Spectroscopic studies of a fluorescent fluoresceinophane formed via a practical synthetic route

Article abstract of DOI:10.1039/b611060f

A practical macrocycle synthesis incorporating a highly fluorescent fluorescein was developed. Photophysical, crystallographic and dynamic-NMR studies showed the alkyl tether forces a constrained conformation of the fluoresceinophane, which enhances the f

Full text of DOI:10.1039/b611060f

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Spectroscopic studies of a fluorescent fluoresceinophane formed via a
practical synthetic routew
´
´
Sergio Andres Perez Guarın, Derek Tsangz and W. G. Skene*
Received (in St Louis, MO, USA) 1st August 2006, Accepted 30th November 2006
First published as an Advance Article on the web 19th December 2006
DOI: 10.1039/b611060f
A practical macrocycle synthesis incorporating a highly fluorescent fluorescein was developed.
Photophysical, crystallographic and dynamic-NMR studies showed the alkyl tether forces a
constrained conformation of the fluoresceinophane, which enhances the fluorescence quantum
yields by reducing the excited-state deactivation pathways. Enhanced temperature-dependent
fluorescence relative to its linear analogue was also found as a result of the constrained
macrocycle conformation, while a manifold shift from the singlet to the triplet state still occurred
in different polar solvents.
Moreover, most fluorescein derivatives are ionic in nature,
Introduction
which precludes their use in most organic solvents.34,35
This contribution reports the spectroscopic studies in addi-
tion to the crystallographic data of a fluoresceinophane that
exhibits enhanced fluorescent properties relative to its linear
analogue. The practical synthesis of the new fluorescent
macrocycle is also presented.
The investigation of macrocycles has been pursued along
many avenues due to their intriguing uses such as ion coordi-
nation, spectroscopic sensors, nanoactuators and molecular
machines.1–5 As interesting as their properties are, the synth-
esis of these compounds poses many challenges. Conventional
macrocyclization approaches often require extreme dilution,6
coordinating templates,7–9 slow reagent addition,10,11 ring-
closing metathesis requiring expensive catalysts12,13 and strin-
gent reaction conditions14 and/or and photocyclization.15
Such approaches also suffer from extremely low yields and
multiple secondary products.16–20 These challenges have
prompted many groups to develop more efficient synthetic
protocols for new materials with desired functional
properties.10,11,21,22
Results and discussion
Synthesis of macrocycle 1 (Fig. 1) was achieved in three steps
starting from fluorescein (3). The transformation of the neu-
tral carboxylic acid into the methyl ester proceeds in high yield
and simple precipitation affords the pure ester. This inter-
mediate serves as the required precursor for subsequent
cyclization. Alkylation of the aryl alcohol proceeds smoothly
with an a-bromo-o-alkanol with mild heating in the presence
of a base. The bromoalkanol length selected at this step
determines the resulting macrocycle size, which provides an
attractive handle for macrocycles of different sizes.
Our group’s interest in the spectroscopic properties of
fluorescein has led to the development of a practical synthetic
route to macrocycles containing fluorescein. Having developed
a three-step synthetic route, we have gone on to make a
fluorescent macrocycle using this improved method from
readily available reagents. Fluorescein was examined as the
macrocycle core unit to make a fluoresceinophane because of
its well characterized fluorescence properties. The resulting
constrained macrocycle was expected to enhance the spectro-
scopic properties, including fluorescence of the fluorophore
because subtle environmental changes are known to influence
fluorescein’s emission.23–33 Significant fluorescent changes
were anticipated for the fluoresceinophane as to make it
suitable for high-temperature analyses in organic solvents.
This is of particular interest because most temperature-depen-
dent organic dyes are appropriate only for aqueous analyses.
The subsequent step, involving intramolecular cyclization
for the tethered compound, was achieved by base mediated
transesterification as described in Scheme 1. Interestingly, the
intramolecular cyclization reaction occurred under standard
reaction concentrations of 12 mM without any special dilute
reaction requirements. This is in contrast to other
Department of Chemistry, University of Montreal, Pavillon J. A.
Bombardier, C.P. 6128, succ. Centre-ville, Montreal QC, Canada
H3C 3J7. E-mail: w.skene@umontreal.ca; Fax: (514) 340-5290;
Tel: (514) 340-5174
w Electronic supplementary information (ESI) available: NMR
spectra. See DOI: 10.1039/b611060f
z Current address: Department of Chemistry, University of Toronto,
80 St. George Street, Toronto ON, Canada M5S 3H6.
Fig. 1 Fluoresceinophane structures and their linear analogues.
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Fig. 3 ORTEP representation of crystal structure 1 with ellipsoid
probability drawn at 60%.
Scheme 1 Reagents and conditions: (i) catalytic H2SO4 reflux in
MeOH; (ii) K2CO3 with Br(CH2)11OH in DMF at 75 1C, N2; (iii)
NaH, DMF at 80 1C, N2.
evident from the diastereotopic methine protons observed at
3.8 ppm (Fig. 2) that are ascribed to the protons on C21 (Fig. 3).
The NMR spectra at 500 MHz also showed the diaster-
eotopic pattern for the protons on C31 at ca. 4.1 ppm. The
presence of the chiral centers implies a significant rotational
barrier around the xanthene and benzyl axis.36,37 Coalescence
of the diastereotopic methine peaks at high temperature would
provide information regarding the activation energy for the
rotational barrier around the xanthene–benzyl axis. Unfortu-
nately, such high-temperature NMR measurements failed to
provide any noticeable coalescence even at 425 K (see ESIw).
This implies a high rotational barrier whereby the macrocycle
cannot undergo complete rotation around the xanthene–ben-
zyl axis. A lower limit of 77 kJ molꢁ1 for the free energy
activation barrier around the aromatic axis can be estimated
from the temperature study. A high activation barrier for
rotation is supported by theoretical calculations found to be
conventional macrocyclization approaches that often require
particular reaction conditions such as extreme dilution,6,22
coordinating templates,7–9 slow and stepwise reagent addi-
tion,10,11 and ring-closing metathesis.12 Of further interest, our
synthetic method does not lead to any secondary products and
afforded exclusively the fluoresceinophane 1. This is unlike
many other approaches that form multiple secondary products
and suffer from low yields.16–20 The macrocycle synthesis
described by this approach represents, to the best of our
knowledge, one of the few examples of efficient cyclization
based on a highly fluorescent core. It thus represents a viable
means of forming various sized macrocycles such as 2 that
incorporate the highly fluorescent fluorescein moiety.
The 1D and 2D NMR spectra of the macrocycle and its
linear analogues are only subtly different. The 1H NMR
spectrum however illustrates the chiral nature of 1. This is
ca. 125 kJ molꢁ1 38
Similarly, low-temperature measurements
.
provided only temperature induced chemical shifts and no
coalescence. The observed variable-temperature induced shifts
suggests the protons experience different environments at low
temperatures, but nonetheless the macrocycle remains chiral.39
Confirmation of macrocycle formation for 1 and its abso-
lute assignment was possible from its X-ray crystal structure
(Fig. 3). The structure illustrates that 1 comprises two aryl
units: xanthene and benzoate moieties, which are bridged by
an undecanyl alkyl tether. An interesting observation is the
low energetic strain induced by the tether. This is evidenced by
the xanthene and benzyl moieties that adopt nearly a peri-
planar low-energy conformation. In fact, the tether forces the
benzyl moiety to further rotate such that the mean average
angle between the xanthene and benzyl planes is reduced to
731. The 171 twist from perpendicularity allows the macrocycle
to accommodate the long tether, which is clearly seen in Fig. 4.
This is in contrast to known linear fluorescein derivatives that
have xanthene–benzyl mean average planes that are between
85 and 901.40–44 The crystal structure of 1 also shows the
aromatic moieties are planar, unlike other crystallographic
fluorescein examples in which the xanthene is puckered.45,46
Fig. 2 Variable-temperature NMR of 1 in deuterated methanol: (A)
289, (B) 252, (C) 228, (D) 216, (E) 206, (F) 195 and (G) 185 K. Water
(3.2 ppm) and MeOD (2.5 ppm) peaks are present.
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a weak van der Waals interaction between the alkyl chains
lead to the higher ordered crystal structure shown in the
bottom of Fig. 5. This structure is reinforced by six CHꢂ ꢂ ꢂO
weak intermolecular hydrogen bonds leading to the supramo-
lecular network represented in the top of Fig. 5. Two such
hydrogen bond interactions occur between C6–H3ꢂ ꢂ ꢂO2 of
two separate molecules of 1 and these are complemented by
two additional bonds involving the donor–acceptor
C8–H4ꢂ ꢂ ꢂO1. The donor–acceptor pairs are separated by
3.344 and 3.455 A, respectively, and form a dimer-like struc-
ture.47 Two additional hydrogen bonds are present between
two complementary molecules involving C10–H5ꢂ ꢂ ꢂO3
separated by 3.348 A.
Fig. 4 Crystal structure representation of 1 showing the large volume
within the fluoresceinophane. The oxygen atoms are represented as
spheres for clarity.
Preliminary investigation of the ground state absorption
and fluorescence was undertaken to examine the influence of
the constrained cycle. In various solvents, the two spectro-
scopic properties observed are solvent independent (Fig. 6)
with the absorption and emission centered at 456 and 560 nm,
respectively. This behavior is characteristic of n–p* charge
transfer transitions. Even though fluorescein is known to have
many tautomers that each possess unique absorption and
emissive properties,48 the spectroscopically observed values
are consistent with the quinoid structure depicted in Fig. 1.
The mutual overlap of the normalized absorption and emis-
sion spectra give the absolute energy gap between the S1 and
A weak intramolecular C–Hꢂ ꢂ ꢂp interaction is also present in
the macrocycle, contributing to the observed conformation.
This interaction occurs between C23–H15 and the centroid
ring of the xanthene described by C1–C6. These are separated
by 3.82 A and H15 is rotated 1511 from the mean plane of the
C1–C6 aromatic centroid.
Interestingly, the flexible alkyl tether adopts a well defined
rectangular conformation that is 9.7 A wide by 3.9 A in height.
This is in contrast to an expected amorphic shape because of
the high degree of freedom arising from the 11 carbon flexible
aliphatic chain. p–p Stacking between the rigid xanthenes and
Fig. 5 Top: Schematic representation of intermolecular hydrogen bonding involving two different CHꢂ ꢂ ꢂO donor–acceptor pairs between
different molecules of 1 leading to a supramolecular network. The hydrogens are omitted and the heteroatoms are drawn as ellipsoids at 50%
probability for clarity. Bottom: Sheets of molecules resulting from p–p stacking between the xanthene units of different molecules and van der
Waals interaction between the alkyl chains.
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enhanced fluorescence implies the alkylated phenol does not
undergo significant rotation. Therefore, it is not an efficient
mode for fluorescence deactivation. Fluorescein on the other
hand has the added pathway of rotation around the xanthene–
benzyl axis for dissipating energy. The high activation barrier
for rotation precludes this process as an efficient deactivation
mode. The observed high fluorescence yield of 1 implies that
few efficient fluorescent deactivation modes are available. The
alkyl chain therefore cannot undergo efficient energy dissipa-
tion by rotation since it is linked to the benzyl moiety. This is
compounded by a limited range of rotation around the
xanthene–benzyl axis imposed by the tether in addition to
Hꢂ ꢂ ꢂH steric interaction between the two aryl groups. Such
hindered rotation leads to a metronome type movement in
which the two aryl groups simply swing back-and-forth in a
limited range of motion of 921 compared to 1201 for its linear
analogue. This is further supported by the NMR results and
the temperature-dependent fluorescence behavior for 1 and 4
(vide infra). The only mode that would significantly lead to
fluorescence quenching would be a skipping rope-like motion
in which the tether would rotate completely around the
xanthene. This however cannot occur because the tether is
insufficiently long.
Fig. 6 Absorption spectra of 1 recorded at 25 1C in (’) acetonitrile,
(m) methanol, (K) DMSO; Fluorescence spectra of 1 in (&) aceto-
nitrile, (n) methanol, (J) DMSO.
the S0 states. The measured value of 239 kJ molꢁ1 is identical
to previously reported values for 349 and suggests that the
macrocycle exerts a minimal effect on the steady-state stability
of both ground and excited states at room temperature. Only a
slight change in the vibrational structure was observed for the
macrocycle in different polar solvents.
The temperature-dependent fluorescence of 1 relative to its
linear analogue 4 would further provide the mode of fluores-
cence deactivation and would demonstrate the suitability of
the macrocycle as a high-temperature fluorescent probe. The
temperature–fluorescence relationship in Fig. 7 shows the
diminished temperature response of 1 relative to 4. The
temperature induced behavior is thoroughly reproducible
without any hysteresis upon temperature cycling. In addition
to calculating the fluorescence activation energies of 10 and
8.8 kJ molꢁ1 for 1 and 4, respectively, the temperature
measurements also provide information relating to the upper
temperature limit for fluorescence. By extrapolating the tem-
perature relationships, 1 is anticipated to exhibit an appreci-
able amount of fluorescence even at 333 1C, at which
temperature the fluorescence from 4 would be completely
quenched. Given that most processing of polymers occur
between 200 and 350 1C,35 the high temperature at which 1
still fluoresces makes it suitable for high-temperature fluores-
cence studies in organic solvents and polymer processing. This
is of particular interest owing to the limited number of
uncharged fluorophores. Moreover, the macrocycle could be
used as an alternative highly fluorescent neutral probe for
The tether in 1 was expected to further restrict an already
hindered rotation around the xanthene–benzyl axis. It was
therefore anticipated that such hindered rotation would
decrease the available modes of energy dissipation and subse-
quently affect the fluorescent yields. As a result, enhanced
fluorescence of 1 relative to 4 evidenced by an increase in
quantum yield was expected. Surprisingly, the measured
quantum yields for the linear and macrocycle fluoresceins
reported in Table 1 are similar. Since deactivation of excited
xanthene states, such as rhodamine, normally proceed by bond
rotation of the substituent groups located around the xanthene
core, alkylation of the phenolic group would provide an
efficient means of fluorescence quenching by such a bond
rotation. This is the case for 5 that exhibits roughly a 70%
fluorescence reduction relative to 3.50 In methanol, 1 should
therefore exhibit a Ffl B0.2. Since the measured value is three
times greater than expected and is similar to 4, the observed
Table 1 Fluorescent quantum yielda and lifetime data of fluorescein containing moleculesb recorded at 25 1C
1
4
Solvent
Ffl
tfl/ns
krd/10ꢁ8 sꢁ1
kre/10ꢁ8 sꢁ1
Ffl
tfl/ns
krd/10ꢁ8 sꢁ1
kre/10ꢁ8 sꢁ1
c
FT
c
FT
Methanol
DMSO
0.63
0.09
0.08
0.004
3.2
1.9
1.9
2.0
0.34
0.8
0.89
0.97
1.9
0.5
0.4
0.02
1.2
4.8
4.9
4.9
0.79
0.19
0.09
3.8
1.7
0.9
0.18
0.78
0.88
2.1
1.1
1.00
5.5
4.8
1.0
Acetonitrile
Cyclohexane
a
f
f
—
—
Relative to fluorescein disodium salt (F = 0.92) in alkaline methanol.64 b
lex = 456 nm and lobserved = 560 nm. Calculated according to FIC +
c
e
F
Fl + FT = 1 and assuming internal conversion (IC) is 0.03.63 d Calculated according to kr = Ffl/tfl. Calculated according to knr = kr(1 ꢁ Ffl)/
f
Ffl. Not sufficiently soluble for homogeneous measurements.
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state on the basis of the observed signals that were quenched
with oxygen, 1,4 cyclohexadiene and 2-methylnaphthalene,
concomitant with observed monoexponential decays. Unlike
other reports, the fluorescein transients exhibited only triplet
formation and not any radical ionic transients.52,53 The mea-
sured lifetimes from the monoexponential decays are 20 ms and
10 ms for 1 and 4, respectively, that are completely quenched
when the transient analyses are done in methanol. Moreover,
diffusion controlled triplet state quenching with 1,3-cyclohex-
adiene and 2-methylnaphthalene was observed that provides an
upper triplet energy limit of 173 kJ molꢁ1 for the two fluor-
esceins. This is approximately 25 kJ molꢁ1 lower than the
corresponding fluorescein dianion triplet.54 Unfortunately due
to the strong overlapping ground state absorptions of these
compounds and the typically used visible triplet probe,
2-methylnaphthalene, determination of the absolute triplet
quantum yields of 1 and 4 were not possible. This is further
complicated by the lack of reliable triplet molar extinction
coefficients (e) values for the neutral quinoid fluorescein triplet.
A rough estimate however of fT = 0.4 for 1 and 4 can be made
through laser power dependence relative to the fluorescein
dianion,55–57 assuming the same triplet e for the two neutral
fluoresceins. The high value is further supported by the fact that
no ionic transient species were observed and no nonradiative
deactivation modes are known for fluorescein.58,59
Fig. 7 Relative fluorescence change with temperature 1 (’) and 4
(&) in DMSO. Inset: Fluorescence intensity change of 1 with
temperature increase in DMSO; (’) 25, (m) 35, (n) 45, (K) 55,
(J) 65, (.) 75, (,) 85 1C, (&) cooled again to 25 1C.
studies in organic solvents, for which there are few. Such a
compound can further be used in a range of useful working
temperatures without undergoing any temperature-dependent
quenching, degradation, or spectral shifts,33,34 which is not the
case with most fluorescent probes.34,35,51
By understanding the normal deactivation processes of
fluorescent molecules, the solvent variable quantum yields
observed in Table 1 can be ascribed. Typical deactivation
of excited states involves quenching by solvent, increased rate
of intersystem crossing leading to triplet state formation, and/
or energy dissipation through bond rotation or vibrations.60,61
The options can further be limited to two possibilities namely:
nonradiative deactivation by internal conversion (IC) from
S1 - S0, and intersystem crossing from S1 - T1.62 Since little
difference in the fluorescence monoexponential lifetimes (t)
was observed between 1 and 4 (Table 1), the same deactivation
mode is expected for the two fluorescein compounds. These
results combined with the steady-state fluorescence lead to the
following solvent dependent observations. In polar protic
solvents, the deactivation pathway is predominately from the
singlet state via fluorescence and minor nonradiative deactiva-
tion. Conversely, intersystem crossing to the triplet state is
highly favored in aprotic solvents. This manifold shift from
singlet to triplet is responsible for the reduced fluorescence
emission noted in Table 1, also confirmed by the observed
triplet by LFP in acetonitrile. Crude estimates of the triplet
formation can be calculated according to Ffl + FT + FIC B 1,
assuming the amount of internal conversion (IC) is minimal
for the examples studied.63 This is reasonable given the
calculated nonradiative decay constants (knr) are consistent
for both compounds in the various solvents. The resulting
calculated triplet quantum yield is the same magnitude as
those roughly obtained by laser flash photolysis. The slight
polarity change appears to perturb the narrow excited single-
t–triplet energies levels of the neutral quinoid fluoresceins to
open an efficient means for energy dissipation via intersystem
crossing to the triplet manifold. This is schematically repre-
sented in Fig. 9. The observed solvent behavior is similar to
previous reports for fluorescein with spin orbit couplers.48
Laser flash photolysis was used to further investigate the
excited-state properties of 1 and 4. The transient absorption
spectra obtained by this method, shown in Fig. 8, are similar
for the linear and macrocyclic compounds. The spectra show a
strong oxygen insensitive ground state bleaching component
around 450 nm, which is the mirror image of the ground state
absorption. The transient absorptions in acetonitrile, centered
at 525 nm for 1 and 535 nm for 4, are ascribed to the triplet
Fig. 8 Transient absorption spectra of 1 (’) and 4 (&) recorded at
19.0 and 16.8 ms, respectively, after laser excitation at 355 nm in
deaerated and anhydrous acetonitrile. Inset: Triplet decay trace of 1
recorded at 525 nm in acetonitrile.
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hydroxide. The solid was subsequently chromatographed
(SiO2) with 3% methanol/dichloromethane to afford the pro-
1
duct as a red solid (1.28 g, 52%). Mp 98–104 1C. H NMR
(200 MHz, [D]chloroform): d 8.19 (d, 1H), 7.62 (m, 2H), 7.28
(dd, 1H), 6.86 (m, 4H), 6.46 (dd, 2H), 6.40 (d, 2-H), 4.01 (t,
2H), 3.61 (t, 2H), 3.54 (s, 3H), 1.77 (m, 2H), 1.26 (m, 20H).
13C NMR (50 MHz, [D]chloroform): d 185.7, 165.7, 163.9,
159.1, 154.4, 150.7, 134.6, 432.8, 131.2, 130.6, 129.7, 128.9,
117.4, 114.7, 114.0, 105.7, 100.8, 68.9, 62.8, 52.5, 32.9, 29.5,
28.9, 25.9, 25.9. FAB-MS: m/z 517.1 ([M + 1]+, 100%).
Fig. 9 Schematic representation of solvent dependent Jablonski
diagram with the arrow indicating the major deactivation pathway.
2-(6-Hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid undeca-
noic ester (1). In anhydrous THF (40 mL) was added 2-[6-
(11-hydroxyundecyloxy)-3-oxo-3H-xanthen-9-yl]benzoic acid
methyl ester (7) (253 mg, 0.49 mmol) and cooled to 0 1C under
argon. To this solution was added sodium hydride (380 mg,
9.5 mmol) and then the solution was allowed to warm to room
temperature. The mixture was subsequently stirred for 12 h at
room temperature and refluxed for 8 h under nitrogen until no
starting material was detected by TLC. The solvent was
eventually removed and the paste was taken up in ethyl
acetate, washed with aqueous sodium carbonate and chroma-
tographed (SiO2) with 5% methanol–dichloromethane.
The product was isolated as an orange solid (100 mg, 85%).
Experimental
General experimental details
All reagents used were commercially obtained from Aldrich
and were used without further purification except where
otherwise stated. All spectrophotometric measurements were
done with 10 ꢃ 10 mm cuvettes using spectroscopic grade
solvents. Absorption measurements were done with a Cary
500 temperature controlled spectrophotometer and the uncor-
rected fluorescence measurements were performed with an
Edinburgh Instruments FLS-920 combined stead-state and
lifetime dual fluorimeter. The samples were deaerated with
nitrogen prior to use to remove residual oxygen that would
otherwise quench the excited state. The temperature was
controlled with a water-circulating bath. Laser flash photolysis
for triplet analyses was done with a Luzchem mini-LFP with a
Continuum Sure-Lite Nd-YAG as the excitation source at 355
nm. 2D NMR spectra were recorded on a Varian 500 MHz
instrument while temperature measurements were performed
on a Bruker 300AX instrument.
1
Mp = 197–199 1C. H NMR (200 MHz, [D]chloroform): d
8.19 (d, 1H), 7.69 (m, 2H), 7.30 (dd, 1H), 6.93 (dd, 2H), 6.75
(s, 1H), 6.74 (d, 1H), 4.17 (t, 2H), 3.99 (m, 1H), 3.79 (m, 1H),
1.81 (t, 2H), 1.47 (t, 2H), 0.94 (m, 16H). 13C NMR (50 MHz,
[D]chloroform): d 185.75, 166.15, 163.79, 158.89, 154.31,
133.67, 132.50, 131.53, 131.26, 130.42, 130.00, 129.74,
129.32, 117.66, 114.92, 112.81, 105.87, 101.53, 91.89, 67.45,
65.98, 30.96, 29.44, 28.22, 27.83, 27.66, 27.61, 27.18, 26.01,
25.07, 23.59. FAB-MS: m/z 485.4 ([M + 1]+, 100%). HR-
MS(+) calc. for [C31H32O5 + H]+: 485.23225, found:
485.2322.
2-(6-Hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid methyl
ester (4). Fluorescein (3) (2.76 g, 8.3 mol) was dissolved in
methanol (200 mL) followed by the addition of concentrated
sulfuric acid (1 mL). The orange–red solution was refluxed for
12 h then poured onto ice-water (100 mL). The resulting
precipitate was filtered off then chromatographed (SiO2) with
5% methanol–dichloromethane to yield the product as an
orange solid (2.76 g, 92%). Mp 228 1C. 1H NMR (200
MHz, [D4]methanol): d 7.80 (d, 1H), 7.75 (m, 2H), 7.41 (d,
2-(6-Hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid hexanoic
ester (2). In DMF (70 mL) was added 2-(6-Hydroxy-3-oxo-
3H-xanthen-9-yl)benzoic acid methyl ester (535 mg, 1.54
mmol) followed by potassium carbonate (238 mg, 1.72 mmol).
The slurry was stirred for 15 min to which was then added
1,6-dibromohexane (100 ml, 0.65 mmol) and then refluxed for
3 days. The solvent was removed and the residue was taken up
in ethyl acetate and then washed with aqueous sodium carbo-
nate. The product was isolated as an orange solid (79 mg,
30%) in addition to unreacted 2 (65%) after chromatography
(SiO2) with 5% methanol–dichloromethane. 1H NMR (200
MHz, [D]chloroform): d 8.06 (d, 1H), 7.73 (m, 2H), 7.63 (m,
1H), 7.08 (d, 2H), 6.88 (s, 1H), 6.53 (d, 1H), 6.44 (s, 1H), 4.39
(m, 2H), 3.91 (m, 2H), 1.87 (m, 1H), 1.53 (m, 1H), 1.23 (4H),
0.72 (m, 2H). 13C NMR (50 MHz, [D]chloroform): d 166.9,
164.7, 132.9, 132.0, 130.0, 129.8, 116.4, 116.2, 106.5, 66.4, 29.4,
25.6, 25.09. FAB-MS: m/z 415.1 ([M + 1]+, 100%).
1H), 6.99 (d, 2H), 6.73 (s, 2H), 6.65 (dd, 2H), 3.59 (s, 3H). 13
C
NMR (50 MHz, [D4]methanol): d 174.3, 170.0, 161.6, 160.2,
154.3, 136.6, 134.3, 133.3, 132.4, 131.6, 131.2, 13.3, 126.0,
125.6, 121.9, 117.6, 113.8, 111.6, 103.9, 103.6. FAB-MS: m/z
347.1 ([M + 1]+, 100%). HR-MS(+) calc. for [C21H14O5 +
H]+: 347.0914, found: 347.0920.
2-[6-(11-Hydroxyundecyloxy)-3-oxo-3H-xanthen-9-yl]benzoic
acid methyl ester (5). To DMF (100 mL) was added 2-(6-
hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid methyl ester (4)
(1.67 g, 4.8 mmol) followed by potassium carbonate (1.43 g,
10.3 mmol) then 11-bromoundecan-1-ol (1.28 g, 5.0 mmol).
The resulting slurry was heated to 60 1C under nitrogen for 2
days then poured onto water (300 mL). The resulting red
precipitate was filtered off and washed with aqueous sodium
Crystal structure determination
Diffraction data for 1 were collected on a KappaCCD
diffractometer using graphite-monochromatized Mo-Ka radia-
tion with l = 0.710 73 A (Table 2). The structure was solved
by direct methods. All non-hydrogen atoms were refined based
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Table 2 Details of crystal structure determination of 1
2 J. F. Stoddart and H.-R. Tseng, Proc. Natl. Acad. Sci. USA, 2002,
99, 4797–4800.
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Formula
Mn; F(000)
Crystal color, form
Crystal size/mm
T/K
Crystal system
Space group
a/A
C31H32O5
484.60; 516
Colorless, prism
0.25 ꢃ 0.14 ꢃ 0.10
173
Triclinic
ꢀ
P1
7.8781(2)
12.7652(3)
12.8795(3)
91.972(5)
102.869(5)
92.200(5)
1260.54(5); 2
1.28
b/A
c/A
a/1
b/1
g/1
V/A3, Z
Dc/g cmꢁ3
y Range/1
Reflections: collected/independent; Rint
2.5–30.99
11722/8005; 0.040
0.086
m/mmꢁ1
Abs. Corr.
None
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R1(F); wR(F2) (all data)
GoF (F2)
0.047; 0.232
0.120; 0.064
1.083
Max. Dr/e Aꢁ3
0.297
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2
on Fobs while hydrogen atoms were refined on calculated
positions with fixed isotropic U, using riding model
techniques.
CCDC reference number 251400.
For crystallographic data in CIF or other electronic format
see DOI: 10.1039/b611060f
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core. The versatile synthetic method allows different tether
lengths along with different fluorophores and potentially other
heterocycles to be used leading to variously sized macrocycles
with tunable absorption and emission properties. The practical
synthetic route also allows for the easy incorporation of other
steric elements that limit conformational motion of the macro-
cycle resulting in many interesting properties such as molecu-
lar machines. The photophysical studies showed the
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The authors acknowledge financial support from the Natural
Sciences and Engineering Research Council Canada, the
University of Montreal, and additional equipment funding
from the Canada Foundation for Innovation. D. T. thanks
NSERC for a UGA scholarship. We also thank Profs. G. Cosa
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