PEGylated meso-arylporpholactone metal complexes as optical cyanide sensors in water

Article abstract of DOI:10.1039/c4ob00697f

The colorimetric cyanide sensing ability of free base porpholactone, a pyrrole-modified porphyrin in which a porphyrin β,β′-double bond was replaced by a lactone functionality, and its zinc(ii), platinum(ii), and gallium(iii) complexes in aqueous solution are reported. Water-solubility of the parent meso-pentafluorophenyl-derivatized porphyrinoids was assured by PEGylation of the p-aryl positions using a nucleophilic aromatic substitution reaction with thiol-terminated PEG chains. A central metal-dependent sensing mechanism was revealed: While the CN^- adds to the zinc(ii) complex as an axial ligand, resulting in a minor response in its UV-vis spectrum, it undergoes a nucleophilic addition to the lactone moiety in the platinum(ii) and gallium(iii) complexes, leading to a much more prominent optical response. Nonetheless, these chemosensors are less sensitive than many other sensors reported previously, with detection limits at pH 7 for the zinc, gallium, and platinum complexes of 2 mM (50 ppm), 240 μM (6 ppm), and 4 mM (100 ppm), respectively. The gallium(iii) complex is weakly fluorescent (= 0.8%) and cyanide addition leads to fluorescence intensity quenching; the cyanide adduct responds with a fluorescence switch-on response but the signal is weak (< 10^-2%). Lastly, we report on the fabrication of a unique optical cyanide-sensing membrane. The PEGylated gallium-complex was incorporated into a Nafion membrane (on a PTFE carrier film). It was shown to be stable over extended periods of time and exhibiting a reversible and selective response within minutes to cyanide, with a 5 mM (130 ppm) detection limit. This largely fundamental study on the ability to utilize the once rare but now readily available class of pyrrole-modified porphyrins as chemosensors highlights the multiple principle ways this chromophore platform can be modified and utilized. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00697f

Organic &
Biomolecular Chemistry
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PEGylated meso-arylporpholactone metal
complexes as optical cyanide sensors in water†‡
Cite this: Org. Biomol. Chem., 2014,
12, 3991
Jill L. Worlinsky, Steven Halepas and Christian Brückner*
The colorimetric cyanide sensing ability of free base porpholactone, a pyrrole-modified porphyrin in
which a porphyrin β,β’-double bond was replaced by a lactone functionality, and its zinc(II), platinum(II),
and gallium(III) complexes in aqueous solution are reported. Water-solubility of the parent meso-penta-
fluorophenyl-derivatized porphyrinoids was assured by PEGylation of the p-aryl positions using a nucleo-
philic aromatic substitution reaction with thiol-terminated PEG chains. A central metal-dependent sensing
mechanism was revealed: While the CN− adds to the zinc(II) complex as an axial ligand, resulting in a
minor response in its UV-vis spectrum, it undergoes a nucleophilic addition to the lactone moiety in the
platinum(II) and gallium(III) complexes, leading to a much more prominent optical response. Nonetheless,
these chemosensors are less sensitive than many other sensors reported previously, with detection limits
at pH 7 for the zinc, gallium, and platinum complexes of 2 mM (50 ppm), 240 μM (6 ppm), and 4 mM
(100 ppm), respectively. The gallium(III) complex is weakly fluorescent (ϕ = 0.8%) and cyanide addition
leads to fluorescence intensity quenching; the cyanide adduct responds with a fluorescence switch-on
response but the signal is weak (ϕ < 10−2%). Lastly, we report on the fabrication of a unique optical
cyanide-sensing membrane. The PEGylated gallium-complex was incorporated into a Nafion® mem-
brane (on a PTFE carrier film). It was shown to be stable over extended periods of time and exhibiting a
reversible and selective response within minutes to cyanide, with a 5 mM (130 ppm) detection limit. This
largely fundamental study on the ability to utilize the once rare but now readily available class of pyrrole-
modified porphyrins as chemosensors highlights the multiple principle ways this chromophore platform
can be modified and utilized.
Received 2nd April 2014,
Accepted 1st May 2014
DOI: 10.1039/c4ob00697f
www.rsc.org/obc
Large quantities of cyanides are used in industry, e.g., in the
synthesis of plastics, inks, fertilizers, nylon, fishing, tanning,
Introduction
The high toxicity of cyanide (CN−), combined with its wide- gold mining, for the case hardening of steel, and in metal electro-
spread technical use, urge the development of sensing plating.1,2 Its wide-spread use raises the risk for accidental
methods for this anion.1 As little as 0.5–3.5 mg cyanide per kg or intentional release into the water stream. The WHO
of body weight are lethal to humans.1,2 Cyanide inhibits cellu- recommended limit for cyanide in drinking water is 0.07 mg L−1 2
.
lar respiration. The primary toxic effect of cyanide lies in its
Optical chemosensors hold much appeal for the simple
ability to strongly bind to iron in heme proteins, whereby the and rapid chemoselective detection of many analytes,3,4
crucial target in the mammalian body is cytochrome c oxidase. including cyanide. The current state of the art of colorimetric
Cyanides (typically in the form of cyanogenic glycosides) and fluorometric cyanide chemosensing methods was recently
are widespread in nature. They occur in certain seeds and fruit reviewed.1 Some of the detection methods rely on hydrogen
stones, such as those of apple, mango, peach, and bitter bonding interactions but they frequently suffer from poor
almonds, and in cassava, bamboo shoots, and linseed.1,2 selectivity with respect to other anions.5–8 Reaction-based
sensors (or non-reversible chemidosimeters) take advantage of
the nucleophilicity of cyanide toward electron-poor carbonyl
groups (or derivatives) attached to a chromophore,5–15 the
Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060, USA.
strong affinity of cyanide for metal ions,16–20 the ability of
E-mail: c.bruckner@uconn.edu; Fax: (+01) 860-486-2981
†Oxazolochlorins 13. Oxazolochlorins 12. Y. Yu, B. Czepukojc, C. Jacob, Y. Jiang,
cyanide to form Lewis acid–base pairs with triarylboranes,21 or
the ring-opening of a pyrylium moiety. The resulting changes
of the optical spectra or luminescence lifetimes upon cyanide
addition were tracked.1,18 Even though real life cyanide
detection is, in most cases, expected to take place in water,
M. Zeller, C. Brückner and J.-L. Zhang, Org. Biomol. Chem., 2013, 11, 4613–4621.
‡Electronic supplementary information (ESI) available: A reproduction of key
1H, 13C NMR, IR, UV-vis, and fluorescence spectra of the novel compound
described herein, including images of the setup and a membrane. See DOI:
10.1039/c4ob00697f.
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most sensors reported to date require organic solvents or a
mixture of an organic solvent with some water.1,6,8–10,13,21 Only
a few sensors were reported to operate in a purely aqueous
system.16,17,19,20
For their strong colors, fluorescence, electrochemical
activity, ability to coordinate to a variety of metals, and chemi-
cal stability, porphyrins and many other porphyrinoids are
well suited for use in sensing applications.22–27 Metallo-
porphyrins can act as cyanide sensors because of the intrinsic
affinity of cyanide for some metals coordinated to the por-
phyrin, such as zinc, rhodium, copper, silver and gold, thus
exchanging or adding axial ligands.28–33 In this fashion, [meso-
tetraphenylporphyrinato]zinc(II) (1Zn),29,33 [meso-tetrakis(4-carb-
oxyphenyl)porphyrinato]copper(II),30 or [meso-tetrakis(4-sulfo-
natophenyl)porphyrinato]rhodium(III) (2Rh)28 were used for
the optical detection of cyanide (Fig. 1). One refined approach
utilized a two-point recognition of sodium or potassium
cyanide by zinc porphyrin crown ether conjugate 3Zn.31,32
However, the coordination of the cyanide to the central metal
generally elicits only modest changes to the optical spectra of
the metalloporphyrins, diminishing their practicality as
sensors (see also below).28–33
Porpholactones 5 are derived from porphyrins 4 by replace-
ment of a β,β′-double bond with a lactone functionality; in
effect, a pyrrole moiety was exchanged for an oxazolone.26,34–37
Though known for some time,34,35 they have only more
recently become readily available along two complementary
routes: The one-step Ru-catalyzed direct oxidation of a por-
phyrin,38 or a two-step route involving the OsO4-mediated di-
hydroxylation of a porphyrin, followed by MnO4−-oxidation of
the intermediate dihydroxychlorin (Scheme 1).26,37,39,40 Both
pathways produce the porpholactones 5 and 6 in good yields.
The introduction of the external lactone functionality into
the chromophore influences its electronic properties.35,37 The
lactone functionality can also serve as a synthetic handle
toward the generation of other porphyrinoids.27,37,42,43 Most
important in the current context, the lactone functionality at
the periphery of the macrocycle is electronically strongly
coupled to the chromophore. This renders porpholactones to
be excellent sensor platforms: The lactone moiety serves as the
key functionality in the use of 6Pt, and related derivatives, as
high pH indicators.26,44 At pH values above 11.5, hydroxide
attacks the lactone carbonyl group, forming a cyclic orthoester
Fig. 1 Spectrophotometric CN− titration of the PEGylated porpholac-
tones investigated, all in an aqueous pH 7 phosphate buffer and CN− in
the form of an aqueous NaCN solution; any dilution effects <2%. A:
6-PEG1000 (6.06 × 10−6 M). B: 6Pt-PEG1000 (3.97 × 10−6 M). C: 6GaCl-
PEG1000 (5.10 × 10−6 M). Dye concentrations in the images of the cuv-
ettes ∼5 × 10−5 M.
anion. This sp2-to-sp3 conversion of the lactone β-carbon
induces a ∼100 nm red-shift of the optical spectrum. Interest-
ingly, the presence of the lactone moiety also indirectly
influences the sensing ability of the chromophore as the [por-
pholactonato]platinum(II) complex 6Pt proved to be a more
effective oxygen-sensing dye in pressure-sensing paints than
the corresponding porphyrin platinum complex.45–47 We have
recently also demonstrated that the porpholactone chromo-
phore can be modulated by conversion to a thionolactone.27
The hypochlorite-selective conversion of the non-fluorescent
thionolactone to the fluorescent lactone forms the basis
for the use of thionoporpholactones as fluorescence-based
chemodosimeters for hypochlorite.27
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Scheme 1 Formation of tetraarylporpholactone 5 and 6 by oxidation of
the corresponding porphyrins 4. Reaction conditions: (i) for
R =
Ph:26,37,41 1. OsO4, pyridine, CHCl3, r.t., up to 7 d; 2. H2S, followed by
column chromatography; 3. Cetyltrimethylammonium permanganate
(CTAP), CH2Cl2, r.t., 12 h, followed by column chromatography. (ii) For
R = C6F5:40 1. OsO4, pyridine, CHCl3, r.t., 24 h, then removal of ∼50%
solvent by rotary evaporation; 2. Addition of a saturated MeOH–H2O
(1 : 1) solution of NaHSO3 to the reaction mixture, r.t., up to 2 d, followed
by column chromatography; 3. CTAP, CH2Cl2, r.t., ∼3 h, followed by
column chromatography.
Herein we report the evaluation of a number of metallo-
porpholactone derivatives as colorimetric and fluorimetric
cyanide sensors, whereby we directly compare the effectiveness
of cyanide sensing by coordination to a central metal (in the
case of the Zn(II) complexes) or by nucleophilic attack on the
lactone carbonyl group (in the free base and Pt(II) and Ga(III)Cl
complexes). Importantly, the particular meso-pentafluoro-
phenyl-substituted porpholactones utilized are readily suscep-
tible to conversion to novel water-soluble derivatives. Thus, we
report on the selective and sensitive detection of cyanide in
pure water. Lastly, we report on the incorporation of the sensi-
tive [porphyrinato]gallium(III) chloride-based sensor dye into a
Nafion® membrane, resulting in the formation of chemically
robust optical cyanide sensor membranes.
Scheme 2 Formation of metalloporpholactones 6M by insertion of
metal ions into free base lactone 6 and formation of the PEGylated
derivatives. Reaction conditions: (i) Zn(OAc)2–MeOH, CHCl3, reflux; (ii)
Pt(acac)2, PhCN, reflux; (iii) GaCl3, NaOAc·3H2O, CH3CO2H, MW; (iv)
H-MET or H-PEG1000, DMF, NEt3 (2 : 1), reflux.
tible to this reaction. Thus, reaction of 6M with at least a
4-fold molar excess of 2-(2-methoxyethoxy)ethanethiol (MET-H)
under basic conditions (33% NEt3 in DMF) provided 6M-MET
in excellent yields (Scheme 2).
The clean and diagnostic 1H NMR spectra of these com-
pounds confirmed the presence of four short MET chains.
However, full water-solubility could not be achieved with the
short chains. We therefore reacted 6M with a longer thiol-
terminated PEG of average molecular weight of 1000 amu,
PEG1000. The molecular weight heterogeneity of the longer
PEG chains made the characterization of the resulting
less homogenous products more difficult. ESI-MS allowed only
the detection of peak clusters around a mass that suggested
tetra-substitution had taken place and the 1H NMR of the com-
pounds was dominated by the large number of methylene
protons. On the other hand, the products 6M-PEG1000 proved
to be freely water-soluble. They also possessed optical spectra
that were comparable to those of the parent compounds in
organic solvents (see below). In the sensing experiments
described in the following, we use only the PEG1000 derivatives
in purely aqueous solutions (or aqueous phosphate buffers).
Results and discussion
Syntheses of metalloporpholactones 6M
The metalloporpholactones, known 6Zn, 6Pt26,36,44 and novel
derivative 6Ga, were synthesized by metalation of free base
meso-tetrakis(pentafluorophenyl)porpholactone 6 using stan-
dard reaction conditions (in case of 6Ga, microwave heating)
(Scheme 2).48–50 The novel gallium(III) complex showed all the
expected spectroscopic and analytical properties (see ESI‡). It
was prepared as the square pyramidal complex carrying an
axial chloride ligand, thus forming an overall neutral complex.
Synthesis of PEGylated metalloporpholactones 6M-MET/
6M-PEG1000
Optical properties of 6M and their PEGylated derivatives
meso-Pentafluorophenyl groups are susceptible to a nucleo- As described previously, the UV-vis spectra of free base porpho-
philic aromatic substitution of the p-F atom with soft nucleo- lactones in organic solvents are porphyrin-like, and those of
philes, such as sulfides. This reaction was frequently utilized their metal complexes possess characteristics of metallochlo-
to functionalize porphyrins.51–57 We have also shown that rins.35,37 The introduction of the thiol PEG chains to the meso-
meso-pentafluorophenyl-substituted oxazolochlorins are sus- aryl groups of the porpholactones affects their optical spectra
ceptible to this reaction, allowing the preparation of water- only to a minor degree: the spectra do not change their charac-
soluble derivatives when using thiol-terminated PEG chains as teristic shapes but blue-shift their absorption peak maxima a
nucleophiles.58 As expected, the related meso-pentafluoro- few nm. The compounds are subject to larger, but overall still
phenyl-substituted metalloporpholactones 6M are also suscep- small, solvochromic shifts. Taken together, the high-energy
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Fig. 3 Rate of optical response at λ = 708 nm of 6Ga-PEG1000 (7.9 ×
10−6 M in pH 7 phosphate buffer, 20 °C) upon addition of 133 mM CN−.
Fig. 2 Spectrophotometric CN− titration of the PEGylated zinc com-
plexes investigated, all in H2O and CN− in the form of an aqueous NaCN
solution; any dilution effects <2%. A: 6Zn-PEG1000 (4.48 × 10−6 M). B:
8Zn-PEG1000 (5.10 × 10−6 M). Dye concentrations in the images of the
cuvettes ∼5 × 10−5 M.
bands in the UV-vis spectrum of 6-PEG1000 in water (λmax
values at 417, 514, 552, 589, and 643 nm; Fig. 1A) are up to
11 nm bathochromically shifted compared to the corres-
ponding bands of the parent compound 6 in CH2Cl2 (λmax
values at 406, 508, 542, 590, and 644 nm);35 of note is that the
longest wavelength transition is essentially unchanged. The
metallochlorin-like spectra of the PEGylated platinum(II) com-
plexes are, except for smaller shifts, likewise as previously
described for the platinum porpholactone complexes, respecti-
vely (Fig. 1B).36 The spectra of the novel gallium complexed
are also as expected,48–50 and resemble those of the zinc complex
(cf. Fig. 1C and 2A), that itself is as described previously.36
Scheme 3 Proposed cyanide sensing mechanism of 6Pt-PEG1000 and
6Zn-PEG1000
.
platinum 6Pt-PEG1000 (not shown) and gallium 6GaCl-PEG1000
complexes (Fig. 3).
The optical response to cyanide is qualitatively equivalent,
albeit slower, to that observed for 6Pt (and other metal com-
plexes) when exposed to pH values above 11.5.26,44 Thus, we
interpret the cyanide-induced shift of the optical spectrum
correspondingly, namely as a nucleophilic attack of CN− onto
the lactone. This converts the sp2-hybridized lactone carbonyl
to an sp3-hybridized cyanohydrin-like β-carbon (Scheme 3).
Chemical reduction of the lactone moiety also leads to large
optical changes in the resulting chromophore.37,41 The anionic
charge of the cyanohydrin-like addition species is likely stabil-
ized by interaction with the adjacent pentafluorophenyl moiety.
The design of multiple other cyanide sensors also relied on the
ability of cyanide to attack carbonyl groups5–13 (or vinylogous
carbonyl groups14 or carbonyl derivatives15). Some of the result-
ing cyanohydrin adducts were also stabilized through intramole-
cular interactions, mainly hydrogen bonds.5,8,11
Colorimetric cyanide sensing
Free base, Pt-, and Ga-complexes. Free base porpholactone
6-PEG1000, as well as the two metal complexes 6Pt-PEG1000
,
6Zn-PEG1000, and 6GaCl-PEG1000 showed an optical response
upon addition of cyanide (in the form of an aqueous solution
of NaCN), but their response profiles vary from each other
(Fig. 1A–C; the zinc complex is discussed below, Fig. 2).
Addition of cyanide to unmetallated 6-PEG1000 caused a color
change from purple-orange to yellow-brown (Fig. 1A). The pink
color of 6Pt-PEG1000 switched to light pink with an orange
tinge upon cyanide addition (Fig. 1B). The addition of cyanide
led to a decrease of the Soret band, the regular metallo-
chlorin-type side bands diminished in intensity, and a single
Free base porpholactone 6-PEG1000 showed a qualitatively
similar response (Fig. 1A) to the corresponding platinum
complex 6Pt-PEG1000 that we therefore also explain with a
nucleophilic CN− attack onto the lactone. This is interesting as
exposure of free base porpholactone 6 to more basic – though
new, broad, and much red-shifted band appeared (λmax
=
703 nm). In µM dye solutions, the color changes require at
ambient temperature several minutes to fully develop for the
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Table 1 Cyanide sensing data
Cyanide detection limitb
Concentration
1.5 mM
Mass fraction
40 ppm
Kd
a
6-PEG1000
87 mM
6Pt-PEG1000
At pH 7.0
4.0 mM
0.9 mM
240 µM
5 mM
2.0 mM
3.4 mM
100 ppm
47 ppm
6 ppm
130 ppm
50 ppm
90 ppm
210 mM
99 mM
9.7 mM
n/d
14 mM
45 mM
At pH 8.0
a
6Ga-PEG1000
In Nafion membranea
a
6Zn-PEG1000
8Zn-PEG1000
a
Scheme 4 Formation of [porpholactonato]Zn(II) 8Zn-PEG1000. Reaction
conditions: (i) H-PEG1000, DMF, NEt3 (2 : 1), reflux.
a At pH 7.0. b Determined as 3σ/m, with σ = standard deviation, and
m = slope of the response at the lower linear limit, ΔA/Δ[CN−].59
(Fig. 2A). This response is comparable of the shifts of the metallo-
porphyrin spectra of the metalloporphyrin [meso-tetrakis-
(pentafluorophenyl)porphyrinato]zinc(II) (8Zn) lacking the
lactone functionality (Fig. 2B; water-soluble zinc porphyrin
8Zn-PEG1000 was prepared from zinc porphyrin 7Zn analogous
to the water-soluble porpholactones (Scheme 4)) and other
zinc porphyrin-based sensors,29,31–33 although the visible color
change from purple to yellow is more significant. It thus can
be attributed to axial ligation of the cyanide to the central
metal (Scheme 3). The formation of square pyramidal com-
plexes for the zinc porphyrinoids is well known.60 Evidently,
the association constant for this process is significantly higher
than for the nucleophilic attack of cyanide to the lactone
moiety of 6Zn-PEG1000, for which we find no evidence.
The response of the zinc complexes is much faster than
that of the other dyes and completed upon mixing. The sensi-
tivity of the zinc lactone complex for CN− is high, with a detec-
tion limit of 2.0 mM, i.e., in the same order of magnitude as
the platinum complex, and lower than for the parent zinc por-
phyrin 8Zn-PEG1000 (3.4 mM). We attribute this to the generally
decreased Lewis basicity of the oxidized porpholactone com-
pared to the porphyrin;26 this renders the coordinated metal
ion to be a better Lewis acid,61 with a corresponding higher
binding affinity for cyanide (with a Kd of 14 mM for porpho-
lactone complex 6Zn-PEG1000 compared to 45 mM for the
porphyrin complex 8Zn-PEG1000).
less nucleophilic – hydroxide ions merely deprotonated the
inner nitrogen(s).26 The response of the platinum complex 6Pt-
PEG1000 toward cyanide under identical [CN−] is significantly
stronger than that of the free base 6-PEG1000 (cf. Fig. 1A and
B), a finding that does not surprise. The presence of a dication
of a strongly electronegative element in the center of the por-
phyrin is expected to increase the susceptibility of the ligand
to nucleophilic attack.44 At pH 7, we determined a detection
limit for CN− using 6Pt-PEG1000 of 4.0 mM; at a higher pH of
8.0, of 0.9 mM (all detection limits and Kd values are summar-
ized in Table 1). Cyanide is the conjugated base of the weak
acid HCN (with a pKa value of 9.2). Thus, the higher pH
value increases the effective cyanide concentration. Free base
6-PEG1000 possesses a detection limit of 1.5 mM.
The green color of 6Ga-PEG1000 switched to yellow upon
cyanide addition. The response profile of the gallium complex
6Ga-PEG1000 to cyanide is similar to that of the platinum
complex 6Pt-PEG1000 and thus also suggestive of a nucleophilic
attack onto the lactone (Fig. 1C). Surprisingly, however, the
response is significantly more sensitive compared to the plati-
num complex, with a detection limit of 240 µM CN−. The
increased sensitivity is possibly a reflection of the higher
charge of the central metal. We could not find any indication
that the hard gallium(III) center has any affinity for cyanide as
an axial ligand (in comparison, see for the sensing mechanism
of the zinc complexes described previously,29,31–33 and below).
The addition of cyanide to the lactone moiety could be
demonstrated to be, as expected, reversible (see also below for
the demonstration of reversibility of the dye embedded into a
membrane). Thus, addition of molar excess Zn(II) chloride to a
solution of 6Ga-PEG1000 and cyanide in pH 7 buffer removes
the cyanide from the lactone–cyanohydrin equilibrium by pre-
cipitation as Zn(CN)2. Consequently, the native UV-vis
spectrum of the sensor is restored (after the removal of the pre-
cipitate by filtration; see ESI‡).
Selectivity of cyanide sensing in aqueous solutions
In the pH range between 5 and 9, the selectivity of the
response for cyanide in water is excellent. At solutions
buffered at pH 7 (phosphate buffer) or in water at ambient
conditions, no other commonly occurring anion (F−, Cl−, Br−,
I−, AcO−, ClO4−, NO3−, NO2−, H2PO4−, N3−, SCN−, or OCN−),
applied as their Na+ or K+ salts elicited a colorimetric response
with 6Ga-PEG1000, even in the presence of a 30-fold molar excess
of the anions (Fig. 4). The gallium complex was also suitable to
sense mM quantities of CN− in the presence of 2 M Cl− ions
(30-fold molar excess, in the form of NaCl or KCl). Alas, at pH
values well below 2, the free base porphyrin will become proto-
nated and change its UV-vis spectrum;26 at pH values above
10, the platinum complex can act, as described previously, as a
high pH sensor.26 The ability of the sensor to selectively detect
Zn-complexes. The optical response of the zinc complex
6Zn-PEG1000 to cyanide differs fundamentally from that of the
free base, platinum, and gallium complexes. Addition of
cyanide causes the green color of the metallochlorin-type spec-
trum to take on a yellowish tone and only a modest (∼10 nm)
bathochromic shifts of the Soret and Q bands is observed
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rescence cyanide sensor is that fact, however, that the absolute
fluorescence intensity of the cyanohydrin anion species (cf.
Scheme 3) is very weak (less than 1% of the intensity of 6Ga-
PEG1000, with an estimated ϕ of less than 0.01%). We suspect
that the electron-rich cyanohydrin anion species leads to
fluorescence quenching through a PET mechanism.66
An optode membrane for optical cyanide-sensing
Optical solid chemosensors (optodes) are based on a sub-
strate-specific change of the absorbance or luminescence of a
solid into which a sensor dye is chemically or physically
immobilized. Optodes overcome several limitations of solu-
tion-based sensing methods. For instance, they are suitable to
continuously monitor solution streams and readily allow
remote sensing.67,68 The requirements for an ideal optode are
well established and include a strong color change, rapid
response time, reversibility, and long-term stability.67,68 As we
will demonstrate, the optode material prepared largely fulfills
these requirements.
Water-soluble porphyrins (generally, meso-tetrakis(4-sulfona-
tophenyl)-substituted derivatives) have been incorporated into
Nafion® (a sulfonated polytetrafluoroethylene polymer)
before.69 We opted for the incorporation of the most cyanide-
sensitive dye, the PEG-derivatized gallium porpholactone
complex 6Ga-PEG1000. The dye was added to the precursor
Nafion® solutions from which the membranes were fabricated
(as Nafion® – 0.018 mm (0.7 mil) PTFE film–Nafion® sandwich
of overall minimum thickness of 0.025 mm (∼1–2 mil)), accord-
ing to the literature.70 The Nafion® matrix was chosen for its
transparency, high chemical and thermal stability, strength,
hydrophilicity, and known ion conduction properties.70
Fig. 4 Relative absorbance intensity response at λ = 712 nm of 6Ga-
PEG1000 (5.10 × 10−6 M) in pH 7 buffer or water upon the addition of
various anions (50 equiv., unless noted otherwise).
cyanide even in high ionic strength solutions over a broad pH
range may make this sensor particularly useful.
Fluorimetric cyanide sensing
Fluorimetric sensing modes are generally more sensitive than
comparable colorimetric modes.63 The porpholactone zinc
complex 6Zn-PEG1000 is, like most zinc porphyrins, highly fluo-
rescent but this compound was deemed not to possess a large
enough signal separation to be an attractive cyanide sensor
(Fig. 2A). Porphyrin platinum complexes are strongly lumines-
cent but this luminescence is partial oxygen pressure-depen-
dent.47,64 We thus also did not consider this compound to be
a practical fluorimetric sensor for cyanide. Gallium porphyrin
complexes are chemically robust with respect to the metal oxi-
dation state and their resistance toward demetalation.65 And,
like all closed-shell metalloporphyrins, they are fluorescent.
These characteristics provided the impetus to prepare and
study the gallium(III) complex 6Ga and its PEGylated deriva-
tives 6Ga-MET and 6Ga-PEG1000 in the first place.
Unlike other examples of porphyrins embedded into
Nafion® membranes,69 6Ga-PEG1000 does not display any
altered optical absorption spectra as compared to the com-
pound in aqueous solution (Fig. 6; cf. to Fig. 1C). This indi-
cates that it does not form aggregate structures and further
highlights the excellent solubilization properties of the PEG
chains. Addition of cyanide to a pH 7 buffer solution in which
the membrane is mechanically suspended elicits an optical
response much similar to that of the dye in solution, with a
Indeed, the porpholactone gallium complex 6Ga-PEG1000 in
water is fluorescent. The two-band emission spectrum (λmax
=
610 nm) is metallochlorin-like (Fig. 5), with a relatively low
fluorescence yield ϕ of 0.8%. Addition of cyanide reduces, as
expected, the fluorescence intensity by this fluorescent
species. In turn, the fluorescence of the cyanide adduct
increases (at λmax = 745 nm; note the weak emission in the
main graph of Fig. 5, amplified in the insert). Most damaging
to the potential utility of 6Ga-PEG1000 as a switch-on fluo-
Fig. 5 Fluorescence emission titration of 6Ga-PEG1000 (5.10 × 10−7 M)
in H2O with 0–40 mM aq. NaCN; λex = λSoret = 418 nm. Insert: Emission
intensity in the region between 700 and 800 nm recorded with
amplified sensitivity.
Fig. 6 Spectrophotometric CN− titration of the PEGylated porpho-
lactone 6Ga-PEG1000 in Nafion® membrane in pH 7 phosphate buffer
and CN− in the form of an aqueous NaCN solution.
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peak separation between the spectra of the ‘off’ and ‘on’ stages
of both sensors are similar and equally attractive, making these
sensors suitable for ratiometric sensing methods, and dis-
tinguish these sensors from their zinc analogue and most other
known cyanide sensors.1,28–33 Valid direct cyanide sensing per-
formance comparisons to other cyanide sensors are difficult.
Most were not tested in aqueous solutions or operated at lower
pH values to enhance the cyanide concentrations.62
The gallium(III) complex is also a fluorescence switch-on
sensor for cyanide but the signal is very weak. Only weakly
fluorescent in water in its native form, its cyanide adduct is
further quenched.
Fig. 7 UV-vis signal of the 6Ga-PEG1000-containing Nafion® mem-
brane upon repeated exposure to 0.5 M NaCN (in pH 7 buffer) for
10 min, followed by pH 7 buffer for 60 min each.
Beyond the introduction of a highly selective sensor for
cyanide in water suitable to detecting high µM to single digit
mM cyanide concentrations, the value of this work lies in the
demonstration that the functionalities of suitably pyrrole-
modified porphyrinoids can be readily utilized for analyte
capture and signal transmission to the porphyrinic chromo-
phore.26,27 Once rarities, porpholactones (and closely related
derivatives)27,43 are now readily accessible.26,37,38 We hope that
this third example in which a porpholactone or porpholactone
derivative was utilized as a chemosensor (or chemodosimeter),
the demonstration of their robustness and strong light absorp-
tion qualities, and their ability to be converted to water-soluble
derivatives, will inspired further work on the intriguing class
of pyrrole-modified porphyrins.
reduced – but still respectable – sensitivity (detection limit =
5 mM CN−, 130 ppm). We rationalize the abated sensitivity of the
dye to its location within an anionic polymer matrix. The reduced
sensitivity of this sensor may be of utility in the determination of
high cyanide concentrations frequently used in industry.
Importantly, the optode material showed
a reversible
response. Upon exchanging the cyanide solution with cyanide-
free pH 7 buffer, the optical response reverted nearly comple-
tely within 40 min (Fig. 7). The intensity fluctuations observed
from one cyanide signal maximum to the next are attributed to
slight position changes of the flexible membrane in the solu-
tion (for the setup, see ESI‡). Nonetheless, some increase of
the baseline signal was noted. The membrane remained stable
and transparent even after days in aqueous solutions.
Experimental section
All solvents and reagents (Aldrich, Acros) were used as
received. For the materials used in the fabrication of the mem-
branes, see below. Flash column silica gel (premium grade,
60 Å, 32–63 µm) was provided by Sorbent Technologies,
Atlanta, GA. Porpholactone 6 and metalloporpholactones 6Zn
and 6Pt were prepared as described previously.26,36,44 1H and
13C NMR spectra were recorded on a Bruker Avance II 400
instrument in the solvents indicated. UV-vis spectra were
recorded on a Cary 50 and fluorescence spectra on a Cary
Eclipse spectrophotometer, both Varian Inc. The fluorescence
quantum yield (ϕ) of 6Ga-PEG1000 was determined relative to
that of meso-tetraphenylporphyrin (ϕ = 0.11 in benzene,71
calculated to be 0.08 in CH2Cl2); λexcitation = λSoret. High and
low resolution mass spectra were provided by the Mass
Spectrometry Facilities at the Department of Chemistry,
University of Connecticut.
Conclusions
We have shown that a class of pyrrole-modified porphyrins car-
rying a lactone functionality at the chromophore periphery can
be utilized as optical cyanide sensors, albeit these sensors
possess only modest sensitivities. The sensing mechanism
relies on a nucleophilic attack of the cyanide onto the lactone
moiety. The induced change in the hybridization of the
carbonyl carbon that is electronically strongly coupled to the
chromophore elicits the expression of
a
dramatically
(∼100 nm) red-shifted new band and a reduction of the Soret
band intensity upon cyanide addition, thus enabling the ratio-
metric sensing of cyanide. Further, the pentafluorophenyl-
substituted derivatives utilized allowed the conversion to freely
water-soluble derivatives through PEGylation, thus allowing
the cyanide sensing in purely aqueous solutions. We also
demonstrated the influence of the presence and nature of the
central metal on the sensing profile.
meso-Tetrakis(4-[2-(2-methoxyethoxy)ethane]thioxy-2,3,5,6-
tetrafluorophenyl)porpholactone (6-MET)
Free base porpholactone 6 (20 mg, 2.0 × 10−5 mol) was dis-
From a practical colorimetric assay point of view, the plati- solved in DMF–NEt3 (2 : 1, 10.5 mL). 2-(2-Methoxyethoxy)ethane-
num and gallium complexes are the best sensors. The more thiol (4 equiv., 11 μL) was added and the solution heated to
costly platinum complex 6Pt-PEG1000 possesses a larger colori- reflux for 1 h. The resulting solution was evaporated to dryness
metric response (i.e. larger relative increase of the intensity of by rotary evaporation and purified by column chromatography
the band at 703 nm), while the less costly gallium complex (silica gel, CH2Cl2–5% MeOH) to provide 6-MET in near-quan-
1
6Ga-PEG1000 possesses the highest sensitivity. The ∼100 nm titative yield (29 mg). H NMR (400 MHz, CDCl3, δ): 8.98–8.97
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(m, 1H), 8.92 (d, J = 5.4 Hz, 2H), 8.85–8.84 (m, 1H), 8.85–8.80 114 mg) in DMF–Et3N (2 : 1, 10.5 mL) as described for the syn-
(m, 1H), 8.72 (t, J = 4.7 Hz, 1H), 8.64 (d, J = 4.7 Hz, 1H), thesis of 6Pt-MET. 1H NMR (400 MHz, CDCl3, δ): 8.78–8.75 (m,
3.93–3.86 (m, 7H), 3.77 (dd, J = 8.2, 4.5 Hz, 1H), 3.70–3.66 (m, 1H), 8.72–8.67 (m, 3H), 8.66–8.58 (m, 2H) 3.72–3.32 (m, >400
7H), 3.54 (td, J = 5.9, 3.3 Hz, 8H), 3.46–3.41 (m, 9H), 3.31–3.30 H), ppm. UV-vis λmax (H2O) (log ε): 424 (5.4), 563 (4.0), 609
(m, 14H), 3.10 (t, J = 3.0 Hz, 1H), 3.07–3.02 (m, 2H), 2.89 (q, J = (4.4) nm. HR-MS (ESI+ ionization, 0.5% formic acid in CH3CN,
5.7 Hz, 1H), −1.73 (s, 1H), −2.03 (s, 1H) ppm. UV-vis λmax with Q-TOF detection): clusters of peaks of corresponding
(CH2Cl2) (log ε): 408 (5.10), 502 (3.75), 538 (3.60), 596 (3.55), to different degrees of protonation, all indicative of the
634 (3.60) nm. HR-MS (ESI+) calc’d for C63H53F16N4O10S4 quadruple addition of PEG1000-S-chains (with n = 18–21).
[MH]+: 1457.2389, obs. 1457.2427.
[meso-Tetrakis(4-PEG1000thioxytetra-2,3,5,6-fluorophenyl)-
meso-Tetrakis(4-PEG1000thioxytetra-2,3,5,6-fluorophenyl)-
porpholactone (6-PEG1000
porphyrinato]zinc(II) (8Zn-PEG1000
Prepared from 7Zn72 (30 mg, 6.05 × 10−6 mol), poly(ethylene
)
)
Synthesized using 6 (50 mg, 5.0 × 10−5 mol) and poly(ethylene glycol) methyl ether thiol (average Mn ∼ 1000) (∼4 equiv.,
glycol) methyl ether thiol (average Mn = 1000) (∼4 equiv., 120 mg) in DMF–Et3N (2 : 1, 10 mL) as described for the syn-
202 mg) as described for the synthesis of 6-MET. 1H NMR thesis of 6Pt-MET. 1H NMR (400 MHz, CDCl3, δ): 8.96 (br s,
(400 MHz, CDCl3, δ): 8.96–8.93 (m, 1H), 8.90–8.87 (m, 2H), 1H), 3.95 (t, J = 6.4 Hz, 1H), 3.75 (overlapping t, 2H) 3.6–3.4
8.83–8.78 (m, 1H), 8.69–8.68 (m, 1H), 8.62–8.60 (m, 1H), (m, 47 H; 44 H is theoretical value) ppm. UV-vis λmax (H2O)
3.94–3.37 (m, >400 H), −1.77 (s, 1H), −2.08 (s, 1H) ppm. UV-vis (log ε): 422 (5.4), 554 (4.3) nm. HR-MS (ESI+ ionization, in
λmax (H2O) (Rel. Int.): 417 (1.0), 514 (0.07), 552 (0.05), 589 CH3CN, with Q-TOF detection): clusters of peaks of corres-
(0.04), 643 (0.05) nm. HR-MS (ESI+ ionization, 0.5% formic ponding to different degrees of protonation, all indicative of
acid in CH3CN, with Q-TOF detection): clusters of peaks the quadruple addition of PEG1000-S-chains (with n = 18–21).
corresponding to different degrees of protonation, all indica-
Chloro-[meso-tetrakis(pentafluorophenyl)porpholactonato]-
tive of the quadruple addition of PEG1000-S-chains (with n =
gallium(III) (6Ga)
18–21).
In a 10 mL thick-walled tube containing a stir bar were placed
[meso-Tetrakis(4-[2-(2-methoxyethoxy)ethane]thioxytetra-
2,3,5,6-fluorophenyl)porpholactonato]platinum(II) (6Pt-MET)
free base meso-tetrakis(pentafluorophenyl)porpholactone
6
(50 mg, 5.04 × 10−4 mol), GaCl3 (44 mg, 5 equiv.), NaOAc·3H2O
Prepared from 6Pt (25 mg, 2.1 × 10−5 mol) dissolved in DMF– (45 mg, 3.14 × 10−4 mol) and acetic acid (5 mL). The vessel was
Et3N (2 : 1, 10.5 mL). 2-(2-Methoxyethoxy)ethane (4 equiv., sealed with a septum and placed in a microwave cavity (CEM
12 μL,) was added and the solution was heated to reflux for Discover Scientific Microwave). Using an initial microwave
3 h. The resulting solution was evaporated to dryness by rotary power of 200 W, the reaction mixture was heated to 180 °C and
evaporation and purified by column chromatography (silica, held at that temperature for 20 min, then cooled to 25 °C. The
CH2Cl2–3% MeOH) to provide 6Pt-MET in near-quantitative reaction mixture was evaporated to dryness using rotary evap-
1
yield (31 mg). H NMR (400 MHz, CDCl3, δ): 8.78 (t, J = 2.5 Hz, oration and the resulting crude product was purified by
2H), 8.75 (s, 4H), 3.97–3.90 (m, 8H), 3.76–3.75 (m, 7H), column chromatography (silica, CH2Cl2–50% hexane) to give
3.66–3.65 (m, 7H), 3.59–3.56 (m, 1H), 3.48–3.41 (m, 20H), 2.92 6Ga (22 mg) in 40% yield, with 55% recovery of 6. Rf (silica,
(t, J = 6.8 Hz, 1H) ppm. UV-vis (CH2Cl2) (log ε): 396 (5.25), 533 CH2Cl2–50% hexane) = 0.39. UV-vis λmax (CH2Cl2) (log ε): 418
(4.20), 573 (4.79) nm. HR-MS (ESI+) calc’d for (5.25), 564 (3.80), 611 (4.42) nm. IR: ν = 1782.6 (CvO) cm.
C63H50F16N4O10S4Pt [M + H2O]+: 1667.1908, obs. 1667.3102.
Fluorescence (CH2Cl2, λex = 418) (Rel. Int.) 614 (1.0), 673 (0.09)
nm, ϕ = 0.008. 1H NMR (400 MHz, CDCl3, δ): 9.00 (t, J = 5.3 Hz,
1H), 8.93 (dq, J = 16, 4.3 Hz, 3H), 8.90 (dt, J = 8.9, 4.6 Hz, 2H),
1H ppm. 13C NMR (100 MHz, CDCl3, δ): 170.9, 168.9, 163.2,
[meso-Tetrakis(4-PEG1000thioxy-2,3,5,6-tetrafluorophenyl)-
porpholactonato]platinum(II) (6Pt-PEG1000
)
Prepared from 6Pt (50 mg, 4.2 × 10−5 mol), poly(ethylene 154.1, 153.1, 150.9, 150.5, 150.0, 147.2, 147.1, 145.1, 144.2,
glycol) methyl ether thiol (average Mn = 1000) (∼4 equiv., 141.7, 139.7, 139.53, 139.51, 137.2, 137.1, 137.0, 136.9, 134.8,
169 mg) in DMF–Et3N (2 : 1; 19.5 mL) as described for the syn- 133.0, 132.9, 131.8, 131.2, 131.1, 130.1, 129.1, 126.3, 114.3,
thesis of 6Pt-MET. 1H NMR (400 MHz, CDCl3, δ): 8.76–8.66 (m, 111.0, 110.4, 106.6, 104.4, 86.9, 66.5, 66.4, 64.6, 56.1, 53.7,
6H) 3.91–3.35 (m, >400 H) ppm. UV-vis (H2O) (log ε): 396 (5.3), 32.2, 31.1, 29.9, 24.0, 22.8, 20.5, 14.4 ppm. HR-MS (ESI+ of
534 (4.2), 573 (4.8) nm. HR-MS (ESI+ ionization, 0.5% formic MH+, 100% CH3CN, TOF) m/z for C43H6F20GaN4O2, [M − Cl]+:
acid in CH3CN, with Q-TOF detection): clusters of peaks corres- calc’d 1058.9427, obs. 1058.9401; for C43H8F20GaN4O3, [M − Cl
ponding to different degrees of protonation, all indicative of the + H2O]+: calc’d 1076.9533, obs. 1076.9499.
quadruple addition of PEG1000-S-chains (with n = 18–21).
Chloro-[meso-tetrakis(4-[2-(2-methoxyethoxy)ethane]-
[meso-Tetrakis(4-PEG1000thioxytetra-2,3,5,6-fluorophenyl)-
porpholactonato]zinc(II) (6Zn-PEG1000
thioxytetra-2,3,5,6-fluorophenyl)porpholactonato]gallium(III)
(2Ga-MET)
)
Prepared from 6Zn (30 mg, 2.8 × 10−5 mol), poly(ethylene Prepared from complex 6Ga (22 mg, 2.0 × 10−5 mol) dissolved
glycol) methyl ether thiol (average Mn ∼ 1000) (∼4 equiv., in DMF–Et3N (2 : 1, 10.5 mL), 2-(2-ethoxyethoxy)ethanethiol
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(4 equiv., 11 μL,) as described for the preparation of 6Pt-MET.
The dye 6Ga-PEG1000 (4 mg, 7.9 × 10−7 mol) was dissolved
Chromatography (silica gel, CH2Cl2–3% MeOH) provided 6Ga- in 13 g (∼14 mL) of the commercial Nafion® solution and the
MET in near-quantitative yield (29 mg). 1H NMR (400 MHz, solution was magnetically stirred at ambient temperature for
CDCl3, δ): 9.04–8.84 (m, 6H), 3.99–3.90 (m, 8H), 3.78–3.75 (m, ∼15 min. Then 11 mL of EtOH and 3 mL of DMF were added
7H), 3.65 (d, J = 3.2 Hz, 7H), 3.49–3.39 (m, 22H) ppm. UV-vis and once again stirred for ∼15 min. In a fume hood, a large
λmax (CH2Cl2) (log ε): 408 (5.20), 560 (3.60), 607 (4.30) nm. stone tile was precisely leveled and a box was fitted over it that
HR-MS (ESI+) calc’d for C63H50ClF16GaN4O10S4, [M − Cl]+: allowed a nitrogen stream to flow through it (and to block the
1523.1405, obs. 1523.1370.
light). A sheet of PTFE film was stretched tightly onto a 5 × 5
clean glass plate with polished edges; excess film was rolled up
to make sure none is underneath the plate. The glass was
placed on the leveled tile (Teflon® film up) and ∼10 drops of
EtOH were spread evenly over the entire film while preventing
any spills over the edges. This clarifies the otherwise white
film and defines the area onto which the Nafion film will
spread. The EtOH was allowed to evaporate (and the mem-
brane turned opaque again). Half of the dye-Nafion® solution
prepared above (∼14 mL) was then added onto the film drop-
wise and spread evenly (we used a smooth broad metal
spatula). The plate was allowed to dry overnight under a
stream of nitrogen in the chamber constructed. The second
half of the solution was capped and left stirring. Once the first
load of the Nafion solution had dried (after about 12–15 h),
the membrane was lifted off the glass plate and flipped over.
This was accomplished using the following process: ∼20–25
drops of DI water were placed on the membrane surface and a
second, clean 5 × 5 glass plate was placed on top. The plate
was pushed down hard to distribute the water evenly between
the glass and membrane surface; the purpose of the water is to
help adhere the membrane to the second glass plate. The
excess Teflon® film sticking out was then transferred from the
edge of the first plate to edge of the new plate. The plates were
then pulled apart carefully while adding drops of DI water into
the small gap forming between the old glass plate and the
membrane (this may require the use of four hands). The mem-
brane thus transferred was then stretched evenly along the
new plate by hand to smooth out any wrinkles (nitrile gloves).
The membrane was dried of any remaining DI water using a
dust-free paper wipe. The second half of the solution was
added onto the flipside of the membrane using the procedure
described above, except that the EtOH priming stage was
omitted. After 24 h drying time, the plate was moved into a
vacuum oven and left to dry for 3 h at 150 °C and 25 torr. The
membrane was pealed off carefully with the help of DI water
between the membrane and the glass plate. After air drying,
the membranes were, cut into smaller pieces, and used as is.
Chloro-[meso-tetrakis(4-PEG1000thioxytetra-2,3,5,6-
fluorophenyl)porpholactonato]gallium(III) (6Ga-PEG1000
)
This compound was prepared from the gallium complex 6Ga
(20 mg, 1.8 × 10−5 mol), poly(ethylene glycol) methyl ether
thiol (average Mn 1000) (4 equiv., 73 mg) in DMF–Et3N (2 : 1,
10.5 mL) as described for the synthesis of 6Pt-PEG1000.
1H
NMR (400 MHz, CDCl3, δ): 9.01–8.79 (m, 6H) 3.75–3.38 (m, >400
H) ppm. UV-vis λmax (H2O) (log ε): 419 (5.4), 563 (4.0), 611 (4.5)
nm. Fluorescence (CH2Cl2, λex = 418) 745 nm, ϕ = <1.0 × 10−3
.
008. HR-MS (ESI+ ionization, 0.5% formic acid in CH3CN, with
Q-TOF detection): clusters of peaks of corresponding to
different degrees of protonation, all indicative of the quadru-
ple addition of PEG1000-S-chains (with n = 18–21).
UV-Vis and fluorescence spectroscopic titrations
All titrations were carried out in standard 1 cm path length
methacrylate cuvettes (Fisher) in H2O or the buffers indicated
at ambient temperature. The PEGylated dyes 6-PEG1000, 6Pt-
PEG1000 and 6Zn-PEG1000 were dissolved in H2O and diluted to
10−6 M concentrations. At pH 7, 5.0 M sodium cyanide (NaCN)
stock solution in H2O was used as the source of CN−. The
absorbance was measured as aliquots of the aqueous CN−
solution were added by micropipette to 3 mL of the sensor dye
solutions (the absolute quantity of the additions ranged typi-
cally below 100 µL). The concentration of 6Ga-PEG1000 in the
UV-vis titrations as well as in the fluorescence measurements
was 5.10 × 10−6 M and a 1.0 × 10−2 M sodium cyanide stock
solution was used as the source of CN−. All spectra are
uncorrected.
Two 1.5 cm diameter stainless steel washers were braised
parallel to each other to the ends of a pair of stainless steel
curved tweezers. A ∼1.6 cm diameter piece of the sensor mem-
brane was held taught between the washers and the tweezers
were held clamped shut using a metal clip. The washers
holding the membrane were submersed in a 5 × 5 × 1 cm glass
cuvette containing the desired aqueous solutions, with the
1 cm path length of the cuvette perpendicular to the washer,
and the hole in the washer carefully placed into the center of
the beam of the UV-vis spectrometer.
Acknowledgements
Sensing membrane
We thank Philip Baker and Leonard Bonville, Center for Clean
The Nafion® membranes were prepared as Nafion®-PTFE-Na- Energy Engineering C2E2), University of Connecticut, for tech-
fion® sandwiches using Tetratex PTFE Film (0.7 mil) and nical assistance in the preparation of the Nafion® membranes.
using Nafion® solutions (Ion Power, Inc., 5% DuPont™ D521 This material is based upon work supported by the
Nafion® solution in H2O–iPrOH, EtOH) according to methods National Science Foundation under Grants CHE-0517782,
adopted from the literature.70
CHE-1058846, and CMMI-0730826 (to CB).
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25 Y. Xie, T. Morimoto and H. Furuta, Angew. Chem., Int. Ed.,
2006, 45, 6907–6910.
Notes and references
1 Z. Xu, X. Chen, H. N. Kim and J. Yoon, Chem. Soc. Rev., 26 G. E. Khalil, P. Daddario, K. S. F. Lau, S. Imtiaz, M. King,
2010, 39, 127–137.
2 K. W. Kulig, Cyanide Toxicity, U.S. Department of Health
and Human Services, Atlanta, GA, 1991.
M. Gouterman, A. Sidelev, N. Puran, M. Ghandehari and
C. Brückner, Analyst, 2010, 135, 2125–2131.
27 Y. Yu, B. Czepukojc, C. Jacob, Y. Jiang, M. Zeller,
C. Brückner and J.-L. Zhang, Org. Biomol. Chem., 2013, 11,
4613–4621.
28 P. Hambright and R. Langley, Inorg. Chim. Acta, 1987, 137,
209–212.
29 L. D. Chen, X. U. Zou and P. Buhlmann, Anal. Chem., 2012,
84, 9192–9198.
30 J. A. Legako, B. J. White and H. J. Harmon, Sens. Actuators,
B, 2003, 91, 128–132.
31 H. Liu, X.-B. Shao, M.-X. Jia, X.-K. Jiang, Z.-T. Lia and
G.-J. Chen, Tetrahedron, 2005, 61, 8095–8100.
32 Y.-H. Kim and J.-I. Hong, Chem. Commun., 2002, 512–
513.
33 H. Yoon, C.-H. Lee, Y.-H. Jeong, H.-C. Gee and W.-D. Jang,
Chem. Commun., 2012, 48, 5109–5111.
34 M. J. Crossley and L. G. King, J. Chem. Soc., Chem.
Commun., 1984, 920–922.
3 A. P. d. Silva, H. Q. N. Gunaratne, T. Gunnlaugsson,
A. J. M. Huxley, C. P. McCoy, J. T. Rademacher and
T. E. Rice, Chem. Rev., 1997, 97, 1515–1566.
4 F.-G. Banica, Chemical Sensors and Biosensors: Fundamentals
and Applications, Wiley, Chichester, UK, 2012.
5 D.-S. Kim, Y.-M. Chung, M. Jun and K. H. Ahn, J. Org.
Chem., 2009, 74, 4849–4854.
6 Y.-D. Lin, Y.-S. Peng, W. Su, C.-H. Tu, C.-H. Sun and
T. J. Chow, Tetrahedron, 2012, 68, 2523–2526.
7 Y. Sun, Y. Liu, M. Chen and W. Guo, Talanta, 2009, 80,
996–1000.
8 Y. Ding, T. Li, W. Zhu and Y. Xie, Org. Biomol. Chem., 2012,
10, 4201–4207.
9 M. Tomasulo and F. M. Raymo, Org. Lett., 2005, 7, 4633–
4636.
10 M. Tomasulo, S. Sortino, A. J. P. White and F. M. Raymo,
J. Org. Chem., 2006, 71, 744–753.
11 Y. M. Chung, B. Raman, D.-S. Kim and K. H. Ahn, Chem.
Commun., 2006, 186–188.
35 M. Gouterman, R. J. Hall, G. E. Khalil, P. C. Martin,
E. G. Shankland and R. L. Cerny, J. Am. Chem. Soc., 1989,
111, 3702–3707.
12 A. Afkhami and N. Sarlak, Sens. Actuators, B, 2007, 122, 36 G. Khalil, M. Gouterman, S. Ching, C. Costin, L. Coyle,
437–441.
S. Gouin, E. Green, M. Sadilek, R. Wan, J. Yearyean and
B. Zelelow, J. Porphyrins Phthalocyanines, 2002, 6, 135–145.
37 C. Brückner, J. Ogikubo, J. R. McCarthy, J. Akhigbe,
M. A. Hyland, P. Daddario, J. L. Worlinsky, M. Zeller,
J. T. Engle, C. J. Ziegler, M. J. Ranaghan, M. N. Sandberg
and R. R. Birge, J. Org. Chem., 2012, 77, 6480–6494.
13 H. Lee and H.-J. Kim, Tetrahedron Lett., 2012, 53, 5455–
5457.
14 R. Gotor, A. M. Costero, S. Gil, M. Parra, R. Martínez-
Máñez, F. Sancenón and P. Gaviña, Chem. Commun., 2013,
49, 5669–5671.
15 H. Tavallali, G. Deilamy-Rad, A. Parhami and S. Kiyani, 38 Y. Yu, H. Lv, X. Ke, B. Yang and J.-L. Zhang, Adv. Synth.
Spectrochim. Acta, Part A, 2014, 121, 139–146. Catal., 2012, 354, 3509–3516.
16 X. Lou, L. Zhang, J. Qin and Z. Li, Chem. Commun., 2008, 39 J. R. McCarthy, P. J. Melfi, S. H. Capetta and C. Brückner,
5848–5850. Tetrahedron, 2003, 59, 9137–9146.
17 L. Yao, J. Zhou, J. Liu, W. Feng and F. Li, Adv. Funct. Mater., 40 M. A. Hyland, M. D. Morton and C. Brückner, J. Org.
2012, 22, 2667–2672. Chem., 2012, 77, 3038–3048.
18 P. Anzenbacher Jr., D. S. Tyson, K. Jursíková and 41 J. R. McCarthy, H. A. Jenkins and C. Brückner, Org. Lett.,
F. N. Castellano, J. Am. Chem. Soc., 2002, 124, 6232–
6233.
19 Y.-Y. Guo, X.-L. Tang, F.-P. Hou, J. Wu, W. Dou, W.-W. Qin,
2003, 5, 19–22.
42 J. Ogikubo, E. Meehan, J. T. Engle, C. Ziegler and
C. Brückner, J. Org. Chem., 2012, 77, 6199–6207.
J.-X. Ru, G.-L. Zhang, W.-S. Liu and X.-J. Yao, Sens. 43 J. Akhigbe, J. P. Haskoor, J. A. Krause, M. Zeller and
Actuators, B, 2010, 181, 202–208. C. Brückner, Org. Biomol. Chem., 2013, 11, 3616–3628.
20 A. Sola, A. Tárraga and P. Molina, Org. Biomol. Chem., 2014, 44 J. L. Worlinsky, G. Zarate, M. Zeller, M. Ghandehari,
12, 2547–2551.
G. Khalil and C. Brückner, J. Porphyrins Phthalocyanines,
2013, 17, 836–849.
45 M. Gouterman, J. Callis, L. Dalton, G. Khalil, Y. Mebarki,
K. R. Cooper and M. Grenier, Meas. Sci. Technol., 2004, 15,
1986–1994.
46 G. E. Khalil, C. Costin, J. Crafton, G. Jones, S. Grenoble,
M. Gouterman, J. B. Callis and L. R. Dalton, Sens. Actuators,
B, 2004, 97, 13–21.
47 B. Zelelow, G. E. Khalil, G. Phelan, B. Carlson,
M. Gouterman, J. B. Callis and L. R. Dalton, Sens. Actuators,
B, 2003, 96, 304–314.
21 K. C. Song, K. M. Lee, N. V. Nghia, W. Y. Sung, Y. Do and
M. H. Lee, Organometallics, 2013, 32, 817–823.
22 T. Malinski, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guilard, Academic Press, San Diego,
2000, vol. 6, pp. 231–256.
23 M. Balaz, K. Bitsch-Jensen, A. Mammana, G. A. Ellestad,
K. Nakanishi and N. Berova, Pure Appl. Chem., 2007, 79,
801–809.
24 S.-i. Sasaki, Y. Kotegawa and H. Tamiaki, Tetrahedron Lett.,
2006, 47, 4849–4852.
4000 | Org. Biomol. Chem., 2014, 12, 3991–4001
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
48 A. Coutsolelos, R. Guilard, D. Bayeul and C. Lecomte, Poly- 61 E. Mishra, J. L. Worlinsky, T. M. Gilbert, C. Brückner and
hedron, 1986, 5, 1157–1164.
V. Ryzhov, J. Am. Soc. Mass Spectrom., 2012, 23, 1135–1147.
Erratum (correction of systemic typesetting errors): J. Am.
Soc. Mass Spectrom., 2012, 23, 1428–1439.
49 P. D. Harvey, N. Proulx, G. Martin, M. Drouin, D. J. Nurco,
K. M. Smith, F. Bolze, C. P. Gros and R. Guilard, Inorg.
Chem., 2001, 40, 4134–4142.
50 J. Wojaczynski and L. Latos-Grazynski, Inorg. Chem., 1995,
34, 1054–1062.
62 R. Gotor, A. M. Costero, S. Gil, M. Parra, R. Martınez-
Manez, F. Sancenonacd and P. Gavina, Chem. Commun.,
2013, 49, 5669–5671.
51 K. M. Kadish, B. C. Han, M. M. Franzen and C. Araullo- 63 G.-L. Fu and C.-H. Zhao, Tetrahedron, 2013, 69, 1700–
McAdams, J. Am. Chem. Soc., 1990, 112, 8364–8368. 1704.
52 P. Battioni, O. Brigaud, H. Desvaux, D. Mansuy and 64 M. Gouterman, J. Chem. Educ., 1997, 74, 697–702.
T. G. Traylor, Tetrahedron Lett., 1991, 32, 2893–2896.
53 S. J. Shaw, C. Edwards and R. W. Boyle, Tetrahedron Lett.,
1999, 40, 7585–7586.
54 S. J. Shaw, K. J. Elgie, C. Edwards and R. W. Boyle, Tetrahe-
dron Lett., 1999, 40, 1595–1596.
65 J. W. Buchler, in Porphyrins, ed. D. Dolphin, 1978, vol. 1,
pp. 389–483.
66 N. J. Turro, V. Ramamurthy and J. C. Scaiano, Modern
Molecular Photochemistry of Organic Molecules, University
Science Books, California, 2010.
55 D. Samaroo, M. Vinodu, X. Chen and C. M. Drain, J. Comb. 67 R. D. Johnson and L. G. Bachas, Anal. Bioanal. Chem., 2003,
Chem., 2007, 9, 998–1011. 376, 328–341.
56 T. Bříza, R. Kaplánek, M. Havlík, B. Dolenský, Z. Kejík, 68 G. Orellana and D. Haigh, Curr. Anal. Chem., 2008, 4, 273–
P. Martásek and V. Král, Supramol. Chem., 2008, 20, 267–
242.
57 J. Tüxen, S. Eibenberger, S. Gerlich, M. Arndt and
M. Mayor, Eur. J. Org. Chem., 2011, 4823–4833.
295.
69 M. A. Castriciano, A. Carbone, A. Sacca, M. G. Donato,
N. Micali, A. Romeo, G. De Luca and L. M. Scolaro,
J. Mater. Chem., 2010, 20, 2882–2886.
58 J. Ogikubo, J. L. Worlinsky, Y.-J. Fu and C. Brückner, Tetra- 70 V. Ramani, H. R. Kunz and J. M. Fenton, J. Power Sources,
hedron Lett., 2013, 54, 1707–1710. 2005, 152, 182–188.
59 D. C. Harris, Quantitative Chemical Analysis, W H Freeman, 71 T. L. C. Figueiredo, R. A. W. Johnstone, A. M. P. SantaAna
New York, NY, 8th edn, 2010, pp. 103–105.
60 R. W. Scheidt, in The Porphyrin Handbook, ed.
Sørensen, D. Burget and P. Jacques, Photochem. Photobiol.,
1999, 69, 517–528.
K. M. Kadish, K. M. Smith and R. Guilard, Academic Press, 72 P. J. Spellane, M. Gouterman, A. Antipas, S. Kim and
San Diego, 2000, vol. 3, pp. 49–112.
Y. C. Liu, Inorg. Chem., 1980, 19, 386–391.
This journal is © The Royal Society of Chemistry 2014
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