described below. For this preparative work, solvents of reagent grade quality were purchased commercially and used without further purification. Metal salts were purchased from Alfa AESAR (Ward Hill, MA). LZY-54 zeolite was purchased from UOP (Des Plaines, IL). Ambersep 900 (OH) anion-exchange resin was purchased from Rohm and Haas Co. (Philadelphia, PA). Thin-layer chromatography (TLC) of the metallotexaphyrin complexes was carried out using a 4:1:2 v/v/v mixture of 1-butanol, acetic acid, and water, respectively, on Whatman K6F silica gel plates. Merck Type 60 (230-400 mesh) silica gel was used for column chromatography. For the purposes of initial characterization, electronic spectra were recorded on a Hitachi-U3000 spectrophotometer in methanol. All low- and high-resolution FAB and electrospray mass spectra were obtained from the University of California Mass Spectrometry Laboratory, Berkeley, CA. All elemental analyses were performed by Schwarzkopf Microanalytical Laboratory, Woodside, NY. The purity of all new metallotexaphyrins employed in this study was established via HPLC analysis. The system employed was from Waters/Millipore and consisted of a 600E systems controller with a 510 pump, a 717 autosampler, and a 996 photodiode array detector. The detector monitored the elution profile from 250 to 800 nm. A C18 reversed-phase column was employed (Inertsil ODS2, 5 µM particle, from GL Science, Japan; packed by Metachem; the final column dimensions were 150 mm × 4.6 mm). All mobile-phase media were HPLC grade and obtained from Baxter. These mobile phases consisted of a 100 mM ammonium acetate buffer (pH adjusted to 4.3 with glacial acetic acid) and acetonitrile. The column was first eluted with 72% (17) Sessler, J. L.; Miller, R. A. Biochem. Pharmacol. 2000, 59, 733739. (18) Blumenkranz, M. S.; Woodburn, K. W.; Qing, F.; Verdooner, S.; Kessel, D.; Miller, R. Am. J. Opthalmol. 2000, 129, 353-362. (19) Grosswiner, L. I.; Biligin, M. D.; Berdusis, P.; Mody, T. D. Photochem. Photobiol. 1999, 70, 138-145. (20) Miller, R. A.; Woodburn, K.; Fan, Q.; Renschler, M.; Sessler, J. L.; Koutcher, J. A. Int. J. Biol. Radiat. Oncol. 1999, 45, 981-989. (21) Sessler, J. L.; Tvermoes, N. A.; Guldi, D. M.; Mody, T. D.; Allen, W. E. J. Phys. Chem. A 1999, 103, 787-794.
Photophysical Properties of Texaphyrin 100 mM ammonium acetate buffer and 28% acetonitrile for 28 min. A linear gradient was then applied over the next 10 min to reach 20% 100 mM ammonium acetate buffer and 80% acetonitrile. The flow rate was 1.5 mL/min with the column temperature set at 40 °C. General Procedure for the Synthesis of the Nd(III), Sm(III), and Tb(III) Complexes of Bis(acetato-O)[9,10-diethyl-20,21-bis[2-[2-(2methoxyethoxy)ethoxy]ethoxy]-4,15-dimethyl-8,11-imino-3,6:16,13dinitrilo-1,18-benzodiazacycloeicosine-5,14-dipropanolato-N1, N18, N23, N24, N25] (i.e., Nd-Tex, Sm-Tex, and Tb-Tex). One equivalent of the hydrochloride salt of the so-called sp3 texaphyrin precursor, 9,10-diethyl-7,12-dihydro-20,21-bis[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-4,15-dimethyl-3,6:8,11:13,16-triimino-1,18-benzodiazacycloeicosine-5,14-dipropanol hydrochloride (sp3-Tex; Figure 1),12 1.0-1.5 equiv of the relevant M(OAc)n+1‚xH2O salt, and 10 equiv of triethylamine were mixed together in methanol (1 mL/4-40 mg of macrocycle) and heated to reflux while left exposed to air.12 During the course of the reaction, air was periodically bubbled directly into the reaction vessel using a dispersion tube. The progress of the reaction was monitored by UV/vis spectroscopy and TLC. After the reaction was deemed complete, the deep green solution was cooled to room temperature, filtered through a pad of Celite, and stripped of solvent under reduced pressure. The resulting complex was then purified using the following procedure: (1) acetone trituration, (2) removal of free metal by zeolite extraction, (3) counterion exchange by acetic acid-washed Ambersep 900 resin, and (4) crystallization from a mixture of ethanol and n-heptane as described further below. The crude metallotexaphyrin product, dark green solid, was suspended in acetone (25 mL/g of starting nonaromatic macrocycle), stirred for 30 min at room temperature, and then filtered to wash away the red/brown impurities (incomplete oxidation products and excess triethylamine). The resulting green solid was dried in vacuo. A weighed quantity of this material was then dissolved in MeOH using 35 mL of solvent/g of crude metallotexaphyrin complex, stirred for ∼30 min, and then filtered through Celite into a 1-L Erlenmeyer flask. Deionized water (3.5 mL/g of crude complex) was added to the flask along with LZY-54 zeolite that had been pretreated with acetic acid (5 g of zeolite/g of crude complex). The resulting mixture was agitated or shaken for 1-3 h and then filtered through Celite to remove the zeolite. This latter procedure, which constitutes a free metal extraction, was performed twice in order to ensure that the residual levels of free metal were low (i.e.,
