Chemically reversible reactions of hydrogen sulfide with metal phthalocyanines

Article abstract of DOI:10.1021/ic500664c

Hydrogen sulfide (H₂S) is an important signaling molecule that exerts action on various bioinorganic targets. Despite this importance, few studies have investigated the differential reactivity of the physiologically relevant H₂S and

Full text of DOI:10.1021/ic500664c

Communication
pubs.acs.org/IC
Open Access on 05/01/2015
Chemically Reversible Reactions of Hydrogen Sulfide with Metal
Phthalocyanines
Matthew D. Hartle, Samantha K. Sommer, Stephen R. Dietrich, and Michael D. Pluth*
Department of Chemistry and Biochemistry, Materials Science Institute, University of Oregon, Eugene, Oregon 97403-1253, United
States
S
* Supporting Information
reactivity including the reversible binding of NO, CO, and O2 to
heme mimics21 and the reduction of CO.22 Metal phthalocyanine
ABSTRACT: Hydrogen sulfide (H2S) is an important
signaling molecule that exerts action on various bio-
inorganic targets. Despite this importance, few studies have
complexes have characteristic UV−vis spectroscopic signatures23
including the Q band (600−700 nm), which provides
investigated the differential reactivity of the physiologically
information on the oxidation state and binding modes of the
relevant H2S and HS− protonation states with metal
central metal ion, as well as the B band (300−400 nm) and
complexes. Here we report the distinct reactivity of H2S
window region (400−550 nm), which provide information about
and HS− with zinc(II) and cobalt(II) phthalocyanine (Pc)
bound ligands and the metal oxidation state.24 On the basis of
complexes and highlight the chemical reversibility and
these characteristics, as well as the solubility23 and redox
cyclability of each metal. ZnPc reacts with HS−, but not
properties,24 we viewed ZnPc and CoPc as promising initial
H2S, to generate [ZnPc-SH]−, which can be converted
platforms on which to investigate the differential reactivity of H2S
back to ZnPc by protonation. CoPc reacts with HS−, but
and HS− with redox-inactive and -active metal complexes.
not H2S, to form [CoIPc]−, which can be reoxidized to
Because of its redox inactivity, we reasoned that the treatment
CoPc by air. Taken together, these results demonstrate the
of ZnPc with H2S or HS− would result in metal ligation rather
than metal-based redox chemistry. To probe such reactivity, we
titrated ZnPc in tetrahydrofuran (THF) with H2S gas (up to 100
equiv or by bubbling for 15 min) but failed to observe any
reaction by UV−vis spectroscopy. By contrast, titration of ZnPc
in THF with NaSH dissolved in dimethyl sulfoxide (DMSO)
resulted in clean conversion to a new species, as evidenced by a 5
nm bathochromic shift of the Q band, the appearance of a broad
absorbance centered at 410 nm, and well-anchored isosbestic
points at 329, 381, and 667 nm (Figure 1a). Control experiments
titrating ZnPc in THF with DMSO, H2O, KOH in DMSO, H2S
chemically reversible reaction of HS− with metal
phthalocyanine complexes and highlight the importance
of H2S protonation state in understanding the reactivity
profile of H2S with biologically relevant metal scaffolds.
ydrogen sulfide (H2S) is an endogenously produced
Hmolecule that plays important and diverse roles in both
vasoregulation and neurotransmission, as well as other
physiological processes.1−10 As a gaseous small-molecule
signaling agent, endogenous H2S joins NO and CO as a
gasotransmitter, and all three mediate important functions
through action on bioinorganic targets.7−10 Unlike NO and CO,
however, H2S exists in different protonation states at
physiological pH, which can facilitate lipid and water solubility
in the diprotic (H2S) and monoanionic (HS−) forms,
respectively. Furthermore, the redox potential, nucleophilicity,
and tendency to form insoluble metal salts also vary with the H2S
protonation state, thus complicating reactivity with transition-
metal centers.3 Despite its widespread importance, the
coordination chemistry of H2S with bioinspired transition-
metal scaffolds remains underexplored by comparison to CO and
NO.11 Although H2S binding to ruthenium- and iron-based
complexes have been reported,11−16 investigations of isolated
porphyrinoid scaffolds remain limited.17−20 Motivated by the
growing interest in the biochemical functions of H2S and the lack
of information on the differential reactivity of H2S and HS− in
bioinorganic contexts, we report here the differential reactivity of
H2S and HS− toward metal phthalocyanine (Pc) complexes and
highlight the chemically reversible reactions of HS− with these
platforms.
Figure 1. (a) UV−vis titration of ZnPc (6.3 μM in THF, black) with
NaSH (0.25 equiv increments of 8 mM NaSH in DMSO up to 5 equiv).
(b) 1H NMR (600 MHz, THF-d8) spectra of 600 μM ZnPc (top, black),
600 μM ZnPc with 2 equiv of KOH in DMSO-d6 (middle, green), and
600 μM ZnPc with 2 equiv of NaSH in DMSO-d6 (bottom, blue).
Phthalocyanines are planar, aromatic porphyrin derivatives
that have been used previously as models of bioinorganic
Received: March 21, 2014
Published: May 1, 2014
© 2014 American Chemical Society
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Inorganic Chemistry
Communication
in DMSO, or S8 failed to change the ZnPc UV−vis spectrum. The
addition of aqueous NaSH to ZnPc in THF resulted in reactivity
identical with that of the DMSO experiments, suggesting that the
availability of weakly acidic protons does not influence the
reactivity. Similarly, the addition of [NBu4][BH4], a stronger
reductant than H2S or HS−,25 failed to change the UV−vis
spectrum of ZnPc, suggesting that HS−-mediated reduction of
the metal or ligand was not occurring. To probe the binding
stoichiometry, we constructed a Job plot by monitoring changes
in absorbance as a function of the ZnPc and NaSH molar ratios,
which resulted in data consistent with 1:1 binding (Figure S2 in
the Supporting Information, SI). Taken together with the above
experiments, these studies suggest the formation of a [ZnPc-
SH]− adduct upon treatment of ZnPc with HS−.
Figure 2. UV−vis spectra of ZnPc (2 μM in THF, black) treated with 10
equiv of NaSH in DMSO (red). Treatment with 10 equiv of AcOH
regenerates the original ZnPc spectrum. This system can be cycled
numerous times (inset).26
To confirm that HS− was binding to the zinc(II) center and
1
not reacting with the Pc ring directly, we used H NMR
spectroscopy to investigate changes in the Pc resonances upon
reaction with NaSH. Treatment of ZnPc in THF-d8 with 2 equiv
of NaSH in DMSO-d6 resulted in an upfield shift in the Pc H
however, resulted in a significant bathochromic shift of the Q
band from 656 to 697 nm, the emergence of a broad absorbance
at 467 nm centered in the window region, and well-anchored
isosbestic points at 316, 370, 555, and 676 nm (Figure 3). These
1
NMR resonances from 9.59 and 8.20 ppm to 9.41 and 8.06 ppm,
respectively (Figure 1b). Furthermore, the dd splitting pattern of
the Pc ring is maintained upon treatment with NaSH, indicating
that C4 rotational symmetry is preserved. This symmetry
preservation precludes the possibility of HS− nucleophilic
addition or HS• radical addition into the Pc ring because such
an addition would lower the overall symmetry of the complex
and subsequently increase the complexity of the coupling.
Treatment of ZnPc in THF-d8 with 2 equiv of KOH in DMSO-d6
1
failed to change the H NMR spectrum of ZnPc significantly,
indicating that the changes in the chemical shift upon treatment
of ZnPc with HS− were not simply derived from acid−base
chemistry (Figure 1b).
Figure 3. UV−vis titration showing the reduction of CoPc (7 μM in
THF, black) to [CoIPc]− (red) by NaSH (1 equiv increments of 21.7
mM NaSH in DMSO up to 10 equiv).
Because ZnPc binds HS− but not H2S, we reasoned that bound
HS− should be acid-labile, thus allowing for chemically reversible
coordination of HS− by the addition of a suitable proton source
(Scheme 1). To test this hypothesis and to demonstrate the
27
new absorbances match the reported spectrum of [CoIPc]−
and also match the spectrum of [CoIPc]− generated from CoPc
and [NBu4][BH4] (Figure S1 in the SI). A Job plot constructed
by monitoring the absorbance at 467 nm as a function of the
CoPc and HS− molar ratio is consistent with a 1:1 reaction of
CoPc with HS− (Figure S3 in the SI). This reaction
stoichiometry, as well as previous work using CoPc to oxidize
thiolates to disulfides, is consistent with the initial oxidation of
HS− to HSSH with potential conversion to further oxidation
products (Scheme 2).29−33
Scheme 1
Scheme 2
chemically reversible binding of HS− to ZnPc, we first generated
[ZnPc-SH]− in situ by treating ZnPc in THF with 10 equiv of
NaSH in DMSO and then added an equimolar amount of AcOH.
As predicted, the characteristic spectral features of [ZnPc-SH]−
at 410 and 670 nm reverted to the 342 and 665 nm absorbances
corresponding to the parent ZnPc (Figure 2). A further addition
of NaSH in DMSO regenerated the 410 and 670 nm [ZnPc-
SH]− spectral features.26
Having established that redox-inactive ZnPc binds HS− but
not H2S, we next investigated the reactions of HS− and H2S with
redox-active CoPc. We chose CoPc because of its well-defined
and readily monitored redox states of blue CoIIPc and green
[CoIPc]−.27,28 Paralleling the chemistry observed for ZnPc, CoPc
does not react with H2S gas (up to 100 equiv or by bubbling for
15 min). Titration of CoPc in THF with NaSH in DMSO,
On the basis of the observed HS−-mediated reduction of
CoPc, we reasoned that the observed reactivity could be reversed
by oxidation with atmospheric O2 to generate a chemically
reversible and cycleable system. To demonstrate this redox
cycling, we first treated a THF solution of CoPc with 10 equiv of
NaSH under N2 to generate [CoIPc]− and then exposed the
solution to air, which resulted in rapid oxidation back to the
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ASSOCIATED CONTENT
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S
* Supporting Information
Experimental procedures, UV−vis data, Job plots, and 1H NMR
data for ZnPc and CoPc after reaction with NaSH. This material
is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail: pluth@uoregon.edu.
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Oregon Medical Research
Foundation and the National Institute of General Medical
Sciences (Grant R00GM092970). The NMR facilities at the
University of Oregon are supported by NSF/ARRA (Grant
CHE-0923589).
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