From nonconjugation to conjugation: Novel meso-OH substituted dipyrromethanes as fluorescence turn-on Zn2+ probes

Article abstract of DOI:10.1039/c3ob40121a

Most reported Zn²⁺ probes suffer from the interference of background fluorescence originated from the conjugated structures of commonly utilized fluorophores. In this work, three novel meso-hydroxyl group substituted dipyrromethanes DPMOH1-DPMO

Full text of DOI:10.1039/c3ob40121a

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Biomolecular Chemistry
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From nonconjugation to conjugation: novel meso-OH
substituted dipyrromethanes as fluorescence turn-on
Zn2+ probes†
Cite this: Org. Biomol. Chem., 2013, 11,
2685
Yubin Ding,a Tong Li,a Xin Li,b Weihong Zhua and Yongshu Xie*a
Most reported Zn2+ probes suffer from the interference of background fluorescence originated from the
conjugated structures of commonly utilized fluorophores. In this work, three novel meso-hydroxyl group
substituted dipyrromethanes DPMOH1–DPMOH3 were synthesized and found to be colourless and
nonfluorescent due to the interruption of the conjugated π system by an sp3 carbon between the two
pyrrolic units. Interestingly, only the addition of Zn2+ to the solutions of DPMOH1–DPMOH3 promoted
their oxidation to dipyrrin forms, and bright fluorescence “turn on” was observed due to the formation
of corresponding dipyrrin complexes with the dipyrrin : zinc stoichiometry of 2 : 1. Zn2+ detection mech-
anism was investigated by UV-Vis, fluorescence, 1H NMR and HRMS analyses, which can be ascribed to
the CHEF type fluorescence enhancement, resulting from good rigidity of the dipyrrin complexes. Hence,
DPMOH1–DPMOH3 can be used as fluorescence turn-on Zn2+ probes with the advantage of no back-
ground fluorescence.
Received 21st January 2013,
Accepted 25th February 2013
DOI: 10.1039/c3ob40121a
www.rsc.org/obc
more desired than fluorescence quenching probes, which may
be nonspecific because the quenching process may be caused
Introduction
Zinc is one of the most important cations in catalytic centers by a number of factors other than the target analyte.7 Thus, a
and structural cofactors of many enzymes and metalloproteins, number of fluorescence turn-on Zn2+ probes have been devel-
and it plays vital roles in numerous physiological and patho- oped based on various fluorescence enhancing mechanisms
logical processes, including brain activity, gene transcription, such as photoinduced electron-transfer (PET), intramolecular
and immune function.1 Thus, the development of Zn2+ probes charge transfer (ICT), fluorescence resonance energy transfer
has been receiving considerable attention in recent years.2 (FRET), excimer, aggregation-induced emission (AIE), chela-
Among various sensing techniques, fluorescence has attracted tion enhanced fluorescence (CHEF) and chemical reactions.8
increasing interest due to its high sensitivity and rapid Typical fluorophores employed for these purposes include flu-
response.3 Ratiometric fluorescent probes allow the measure- orescein, anthracene, naphthalimide, coumarin, cyanine dyes,
ment of emission intensities at two different wavelengths, rhodamine, and BODIPY.9 In this respect, we have recently
which would increase the dynamic range of fluorescence demonstrated that pyrrole derived dipyrrins and tripyrrins can
measurements. However, design of such probes with a large be developed as fluorescence turn-on Zn2+ probes.10 In spite of
ratiometric signal remains very challenging.4 On the other these excellent results, most of the reported probes suffer from
hand, lifetime based probes require the utilization of expen- the interference of weak to medium background fluorescence
sive equipments.5 Hence, probes based on fluorescence turn-on originated from the conjugated structures of the fluorophores,
signaling mechanisms are highly desired, because they are which will decrease the signal-to-noise ratio and thus decrease
relatively simple to design and synthesize, with the advantages the probing sensitivity. Hence, it is highly desirable to develop
of low cost and easy manipulation.6 In addition, they are also probes without background fluorescence.
Shao and co-workers reported that bis(indolyl)methane
with nitro-substituents can be deprotonated by F− and then
oxidized by air to afford bis(indolyl)methene (Scheme 1),
aKey Laboratory for Advanced Materials and Institute of Fine Chemicals, East China
University of Science and Technology, Shanghai, P. R. China.
accompanied by vivid colour changes due to the generation of
a conjugated structure.11 Similar F− promoted deprotonation
and oxidation reactions have been reported by Hill and co-
workers.12 Inspired by these results and our work on dipyrrins
and tripyrrins, we envisioned that if particularly substituted
E-mail: yshxie@ecust.edu.cn; Fax: (+86) 21-6425-2758; Tel: (+86) 21-6425-0772
bDepartment of Theoretical Chemistry and Biology, School of Biotechnology KTH
Royal Institute of Technology, Stockholm, Sweden
†Electronic supplementary information (ESI) available: Full experimental and
crystallographic data and Fig. S1 to S30. CCDC 916622. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/c3ob40121a
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Scheme 1 Typical oxidation reactions of dipyrromethanes and bis(indolyl)-
methanes.
Fig. 1 The low field region of 1H NMR spectra of DPMOH1 (400 MHz, 298 K),
(a) in DMSO-d6, (b) in DMSO-d6 + D2O.
Scheme 2 Structures and synthetic routes for meso-OH substituted
dipyrromethanes.
dipyrromethanes could react with Zn2+ to afford highly fluo-
rescent dipyrrin complexes, it may be possible to develop fluo-
rescence turn-on Zn2+ probes without background fluorescence
due to the fact that dipyrromethanes are usually colorless and
nonfluorescent.13
During our systematic work on dipyrromethanes and dipyr-
rins, we accidentally obtained novel meso-OH substituted
dipyrromethanes DPMOH1–DPMOH3 (Scheme 2). Consistent
with our expectations, these novel compounds are nonfluore-
scent, and addition of Zn2+ promoted their oxidation to form
fluorescent dipyrrin complexes, indicating that they may be
applied as a novel prototype of fluorescence turn-on Zn2+
probes with the advantage of no background fluorescence. To
the best of our knowledge, this is the first report of meso-OH
substituted dipyrromethanes and Zn2+ probes based on
dipyrromethanes.
Fig. 2 Crystal structure of compound DPMOH1 with ellipsoids shown at 20%
probability level.
exchange results were observed for DPMOH2 and DPMOH3
(Fig. S19, S20†). To further elucidate the molecular structures
of these compounds, we tried to grow their single crystals, and
fortunately obtained the single crystals of DPMOH1 by slow
evaporation of its solution in a mixture of methanol and H2O.
The molecule of DPMOH1 really has an OH group attached to
the meso-C1 atom (Fig. 2). The C1–C2, C1–C16, C1–C27 and
C1–O1 bond lengths are 1.538(3), 1.524(3), 1.532(3), and 1.440(3)
Å, respectively. These values are typical of C–C and C–O
single bonds. The bond angles around C1 lie in the range of
106.3(2)–111.9(2)°, indicating that C1 is an sp3 carbon atom.
Thus, the dipyrrolic unit adopts a nonplanar conformation,
with a large dihedral angle of 67.2° between the two pyrrolic
units.
Results and discussion
Synthesis of DPMOH1–DPMOH3
DPMOH1–DPMOH3 were readily synthesized by stirring corre-
sponding dipyrromethanes with 2.0 equiv. of DDQ in CH2Cl2
(Scheme 2), followed by separation on silica gel columns. They
were fully characterized by 1H NMR, 13C NMR, and HRMS
(Fig. S1–S18†). Generally, oxidation of dipyrromethanes with
DDQ would afford corresponding dipyrrins.14 The generation
Titration study
of DPMOH1–DPMOH3 instead of common dipyrrins in these Due to the interruption of the conjugated system by the meso-
reactions may be caused by the reactions of the relatively sp3 carbon atom between the two pyrrolic units, DPMOH1–
stable carbonium intermediates with trace amount of water DPMOH3 show no fluorescence. Interestingly, upon addition
1
presented in CH2Cl2 (See ESI†). For the H NMR spectrum of of Zn2+ to their MeOH solutions, strong fluorescence appeared.
DPMOH1 in DMSO-d6, singlets at 11.65 and 6.62 ppm dis- A titration of DPMOH1 (10 μM) with Zn2+ was carried out to
appeared upon addition of D2O (Fig. 1). Thus, they were assigned study its detection behavior in detail. As depicted in Fig. 3a,
to pyrrolic-NH and meso-OH, respectively. Similar D2O upon addition of 0–6 eq. of Zn2+ to the solution of DPMOH1,
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Fig. 3 (a) Absorption spectral changes during a titration of DPMOH1 (10 μM) with Zn2+ (0–6.0 equiv.) in MeOH. (b) Corresponding fluorescence spectral changes
with λex fixed at 346 nm (one of the isosbestic points).
Fig. 4 (a) Absorption spectral changes during a titration of DPMOH2 (10 μM) with Zn2+ (0–12.0 equiv.) in MeOH. (b) Corresponding fluorescence emission spectral
changes with λex fixed at 345 nm (one of the isosbestic points).
obvious absorption changes were observed. The peak at of the calibration curves (Fig. S21–S23,† inset).15 These values
320 nm gradually decreased, and a new broad peak developed indicate that probes DPMOH1–DPMOH3 are sensitive enough
at about 561 nm, with an isosbestic point observed at 346 nm, for practical detection of Zn2+ in biochemical systems.1b,2b
which indicates the generation of a well-defined new product. These results urged us to further investigate the detailed detec-
Accompanying with these absorption changes, a sharp fluo- tion mechanisms.
rescence “turn on” was observed, with the emission peak cen-
tered at about 594 nm (Fig. 3b). Similar to the results observed
Detection mechanism
for DPMOH1, upon addition of 0–12 eq. of Zn2+ to the solution As above-mentioned that a well-defined new product was gene-
of DPMOH2, the peak at 323 nm gradually decreased, and a rated during the titration of probes DPMOH1–DPMOH3 with
new broad peak developed at about 564 nm, accompanied Zn2+. To understand the product structure, we stirred
with a sharp fluorescence “turn on” at 602 nm (Fig. 4). Similar DPMOH1 with Zn(OAc)2·2H2O in a mixture of MeOH and
UV-Vis and fluorescence spectral changes were also observed CH2Cl2, and successfully obtained a zinc complex Zn(DP1)2
for DPMOH3 (Fig. 5). These observations indicated that these (Scheme 3) in a yield of 66%, with the structure fully character-
compounds may be employed as fluorescence turn-on Zn2+ ized by H NMR and HRMS (Fig. S24, S25†). In the NMR spec-
1
probes. Based on these titration experiments, calibration trum, no OH peak was observed and the pyrrolic hydrogens
curves of DPMOH1–DPMOH3 can be obtained (Fig. S21–S23†). were shifted downfield due to the generation of a large conju-
The fluorescence intensity of DPMOH1 is proportional to the gation system and the coordination of Zn2+. The NH peak also
Zn2+ concentration in the range of 2.3 × 10−6–5.7 × 10−5 disappeared due to deprotonation and subsequent coordi-
M. And the dynamic ranges for DPMOH2 and DPMOH3 are nation. In the mass spectrum, a peak appeared at 1143.4764
6.2 × 10−7–3.9 × 10−5 and 8.1 × 10−7–4.9 × 10−5 M, respectively. (m/z), which corresponds to [Zn(DP1)2 + H]+. Thus, it can be
Respective detection limits for Zn2+ calculated from 3σ/k were concluded that addition of Zn2+ to the solution of DPMOH1
found to be 3.2 × 10−7, 5.0 × 10−7 and 5.5 × 10−7 M, where σ is promoted oxidation of the molecule to its dipyrrin form, and
the standard deviation of the blank solution and k is the slope then a complex formed with a dipyrrin : Zn2+ stoichiometry of
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Fig. 5 (a) Absorption spectral changes during a titration of DPMOH3 (10 μM) with Zn2+ (0–8.0 equiv.) in MeOH. (b) Corresponding fluorescence emission spectral
changes with λex fixed at 350 nm (one of the isosbestic points).
Scheme 3 Proposed detection mechanism of DPMOH1.
2 : 1, and the whole oxidation and subsequent coordination
processes were completed within ca. 2 hours (Fig. S26–S28†).
This reaction may be facilitated by the good stability of the
resulting complex, which has a relatively large conjugation frame-
work. The resulting strong fluorescence can be ascribed to
the CHEF type fluorescence enhancement,8a,b,16 which results
from good rigidity of the dipyrrin complex. In fact, we have
observed similar CHEF type fluorescence enhancement for
dipyrrins.10
Selectivity experiments
Selectivity experiments were carried out in MeOH to indicate
whether the detection of Zn2+ is interfered by other common
Fig. 6 Relative fluorescence intensity of 10 μM DPMOH1 in MeOH upon exci-
tation at 346 nm (one of the isosbestic points): (a) In the presence of various
cations. As shown in Fig. 6a, only the addition of 3 equiv. of
metal ions. (b) White bars represent the addition of 3 equiv. of metal ions. Black
Zn2+ to the solution of DPMOH1 induced a sharp fluorescence
“turn on”, while other metal cations can not induce obvious
fluorescence changes. Competition experiments were also
carried out to further elucidate the cation selectivity. When
3 equiv. of various competing cations were added together
bars represent the addition of 3 equiv. of Zn2+ mixed with 3 equiv. of indicated
metal ions. 1–14: Zn2+, Na+, K+, Mg2+, Ca2+, Cd2+, Hg2+, Co2+, Ni2+, Cu2+, Pb2+
Fe2+, Fe3+, Al3+
,
.
with 3 eq. of Zn2+, only the presence of Cu2+ quenched the fluo- small interference (Fig. 6b). Similar results were also obtained
rescence, but Cu2+ is not typically present at high concen- for compounds DPMOH2 and DPMOH3 (Fig. S29, S30†). These
trations in biochemical systems.17 Hence, the interference of results indicate that the probes can be developed as a novel
Cu2+ in the potential applications of these probes in biochemi- and promising type of selective “turn-on” fluorescent Zn2+
cal systems can be neglected. All other cations showed only probes without background fluorescence.
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Preparation of compound BODPM1
Conclusions
A solution of EtMgBr (18.7 mL, 18.7 mmol, 1.0 M solution in
THF) was added slowly to a flask containing a solution of
DPM1 (2.5 g, 7.5 mmol) in toluene (150 mL) under nitrogen.
The resulting mixture was stirred at room temperature for
30 min. Then, a solution of benzoyl chloride (2.2 mL,
18.7 mmol) in toluene (20 mL) was added over 10 min, and
the resulting solution was stirred for 30 min. Then the reaction
mixture was poured into saturated aqueous NH4Cl (200 mL).
The organic layer was washed with water for three times, dried
(Na2SO4), and filtered. The filtrate was concentrated and then
purified by a silica gel column (Eluent: dichloromethane
(DCM)–petroleum ether (PE) = 4/1 (V : V) then DCM) to afford
the crude product of BODPM1 which was recrystallized from
In conclusion, three novel nonfluorescent meso-OH substituted
dipyrromethanes DPMOH1–DPMOH3 were synthesized.
Addition of Zn2+ to their solutions induced the generation of
strong fluorescence, which may be ascribed to Zn2+ promoted
oxidation of the compounds to corresponding dipyrrins, fol-
lowed by coordination with Zn2+ to afford 2 : 1 Zn2+ complexes.
Hence, these nonfluorescent compounds can be employed as
fluorescence turn-on Zn2+ probes. These results provide
examples of a novel strategy for the development of fluo-
rescence turn-on probes without background fluorescence by
designing nonfluorescent molecules with nonconjugate struc-
tures, which can be converted into conjugate and fluorescent
structures upon selective interaction with a specific target
analyte under aerobic condition. Further modification of the
probes to improve their water solubility and detection behavior
is now under way in our lab.
1
CH2Cl2 and n-hexane (950 mg, yield: 23.5%). H NMR (DMSO-
d6, Bruker 400 MHz, 298 K): δ 12.15 (s, 2H, pyrrolic-NH), 7.77
(d, J = 6.8 Hz, 4H, phenyl-H), 7.60 (t, 2H, phenyl-H), 7.51 (t,
4H, phenyl-H), 7.29 (s, 1H, phenyl-H), 7.18 (d, J = 1.6 Hz, 2H,
phenyl-H), 6.72 (d, J = 3.6 Hz, 2H, pyrrolic-βH), 6.08 (d, J =
4.0 Hz, 2H, pyrrolic-βH), 5.72 (s, 1H, meso-H), 1.26 (s, 18H,
t-butyl-H). 13C NMR (CDCl3, Bruker 100 MHz, 298 K): δ 184.4,
151.4, 141.3, 139.1, 138.4, 131.5, 130.9, 129.6, 128.0, 123.0,
121.5, 120.8, 111.2, 53.5, 45.5, 35.0, 31.5. HRMS: obsd
541.2852, calcd for C37H37N2O2 ([M − H]−): 541.2855.
Experimental
General
Commercial available solvents and reagents were used as
received. Deuterated solvents for NMR measurements were
available from Aldrich. UV-Vis absorption spectra were
recorded by a Varian Cary 100 spectrophotometer and fluo-
rescence spectra were recorded on a Varian Cray Eclipse fluo-
rescence spectrophotometer, with a quartz cuvette (path length
Preparation of compound DPMOH1
BODPM1 (140 mg, 0.26 mmol) was dissolved in 125 mL of
CH2Cl2, then DDQ (71 mg, 0.31 mmol) was added. The
mixture was stirred at room temperature for 3 hours and then
directly purified by a silica gel column (Eluent: CH2Cl2–EA =
20/1) to afford the crude product of DPMOH1 which was
recrystallized from CH2Cl2 and n-hexane (116 mg, yield: 80%).
UV-Vis (MeOH) λmax (nm): 320. m.p.: 162–164 °C. IR (KBr
pellet, cm−1): 3282 (s), 3228 (s), 2963 (s), 2863 (m), 2253 (m),
1594 (s), 1569 (s), 1478 (m), 1449 (s), 1403 (m), 1358 (m), 1333
(m), 1266 (s), 1229 (s), 1171 (s), 1076 (m), 1042 (m), 881 (s),
1
= 1 cm); both spectrophotometers were standardized. H NMR
and 13C NMR spectra were obtained using a Bruker AM 400
spectrometer with tetramethylsilane (TMS) as the internal
standard. High resolution mass spectra (HRMS) were
measured on a Waters LCT Premier XE spectrometer. Elemen-
tal analyses were carried out with an Elmentar Vario EL-III ana-
lyzer. Column chromatography was carried out in air using
silica gel (200–300 mesh). Reactions were monitored by thin-
layer chromatography.
1
835 (w), 798 (m), 781 (m), 727 (m), 694 (m), 615 (m). H NMR
(DMSO-d6, Bruker 400 MHz, 298 K): δ 11.65 (s, 2H, pyrrolic-
NH), 7.80 (t, 4H, phenyl-H), 7.61 (t, 2H, phenyl-H), 7.53 (t, 4H,
phenyl-H), 7.38 (s, 1H, phenyl-H), 7.19 (d, 2H, J = 2.0 Hz,
phenyl-H), 6.72 (d, J = 2.4 Hz, 2H, pyrrolic-βH), 6.62 (s,
1H, –OH), 5.94 (d, 2H, J = 2.4 Hz, pyrrolic-βH), 1.25 (s, 18H,
t-butyl-H). 13C NMR (DMSO-d6, Bruker 100 MHz, 298 K):
δ 183.5, 149.4, 144.6, 143.2, 138.4, 131.7, 130.5, 128.5, 128.4,
121.1, 118.7, 109.9, 74.1, 34.5, 31.2. HRMS: obsd 581.2783,
calcd for C37H38N2O3Na ([M + Na]+): 581.2780. Anal. Calcd for
C37H38N2O3 (%): C, 79.54, H, 6.86, N, 5.01. Found: C, 79.81, H,
6.75, N, 4.86.
UV/Vis absorption spectrum measurements
The absorption spectra of DPMOH1–DPMOH3 (10 μM) were
measured at 25 °C in MeOH. Tested ions Zn2+, Na+, K+, Mg2+,
Ca2+, Cd2+, Hg2+, Co2+, Ni2+, Cu2+, Pb2+, Fe2+, Fe3+ were added
as acetate or chloride salts dissolved in MeOH, and Al3+ was
added as a nitrate salt dissolved in MeOH.
Fluorescence emission spectral measurements
The fluorescence emission spectra of DPMOH1–DPMOH3
(10 μM) were measured at 25 °C in MeOH, with excitation fixed
at λ = 346 nm for DPMOH1, 345 nm for DPMOH2 and 350 nm
Preparation of compound BODPM2
for DPMOH3. The slit width was 5 nm and PMT voltage was A solution of EtMgBr (17.3 mL, 17.3 mmol, 1.0 M solution in
600 V. Tested ions Zn2+, Na+, K+, Mg2+, Ca2+, Cd2+, Hg2+, Co2+, THF) was added slowly to a flask containing a solution of
Ni2+, Cu2+, Pb2+, Fe2+, Fe3+ were added as acetate or chloride DPM2 (2.0 g, 6.9 mmol) in toluene (130 mL) under nitrogen.
salts dissolved in MeOH, and Al3+ was added as a nitrate salt The resulting mixture was stirred at room temperature for
dissolved in MeOH.
40 min. A solution of 4-methoxybenzoyl chloride (3.0 g,
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17.3 mmol) in toluene (20 mL) was added over 10 min, and 2954 (m), 2929 (m), 2834 (m), 2046 (w), 1606 (s), 1557 (s), 1511 (s),
the resulting solution was stirred for 35 min. Then the reaction 1470 (s), 1416 (m), 1337 (m), 1300 (m), 1246 (s), 1171 (s),
mixture was poured into saturated aqueous NH4Cl (200 mL). 1109 (m), 1030 (s), 885 (s), 839 (s), 760 (s), 731 (m), 706 (m),
The organic layer was washed by water three times, dried 623 (m), 565 (w), 511 (w). 1H NMR (CDCl3, 400 MHz, 298 K)
(Na2SO4), and filtered. The filtrate was concentrated and then δ 11.44 (s, 2H, pyrrolic-NH), 7.78 (d, J = 8.8 Hz, 4H, phenyl-H),
purified by a silica gel column (Eluent: DCM then DCM–ethyl 7.45 (d, J = 8.4 Hz, 2H, phenyl-H), 6.88–6.93 (m, 6H, phenyl-H),
acetate (EA) = 20/1) to afford the crude product of BODPM2 6.51 (dd, J1 = 2.4 Hz, J2 = 3.6 Hz, 2H, pyrrolic-βH), 5.93 (t, 2H,
which was recrystallized from CH2Cl2 and n-hexane (830 mg, pyrrolic-βH), 5.60 (s, 1H, meso-H), 3.85 (s, 6H, –OCH3), 3.83
yield: 21.6%). 1H NMR (CDCl3, Bruker 400 MHz, 298 K): δ (s, 3H, –OCH3). 13C NMR (DMSO-d6, Bruker 100 MHz, 298 K):
12.10 (s, 2H, pyrrolic-NH), 7.68–7.76 (m, 8H, phenyl-H), 6.88 δ 182.2, 162.0, 158.0, 141.1, 133.4, 131.0, 130.6, 130.1, 129.2,
(d, J = 8.8 Hz, 4H, phenyl-H), 6.45 (q, J = 3.6 Hz, 2H, pyrrolic- 118.9, 113.6, 109.4, 55.4, 55.0. 42.0. HRMS: obsd 519.1923,
βH), 5.85 (d, J = 2.8 Hz, 2H, pyrrolic-βH), 5.73 (s, 1H, meso-H), calcd for C32H27N2O5 ([M − H]−): 519.1920.
3.85 (s, 6H, –OCH3). 13C NMR (DMSO-d6, Bruker 100 MHz,
298 K): δ 182.3, 162.1, 144.6, 141.8, 139.7, 139.6, 130.9, 130.7,
Preparation of compound DPMOH3
130.4, 128.5, 125.4, 118.9, 113.7, 109.8, 97.3, 55.4, 42.3. HRMS: BODPM3 (270 mg, 0.5 mmol) was dissolved in 160 mL of
obsd 559.1843, calcd for C32H26N2O4F3 ([M + H]+): 559.1845.
CH2Cl2, then DDQ (142 mg, 0.6 mmol) was added. The
mixture was stirred at room temperature for 3 hours and then
directly purified by a silica gel column (Eluent: CH2Cl2–EA =
Preparation of compound DPMOH2
BODPM2 (180 mg, 0.32 mmol) was dissolved in 150 mL of 25/1) to afford the crude product of DPMOH3 which was
CH2Cl2, then DDQ (87 mg, 0.38 mmol) was added. The recrystallized from CH2Cl2 and n-hexane (210 mg, yield:
mixture was stirred at room temperature for 2.5 hours and 74.6%). UV-Vis (MeOH) λmax (nm): 325. m.p.: 131–134 °C. IR
then directly purified by a silica gel column (Eluent: CH2Cl2) (KBr pellet, cm−1): 3290 (m), 2929 (w), 2834 (w), 1603 (s), 1557
to afford the crude product of DPMOH2 which was recrystal- (m), 1509 (m), 1470 (m), 1416 (w), 1333 (w), 1304 (w), 1252 (s),
lized from CH2Cl2 and n-hexane (145 mg, yield: 78%). UV-Vis 1171 (s), 1113 (w), 1026 (m), 889 (m), 843 (w), 802 (w), 764 (m),
1
(MeOH) λmax (nm): 323. m.p.: 121–126 °C. IR (KBr pellet, 711 (w), 619 (w). H NMR (DMSO-d6, 400 MHz, 298 K) δ 11.5
cm−1): 3290 (m), 2921 (m), 2847 (m), 1723 (m), 1660 (w), (s, 2H, pyrrolic-NH), 7.83 (d, J = 8.8 Hz, 4H, phenyl-H), 7.17 (d,
1604 (s), 1558 (s), 1507 (m), 1472 (m), 1411 (m), 1324 (m), 1255 (s), J = 8.8 Hz, 2H, phenyl-H), 7.06 (d, J = 8.8 Hz, 4H, phenyl-H),
1170 (s), 1109 (m), 1034 (m), 972 (w), 885 (m), 839 (m), 802 (m), 6.93 (d, J = 8.8 Hz, 2H, phenyl-H), 6.71 (dd, J1 = 2.8 Hz, J2 = 4.0
765 (m), 706 (w), 648 (w), 623 (w). 1H NMR (DMSO-d6, Hz, 2H, pyrrolic-βH), 6.52 (s, 1H, –OH), 5.95 (dd, J1 = 2.4 Hz,
Bruker 400 MHz, 298 K): δ 11.62 (s, 2H, Pyrrolic-NH), 7.96 (d, J2 = 3.6 Hz, 2H, pyrrolic-βH), 3.84 (s, 6H, –OCH3), 3.76 (s,
J = 8.8 Hz, 2H, phenyl-H), 7.83 (d, J = 8.8 Hz, 4H, phenyl-H), 3H, –OCH3). 13C NMR (DMSO-d6, Bruker 100 MHz, 298 K):
7.45 (d, J = 8.8 Hz, 2H, phenyl-H), 7.06 (d, J = 8.8 Hz, 4H, δ 182.4, 162.1, 158.7, 144.0, 136.7, 130.7, 130.6, 128.2, 117.9,
phenyl-H), 6.79 (s, 1H, –OH), 6.73 (dd, J1 = 2.4 Hz, J2 = 3.6 Hz, 113.7, 113.1, 109.7, 73.5, 55.4, 55.1. HRMS: obsd 535.1872,
2H, Pyrrolic-βH), 6.01 (dd, J1 = 2.8 Hz, J2 = 3.6 Hz, 2H, Pyrrolic- calcd for C32H27N2O6 ([M − H]−): 535.1869. Anal. Calcd for
βH), 3.85 (s, 6H, –OCH3). 13C NMR (DMSO-d6, Bruker C32H28N2O6 (%): C, 71.63, H, 5.26, N, 5.22. Found: C, 71.92, H,
100 MHz, 298 K): δ 182.4, 162.2, 147.1, 142.9, 142.6, 131.0, 5.14, N, 5.03.
130.8, 130.7, 127.5, 124.9, 117.9, 113.7, 109.8, 97.2, 73.5, 59.7,
Preparation of compound Zn(DP1)2
55.4. HRMS: obsd 573.1633, calcd for
C32H24N2O5F3
([M − H]−): 573.1637. Anal. Calcd for C32H25F3N2O5 (%): C, A mixture of DPMOH1 (56 mg, 0.1 mmol) and Zn(OAc)2·2H2O
66.89, H, 4.39, N, 4.88. Found: C, 67.15, H, 4.48, N, 4.99.
(22 mg, 0.1 mmol) was dissolved in a mixture of 40 mL MeOH
and 10 mL CH2Cl2. The solution was stirred at room tempera-
ture for 18 h, then poured into 40 mL water. The organic layer
Preparation of compound BODPM3
A solution of EtMgBr (25.0 mL, 25.0 mmol, 1.0 M solution in was collected, dried and concentrated, and recrystallized from
THF) was added slowly to a flask containing a solution of CH2Cl2 and n-hexane to afford a dark brown solid of Zn(DP1)2
DPM3 (2.5 g, 10.0 mmol) in toluene (170 mL) under nitrogen. (38 mg, yield: 66%). UV-Vis (MeOH) λmax (nm): 561. IR (KBr
The resulting mixture was stirred at room temperature for pellet, cm−1): 3361 (w), 2958 (w), 2917 (w), 2847 (w), 1648 (m),
30 min. A solution of 4-methoxybenzoyl chloride (4.3 g, 1548 (m), 1449 (w), 1362 (w), 1345 (w), 1251 (s), 1175 (w), 1067
25.0 mmol) in toluene (20 mL) was added over 10 min, and (m), 1003 (s), 876 (w), 835 (m), 806 (w), 723 (w), 690 (w), 673
1
the resulting solution was stirred for 35 min. Then the reaction (w). H NMR (CDCl3, 400 MHz, 298 K): 7.72 (t, 8H, Ph-H), 7.55
mixture was poured into saturated aqueous NH4Cl (200 mL). (t, 2H, Ph-H), 7.39 (d, 4H, pyrrolic-βH), 7.34 (t, 4H, Ph-H), 7.18
The organic layer was washed by water three times, dried (t, 8H, Ph-H), 6.56 (q, 8H), 1.43 (s, 36H, –C(CH3)3). HRMS:
(Na2SO4), and filtered. The filtrate was concentrated and then obsd 1143.4764, calcd for C74H71N4O4Zn ([M + H]+): 1143.4767.
purified by a silica gel column (Eluent: DCM then DCM–EA =
X-ray crystallography and crystal data for DPMOH1
25/1) to afford the crude product of BODPM3 which was recrys-
tallized from CH2Cl2 and n-hexane (765 mg, yield: 14.7%). Single crystals suitable for X-ray analyses of DPMOH1 was
m.p.: 97–99 °C. IR (KBr pellet, cm−1): 3236 (s), 3004 (w), obtained by slow evaporation of its methanol–H2O mixed
2690 | Org. Biomol. Chem., 2013, 11, 2685–2692
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solution at room temperature. X-ray diffraction data were col-
lected on a Bruker-AXS APEX diffractometer utilizing MoKR
radiation (λ = 0.71073 Å). The structures were solved by direct
methods and refined with full matrix least-squares technique.
Anisotropic thermal parameters were applied to all non-hydro-
gen atoms. All of the hydrogen atoms in these structures are
located from the differential electron density map and con-
strained to the ideal positions in the refinement procedure. All
calculations were performed using the SHELX-97 software
package.18
Analyst, 2009, 134, 2385–2393; (d) G. He, X. Zhao, X. Zhang,
H. Fan, S. Wu, H. Li, C. He and C. Duan, New J. Chem.,
2010, 34, 1055–1058; (e) X. Cheng, S. Li, H. Jia, A. Zhong,
C. Zhong, J. Feng, J. Qin and Z. Li, Chem.–Eur. J., 2012, 18,
1691–1699; (f) L. Yuan, W. Lin, B. Chen and Y. Xie, Org.
Lett., 2012, 14, 432–435; (g) Y. Chen, L. Wan, X. Yu, W. Li,
Y. Bian and J. Jiang, Org. Lett., 2011, 13, 5774–5777;
(h) L. Yao, J. Zhou, J. Liu, W. Feng and F. Li, Adv. Funct.
Mater., 2012, 22, 2667–2672; (i) J. P. Hill, N. K. Subbaiyan,
F. D’Souza, Y. Xie, S. Sahu, N. M. Sanchez-Ballester,
G. J. Richards, T. Mori and K. Ariga, Chem. Commun., 2012,
48, 3951–3953; ( j) G. R. Deviprasad, B. Keshavan and
F. D’Souza, J. Chem. Soc., Perkin Trans., 1998, 3133–3136;
(k) S. Brovelli, G. Sforazzini, M. Serri, G. Winroth,
K. Suzuki, F. Meinardi, H. L. Anderson and F. Cacialli, Adv.
Funct. Mater., 2012, 22, 4284–4291; (l) O. Fenwick,
J. K. Sprafke, J. Binas, D. V. Kondratuk, F. Di Stasio,
H. L. Anderson and F. Cacialli, Nano Lett., 2011, 11,
2451–2456.
4 (a) J. R. Lakowicz, Topics in Fluorescence Spectroscopy,
Volume 4: Probe Design and Chemical Sensing, Kluwer Aca-
demic Publishers, New York, 2002; (b) W. Lin, L. Yuan,
L. Long, C. Guo and J. Feng, Adv. Funct. Mater., 2008, 18,
2366–2372.
5 (a) Q. Chang, J. R. Lakowicz and G. Rao, Analyst, 1997, 122,
173–177; (b) R. Fudala, M. E. Mummert, Z. Gryczynski,
R. Rich, J. Borejdo and I. Gryczynski, J. Photochem. Photo-
biol., B, 2012, 106, 69–73; (c) X. D. Wang and
O. S. Wolfbeis, Anal. Chem., 2012, 85, 487–508.
6 (a) J. Jo, H. Y. Lee, W. Liu, A. Olasz, C. H. Chen and D. Lee,
J. Am. Chem. Soc., 2012, 134, 16000–16007; (b) X. Peng,
J. Du, J. Fan, J. Wang, Y. Wu, J. Zhao, S. Sun and T. Xu,
J. Am. Chem. Soc., 2007, 129, 1500–1501; (c) A. F. Li, H. He,
Y. B. Ruan, Z. C. Wen, J. S. Zhao, Q. J. Jiang and Y. B. Jiang,
Org. Biomol. Chem., 2009, 7, 193–200; (d) L. Liu, G. Zhang,
J. Xiang, D. Zhang and D. Zhu, Org. Lett., 2008, 10,
4581–4584; (e) K. Huang, H. Yang, Z. Zhou, M. Yu,
F. Li, X. Gao, T. Yi and C. Huang, Org. Lett., 2008, 10, 2557–
2560.
7 (a) Y. Q. Weng, F. Yue, Y. R. Zhong and B. H. Ye,
Inorg. Chem., 2007, 46, 7749–7755; (b) J. Yoshino,
N. Kano and T. Kawashima, J. Org. Chem., 2009, 74,
7496–7503; (c) A. P. de Silva, G. D. McClean and
T. S. Moody, Encyclopedia of Supramolecular Chemistry,
2004, 572–578.
8 (a) Y. Zhou, Z. X. Li, S. Q. Zang, Y. Y. Zhu, H. Y. Zhang,
H. W. Hou and T. C. W. Mak, Org. Lett., 2012, 14, 1214–
1217; (b) M. Mameli, M. C. Aragoni, M. Arca, M. Atzori,
A. Bencini, C. Bazzicalupi, A. J. Blake, C. Caltagirone,
F. A. Devillanova, A. Garau, M. B. Hursthouse, F. Isaia,
V. Lippolis and B. Valtancoli, Inorg. Chem., 2009, 48, 9236–
9249; (c) Z. Guo, G. H. Kim, I. Shin and J. Yoon, Biomater-
ials, 2012, 33, 7818–7827; (d) Y. Hong, S. Chen,
C. W. T. Leung, J. W. Y. Lam, J. Liu, N. W. Tseng,
R. T. K. Kwok, Y. Yu, Z. Wang and B. Z. Tang, ACS Appl.
Mater. Interfaces, 2011, 3, 3411–3418; (e) F. Sun, G. Zhang,
C37H38N2O3, FW = 558.69 g mol−1, 0.10 × 0.08 × 0.02 mm3,
ˉ
Triclinic, P1, a = 9.9120(6) Å, b = 11.6861(9) Å, c = 15.4195(11)
Å, α = 93.9300(10)°, β = 104.033(2)°, γ = 103.177(2)°, V = 1672.6
(2) Å3, F(000) = 596, ρcalcd = 1.109 Mg m−3, μ(MoKα) =
0.070 mm−1, T = 298(2) K, 8551 data measured on a Bruker
SMART Apex diffractometer, of which 5829 were unique
2
(Rint = 0.0470); 448 parameters refined against Fo (all data),
final wR2 = 0.1044, S = 1.063, R1 (I > 2σ(I)) = 0.0603, largest
final difference peak/hole = 0.160 and −0.167 e Å−3. Structure
solution by direct methods and full-matrix least-squares refine-
ment against F2 (all data) using SHELXTL.
Acknowledgements
This work was financially supported by NSFC (21072060), the
Program for Professor of Special Appointment (Eastern
Scholar) at Shanghai Institutions of Higher Learning, Program
for New Century Excellent Talents in University (NCET), Inno-
vation Program of Shanghai Municipal Education Commis-
sion, the Fundamental Research Funds for the Central
Universities (WK1013002), and SRFDP (20100074110015).
Notes and references
1 (a) C. J. Frederickson, J. Y. Koh and A. I. Bush, Nat. Rev.
Neurosci., 2005, 6, 449–462; (b) E. L. Que, D. W. Domaille
and C. J. Chang, Chem. Rev., 2008, 108, 1517–1549;
(c) E. Tomat and S. J. Lippard, Curr. Opin. Chem. Biol.,
2010, 14, 225–230.
2 (a) Z. C. Xu, J. Yoon and D. R. Spring, Chem. Soc. Rev.,
2010, 39, 1996–2006; (b) P. Jiang and Z. Guo, Coord. Chem.
Rev., 2004, 248, 205–229; (c) E. Manandhar, J. H. Broome,
J. Myrick, W. Lagrone, P. J. Cragg and K. J. Wallace, Chem.
Commun., 2011, 47, 8796–8798; (d) M. Chen, X. Lv, Y. Liu,
Y. Zhao, J. Liu, P. Wang and W. Guo, Org. Biomol. Chem.,
2011, 9, 2345–2349; (e) Z. C. Xu, K. H. Baek, H. N. Kim,
J. N. Cui, X. H. Qian, D. R. Spring, I. Shin and J. Yoon,
J. Am. Chem. Soc., 2010, 132, 601–610; (f) L. Xue, Q. Liu and
H. Jiang, Org. Lett., 2009, 11, 3454–3457; (g) Y. Ikawa,
M. Takeda, M. Suzuki, A. Osuka and H. Furuta, Chem.
Commun., 2010, 46, 5689–5691.
3 (a) T. Ueno and T. Nagano, Nat. Methods, 2011, 8, 642–645;
(b) B. Valeur and I. Leray, Coord. Chem. Rev., 2000, 205,
3–40; (c) A. P. de Silva, T. S. Moody and G. D. Wright,
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 2685–2692 | 2691

View Article Online
Paper
Organic & Biomolecular Chemistry
D. Zhang, L. Xue and H. Jiang, Org. Lett., 2011, 13, 6378– 11 L. Wang, W. Wei, Y. Guo, J. Xu and S. Shao, Spectrochim.
6381; (f) E. M. Nolan, J. Jaworski, K. I. Okamoto, Acta, Part A, 2011, 78, 726–731.
Y. Hayashi, M. Sheng and S. J. Lippard, J. Am. Chem. Soc., 12 A. Shundo, J. P. Hill and K. Ariga, Chem.–Eur. J., 2009, 15,
2005, 127, 16812–16823; (g) W. Jiang, Q. Fu, H. Fan and 2486–2490.
W. Wang, Chem. Commun., 2008, 259–261; (h) W. Lin, 13 (a) D. T. Gryko, D. Gryko and C. H. Lee, Chem. Soc. Rev.,
J. Feng, L. Yuan and W. Tan, Sens. Actuators, B, 2009, 135,
512–515.
9 (a) B. Turfan and E. U. Akkaya, Org. Lett., 2002, 4, 2857–
2012, 41, 3780–3789; (b) B. J. Littler, M. A. Miller,
C. H. Hung, R. W. Wagner, D. F. O’Shea, P. D. Boyle and
J. S. Lindsey, J. Org. Chem., 1999, 64, 1391–1396.
2859; (b) D. Maity and T. Govindaraju, Chem. Commun., 14 (a) T. E. Wood and A. Thompson, Chem. Rev., 2007, 107,
2012, 48, 1039–1041; (c) P. N. Basa and A. G. Sykes, J. Org.
Chem., 2012, 77, 8428–8434; (d) H. Sasaki, K. Hanaoka,
1831–1861; (b) Q. Miao, J. Y. Shin, B. O. Patrick and
D. Dolphin, Chem. Commun., 2009, 2541–2543.
Y. Urano, T. Terai and T. Nagano, Bioorg. Med. Chem., 2011, 15 H. T. Niu, D. Su, X. Jiang, W. Yang, Z. Yin, J. He and
19, 1072–1078; (e) X. Lu, W. Zhu, Y. Xie, X. Li, Y. Gao, F. Li J. P. Cheng, Org. Biomol. Chem., 2008, 6, 3038–3040.
and H. Tian, Chem.–Eur. J., 2010, 16, 8355–8364; 16 (a) Y. Li, L. Shi, L. X. Qin, L. L. Qu, C. Jing, M. Lan,
(f) A. E. Lee, M. R. Grace, A. G. Meyer and K. L. Tuck, Tetra-
hedron Lett., 2010, 51, 1161–1165; (g) Z. Han, X. Zhang,
Z. Li, Y. Gong, X. Wu, Z. Jin, C. He, L. Jian, J. Zhang,
G. Shen and R. Yu, Anal. Chem., 2010, 82, 3108–3113;
T. D. James and Y. T. Long, Chem. Commun., 2011, 47,
4361–4363; (b) B. Zhang, K. S. Cao, Z. A. Xu, Z. Q. Yang,
H. W. Chen, W. Huang, G. Yin and X. Z. You, Eur. J. Inorg.
Chem., 2012, 2012, 3844–3851.
(h) J. J. Du, J. L. Fan, X. J. Peng, H. L. Li and S. G. Sun, Sens. 17 N. C. Lim and C. Bruckner, Chem. Commun., 2004, 1094–
Actuators, B, 2010, 144, 337–341. 1095.
10 Y. B. Ding, Y. S. Xie, X. Li, J. P. Hill, W. B. Zhang and 18 G. M. Sheldrick, Acta Crystallogr., Sect. A: Fundam. Crystal-
W. H. Zhu, Chem. Commun., 2011, 47, 5431–5433.
logr., 2008, 64, 112.
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