π-extended dipyrrins capable of highly fluorogenic complexation with metal ions

Article abstract of DOI:10.1021/ja102852v

The synthesis and properties of a new family of π-extended dipyrrins capable of forming brightly fluorescent complexes with metal ions are reported. The metal complexes possess tunable spectral bands and exhibit different emission properties depending on the mode of metal coordination.

Full text of DOI:10.1021/ja102852v

Published on Web 06/28/2010
π-Extended Dipyrrins Capable of Highly Fluorogenic Complexation with Metal
Ions
Mikhail A. Filatov,† Artem Y. Lebedev,‡ Sergei N. Mukhin,† Sergei A. Vinogradov,*,‡ and
Andrei V. Cheprakov*,†
Department of Chemistry, Moscow State UniVersity, 119899 Moscow, Russia, and Department of Biochemistry and
Biophysics, UniVersity of PennsylVania, Philadelphia, PennsylVania 19104
Received April 12, 2010; E-mail: vinograd@mail.med.upenn.edu; avchep@elorg.chem.msu.ru
Scheme 1a
Abstract: The synthesis and properties of a new family of
π-extended dipyrrins capable of forming brightly fluorescent
complexes with metal ions are reported. The metal complexes
possess tunable spectral bands and exhibit different emission
properties depending on the mode of metal coordination.
Boron dipyrrins (BODIPYs) form a popular group of fluoro-
phores because of their high emission quantum yields, excellent
photostability, and versatile chemistry.1 While boron complexes
of dipyrrins are by far the most recognized, dipyrrins have also
long been known to form stable adducts with metal ions.2-4
Metallodipyrrins are typically isolated as homoleptic bis complexes
(ML2, L ) dipyrrin) and mainly find use as building blocks for
construction of various supramolecular assemblies.5 Curiously,
unlike BODIPYs, homoleptic metallodipyrrins practically do not
fluoresce, although there are several important exceptions.6 For
example, Holten, Lindsey, and co-workers6a showed that by
increasing the size of the meso-aryl group in Zn bisaryldipyrrins,
the nonradiative decay could be diminished, affording a considerable
gain in emission. On the other hand, some recently reported
heteroleptic Al3+ and Sn2+ monodipyrrinates (MLXn) exhibit bright
fluorescence,7,8 suggesting that the emissivity of metallodipyrrins
could in part be related to the mode of metal coordination. Overall,
the interplay between the structure and photophysics of metallo-
dipyrrins is not well understood, and metallodipyrrins are generally
considered to be poorly emissive species.1a
Here we report a new family of aromatically π-extended dipyrrin
molecules capable of forming bright fluorescent complexes with
metal ions and exhibiting a unique fluorescence modulation effect
mediated by exciton coupling.9 A recently described approach to
π-extended porphyrins based on 4,7-dihydroisoindole and its
derivatives (Scheme 1)10 paved a new way to π-extended oligo-
pyrroles, including 2,2′-alkoxycarbonyldibenzo[2,3]dipyrrins (BDPs)
and -dinaphtho[2,3]dipyrrins (NDPs). A simple one-pot procedure
leading to BDPs relies on the condensation of 2-substituted 4,7-
dihydroisoindole 1 with aldehydes10c followed by the oxidation of
dipyrromethanes with dichlorodicyanoquinone (DDQ). Similarly,
dinaphthodipyrrins can be synthesized from the corresponding
pyrrole esters reported previously (Scheme 1).10a
a Reagents and conditions: (i) R1CHO, p-toluenesulfonic acid, Bu4NCl,
CH2Cl2, r.t., 12-24 h; (ii) DDQ (3 equiv), THF, r.t., 10-30 min. Yields:
2a, 93%; 2b (R1 ) 3,5-t-Bu2C6H3), 88%; 2c (R1 ) 4-BrC6H4), 92%; 2d
(R1 ) 4-MeO2CC6H4), 87%; 2e (R1 ) 3,5-(MeO)2C6H3), 84%; 2f (R1 )
2-thienyl), 82%; 3, 78%.
LaCl3, GdCl3], their solutions instantly become fluorescent. For
example, upon addition of Zn(OAc)2, purple solutions of BDPs in
N,N-dimethylformamide (DMF) immediately changed color to deep-
blue with the appearance of bright-red fluorescence (Figure 1b). In
contrast, metalation of regular dipyrrins typically requires heating
and/or the presence of bases and leads to nonemissive products.
The optical transitions of the new π-extended dipyrrinates span
the entire red spectral range (Figure 1a), resembling in shape
the bands of BODIPY, dibenzo-BODIPY,12 and dibenzoaza-
BODIPY.13 The emission quantum yields reach as high as 0.7 in
the case of ZnBDPs (Table 1). The fluorescence quantum yields
of the NDP complexes are somewhat lower, reflecting a ∼100 nm
red shift in the NDP transition and subsequent enhancement of the
nonradiative decay.14 The unusually high emissivity of BDP and
NDP complexes is probably related to the structures of the
π-extended dipyrrin ligands themselves, which are different than
those of other dipyrrins reported to date. By comparison, in similarly
π-extended porphyrins, the S1 f S0 radiative rate was found to be
higher than in the corresponding nonaromatically extended ana-
logues.15 From the practical point of view, the red absorption bands
of BDPs and NDPs and their strongly fluorogenic complexation
make these dipyrrins promising as probes for biological sensing of
metal ions (e.g., Zn2+).
All of the synthesized dipyrrins exhibit broad absorption bands
(ε ) 4-7 × 104 M-1 cm-1) ranging from 550-570 nm for BDPs
(2a-f) to 660-700 nm for NDP 3. Taken as free bases, BDPs and
NDPs fluoresce very weakly (φfl ) 0.01-0.02 at 22 °C); however,
upon addition of metal salts [e.g., Zn(OAc)2, Ca(OAc)2, YCl3,
† Moscow State University.
‡ University of Pennsylvania.
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10.1021/ja102852v  2010 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. (a) Structures of heteroleptic metal complexes of BDPs and
NDPs. (b) Color changes upon addition of Zn(OAc)2 to a solution of 2a in
DMF (1 and 2), upon illumination of the solution with a red light-emitting
diode (λmax ) 635 nm) from the side (3), after addition of a few crystals of
Zn(OAc)2 (4), and after the solution was shaken (5). (c) Absorption and
emission spectra of Zn complexes of BDP 2d (blue) and NDP 3 (green).
The complexes were prepared in situ by adding Zn(OAc)2 to solutions of
free-base dipyrrins (∼5 × 10-6 M) in DMF (X ) OAc).
Figure 2. (a) Changes in the absorption and emission spectra (λex ) 560
nm) of Zn-2d (ML2) upon addition of excess Zn(OAc)2: ML2 in pyridine
before addition of Zn(OAc)2 (black) and 2 h (red) and 16 h (blue) after
addition. Inset: exciton splitting effect; the line thickness reflects the
1
transition probability. (b) Aromatic regions of the H NMR spectra of the
ML2 and MLX forms of Zn-2d in pyridine-d5 [solvent resonances are
marked in blue; assignments are based on 1H COSY experiments (Figures
S2 and S4) and refer to the structure on the right]. (c) Optimized structure
of the homoleptic Zn-2e complex [B3LYP/6-31G(d); pendant groups have
been omitted for clarity]. Dotted arrows show the orientations of the
transition dipole moments (µ1 and µ2) of the individual dipyrrin units.
Table 1. Optical Properties of Zn and Ca Complexes of
π-Extended Dipyrrins in DMFa
abs λmax
(nm)
em λmax
(nm)
abs λmax
(nm)
em λmax
(nm)
complex
φflb
complex
φflb
Zn-2a
Zn-2d
Zn-3
637
631
740
650
639
761
0.70 Ca-2a
0.65 Ca-2d
0.08 Ca-3
639
638
737
650
645
762
0.64
0.58
0.05
and/or electronic effects of 2,2′-alkoxycarbonyl groups,19 which
may weaken the coordination bonds and facilitate exchange
reactions.
Direct evidence that heteroleptic BDP complexes are highly
fluorescent was obtained by synthesizing a Zn dipyrrin-ꢀ-diketonate
by way of a ligand-exchange reaction. Treatment of 2a with a
stoichiometric amount of Zn(acac)2 in acetone gave the desired
Zn(acac)-2a, which readily precipitated from the reaction mixture.
As expected, Zn(acac)-2a showed absorption features similar to
those of BODIPY and bright-red fluorescence (φfl ) 0.7 in THF)
(Figure S14).
The profound differences in the optical spectra of the mono and
bis complexes and the complete on-off switching of the fluores-
cence suggest the presence of a strong exciton coupling effect in
ML2.9 Exciton coupling has been observed in various chromophore
dimers, including dimers of BODIPY.20 The ML2 molecule may
be viewed a “dimer” of two independent dipyrrin units held close
to one another by the metal ion. In such a dimer, the two transition
dipoles, which are oriented in the individual dipyrrins between the
isoindolic residues (µ1 and µ2 in Figure 2c),17a can interact, resulting
in a pair of nondegenerate states, one shifted up and the other down
relative to the transition of the parent ML complex (Figure 2a inset).
The magnitude of the coupling and the intensities of the corre-
sponding bands depend on the strengths of the transition dipoles
and on their mutual orientation. In particular, a nonplanar orientation
(in different planes at an angle to each other) may produce a splitting
in which the blue-shifted transition is allowed while the red-shifted
one is forbidden.9
The experimental spectra of MLX and ML2 (Figure 2a) appear
to fit the exciton coupling model well. The peaks at 599 and 669
nm, obtained by fitting the absorption spectrum of ML2 with a pair
of Lorentzians (Figure S13), are shifted by 1118 cm-1 up and 629
cm-1 down relative to the principal band of the parent MLX
complex (λmax ) 642 nm). The asymmetry is likely to be caused
by the difference in the vibrational couplings and/or different
a Complexes were generated in situ upon addition of metal acetates
(∼10-fold excess) to solutions of dipyrrins. b Relative to rhodamine 6G
in EtOH (φfl ) 0.94).11
A remarkable feature of the observed complexation is the
complete on-off switching of fluorescence depending on the mode
of metal coordination. For example, when BDP 2d was reacted
with Zn(OAc)2 in acetone, an intensely fluorescent solution formed
instantly (Figure 1b); however, after a few hours, the fluorescence
disappeared, and dark-blue crystals precipitated. These crystals were
poorly soluble in acetone but very soluble in toluene, CH2Cl2, and
pyridine. The solutions revealed different absorption spectra (Figure
2a) and practically no fluorescence. The crystals were unambigu-
ously identified as the homoleptic ML2 complex (p S21, Supporting
Information). Upon reaction of this complex with excess Zn salt
in pyridine, the spectrum again adopted the BODIPY-like shape,
and the fluorescence was fully regained (Figure 2a). The conversion
could be followed by NMR spectroscopy (Figure 2b and Figure
S11, Supporting Information) and absorption and fluorescence
spectroscopy (Figure S10).
The observed spectral changes most likely originate from the
solvent-dependent equilibrium between heteroleptic (MLX) and
homoleptic (ML2) species. At first, the fluorescent MLX complex
forms rapidly, but its subsequent reaction with excess ligand (L)
and/or disproportionation leads to the formation of ML2, which
precipitates out of the solution, thereby shifting the equilibrium.
In coordinating solvents (e.g., pyridine), where the solubilities of
inorganic Zn salts, MLX, and ML2 are high, the equilibrium can
be shifted back to MLX by increasing the concentration of Zn2+
.
Notably, such equilibria are not common for metallodipyrrins, which
typically exist as stable homoleptic adducts, notwithstanding that
some heteroleptic complexes have been reported in the literature.16-18
The higher lability of our dipyrrinates could be a result of the steric
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C O M M U N I C A T I O N S
photophysics of metallodipyrrins, suggesting rational pathways to
fluorogenic dipyrrin-based chelators. These results open up pos-
sibilities for engaging metallodipyrrins in a variety of applications,
including construction of luminescent networks, electrooptical
materials, and biomedical imaging and sensing.
Acknowledgment. This work was supported by Grant 10-03-
01122a from RFBR and Grant EB007279 from NIH. S.A.V. is
grateful to Prof. R. M. Hochstrasser and Dr. L. E. Sinks for
invaluable discussions.
Supporting Information Available: Synthetic procedures, spec-
troscopic data, fluorescence lifetime data, and crystallographic data
(CIF). This material is available free of charge via the Internet at http://
pubs.acs.org.
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solvation of the mono and bis complexes. The ratio of the oscillator
strengths (ML2 vs MLX) was found to be 1.92, which is very close
to the value predicted by the theory (2.0).9 Fast nonradiative
relaxation from the upper to the lower exciton state and slow
emission from the latter, consistent with the low oscillator strength
of the corresponding excitation, make intersystem crossing and
internal conversion the most likely causes for the loss of fluores-
cence in ML2. In toluene at 22 °C, ML2 exhibits a broad emission
(λmax ) 785 nm) with a negligible quantum yield (φfl < 0.01) and
an average lifetime of ∼1.6 ns (Figure S15).
The strong coupling of the transition dipoles suggests that the
mutual orientation of the dipyrrin units in ML2 deviates from strictly
orthogonal (D2h symmetry). The X-ray crystal structure (CCDC no.
749261) of ML2 complex Zn-2e (Figure 3) fully corroborates this
assumption. The angle between the mean-square planes of the
dipyrrins in Zn-2e is only 64.5°, which is smaller than that found
in the majority of known Zn-dipyrrin complexes.21 Similarly
flattened structures have been observed in Zn azadipyrrins
(63-39°)22 and Zn R-methoxydipyrrin (54.7°).23 Also noteworthy
is the quite significant ruffling of the dipyrrin ligands, which
resembles distortions of some nonplanar porphyrins.24
Notably, the computed structure [DFT/B3LYP/6-31G(d)] of
homoleptic Zn-2e (Figure 2c) was also found to be nonorthogonal,
although the angle between the mean-square planes was somewhat
larger (77°). This suggests that the distortion from the orthogonal
geometry is not induced by the crystal packing forces but is an
intrinsic property of the ML2 molecule, which is flattened because
of the propensity of the ligand π systems to align in coplanar
fashion.22 The nonorthogonal geometry may also facilitate interac-
tions between the metal and the proximate carbonyl oxygens, which
have been identified in some other homoleptic dipyrrin
complexes.19b Although the Zn-O distances in Zn-2e are quite
large (dZn-O ) 2.8-2.9 Å vs dZn-N ) 2.0 Å), the carbonyl groups
still could be implicated in the overall ligand-metal bond stabiliza-
tion.19
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Johansson, L. B. A. J. Am. Chem. Soc. 2002, 124, 196. (b) Tleugabulova,
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Guilard, R., Eds.; Academic Press: New York, 2000; Chapter 6.
In conclusion, the developed method of synthesis of fluorogenic
π-extended dipyrrins allows tuning of their optical bands across
the red/near-IR optical spectrum. Metal complexes of π-extended
metallodipyrrins are strongly fluorescent, and their fluorescence can
be switched on and off by changing the mode of metal coordination.
The molecular exciton theory9 provides a new insight into the
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