Extraction and metalation of porphyrins in fluorous liquids with carboxylic acids and metal salts

Article abstract of DOI:10.1021/jp902000v

Porphyrins have found application in a remarkable variety of areas such as sensors, ion selective electrodes, photodynamic therapy, and energy-transfer systems. Here, we demonstrate the extraction of 5,10,15,20-tetraphenylporphyrin (TPhP) and 5,10,15,20-t

Full text of DOI:10.1021/jp902000v

J. Phys. Chem. B 2009, 113, 7449–7456
7449
Extraction and Metalation of Porphyrins in Fluorous Liquids with Carboxylic Acids and Metal Salts
Kristi L. O’Neal and Stephen G. Weber*
Department of Chemistry, UniVersity of Pittsburgh, Pittsburgh, PennsylVania 15260-3900
ReceiVed: March 4, 2009; ReVised Manuscript ReceiVed: April 10, 2009
Porphyrins have found application in a remarkable variety of areas such as sensors, ion selective electrodes,
photodynamic therapy, and energy-transfer systems. Here, we demonstrate the extraction of 5,10,15,20-
tetraphenylporphyrin (TPhP) and 5,10,15,20-tetra(4-pyridyl)porphyrin (TPyP) into a mixture of perfluorohexanes
(FC-72) through noncovalent interactions with Krytox (1), a carboxylic acid terminated perfluoropolyether.
We found that 1 transfers two protons to the TPhP tetrapyrrole ring to create the porphyrin dication (H2TPhP2+)
in FC-72 while up to six protons are transferred to the TPyP pyridyl and tetrapyrrole nitrogens to create a
hexavalent cation macrocycle in the fluorous phase. The total charge on TPyP is controlled by adjusting the
concentration of 1 in the fluorous phase. In addition, we observed extraction of ZnTPyP from CDCl3 with
1/FC-72, while ZnTPhP is not extracted by 1/FC-72. We prepared the Zn salt of 1 and found that it extracts
(from CDCl3) and metalates TPyP but not TPhP. Competitive binding between the porphyrins and an ethanol
cosolvent hinders the extraction of both TPhP and TPyP and inhibits the formation of the TPyP hexacation
in FC-72. By controlling the concentration of porphyrin, 1, and ethanol, it is possible to reversibly solubilize
TPyP in the fluorous phase through noncovalent interactions between the pyridyl moieties and 1 while leaving
the tetrapyrrole ring available to interact with metals or other substrates. In addition, both porphyrins and
ZnTPyP are easily recovered from the fluorous phase using commercially available fluorous solid-phase
extraction cartridges. Understanding noncovalent interactions in fluorous matrices should lead to development
of more robust devices for sensing and energy transfer.
1. Introduction
into a perfluorodecalin solution using an excess of a “heavy
fluorous” (i.e., containing eight perfluorooctyl fragments)
Cu(II)2-tetracarboxylate complex (2).
Porphyrins have interesting optical and electrical properties
resulting from their highly conjugated π-electron system that
is sensitive to changes to the conjugation pathway. This makes
porphyrins and their derivatives particularly useful in optical
sensor development.1-18 In addition, there has been great interest
in synthetic functionalized metalloporphyrins as photosensitizers
in photodynamic therapy, molecular19-21 and ion-pair22 receptors,
electrodes in molecular photovoltaic devices,23,24 and building
blocks in supramolecular chemistry.25,26 Porphyrins and metal-
loporphyrins have been exploited as ionophores in the develop-
ment of ion selective electrodes27-32 and as chemically modified
electrodes27 in amperometric and voltammetric sensors.
In general, chemical sensors involve some sensing material
embedded in a matrix. It is well-known that sensor performance,
although highly dependent on the properties of the sensing
material, is often limited by this supporting matrix.28 A poorly
solvating matrix provides a more selective environment for
chemical sensing by reducing the concentration of interfering
species in the matrix. Fluorous liquids are the ultimate non-
competitive solvent.29 However, solubilization of large organic
molecules, such as porphyrins, in extremely nonpolar fluorous
liquids at room temperature is challenging. There are only a
handful of reports on covalently modified fluorous-tagged
porphyrins that are soluble in fluorous liquids30-34 and even
fewer reports on nonfluorous-tagged porphyrins in a fluorous
matrix.35,36 In fact, there are only a few reports exploiting
noncovalent interactions in perfluorocarbons,35,43-48 and the
fundamental science is not fully understood. El Bakkari et al.35
have demonstrated near-complete reversible extraction of
5,10,15,20-tetra(4-pyridyl)porphyrin (TPyP) from chloroform
The resulting perfluorosoluble 2-TPyP supramolecular as-
sembly showed no evidence of TPyP metalation by copper(II)
ions under the conditions used.37 With an equimolar ratio of 2
to TPyP, a red precipitate formed and was postulated to be a
* To whom correspondence should be addressed. E-mail: sweber@
pitt.edu.
10.1021/jp902000v CCC: $40.75  2009 American Chemical Society
Published on Web 05/05/2009

7450 J. Phys. Chem. B, Vol. 113, No. 21, 2009
O’Neal and Weber
polymeric supramolecular assembly with limited solubility in
perfluorocarbons.35 Because 2 was not able to extract 5,10,15,20-
tetraphenylporphyrin (TPhP), it was concluded that the interac-
tion between 2 and TPyP occurred only through the pyridyl
nitrogens.
(DMF) were purchased from J. T. Baker (Phillipsburg, NJ) and
dried over molecular sieves. meso-Tetraphenylporphyrin (TPhP),
5,10,15,20-tetra(4-pyridyl)porphyrin (TPyP), and 2,2,2-trifluo-
roethanol were purchased from Sigma-Aldrich and used as
received. FC-72 Fluorinert Electronic Liquid (a mixture of
perfluorohexanes) was purchased from 3M (St. Paul, MN), and
Krytox 157FSH (1), from Miller-Stephenson Chemical Co., Inc.
(Danbury, CT). 19F NMR analysis of 1 resulted in a number-
averaged molecular weight of 5150 g mol-1 with an average of
29 polymer repeat units. We have previously reported a
molecular weight of 5840 g mol-1 with 33 repeat units38 from
a different lot.
We have observed38 that Krytox (1), a carboxylic acid ter-
minated poly-hexafluoropropylene oxide, significantly enhances
the extraction of pyridine (100-fold with excess 1 as compared
to 1-free) and substituted pyridines from chloroform into a
mixture of perfluorohexanes (FC-72) while having little effect
on the nonheterocyclic counterparts (i.e., phenol or aniline).
As mentioned above, all CHCl3 solutions within this work
contain ethanol. Solutions made from CDCl3 contain 0.00, 1.00,
or 2.00% (v/v) added ethanol as specified. Separate stock
solutions of 1.0 mM TPhP and TPyP were made in CHCl3 and
CDCl3 with 0.00, 1.00, and 2.00% (v/v) ethanol as the solvent.
All containers of stock solutions were placed in a Cole-Parmer
(Chicago, IL) ultrasonicator bath for 10-30 min to ensure
dissolution of the materials in their respective solvents.
2.2. Preparation of Zinc Salt and Metalloporphyrins. The
following procedure was adapted from Doan et al.42 for the
preparation of the zinc salt of 1 (Zn12). Equal weights (2.0 g
each) of 1 and a 1.0 M ZnCO3 aqueous slurry were mixed in a
separatory funnel and shaken vigorously until an emulsion
formed. To break the emulsion, 2.0 mL each of methanol and
trifluoroethanol were added to the separatory funnel. The
resulting mixture was extracted with 2.0 mL of FC-72 several
times. The FC-72 solution was then stirred over activated
molecular sieves overnight and passed through a 0.22 µm pore-
size nylon syringe filter (Acrodisc) before the solvent was
allowed to evaporate. The resulting Zn12 oil was then dried
overnight at 180 °C. FTIR spectra confirmed the formation of
the salt with the disappearance of the 1-carboxylic acid dimer
band and the appearance of a carboxylate band (Figure S1 in
Supporting Information). 1H NMR spectra taken before and after
formation of Zn12 (Figure S2 in Supporting Information) show
that the 1 proton signal disappears upon salt formation. The
zinc metalloporphyrins, ZnTPhP and ZnTPyP, were synthesized
according to Adler,43 and formation of the metalloporphyrin was
Knowing this, we wondered if the much simpler 1 (compared
to 235,37,39) would effectively extract TPyP. Here, we demonstrate
reversible extraction of both TPhP and TPyP from CHCl3 with
1 in FC-72. Two protons are transferred from 1 to the
macrocyclic tetrapyrrole (tetrapyrrole hereafter) of TPhP. In
addition to the two protons transferred to the tetrapyrrole, four
protons can be transferred from 1 to the TPyP pyridyl nitrogens
for a total of six protons. The overall charge on TPyP is
controlled through adjusting the relative concentrations of 1 and
TPyP. Interestingly, we observed that Zn12 salts effectively
extract and rapidly metalate TPyP in the fluorous phase under
ambient conditions while we saw no interaction with TPhP. The
copper complex (2) previously employed to extract TPyP into
the fluorous phase did not metalate TPyP under similar
conditions.37,39 However, Zn12 is able to metalate TPyP. Easy
recovery of both the porphyrin (metalated and free base) and 1
is achieved using commercially available fluorous solid-phase
extraction (F-SPE) cartridges. The purpose of this work is to
gain a fundamental understanding of the nature of the interac-
tions of porphyrins with 1 in a highly fluorinated matrix, which
leads to the development of more robust and selective porphyrin-
based sensors and devices for energy transfer, optical com-
munication, and data storage in fluorous media.
1
verified using UV/vis and H NMR.
2.3. Fluorous Biphasic Extractions. A series of liquid-
liquid fluorous biphasic extractions was carried out by placing
aliquots of each porphyrin solution and 0.0-20.0 mM 1/FC-72
(phase ratio, Φ ) 1.0 for all extractions) in GC autosampler
vials and shaking for 10 min on a mechanical shaker (in-house
construction) to ensure homogeneity (see Supporting Informa-
tion for photographs). The samples were allowed to rest for 10
min before measurements were taken. Samples of each por-
phyrin solution were extracted with 1-free FC-72 as controls.
The layers were physically separated using a syringe and all
baseline-corrected absorbance values were measured under
1
ambient conditions (22.0 ( 1 °C). H NMR measurements of
the stock solutions and FC-72 receiving phase were carried out.
2. Experimental Section
Extractions of TPhP and TPyP were carried out similar to
those discussed above but with Zn12 in place of 1 in the FC-72
receiving phase. Extractions of ZnTPhP and ZnTPyP from
CHCl3 were also carried out as discussed above.
2.1. Chemicals and Solutions. Chloroform (Fisher Scientific,
Fair Lawn, NJ) and deuterated chloroform (Cambridge Isotope
Laboratories, Inc., Andover, MA) were dried over activated
molecular sieves and treated with potassium carbonate (EM
Science, Cherry Hill, NJ) to neutralize any HCl that had formed
as a result of exposure to light.40,41 Commercially available
CHCl3 contains ∼1% (v/v) ethanol as a stabilizer to prevent
the formation of HCl and phosgene40,41 while deuterated
chloroform does not. Methanol, ethanol, and dimethylformamide
Extractions were carried out to determine the distribution of
ethanol between CDCl3 and FC-72 with and without 1 in FC-
72. One milliliter of CDCl3 with 1.00% (v/v) ethanol was shaken
separately with 1.0 mL of FC-72 and a 10.0 mM solution of
1/FC-72. A 0.3 mL aliquot of each resulting FC-72 solution
was transferred to an NMR tube, and 10.0 µL trifluoroethanol

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J. Phys. Chem. B, Vol. 113, No. 21, 2009 7451
A solution of TPhP/CHCl3 is deep red in color, and the
Q-band region of the spectrum is the typical four-banded
spectrum of the free base. Upon extraction into FC-72, the
solution turns bright green (see Figure S6 in Supporting
Information) and the spectrum changes to the two-banded form
indicative of the dication44 (Figure 2a). This two-banded
spectrum is the only type observed in the FC-72 phase. The
absorbance intensity, but not the shape of the spectrum, changes
with increasing [1]. The two hydrogen bond accepting tetrapy-
rrole nitrogens of TPhP are the only available binding sites for
1. Thus, the macrocycle is “pulled” into the fluorous phase
through interactions between 1 carboxylic acid groups and the
TPhP tetrapyrrole nitrogens. Figure 2b shows that >90% of 0.1
mM TPhP is extracted with an equal volume of 2.0 mM 1.
A series of liquid-liquid fluorous biphasic extractions was
also carried out with 1.0 mM TPyP/CHCl3 in the source phase
and from 0.0 to 20.0 mM 1/FC-72 in the receiving phase.
Absorbance spectra of the FC-72 receiving phase resulting from
these fluorous biphasic extractions along with a plot of the
absorbance as a function of [1] are shown in Figure 3.
The extraction of TPyP (Figure 3) is not as straightforward
as that of TPhP (Figure 2). A solution of TPyP/CHCl3 is deep
red in color, and the Q-band region of the spectrum is the four-
banded spectrum of the free base. Upon extraction into FC-72,
the solution does not turn bright green typical of the fully
protonated tetrapyrrole44 (P) as we observe for TPhP (see Figures
S6 and S9 in Supporting Information). Instead, the spectrum of
a solution of 1-TPyP/FC-72 remains the four-banded type as
seen with the free base, although the relative intensities of the
Q bands have changed. Figure 3b shows that with increasing
[1], the absorbance of the highest energy Q band (516 nm)
reaches a maximum around 12 mM 1. On the other hand, the
absorbance of the lowest energy Q band continues to increase
even though the concentration of TPyP in the receiving phase
remains relatively constant beyond solutions of 12.0 mM 1. As
El Bakkari39 observed in the extraction of TPyP with receptor
2, it is expected that the receptor-TPyP interaction occurs
through the pyridyl nitrogens. However, we have shown in
Figure 2 that receptor 1 extracts TPhP by protonating the
tetrapyrrole nitrogens whereas 2 showed no interaction with
TPhP.45 Consequently, it is possible that 1 has some interaction
with TPyP tetrapyrrole nitrogens. Fleisher46 reported that the
TPyP tetrapyrrole nitrogen atoms are considerably less basic
than the pyridyl nitrogens. Thus, we expect the interaction with
1 to be more favorable with the pyridyl over the tetrapyrrole
nitrogens on TPyP.
Figure 1. Diagram of biphasic extraction experiments. Phase A (source
phase) contains TPhP or TPyP dissolved in CHCl3 with ∼1% (v/v)
ethanol, CDCl3, CDCl3 with 1.00% (v/v) ethanol, or CDCl3 with 2.00%
(v/v) ethanol while phase B contains 1 (concentration varies by sample)
in FC-72 (phase ratio, Φ ) 1.0).
was added as an internal standard. 1H NMR measurements were
taken at 25 °C using a melting-point capillary filled with
deuterated acetone as the locking solvent. Using the same
procedure, extractions with CHCl3 containing ∼1% (v/v) ethanol
in place of CDCl3 were carried out to determine the concentra-
tion of CHCl3 in FC-72.
2.4. Recovery of Porphyrins Using Fluorous Solid-Phase
Extraction. Both TPhP and TPyP were recovered using fluorous
solid-phase extraction (F-SPE). A commercially available 5 g
FluoroFlash F-SPE cartridge (Fluorous Technologies Incorpo-
rated, Pittsburgh, PA) was emptied, and 0.25 g of the fluorous
silica sorbent material was placed into a 1 g capacity tube
(Sigma Aldrich, St. Louis, MO) and topped with a frit. The
cartridge was then conditioned by first loading 0.5 mL of DMF
onto the cartridge using a vacuum and then by passing 2.0 mL
of a hydrophilic eluant (80:20 methanol/H2O) through the
cartridge. After each fluorous biphasic extraction (described
above), the resulting fluorous receiving phase contains the
1-porphyrin complex. The fluorous phase was separated with
a syringe, and 0.3 mL was loaded onto the cartridge under a
vacuum. The porphyrin was then desorbed by passing two 0.5
mL aliquots of a fluorophobic eluent (50:50 CHCl3/ethanol)
through the cartridge. 1 was then recovered separately with two
separate washes of 0.3 mL of FC-72 eluent under vacuum.
2.5. Instrumentation. A Hewlett-Packard 8452A UV-visible
diode array spectrophotometer was used for all UV absorbance
measurements. All samples were measured in a 0.1 cm path
length sample cell (Fisher Scientific, Pittsburgh, PA). A Varian
Excalibur Fourier transform infrared (FT-IR) spectrophotometer
was used for IR measurements, and all samples were measured
in a 0.1 mm path length cell against a blank background at a
resolution of 2 cm-1 with 50 scans averaged. All IR spectra
were smoothed using a 5 point boxcar and baseline corrected.
1H and 19F NMR spectra were collected with a Bruker 300 MHz
spectrometer. For FC-72 samples, a melting point capillary was
filled with CDCl3 and inserted into the NMR tube so that the
fluorous solvent remained unaffected by the locking solvent.
Both TPhP and TPyP can be easily recovered from the
fluorous phase using commercially available F-SPE cartridges.
Figure 4 shows the absorbance spectra of the 1-porphyrin
complex before it is loaded onto the F-SPE cartridge (black
lines) and of an organic eluent containing the porphyrin (gray
lines). F-SPE cartridges contain a silica-based perfluoroalkyl
bonded phase that retains compounds on the basis of fluorine
content. The spectra of the samples following extraction (black
lines, Figure 4) match that of the respective 1-TPhP and
1-TPyP complexes (compare to Figures 2a and 3a). When this
solution was loaded onto the column under vacuum, the
1-porphyrin complex was retained on the F-SPE column
through interactions with 1. The porphyrin was then eluted with
an organic eluent (50:50 CHCl3/ethanol). The Q-band spectra
of the eluted porphyrin in the organic eluent correspond to the
four-banded spectra of the free base. In other words, the
porphyrin is eluted by the organic eluent while 1 is retained
3. Results and Discussion
3.1. Receptor-Based Extractions of TPhP and TPyP into
FC-72. A series of liquid-liquid fluorous biphasic extractions
was carried out with 0.1 mM TPhP/CHCl3 in the source phase
and from 0.0 to 10.0 mM 1/FC-72 in the receiving phase.
Absorbance spectra of the FC-72 receiving phase resulting from
these extractions along with a plot of the absorbance as a
function of [1] are shown in Figure 2.

7452 J. Phys. Chem. B, Vol. 113, No. 21, 2009
O’Neal and Weber
Figure 2. Series of fluorous biphasic extractions of 0.1 mM TPhP/CHCl3 with increasing 1/FC-72 (0.0-10.0 mM) in FC-72 (see Figure 1). (a)
Q-band region of the absorbance spectra from the FC-72 receiving phase following extraction. The arrow indicates direction of change with samples
containing higher [1]. (b) Normalized absorbance of the CHCl3 source phase at 516 nm (squares) and of the FC-72 receiving phase at 645 nm
(circles) as a function of [1]. 1 is nonabsorbing above 205 nm.
Figure 3. Series of fluorous biphasic extractions of 1.0 mM TPyP/CHCl3 with increasing 1/FC-72 (0.0-20.0 mM). (a) Q-band region of the
absorbance spectra from the FC-72 receiving phase following extraction. The arrows indicate direction of change for samples with increasing [1].
(b) Normalized absorbance of the CHCl3 source phase at 514 nm (squares) and of the FC-72 receiving phase at 516 nm (circles) and 638 nm
(triangles). 1 is nonabsorbing above 205 nm.
Figure 4. Q-band region of the absorbance spectrum of a fluorous phase (black) resulting from the extraction of (a) 1.0 mM TPhP and (b) 1.0 mM
TPyP in CDCl3 before loading onto a F-SPE cartridge and of a 50:50 CHCl3/ethanol eluant of the loaded cartridge (gray).
through fluorophilic interactions with the fluorous silica. 1 was
then eluted from the cartridge with FC-72.
solutions in FC-72 are shown in Figure 6. Here, an extraction
of TPyP was carried out with CDCl3 as the source phase in
place of CHCl3, so that the small amount of source phase
dissolved in the receiving phase did not interfere with the
resulting spectrum.
The signals of the H2,6 and H3,5 protons (see structures) of
the peripheral aromatic rings of TPyP shift downfield with
increasing [1] while the difference in chemical shifts (∆δ)
between these two types of protons, as well as the chemical
shift of the tetrapyrrole protons, all remain fairly constant.
Meanwhile, 1 protons are becoming more shielded as the peaks
shift upfield (Figure S3 in Supporting Information). A similar
experiment was performed with TPhP as a control because the
TPhP phenyl moieties are not proton acceptors. The chemical
shifts of the protons associated with the TPhP phenyl groups
(Figure 6b) remain constant with the addition of 1. Therefore,
the downfield shift of the pyridyl protons and concurrent upfield
To investigate further the nature of 1-TPyP interactions,
TPyP was first extracted from CHCl3 with a solution of 1 in
FC-72, then separated from the source phase and titrated with
additional 1 in FC-72. The resulting spectra are shown in Figure
5. Addition of 1 causes the absorbance of the high energy Q
band in the TPyP spectrum to decrease while the low energy
band increases. This is consistent with protonation of the
tetrapyrrole ring.
Absorbance spectroscopy is impractical for studying the
nature of the 1-TPyP pyridyl interactions because protons on
the pyridine nitrogens do not interact significantly with the
1
porphyrin tetrapyrrole conjugation pathway.46,47 Therefore, H
NMR was employed to verify that 1 transfers a proton to the
pyridyl moieties on TPyP in FC-72. The effects of increasing
[1] on the 1H NMR spectra of a series of 1-TPyP and 1-TPhP

Porphyrins in Fluorous Liquids
J. Phys. Chem. B, Vol. 113, No. 21, 2009 7453
macrocycle into the fluorous phase through noncovalent interac-
tions but also the nonpolar fluorous environment can support
such a highly charged species (i.e., a total charge of 6+ for the
four pyridyl moieties and two tetrapyrrole nitrogens).
We have previously performed a detailed study on the
interaction between 1 and pyridine, showing that proton transfer
can occur even in extremely nonpolar fluorous environments.38
A further study on complexation between N-heterocyclic bases
and carboxylic acids in a range of solvents showed that proton
transfer occurs in fluorous environments when both the acid/
base ratio and the difference in pKa between the acid and
conjugate acid of the base (∆pKa) are sufficiently high.48
Specifically, we have observed proton transfer with 3:1 1/base
ratios and ∆pKa in the range from 4.0 to 6.0, where the pKa of
1 is approximately 0.26.48 On the basis of previous observations,
protonation of the TPhP tetrapyrrole (pKa ) 4.049) with excess
1 (∆pKa ) 3.7) is not unexpected. On the other hand, TPyP
has a significantly less basic tetrapyrrole (pKa ) 1.849) as a result
of the four charged pyridine moieties. It seems surprising that
such a highly charged hexacationic macrocycle (P) would exist
in the fluorous phase because ∆pKa ) 1.5 deviates significantly
from the range in which we have previously observed proton
transfer in FC-72. However, TPyP differs from the small bases
studied in that the less basic tetrapyrrole ring is surrounded by
four contact ion pairs. Although the macromolecule is electroni-
cally neutral, the local dipolarity is increased. Thus, the solvation
environment perceived by the tetrapyrrole is substantially more
polar than a solution of 1/FC-72, and we observe proton transfer
as a result.
Figure 5. Q-band region of the spectra resulting from a constant-
volume titration of a 1-TPyP solution in FC-72 with additional 1. Each
sample contains 0.36 mM TPyP. Spectra are labeled according to total
[1], and arrows indicate direction of change with increasing [1]
(nonabsorbing in visible range).
shift of 1 protons can be attributed to the formation of
pyridinium ions, as we have previously seen between 1 and
pyridine-like bases in fluorous solvents.38,48
We draw the conclusion that the interaction between 1 and
TPhP is through protonation of the porphyrin ring while the
interaction between 1 and TPyP depends on the ratio of 1 to
TPyP. At low 1/TPyP ratios, the interaction is primarily through
protonation of the more basic pyridyl moieties while protonation
of the porphyrin tetrapyrrole ring occurs only under a greater
excess of 1.
The Q-band spectrum of TPyP is sensitive to whether the
tetrapyrrole is neutral (N) or fully protonated (P) (refer to
structures) and it is independent of the state of protonation of
the pyridine moieties.46 Despite the presence of charge on the
pyridinium moieties, we will use N and P to refer to the
molecule as a whole. The molar absorptivity (ε) of P at
the wavelength of the high energy Q band (513 nm) is equal to
zero (eq 1).
3.2. Metalloporphyrins. It is well-known that Cu2+ can be
incorporated into porphyrins with an excess of copper(II) acetate
in organic solvents, where the basic acetate anions act to
deprotonate the pyrrole rings.37,50 El Bakkari et al.37 have
demonstrated complete metalation of 5,10,15-tripyridyl-20-
phenylporphyrin after 5 h and of 5,15-dipyridyl-10,20-diphe-
nylporphyrin in less than 10 min in perfluorodecalin with 2.
However, 2 did not metalate TPyP even after several hours of
stirring. On the basis of kinetics experiments and space-filling
models, the authors postulate that steric rather than electronic
effects explain the differences in metalation behavior by the
bulky 2.
The absorbance spectra of the fluorous phase resulting from
an extraction of TPyP from CHCl3 with the zinc salt of 1 (Zn12)
in FC-72 are shown in Figure 8. The absorbance spectrum of
separately synthesized ZnTPyP in CHCl3 is shown for com-
parison in the inset of Figure 8. It is clear that TPyP is metalated
in the fluorous phase. The absorbance increases with increasing
concentration of 1, but the shape of the spectrum does not
change, demonstrating that there is only one form of TPyP in
the fluorous phase. The products of the reaction between TPyP
and Zn12 are ZnTPyP and 1. The interactions between 1 and
the pyridyl groups of ZnTPyP stabilize the complex in the
fluorous phase. An extraction of 0.2 mM ZnTPyP in CHCl3
with 1 in FC-72 resulted in similar spectra, owing to the
formation of the same product in the fluorous phase, a 1-ZnTPyP
supramolecular complex. In both cases, 1H NMR shows
disappearance of the pyrrolic N-H proton signal, indicative of
metalation. We conclude that the Zn12 salt reacts with TPyP,
which yields the metalated porphyrin and 1 in the time it takes
to shake the solutions. In addition, the metalloporphyrin is
recovered when the resulting 1-ZnTPyP complex is subjected
to F-SPE. As discussed above with TPhP and TPyP, the
porphyrin is eluted in the organic fluorophobic eluant while 1
elutes with the fluorous solvent.
εP513 ) 0
(1)
This allows us to determine the concentrations of N, P, and
total TPyP in the fluorous phase (CN, CP, and CT, respectively,
where CT is the sum of CN and CP) from a spectrum containing
both species using only the absorbance (A) at 513 and 638 nm
(see Supporting Information for derivation).
CN ) 1.28A513
(2)
(3)
(4)
CP ) 0.97A638 - 0.097A513
CT ) 1.28A513 + 0.97A638 - 0.097A513
In addition, CT can be determined independently from the
fluorous-phase spectra through mass balance from the source
phase (CT ) CiN - CNf ), where CNi and CfN represent the initial
and final concentration of neutral porphyrin in the source phase,
respectively. CT from mass balance agrees quite well with the
sum of CN and CP in the fluorous phase (see Figure 7).
Protonation of the tetrapyrrole nitrogens follows protonation
of the TPyP pyridyl nitrogens with greater excess 1 (Figure 7).
Thus, it is no surprise that the CP increases with increasing [1].
It is interesting that not only does 1 extract the nonfluorous

7454 J. Phys. Chem. B, Vol. 113, No. 21, 2009
O’Neal and Weber
Figure 6. 1H NMR chemical shifts of peaks due to (a) TPyP pyridyl H3, H5 (square), tetrapyrrole (circle), and pyridyl H2, H6 (diamond) protons
and (b) TPhP phenyl H3, H5 (square), tetrapyrrole (circle), and phenyl H2, H4, H6 (diamond) protons as a function of [1] in FC-72 resulting from
extraction of 1.0 mM porphyrin in CDCl3 with FC-72 containing 1.
Figure 8. UV/vis absorbance Q bands from the fluorous phase resulting
Figure 7. Concentrations of P (9) and N (b) forms of TPyP in the
from an extraction of 0.1 mM TPyP in CHCl3 with Zn12 in FC-72.
receiving phase resulting from an extraction of TPyP from a 1.0 mM
The arrow indicates increasing [Zn12] from 0.0-10.0 mM. Inset:
TPyP solution in a CDCl3 source phase with a 1-containing FC-72
absorbance spectrum of ZnTPyP in CHCl3.
receiving phase, shown as a function of [1]. CT in the fluorous phase
determined by the sum of CN and CP (2) as well as mass balance from
CDCl3 phase measurements ([) is also shown.
phase after being shaken with with CDCl3 containing 1.00%
(v/v) ethanol show that the ethanol fluorous/organic distribution
coefficient (Dc,F/O) is 0.09. This doubles to Dc,F/O ) 0.18 with
10.0 mM 1 dissolved in FC-72.
Similar extractions with TPhP were carried out to confirm
the significance of the 1-pyridyl interaction in solubilizing the
complex. There was no partitioning of 0.1 mM TPhP into the
fluorous phase observed with up to 10.0 mM Zn12. Correspond-
ingly, there was no detectable partitioning of ZnTPhP from
CHCl3 to an FC-72 phase containing up to 20.0 mM 1. Thus,
ZnTPhP showed no interaction with 1. With Zn2+ occupying
the TPhP tetrapyrrole ring, the only possible binding site for 1
would be through axial metal-ligand coordination. The lack
of interaction confirms that axial coordination of a Lewis acid
(ZnTPhP) and carboxylic acid (1) is unfavorable. Thus, we
conclude that it must be the interaction between 1 and the
pyridyl moieties that immobilizes ZnTPyP in FC-72.
The fractions of TPhP and TPyP extracted from CHCl3
containing ∼1% (v/v) ethanol and CDCl3 containing 0.00, 1.00,
and 2.00% (v/v) ethanol with 1 in FC-72 are shown in panels
a and b of Figure 9, respectively. It is evident that the addition
of ethanol significantly hinders the extraction of both TPhP and
TPyP into 1-containing FC-72. For a given [1], the fraction
extracted from CHCl3 with ∼1% (v/v) ethanol and CDCl3 with
1.00% (v/v) ethanol differ. This is because the addition of
ethanol to CHCl3 is from the factory and not quantitatively
accurate, especially after a particular bottle is opened, whereas
the CDCl3 with 1.00% (v/v) ethanol solution was made fresh
before the experiment. In addition to reducing the effectiveness
of the receptor in the receiving phase, ethanol acts as a hydrogen
bond donor in the source phase, therefore reducing the porphyrin
chemical potential and the thermodynamic driving force for
extraction. Thus, to clarify the role of ethanol in the fluorous
phase more completely, we attempted to determine the state of
protonation of TPyP in 1/FC-72 with ethanol.
3.3. Competitive Equilibria. Chloroform was chosen as the
source phase for this study because it is relatively unreactive,
is miscible with most organic solvents, and is minimally soluble
in fluorous solvents at room temperature.51,52 We found that the
1
solubility of CHCl3 in FC-72 is 0.28 M by H NMR measure-
ments. Although common knowledge, it is often overlooked that
commercial chloroform contains approximately 1% (v/v) ethanol
stabilizer to prevent the formation of HCl and phosgene during
storage.40,41 Quantitative 1H NMR measurements of the FC-72
We have described above a method for determining the
absolute concentrations of TPyP in both the protonated (P) and

Porphyrins in Fluorous Liquids
J. Phys. Chem. B, Vol. 113, No. 21, 2009 7455
Figure 9. Fraction of (a) TPhP and (b) TPyP extracted from a 1.0 mM solution in CHCl3 with ∼1% (v/v) ethanol (squares), CDCl3 (circles),
CDCl3 with 1.00% (v/v) ethanol (triangles), and CDCl3 with 2.00% (v/v) ethanol (diamonds). Source phase with a 1-containing FC-72. Receiving
phase shown as a function of [1].
that of the same solution extracted from CDCl3 (ethanol free)
(see Figure S13 in Supporting Information).
4. Conclusion
We have shown that 1 is an effective fluorous receptor for
extracting both TPhP and TPyP from CHCl3 into FC-72. While
1 transfers two protons to the tetrapyrrole ring of TPhP to create
the porphyrin dication (H2TPhP2+), the interaction between 1
and TPyP occurs through protonation of both the pyridyl and
tetrapyrrole nitrogens. It is interesting that a hexacation is formed
in the fluorous environment. Protonation of the TPyP tetrapyrrole
can be attributed to the surrounding contact ion pairs increasing
the polarity of the immediate solvation environment. In other
words, the “solvent” perceived by the tetrapyrrole is substantially
more polar than a solution of 1/FC-72. Thus, the overall charge
on TPyP can be “tuned” by adjusting the relative concentrations
of 1 and TPyP. In addition, the charge on the macromolecular
complex can be manipulated by a competitive cosolvent. Less
Figure 10. Relative total absorbance (638 nm/513 nm) of the receiving
of the fully protonated TPyP (P) is formed in the presence of
ethanol in the fluorous phase because ethanol lowers the acidity
in 1/FC-72. Adjusting the relative concentration of ethanol then
makes it possible to reversibly solubilize TPyP in the fluorous
phase through noncovalent interactions while leaving the
tetrapyrrole ring available to interact with metals or other
substrates.
We have also observed near-complete extraction of ZnTPyP
from CDCl3 with 1 in FC-72 and extraction and metalation of
TPyP with Zn12. However, there was no interaction between
ZnTPhP and 1 or between Zn12 and TPhP. This is because Zn12
metalates TPyP yielding ZnTPyP and 1, and the liberated 1
maintains the solubility of the complex in FC-72 through
interactions with the TPyP pyridyl groups. Once metalated,
ZnTPhP has no binding sites for 1. This is the first report
demonstrating metalation of TPyP in a fluorous environment.
This fundamental understanding of the interactions of porphyrins
and metalloporphyrins with 1 in the fluorous phase should lead
to the development of more robust and selective porphyrin-
based sensors and application to other devices.
phase resulting from an extraction of TPyP from a 1.0 mM TPyP
solution in CHCl3 with ∼1% (v/v) ethanol (9), CDCl3 (b), CDCl3 with
1.00% (v/v) ethanol (2), and CDCl3 with 2.00% (v/v) ethanol ([).
Source phase with a 1-containing FC-72. Receiving phase shown as a
function of [1].
unprotonated (N) form in the fluorous phase. Recall that all four
pyridyl groups are protonated in both species (see Supporting
Information). Unfortunately, the presence of ethanol in FC-72
significantly changes the solvent environment and thus the molar
absorptivities at both 513 and 638 nm. As a result of the multiple
equilibria between ethanol, 1, and TPyP, the previously
described method is no longer applicable. Nonetheless, because
the molar absorptivity of N at 638 nm is much smaller than
that of P at 638 nm (ε6N38 < < ε6P38), the ratio of the absorbances
at 638 and 513 nm (A638/A513) is approximately related to the
ratio of P to N in the fluorous phase. Figure 10 shows A638/A513
in the fluorous phase plotted against [1] from extractions of
TPyP from CHCl3 containing ∼1% ethanol (v/v) and CDCl3
containing 0.00, 1.00, and 2.00% (v/v) ethanol with 1 in FC-
72. Although necessarily approximate, Figure 10 demonstrates
that ethanol decreases the acidity in the fluorous phase, which
inhibits the formation of the hexacation (P). Ethanol, then,
modulates the solution environment in 1/FC-72.
Acknowledgment. This research was funded by the National
Science Foundation (NSF) through Grant CHE0615952.
Interestingly, the inhibitory effect of ethanol on the formation
of the hexacation is reversible. As ethanol evaporates from FC-
72, the absorbance at 597 nm of an FC-72 solution containing
10.0 mM 1 and TPyP that has been extracted from a 1.0 mM
solution of CHCl3 with ∼1% ethanol (v/v) increases to match
Supporting Information Available: Figures S1and S2 show
1
FTIR and H NMR spectra of 1 and the Zn(II)-12 metal-salt,
respectively; Figure S3 shows the 1H NMR position of 1-protons
as a function of concentration in FC-72 resulting from an
extraction of 1.0 mM TPyP in CDCl3 and 1/ FC-72 control; the

7456 J. Phys. Chem. B, Vol. 113, No. 21, 2009
O’Neal and Weber
¨
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derivation of a method for determining absolute concentrations
of neutral and protonated TPyP in 1-containing FC-72; Figure
S4 plots absorbance at 638 nm vs absorbance at 513 nm (b )
0.1 cm) from the receiving phase of an extraction of TPyP from
CDCl3 with 1 in FC-72; Figures S5-S8 show photographs of
the extraction of 1.0 mM TPhP in CHCl3 and CDCl3 with 0, 1,
and 2% ethanol, respectively, with 0-20 mM Krytox in FC-
72; Figures S9-S12 show photographs of the extraction of 1.0
mM TPyP in CHCl3 and CDCl3 with 0, 1, and 2% ethanol,
respectively, with 0-20 mM Krytox in FC-72; and Figure S13
shows the absorbance at 597 nm of an FC-72 solution containing
10.0 mM 1 and TPyP that has been extracted from a 1.0 mM
solution of CHCl3 containing 1% ethanol. This material is
available free of charge via the Internet at http://pubs.acs.org.
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