Article pubs.acs.org/IC
Gold Corroles as Near-IR Phosphors for Oxygen Sensing Christopher M. Lemon,†,‡,§ David C. Powers,†,⊥ Penelope J. Brothers,‡ and Daniel G. Nocera*,† †
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States ‡ School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand S Supporting Information *
ABSTRACT: The triplet state of gold(III) corroles is exploited for optical oxygen sensing. We report intense phosphorescence for gold(III) corroles in the near-IR, an optical window that is ideal for tissue transparency. Moreover, the triplet excited-state emission exhibits significant changes in intensity and lifetime over the 0−160 Torr O2 pressure range. This renders these compounds sensitive at biologically relevant pressures and overcomes the spectral limitations of palladium and platinum porphyrins for oxygen sensing in biology.
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INTRODUCTION The concentration of oxygen is a fundamental parameter in biological systems, with different vessels and tissues displaying varied partial oxygen pressures (pO2). The ∼160 Torr O2 of inspired air drops to 104−150 Torr O2 in the lungs.1 Arterial circulation delivers 50−100 Torr O2 to oxygenate the tissue, whereas the venous system is 20−40 Torr O2 prior to reoxygenation in the lungs.2 Most tissues exhibit pO2 in the 5− 20 Torr range,1 but there are several environments that are hypoxic (pO2 ≤ 5 Torr) such as the niche of stem cells and the tumor microenvironment. The stem-cell microenvironment is dynamic, where signaling cues enable stem cells to persist, grow, and change their fate based on the physiological needs of the organism.3−5 Hypoxia promotes an undifferentiated state in several stem-cell and precursor-cell populations. Stem-cell proliferation and quiescence may be regulated by oxygen gradients within the niche.6 Although hypoxia is a protective feature of stem cells, it is a consequence of cancer pathophysiology in the tumor microenvironment. The tumor vasculature is comprised of heterogeneous vessels that are dilated and leaky, resulting in the inefficient delivery of blood and oxygen.7 To combat this chronic hypoxia, angiogenic therapies may be used; this represents a novel approach to treating cancer by affecting the vessels that are required to maintain the tumor.8 One may transiently normalize the tumor vasculature and subsequently treat it with a high dose of chemotherapeutics once the flow of drugs and oxygen has increased to have a maximal effect on the tumor.9 By monitoring pO2 changes in the tumor microenvironment as a function of chemotherapy or disease progression, clinicians may gain insight into therapeutic protocols that will lead to improved patient outcomes. © XXXX American Chemical Society
Various methods have been employed to quantify oxygen in biological media: polarographic microelectrodes, magnetic resonance imaging, electron paramagnetic resonance, positron emission tomography, hemoglobin saturation spectrometry, and phosphorescence quenching.10 Of these, phosphorescence quenching is noninvasive and provides measurements of the oxygen levels with high spatial resolution ( 100 ns (Radj2 > 0.99). For aerated samples, a monoexponential decay was observed, with the lifetime increasing from 600 ns for 1 to 1250 ns for 4. A 100−180 ns increase in the lifetime of the aerated sample per bromine atom indicates a monotonic perturbation of triplet-state dynamics with increasing bromination. Conversely, the lifetime in the absence of oxygen (τ0) is nearly identical for all four compounds, displaying biexponential decay kinetics with 95 and 15 μs components in a 20:80 ratio. This result is consistent with the emission lifetime data, which demonstrated that τ0 is similar for all compounds (i.e., unaffected by bromination). It should be noted that biexponential kinetics were also observed for H3-1, which exhibited 150 and 20 μs components in a 20:80 ratio.36 Given the irregular shape of the band, it is conceivable that it is a convolution of two triplet states, each with a distinct lifetime. The luminescence lifetimes of the bands at ∼580 and ∼660 nm were determined for fpt samples of 1−4. The data best fit a monoexponential decay function (the two lifetime components of the biexponential fit are inconsistent across the series of compounds and the relative amplitudes varied over different samples of the same compound; Table S3) with lifetimes of 20−25 μs for the band at 580 nm and 10−35 μs for the band at 660 nm (Table S4). Variability of the results is a consequence of the weaker signal observed for these emission features, which is 10−100 times less than that of the T(0,0) band for the same samples. The microsecond lifetimes are consistent with a triplet state, but the steady-state spectra suggest that these features are due to fluorescence (i.e., small Stokes shift and insensitivity to oxygen), consistent with the behavior for delayed fluorescence, as has been observed for β-iodinated aluminum and gallium corroles.45 Alternatively, the 580 and 660 nm emissions may also result from singlet−triplet mixing to yield spin−orbit states. Oxygen Sensing. Steady-state and time-resolved O2dependent experiments (λex = 570 nm) were performed to quantify the oxygen sensing properties of the gold corrole complexes. The T(0,0) phosphorescence is quenched signifiD
DOI: 10.1021/acs.inorgchem.7b01302 Inorg. Chem. XXXX, XXX, XXX−XXX
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consistent with the five-point Stern−Volmer plots (Figure S11).
cantly by air, establishing that these compounds are responsive to oxygen in the 0−160 Torr range (Table 2 and Figures 4 and
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CONCLUSIONS
The observed emission from the gold(III) corroles is noteworthy inasmuch as gold(III) compounds typically do not emit,46 although recent reports have shown that cyclometalation of gold(III) centers promotes luminescence.24 Moreover, the photophysical properties of corroles 1−4 are markedly distinct from analogous gold(III) porphyrins,47 which are phosphorescent at 77 K with emission maxima 700−800 nm48 but are nonemissive at room temperature owing to the presence of thermally accessible charge-transfer states.49 The gold(III) complex of N-confused tetraphenylporphyrin (NCTTP) is emissive in solution at room temperature with an emission maximum at ∼790 nm; however, the observed lifetimes are several nanoseconds.50 In this regard, the gold(III) corroles combine the favorable photophysical properties of [AuTPP]+ and AuNCTPP (TPP = tetraphenylporphyrin) into a single molecule: long-lived phosphorescence at room temperature in a fluid solution. These photophysical properties of the gold(III) corroles provide an attractive alternative to palladium(II) and platinum(II) porphyrin complexes, which are well-established oxygen sensors.14−17 We note that OsVIN corrole complexes have also been reported as optical oxygen sensors.51 The spectral features of gold(III) corroles 1−4 are red-shifted relative to palladium(II) and platinum(II) tetraarylporphyrins. Most notably, the maximum of the most intense Q band of the gold(III) corroles (which is nearly twice as intense as that for porphyrins) is observed at ∼570 nm, whereas similar features occur at 524 and 510 nm for PdTPP and PtTTP, respectively.15 Similarly, the emission of the gold(III) corroles is also redshifted [λem,max(1−4) = 780−795 nm, λem,max(PdTPP) = 688 nm, and λem,max(PtTPP) = 654 nm].52 Together, these properties render gold corroles attractive alternatives to platinum/palladium porphyrins with respect to biological sensing applications because they are better absorbers at longer wavelengths, thus mitigating scattering from tissue for biological sensing applications. The only disadvantage in using gold corroles for chemosensing applications is the lower phosphorescence quantum yield (0.3%) of the gold(III) corroles at 298 K compared to those of palladium(II) (∼2%)20 and platinum(II) (∼15%)52 porphyrins. Although the gold corroles exhibit dark cytotoxicity53 and sensitize the generation of singlet oxygen (1O2),35,40 these potential limitations are minimized in a micelle-encapsulated donor− acceptor sensor construct with a QD.54 This is a simple method of preparing ratiometric sensors amenable for biological applications. We have previously demonstrated that micellebased sensors with a palladium(II) porphyrin do not release 1 O2,21 even though these compounds are efficient photosensitizers for 1O2 (ϕ ∼ 1).55 We expect that the advantages of extending the detection wavelength further into the near-IR will offset the lower detection intensity of gold(III) corroles for selected sensing applications in the biologically relevant pressure window of 0−160 Torr O2.
Figure 4. (a) O2-dependent emission spectra (λexc = 570 nm) of 1 in toluene. The emission intensity is quenched by 136-fold in ambient air (1930 μM) relative to the fpt sample. (b) Representative examples of lifetime-based Stern−Volmer plots for compounds 1 (gray ■), 2 (red ●), 3 (green ▲), and 4 (blue ◆) based on lifetime measurements. The slopes of the Stern−Volmer plot yield kq = 8.41 × 108 M−1 s−1 (1), 4.96 × 108 M−1 s−1 (2), 4.37 × 108 M−1 s−1 (3), and 3.71 × 108 M−1 s−1 (4).
S10). The rate constant for the quenching reaction was determined from Stern−Volmer phosphorescence and TA lifetime measurements,13 τ0 = 1 + kqτ0[O2 ] (1) τ where τ0 is the natural lifetime of the triplet state in the absence of a quencher, τ is the lifetime of the triplet at a given oxygen concentration [O2], and kq is the bimolecular quenching rate constant. The Stern−Volmer kinetics were determined for measurements of the phosphorescence lifetime for 1−4 in toluene solutions under ambient air (1930 μM O2), 10% O2 (919 μM O2), 5% O2 (460 μM O2), 1% O2 (92 μM O2), and argon (0 μM O2). The data from these experiments for compounds 1−4 are presented in Figure S11, and the measured values of kq are presented in Table 2. The kq values slightly decrease with increasing bromination, as opposed to the behavior of the free-base derivatives of these compounds,36 which exhibit a constant value of kq = 2 × 109 M−1 s−1 upon bromination of the corrole ring. Additional O2-dependent data at varying oxygen concentrations were acquired using a fiberoptic probe to measure dissolved oxygen concentrations (Figure 4b). This methodology gives kq values that are E
DOI: 10.1021/acs.inorgchem.7b01302 Inorg. Chem. XXXX, XXX, XXX−XXX
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.7b01302. Summaries of crystallographic data, 1H and 19F NMR, TA, and absorption and emission spectra, and additional experimental details (PDF) Accession Codes
CCDC 993647 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
David C. Powers: 0000-0003-3717-2001 Daniel G. Nocera: 0000-0001-5055-320X Present Addresses §
C.M.L.: Miller Institute for Basic Research in Science and Department of Molecular and Cell Biology, University of CaliforniaBerkeley, Berkeley, CA 94720. ⊥ D.C.P.: Department of Chemistry, Texas A&M University, College Station, TX 77843. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This research was supported by the National Science Foundation (NSF) under Grants CHE-1464232 (to D.G.N.) and IIA-1414645 (to C.M.L). C.M.L. acknowledges the U.S. Department of State and Fulbright New Zealand for the award of a Fulbright Fellowship for funding in New Zealand and the NSF’s Graduate Research Fellowship Program for funding in the United States. D.C.P. acknowledges a Ruth L. Kirchenstein National Research Service award (F32GM103211). We thank Dr. Sunia Trauger for acquiring mass spectrometry data and Dr. Yu-Sheng Chen for assistance with X-ray crystallography at ChemMatCARS, Advanced Photon Source (APS). ChemMatCARS Sector 15 is principally supported by the NSF/ Depertment of Energy (DOE) under Grant CHE-0822838. Use of the APS was supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences, under Contract DEAC02-06CH11357.
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