Profluorescent verdazyl radicals - synthesis and characterization

Article abstract of DOI:10.1039/c5sc00724k

The synthesis and characterization of various 6-oxo-verdazyl radicals and their diamagnetic styryl radical trapping products are presented. It is shown that styryl radical trapping products derived from N-phenyl verdazyls show fluorescence whereas the N-m

Full text of DOI:10.1039/c5sc00724k

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Profluorescent verdazyl radicals – synthesis and
characterization†
Cite this: DOI: 10.1039/c5sc00724k
a
a
b
David Matuschek, Steffen Eusterwiemann, Linda Stegemann,
c
a
a
d
Carsten Doerenkamp, Birgit Wibbeling, Constantin G. Daniliuc, Nikos L. Doltsinis,*
Cristian A. Strassert,* Hellmut Eckert* and Armido Studer*a
b
ce
The synthesis and characterization of various 6-oxo-verdazyl radicals and their diamagnetic styryl radical
trapping products are presented. It is shown that styryl radical trapping products derived from N-phenyl
verdazyls show fluorescence whereas the N-methyl congeners are non-fluorescent. In the parent
N-phenyl verdazyls fluorescence is fully quenched which renders these compounds highly valuable
profluorescent radical probes.
Received 27th February 2015
Accepted 26th May 2015
DOI: 10.1039/c5sc00724k
www.rsc.org/chemicalscience
6
-Oxo-verdazyl radicals have been widely used as building diphenylcarbonohydrazide (Table 1, for details, see ESI†).
1
blocks for construction of magnetic materials; however, there Radical precursor tetrazinan-3(2H)-ones 1–7 were obtained in
is no report on their application as prouorescent persistent moderate to good yields by acetalization of different aromatic
radicals to be applied as radical probes. Along these lines, aldehydes with 2,4-diphenylcarbonohydrazide. Oxidation with
nitroxyl radicals conjugated with a uorophore have been 1,4-benzoquinone afforded the verdazyl radicals 8–12. In case of
successfully used as prouorescent probes for detection of the anthracenyl-derivative 11, oxidation was carried out without
2
transient radicals. Whereas the nitroxide moiety in these prior isolation of the acetal. In contrast to the established ver-
5,6
conjugates fully quenches uorescence of the chromophore, dazyl syntheses of Barbier and Milcent et al., the applied
nitroxide trapping of a transient C-radical leads to the corre- method allows readily varying the C3-substituent of the
sponding closed shell alkoxyamine thereby restoring uores- 1,5-diphenyl-6-oxo-verdazyl radicals. The bisverdazyls 13, 14
cence. This interesting property allows such prouorescent and the trisverdazyl 15 were prepared in analogy starting with
nitroxides to be used for radical detection. Transient radical the corresponding bis and trisaldehydes, respectively. These
intermediates play important roles in environmental chemistry, bis- and tris-radicals are planar structures with up to 7 aromatic
3
biological chemistry, polymer chemistry and organic synthesis.
moieties, which exert strong p–p interactions. It is therefore not
Therefore, development of methods for radical detection is of surprising that these interactions strongly reduce solubility of
importance. Herein we present the synthesis of a series of novel these radicals.
7
verdazyl radicals and discuss their application as prouorescent
By using the atom transfer coupling reaction with styryl
bromide as a C-radical precursor, the diamagnetic tetrazin-3-
persistent radicals for detection of C-centred radicals (Fig. 1).
The 1,5-diphenyl-6-oxo-verdazyl radicals 8–15 were prepared ones 16–23 were obtained in good to excellent yields (Table 1).
4
using a modied literature procedure starting with 2,4-
The well soluble 1,5-diphenyl-6-oxo-verdazyl monoradicals
8–12 were analysed by UV/Vis spectroscopy (see ESI, Fig. S2 and
S3†). Verdazyls 8–12 were also investigated by solution phase
EPR spectroscopy (ESI, Fig. S1†) and the naphthyl 10 and
anthracenyl radical 11 were further characterized by X-ray
structure analysis (Fig. 2).
a
Institute of Organic Chemistry, Westf a¨ lische Wilhelms-Universit a¨ t M u¨ nster,
Corrensstrasse 40, 48149 M u¨ nster, Germany. E-mail: studer@uni-muenster.de; Tel:
+
b
49 (0)251-83-33291
Institute of Physics and Center for Nanotechnology, Westf a¨ lische Wilhelms-Universit a¨ t
M u¨ nster, Heisenbergstrasse 11, 48149 M u¨ nster, Germany. E-mail: ca.s@uni-muenster.
de
c
Institut f u¨ r Physikalische Chemie, Westf a¨ lische Wilhelms-Universit a¨ t M u¨ nster,
Corrensstrasse 28/30, 48149 M u¨ nster, Germany. E-mail: eckerth@uni-muenster.de
d
Institut f u¨ r Festk ¨o rpertheorie and Center for Multiscale Theory & Computation,
Westf a¨ lische Wilhelms-Universit a¨ t M u¨ nster, Wilhelm-Klemm-Straße 10, 48149
M u¨ nster, Germany. E-mail: nikos.doltsinis@uni-muenster.de
e
Instituto da F ´ı sica em Sao Carlos, Universidade de Sao Paulo, Avenida Trabalhador
Saocarlense 400, Sao Carlos, SP 13590, Brazil
†
Electronic supplementary information (ESI) available. CCDC 1051008–1051011.
For ESI and crystallographic data in CIF or other electronic format see DOI:
0.1039/c5sc00724k
Fig. 1 Profluorescent verdazyls as radical probes.
1
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Table 1 Synthesis of various verdazyl radicals and the corresponding
styryl radical trapping products (yields for the individual steps in
a
brackets)
1
2
(91%)
(32%)
8 (62%)
9 (62%)
16 (72%)
17 (52%)
3
(63%)
10 (98%)
11 (30%)
18 (82%)
19 (61%)
—
4
(69%)
12 (96%)
20 (93%)
5
6
7
(69%)
(81%)
(48%)
13 (88%)
14 (66%)
15 (68%)
21 (60%)
22 (68%)
23 (63%)
Fig. 2 X-ray structure of 10 (top) and 11 (bottom) (thermals ellipsoids
are shown with 30% probability).
a
ꢀ
Conditions: (a) 2,4-diphenylcarbonohydrazide (1.0 equiv.), 80 C, 3–6 characteristic UV-band can be taken as a measure for the
ꢀ
h; (b) 1,4-benzoquinone (1.5 equiv. – excess), DCM, 60 C, 3 h; (c)
conjugation of the R-substituent with the verdazyl heteroarene.
This view is further corroborated by our DFT calculations in
the gas phase. They conrm that 11 has a larger torsion angle
II
(
(
1-bromoethyl)-benzene (1.1 equiv.), Cu OTf
4 mol%), benzene, 80 C, 24 h.
2
(2 mol%), BBBPY
ꢀ
ꢀ
ꢀ
(64 ) than 10 (44 ) and indeed predict a red-shied absorption
band of 10 at 524 nm. The same argument explains why the
In the UV/Vis spectra of these radicals we noted a charac- absorption spectrum of 9, which also exhibits a pronounced
ꢀ
teristic UV band at 494–559 nm which is strongly inuenced by torsion angle of 62 , is in a similar region as that of 11. At the
ꢀ
the R-substituent of the verdazyl radicals (8 (R ¼ Ph): 559 nm; 9 other extreme, the torsion angle of 8 is computed to be 9 in
8
(
(
R ¼ mesityl): 506 nm; 10 (R ¼ 1-naphthyl): 528 nm; 11 agreement with the X-ray structure and its theoretical absorp-
R ¼ anthracenyl): 494 nm; 12 (R ¼ pyrenyl): 510 nm). By tion is red-shied relative to 11 by 58 nm, close to the experi-
looking at the X-ray structure of 11, we noted the bulky mental shi of 65 nm.
anthracenyl moiety to lie with a torsion angle of 87.9(5) nearly
ꢀ
EPR spectra of the 1 mM solutions of 8–12 in degassed
orthogonal with respect to the verdazylheteroarene plane dichloromethane showed the typical lineshapes (quintets of
(
Fig. 2). However, in the naphthyl congener 10, the torsion angle quintets) dominated by the isotropic hyperne coupling with
ꢀ
was only 47.2(2) which allows for better conjugation of the two distinct sets of two nitrogen atoms, consistent with data
R-arene-substituent with the heteroarene of the verdazyl. This reported in the literature on other types of verdazyl radicals.
8–10
conjugation leads to a red shi of the given UV band. In fact, the The spectroscopy of the di- and tri-radicals was restricted by
8
reported X-ray structure of the phenyl verdazyl 8 showed a severe solubility limitations, however, this problem could be
ꢀ
small torsion angle (12.3 ) which is well reected by the red overcome by examining p-alkoxy-substituted analogues. Fig. 3
shied UV-absorbance (559 nm). Hence the shi of the shows a typical result obtained on 1,3-bis(1,5-di-(4-octyloxy)
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Fig. 3 EPR spectrum of 1,3-bis(1,5-di-(4-octyloxy)phenyl-6-oxo-3-
verdazyl)benzene (black)(14) and simulation (red).
Fig. 4 Visualization and energies of the HOMOs and LUMOs of 16, 18,
and 20 calculated with the PBE0 functional and the 6-31G* basis set at
the optimized ground state geometry.
phenyl-6-oxo-3-verdazyl)benzene 14* including the simulation.
Table 2 gives a summary of all the Aiso values obtained.
For the naphthyl 18 and anthracenyl derivate 19, the struc-
ture was further characterized by X-ray analysis (for structures,
see ESI, Fig. S35 and S36†). As for the verdazyl radicals, the
anthracenyl moiety in tetrazin-3-one 19 has a far larger torsion
effective conjugation with the heteroarene. Nonetheless,
between 17 and 19, a clear trend can be observed regarding
bathochromic absorption shis and increasing delocalization.
In all cases, however, the vertical S –S transitions can be
ꢀ
angle with respect to the heterocycle (torsion angle ¼ ꢁ67.4 )
0
1
ꢀ
assigned to nearly pure HOMO–LUMO excitations, as indicated
by our TD-DFT calculations. In fact, the LUMO is mainly centred
on the aromatic moiety and appears increasingly stabilized with
the degree of delocalization. This trend is illustrated in Fig. 4,
which compares the shapes and energies of the LUMOs of
compounds 16, 18, and 20 (the LUMOs of all compounds 16–23
are compared in Fig. S29 of the ESI†). On the other hand, the
HOMO is mainly associated to the heterocycle, with minor
contributions from the arene substituents in the cases of 19 and
20. The latter possess a larger intrinsic p–p conjugation on the
arene moiety that originates a signicant admixture of the
occupied arene-centred orbitals with the heteroarene-centred
HOMO. Fig. 4 shows for the examples 16, 18, and 20 how the
delocalization of the HOMO onto the arene substituent
becomes more pronounced with increasing size of the arene.
However, it can also be seen that this goes hand in hand with a
withdrawal of electron density from the phenyl rings explaining
the fact that the HOMO energy remains practically unchanged.
In the series comprising compounds 16 and 21–23, a maxi-
mized delocalization can be observed for the para-substitution
than the naphthyl substituent (17.0 ). This is conrmed by our
theoretical optimized gas phase structures, which exhibit
ꢀ
ꢀ
torsion angles of ꢁ64 and 27 , respectively. A detailed
comparison of X-ray and theoretical geometries can be found in
the ESI (Table S2†).
In contrast to the structures of the parent verdazyl radicals 10
and 11, where the heteroarene has a nearly planar structure due
to the delocalization of the spin, the crystal structures of 18 and
1
9 reveal distortion of the tetrazin-3-one core moiety. Theoret-
ꢀ
ical CNNC dihedral angles in the heterocycle range from 30 to
ꢀ
45 and show an asymmetry within the ring (see ESI, Table S2†
for more details).
The well soluble, diamagnetic tetrazin-3-ones 16–25 were
analysed by UV/Vis, steady-state and time-resolved uorescence
spectroscopy, the corresponding UV/Vis absorption spectra are
given in the ESI (Fig. S4†). With increasing delocalization of the
substituent (compounds 16, 18 and 20), a red-shi of the
absorption maxima can be observed (Fig. S4†). Interestingly,
compounds 17 and 19 signicantly deviate from this trend,
which goes along with their larger torsion angles that hinder an
Table 2 Summary of the Aiso values (in Gauss) and g-values for radicals 8–12 and 14. Asterisks denote measurements on the p-alkoxy derivatives
of 8 and 14
Sample
A(N-1,5)
A(N-2,4)
g-value
8
9
1
1
1
1
*
1,5-Di-(4-methoxy)phenyl-3-phenyl-6-oxo-verdazyl*
4.866
4.634
4.632
4.691
4.689
3.858
6.198
6.510
6.479
6.441
6.434
4.930
2.00391
2.00399
2.00397
2.00403
2.00382
2.00375
1,5-Diphenyl-3-mesityl-6-oxo-verdazyl
0
0
0
0
1
2
4*
1,5-Diphenyl-3-(1 -naphthyl)-6-oxo-verdazyl
1,5-Diphenyl-3-(9 -anthracenyl)-6-oxo-verdazyl
1,5-Diphenyl-3-(1 -pyrenyl)-6-oxo-verdazyl
1,3-Bis(1,5-di-(4-octyloxy)phenyl-6-oxo-3-verdazyl)benzene
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Table 3 Experimental and theoretical photophysical data of 16–25.
The theoretical data were calculated at the PBE0/6-31G* level
including the effect of the acetonitrile solvent at the PCM level. The
emission wavelengths of 16 and 19 were obtained by averaging over 10
configurations sampled randomly from an MD simulation in the S
state. Quantum yields (F ) were obtained by comparative method with
quinine sulfate in 0.5 M H
1
fl
11
SO
2 4
(0.564) as a reference
a
l
Abs
l
Abs,calc
l
Em
l
Em,calc
s
f

r
k /knr
(10 s )
5
ꢁ1
(nm) (nm)
(nm) (nm)
(ns)
(%)
1
1
1
1
2
2
2
2
2
2
2
6
7
8
9
0
1
2
3
4
332
305
336
394
368
368
338
348
253
339
332
366
405
407
396
361
371
397
435
484
441
515
503
470
482
—
438
459
493
449
528
531
483
493
1.43 0.27
2.80 0.03
0.88 1.29
0.87 0.39
0.62 1.88
2.80 5.96
0.90 1.21
1.94 1.84
19/6974
1/3570
147/11 217
45/11 449
303/15 826
213/3359
134/10 977
95/5060
—
—
—
4* 254
258
—
485
—
—
—
—
5
1.12 <0.01
a
Amplitude-averaged lifetime.
pattern (21), which favors the most effective p-delocalization,
compared to the meta-substitution pattern (22). Introduction of
0
a further heteroarene unit on the meta -position (23) enhances
delocalization and bathochromic shis, but without reaching
the effective conjugation attained for 21.
In contrast to the verdazyl radicals, all tetrazin-3-ones 16–25
display a measurable uorescence. TD-DFT excited state
geometry optimizations indicate that the radical species
possess easily accessible conical intersections between the S
and the S states, leading to a fast radiationless deactivation.
1
0
For compounds 16, 18 and 20, the uorescence emission
maxima follow the same trends as described for their absorp-
tion spectra (vide supra), and the observed radiative rate
constants are enhanced along with the p–p delocalization.
Compounds 17 and 19, which display comparable emission
maxima despite the quite different intrinsic p–p delocalization
of their arene substituents, do not follow these trends. This can
be explained by their larger coplanar torsion angles that hinder
an effective conjugation with the heteroarene. The rotational
freedom of the phenyl moiety on compound 16 explains its high
radiationless rate constant, as opposed to 17 for which the
sterical hindrance of the methyl groups impose a xed orthog-
onal conformation between the heterocycle and the substituent.
The broad emission of compound 19 is due to numerous
1
dynamically accessible conformations in the excited S state, as
revealed our by ab initio molecular dynamics simulations (ESI,
Section 5†). The emission shoulder at 660 nm, in particular,
provides evidence that conformations with a small HOMO–
Fig. 5 Normalized emission spectra in acetonitrile at room temper-
ature ((a): 16–20; (b): 16–25) and at 77 K in a frozen glassy matrix of
butyronitrile ((c): 16–24*; (d): 16–25).
LUMO gap are visited in the S
of energetically accessible pathways for radiationless decay via a
conical intersection, which is conrmed by its relatively high nicely correlates with the increasing p–p delocalization.
non-radiative deactivation rate constant knr (see Table 3). However, compound 16 exhibits a similar red-shi as 18,
1
state. This suggests the existence
A further corroboration for this model is provided by the 77 K despite the different degree of p–p delocalization on its
measurements, showing a bathochromic shi from 17–20 that substituent, most likely due to the lack of rotational constraints
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radicals are uorescent. This prouorescent behavior renders
these verdazyl valuable spin probes. We also found that the N-
phenyl substituents at the tetrazin-3-one moieties are of key
importance to obtain uorescence.
Acknowledgements
Financial support for this project was provided by the Deutsche
Forschungsgemeinscha (SFB 858 and TRR61).
Fig. 6 N-Methyl tetrazin-3-ones 24, 24* and 25.
Notes and references
1
B. D. Koivisto and R. G. Hicks, Coord. Chem. Rev., 2005, 249,
2612–2630.
that, in turn, enable a signicant coplanarization of the phenyl
unit with the heteroarene. Indeed, compound 17, which bears
two methyl groups that x an orthogonal conformation between
the arene and heteroarene rings, appears blue-shied as
compared to 16 and 18.
Finally, we looked at the effect of the N-phenyl substituents
in the tetrazin-3-ones on their uorescence behavior. For this
purpose, 24, 24* and 25, which are analogues of 16 and 23,
respectively, in which all N-phenyl groups have been replaced by
N-methyl substituents, were successfully prepared (Fig. 6). To
our surprise, neither 24 nor 24* showed any uorescence at
room temperature, clearly documenting the key importance of
the N-phenyl groups on the uorescence properties of these
tetrazin-3-ones. Compound 25, on the other hand, only dis-
played a weak, non-quantiable luminescence. The calculated
oscillator strength of compound 24 is indeed signicantly
2 J. P. Blinco, K. E. Fairfull-Smith, B. J. Morrow and S. E. Bottle,
Aust. J. Chem., 2011, 64, 373–389.
3 C. Chatgilialoglu and A. Studer, Encyclopedia of Radicals in
Chemistry, Biology and Materials, John Wiley and Sons,
Chichester, 2012.
4 Y. Masuda, M. Kuratsu, S. Suzuki, M. Kozaki, D. Shiomi,
K. Sato, T. Takui and K. Okada, Polyhedron, 2009, 28, 1950–
1954.
5 R. Milcent, G. Barbier, F. Mazouz and K. Ben Aziza, France
Pat., WO/1989/004309, 1989.
6 R. Milcent, G. Barbier, S. Capelle and J.-P. Catteau, J.
Heterocycl. Chem., 1994, 31, 319–324.
7 K. Matyjaszewski, B. E. Woodworth, X. Zhang, S. G. Gaynor
and Z. Metzner, Macromolecules, 1998, 31, 5955–5957, For
further C-N coupling methods on verdazyl radicals, see:
E. K. Y. Chen, S. J. Teertstra, D. Chan-Seng, P. O. Otieno,
R. G. Hicks and M. K. Georges, Macromolecules, 2007, 40,
8609–8616; A. Yang, T. Kasahara, E. K. Y. Chen,
G. K. Hamer and M. K. Georges, Eur. J. Org. Chem., 2008,
4571–4574; C. W. Johnston, T. R. Schwantje,
M. J. Ferguson, R. McDonald and R. G. Hicks, Chem.
Commun., 2014, 50, 12542–12544.
8 F. A. Neugebauer, H. Fischer and C. Krieger, J. Chem. Soc.,
Perkin Trans. 1, 1993, 2, 535–544.
9 M. Chahma, K. Macnamara, A. Van der Est, A. Alberola,
V. Polo and M. Pilkington, New J. Chem., 2007, 31, 1973–
1978.
1 0 1
smaller than that of 16. The S –S energy gap at the S minimum
is smaller for 24 than for 16, in line with the red-shi observed
in the emission spectrum of 24 relative to 16 at 77 K (see Fig. 5c),
also increasing the probability for nonradiative deactivation.
In summary, we have presented an efficient synthesis for the
preparation of various 1,5-diphenyl-6-oxo-verdazyl radicals. The
method was also applied to the synthesis of bis- and tris-ver-
dazyl radical systems. Verdazyls were characterized by UV/VIS
and EPR spectroscopy. Analysis of the X-ray structure of two
verdazyls allowed understanding the blue shi of the major UV
band as a function of the C3-verdazyl substituent in the radi-
cals. Importantly, we found that the verdazyl radicals do not
have any uorescence properties, which could be ascribed by 10 J. B. Gilroy, S. D. J. McKinnon, P. Kennepohl, M. S. Zsombor,
TD-DFT calculations to the presence of S –S conical intersec-
tions. However, the corresponding diamagnetic tetrazin-3-ones,
M. J. Ferguson, L. K. Thompson and R. G. Hicks, J. Org.
Chem., 2007, 72, 8062–8069.
1
0
readily obtained upon reacting the verdazyls with C-centred 11 A. M. Brouwer, Pure Appl. Chem., 2011, 83, 2213–2228.
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