Photoinduced Electron Transfer (PET)-Mediated Fragmentation of Picolinium-Derived Redox Probes

Article abstract of DOI:10.1002/chem.201801684

The photolysis of covalently linked N-alkyl picolinium phenylacetate—carbazole dyads was analyzed experimentally and by using density functional theory (DFT) and time dependent-DFT (TD-DFT) calculations. In contrast to earlier observations efficient one and two-photon fragmentations conditions were found for 15 c (δ_u=0.16 GM at 730 nm) opening the way for the design of a novel class of “caged” compounds.

Full text of DOI:10.1002/chem.201801684

A Journal of
Accepted Article
Title: Photoinduced Electron-Transfer (PET) Mediated Fragmentation
of Picolinium-Derived Redox Probes
Authors: Petra Dunkel, Anna Barosi, Hamid Dhimane, Francois Maurel,
and Peter I. Dalko
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To be cited as: Chem. Eur. J. 10.1002/chem.201801684
Link to VoR: http://dx.doi.org/10.1002/chem.201801684
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Photoinduced Electron-Transfer (PET) Mediated Fragmentation of
Picolinium-Derived Redox Probes
Petra Dunkel,[a][b] Anna Barosi,[a][b] Hamid Dhimane,[a] François Maurel,*[c] and Peter I. Dalko*[a]
Abstract: The photolysis of covalently linked N-alkyl picolinium
phenylacetate — carbazole dyads was analyzed experimentally and
by using density functional theory (DFT) and time dependent-DFT
(TD-DFT) calculations. In contrast to earlier observations efficient
one and two-photon fragmentations conditions were found for 15c
(δu = 0.16 GM at 730 nm) opening the way for the design of a novel
class of “caged” compounds.
photolysis experiments, neither significant fluorescence was
observed, authors suggested that the competing back electron
transfer was the main deactivation path that occurred faster than
the bond cleavage.9 Also, a fluorene-sensitized picolinium
derivative sensitive to two-photon activation has been prepared
by the Anderson group.13,14 The construct suffered, however,
hydrolytic instability and low uncaging efficiency, presumably
due to the fast back electron transfer, as was hypothesized in
the earlier experiment.
In the wake of our program on the development of light-
sensitive probes,15 we were interested in examining the
perspectives and pertinence of picolinium derivatives as redox-
sensitive elements in covalently linked electron donor-acceptor
dyads under PET conditions. Here we wish to disclose a first
systematic study on the NAP platform.
Introduction
Light-sensitive probes (“caged compounds”) became popular
tools in cellular biology, physiology and neurosciences and are
used for the controlled release of a variety of biologically
relevant substrates.1 Although sensitized probes, in which the
light-harvesting and working elements are functionally
disconnected, allow considerably larger flexibility in the
optimization process, somewhat surprisingly only modest
interest has been paid for the development of such probes.2
Redox-gated systems are among those, developed essentially
around the 4-picolyl family.3 The reduction potentials of the
parent phenacyl (Ered = –2.20 V vs SCE) and 4-picolyl esters
(Ered = –2.62 V vs SCE) were improved by N-alkylation of the
heterocycle (N-methyl-4-picolinium: Ered = –1.10 V vs SCE), and
also by adding electron-withdrawing groups to the pyridinium
ring (2-cyano-picolinium esters Ered ≈ –0.50 V vs SCE).4 In
parallel, N-alkylpicolinium (NAP)+ mediator systems with
Results and Discussion
N-Methyl picolinium phenylacetates 7, 9 and 11 (Scheme 1, path
A) were prepared by reduction of the corresponding pyridine
carboxaldehydes followed by acylation using phenylacetyl
chloride, and N-methylation of the resulting picolines
(compounds 1, 3 and 5) in the presence of methyl triflate (for
further details see the Experimental section). In turn, compounds
8, 10 and 12 were prepared by addition of methylmagnesium
bromide to the corresponding aldehydes followed by acylation,
using phenylacetyl chloride and quaternarization in the presence
of methyl triflate (Scheme 1, path B).
ketocoumarin
dyes,5
gold
nanoparticles6
and
tris(bipyridyl)ruthenium(II) (Ru(bpy)) dyes4 were developed for
the liberation of carboxylic acids, amino acids, phosphates,
primary aliphatic and aromatic amines, under redox conditions.7
Liu et al. described a release system composed by an electron
donor, typically L-cysteine or DTT, a semiconductor quantum dot
electron shuttle and NAP ester prodrug as acceptor.8 Most of the
biological applications require water-soluble probes with
controlled, covalently linked donor-acceptor structure, however.
Surprisingly the use of the tethered N-alkyl picolinium
phenylacetate - carbazole dyad turned inefficient. 9,10,11 Although
the unlinked analogues released the carboxylate ligands, in the
presence of an appropriate sensitizer with high efficiency, the
tethered probe was inert even under prolonged irradiation.9,12 As
no charge-transfer intermediates were detected in laser flash
H
H
O
O
1) NaBH4
MeOH
Ph
Ph
MeOTf
O
O
N
2) PhCH2COCl
N
OTf
DCM
Me
A
1 C(4)
3 C(3)
5 C(2)
7 C(4)
9 C(3)
11 C(2)
4
CHO
3
2
N
Me
Me
N
O
O
1) MeMgBr
THF
B
Ph
Ph
MeOTf
DCM
O
O
2) PhCH2COCl
N
OTf
Me
2 C(4)
4 C(3)
6 C(2)
8 C(4)
10 C(3)
12 C(2)
[a]
Dr P. Dunkel, Dr A. Barosi, Pr Dr H. Dhimane, Dr P. I. Dalko
Université Paris Descartes, Laboratoire de Chimie et Biochimie
Scheme 1. Synthesis of N-methyl picolinium phenylacetates 7-12.
Pharmacologiques
et
Toxicologiques,
UMR8601
45, rue des Saints-Pères, 75270, Paris Cedex 06, France
E-mail: peter.dalko@parisdescartes.fr
Dr P. Dunkel and Dr A. Barosi contributed equally to this work.
Pr Dr F. Maurel
Université Paris Diderot, Sorbonne Paris Cité, ITODYS,
UMR CNRS 7086, 15 rue J-A de Baïf, 75013, Paris, France
E-mail: maurel@univ-paris-diderot.fr
Redox potentials of the prepared phenylacetates were
measured by cyclic voltammetry (Figure 1). Electrochemical
experiments were performed at c = 1.0 mM concentration of the
picoliniums, in dry ACN with [Bu4N][PF6] as the supporting
electrolyte (scan rate: 100 mV/s). Glassy carbon working and
platinum auxiliary electrodes were used and the potential was
[b]
[c]
Supporting information for this article is given via a link at the end of
the document.
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measured relative to ferrocene / ferrocenium reference. Cyclic
voltammograms (see SI) showed irreversible redox processes
for all six substrates, 7-12. The first reduction potential was
4.43 eV.18 Experimental values were compared in Figure 1.
Noteworthy, calculated values correlate well with the
experimental data (Figure 1).
observed between Ered = −1.09 V and Ered = −1.37 V, with Ered
=
The UV–Vis spectra of 7 (c = 0.1 mM) did not show
appreciable solvatochromism as was deduced by comparing
spectra in dichloromethane, acetonitrile, methanol and in a
mixture of acetonitrile / TRIS buffer (1 / 1) solution at 293 K (see
SI-Figure 1). Absorption spectra of compounds 7-12 in
acetonitrile / TRIS buffer (1 / 1) showed maxima around 257-264
nm with a shoulder corresponding to a π-π* transition and a very
weak absorbance above 300 nm. Upon irradiation at 255 nm,
−1.11 V for 7 which is very close to the reported Ered = −1.08 V
value measured for the corresponding perchlorate salt.3
Compounds 7, 8 and 11, 12 (i.e. the C(2) and C(4) regioisomers)
showed invariably smaller reduction potential than C(3)
derivatives, 9 and 10. The nature of the side-chains i.e. primary
vs secondary esters affected only marginally the reduction
potentials.
the solution of compounds 7-12 exhibited
photoluminescence (PL) with a single peak at the 259 - 266 nm
region, respectively (Table 1).
a
blue
O
R
R
Ph
O
O
Ph
R
O
O
N
OTf
Me
O
N
N
OTf
Ph
OTf
Me
Table 1. Photophysical properties of compounds 7-12.
Me
11 R=H
12
-1.09 V (-1.03 V)
R=CH3 -1.15 V (-1.12 V)
9 R=H
10 R=CH3 -1.37 V (-1.24 V)
-1.35 V (-1.18 V)
7 R=H
-1.11 V (-1.14 V)
max
max
λabs
εmax
λem
Stokes shift
Qu
8
R=CH3 -1.14 V (-1.14 V)
(nm)[a]
257
257
263
263
264
264
(M−1cm−1
)
(nm)
260
259
265
266
266
266
(103cm−1
)
(%)b
a
Figure 1. Experimental and calculated (in parenthesis) reduction potentials of
7
4250
4200
4300
4500
6650
5450
0.45
0.36
0.45
nd
N-methyl picolinium phenylacetates.
8
0.30
9
0.30
The ET ability of compounds 7-12 was analysed by DFT
calculations as well.16,17 Redox potentials were calculated at the
most stable conformations according to the thermodynamic
cycle depicted in Scheme 2.
10
11
12
0.40
nd
0.30
0.21
0.25
0.30
ΔGgas
redox
M+ (g)
M (g)
[a] Stokes shift = 1/λabs – 1/λem. [b] See SI for details.
ΔGACN (M+)
ΔGACN (M)
Among various sensitizers, 9-methylcarbazole (9-MC) was
selected for the PET study. 9-MC is a well characterized
ΔGACN
redox
chromophore, with a relatively high wavelength absorption
M+ (ACN)
M (ACN)
max
maximum (λabs
= 345 nm) and it is a strong reducing agent at
the excited state with an Eox* = –2.51 V vs SCE.19 Tethered
dyads 14-19 were prepared from picolyl phenylacetic esters 1-6,
by using carbazoles 13a-c, having propyl-, hexyl-, or, dodecyl
triflate side chains, respectively (Scheme 3). Similar to the non-
tethered analogues, no appreciable solvatochromic effect was
found for 14a in dichloromethane, acetonitrile, methanol and in a
mixture of ACN / TRIS buffer (1 / 1) solution, at a concentration
of c = 0.1 mM at 293 K between 250 – 500 nm (SI-Figure 3). UV
spectra of 14–19 were recorded in ACN / TRIS buffer 1 / 1 (SI-
Figures 4-9). All spectra appeared qualitatively similar, showing
essentially the strong absorption of the tethered carbazole due
to the larger molar extinction coefficient in the 300 – 450 nm
Scheme 2. The thermodynamic cycle of the one-electron reduction of
picolinium probes in acetonitrile (ACN) solution.
The standard Gibbs free energy of the overall reaction in
solution can be expressed as follows:
!"#
Δꢀ
= Δꢀ!!""##$% − Δꢀ!"# ꢀ! + Δꢀ!"#
ꢀ
!"#$%
!"#
Δꢀ
= Δꢀ!"# + ΔΔꢀ!"#
!"#$%
!"#$%
where
and
!"#
!"#$%
Δꢀ
= ꢀ!"# ꢀ − ꢀ!"#(ꢀ!)
region compared to picoliniums. First absorption maxima located
max
around λabs
= 341 – 346 nm with molar extinction at the
absorption maxima between εmax = 2250 and 3600 M-1cm-1 (SI-
Figures 4-9). Differences were observed, however, in the UV
absorption spectra between regioisomers and compounds
having different spacer lengths. Longer spacers resulted
ΔΔꢀ!"# = Δꢀ!"# ꢀ − Δꢀ!"# ꢀ!
!"#
and the redox potential is related to Δꢀ
as
!"#$%
!"#
= −ꢀꢀ!°"#$%
invariably in bathochromic shifts: 14a–19a having propyl spacer
Δꢀ
!"#$%
max
(n = 3) were slightly blue-shifted (λabs
= 341 and 342 nm)
where F is the Faraday constant, 23.06 kcal·mol-1·V-1. The
standard hydrogen electrode potential, VSHE was taken as
compared to the free 9-MC, while for 14c–19c (n=12) maxima
were slightly red-shifted (λabsmax = 346 nm) respectively (Table 2).
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Noteworthy, propyl tethered analogs 14a–17a showed a broad
weak absorption shoulder between 350 and 410 nm (C(3) and
C(4) isomers).
The low-lying LUMOs of 7–12 suggest that photoactivated
N-methyl carbazole may easily reduce these substrates.20
Noteworthy, the energy of the charge-transfer (CT) states of N-
methyl picoliniums, and also dyads, were estimated beneath of
the lowest optically strongest allowed excited states.
The fragmentation of compounds 7-12 was studied in the
absence and in the presence of 9-MC sensitizer, as well as for
the tethered analogs 14-19 in TRIS / ACN (1 / 1) mixture under
modified Falvey’s conditions at 366 nm, using a 8 W Carl Roth
lamp (Scheme 4; for details see Experimental part). Esters 7-12
having only very weak transitions at 366 nm showed no
fragmentation upon photolysis under prolonged irradiation (2 h),
thus compounds 7-12 can be considered as photochemically
inert under the examined conditions. The sensitized PET study
of 7-12 was performed in the presence of a stoichiometric
amount of 9-MC in TRIS / ACN (1 / 1) mixture at c = 0.1 mM,
and the kinetic course of the photolysis is depicted in Figure 2.
Noteworthy, efficient fragmentation was observed for all C(2)
and C(4) isomers respectively (7, 8, 11 and 12), C(3) derivatives
were inert in the presence, or, absence of 9-MC.
R
N
R
O
O
Ph
4
Ph
n
3
2
OTf
O
O
N
N
OTf
n
N
13a n = 3
b n = 6
c n = 12
1 C(4) R = H
2 C(4) R = Me
3 C(3) R = H
4 C(3) R = Me
5 C(2) R = H
6 C(2) R = Me
14 C(4) R = H; a n = 3; b n = 6; c n = 12
15 C(4) R = Me; a n = 3; b n = 6; c n = 12
16 C(3) R = H; a n = 3; b n = 6; c n = 12
17 C(3) R = Me; a n = 3; b n = 6; c n = 12
18 C(2) R = H; a n = 3; b n = 6; c n = 12
19 C(2) R = Me; a n = 3; b n = 6; c n = 12
Scheme 3. Synthesis of tethered picoline phenylacetate-carbazole dyads 14-19.
Table 2. Photophysical properties of compounds 14-19.
The time course of the PET reaction was followed by HPLC
and the consumption of the starting materials against the time is
plotted in SI-Figures 18 and 19.
max
max
λabs
εmax
λem
Stokes shift
Qu
a
(nm)
342
345
346
342
345
346
342
345
346
342
345
346
342
345
346
341
345
346
(M−1cm−1
)
(nm)
354
354
350
354
354
350
354
354
351
354
354
351
354
354
352
354
354
352
(cm−1
1.00
0.75
0.35
1.00
0.75
0.35
1.00
0.75
0.40
1.00
0.75
0.40
1.00
0.75
0.50
1.10
0.75
0.50
)
(%)b
N
R
R
Me
O
OH
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
17c
18a
18b
18c
19a
19b
19c
3300
2950
2450
2600
2600
2300
3200
3150
2900
3550
2850
2900
3600
3050
2850
3050
2750
2700
0.02
0.11
0.91
0.06
0.12
2.06
nd
4
4
Ph
365 nm
3
2
3
2
HO
Ph
O
+
O
N
N
H2O / ACN 1 / 1
pH = 7.4
Me
Me
OTf
OTf
7 C(4) R = H
8 C(4) R = Me
11 C(2) R = H
12 C(2) R = Me
Scheme 4. Photolysis of picoline phenylacetates 7, 8 and 11, 12 in the
presence of N-methylcarbazole sensitizer.
nd
nd
nd
nd
nd
0.01
0.07
0.46
0.12
0.06
0.69
Figure 2: Relative time course of the photolysis of compounds 7, 8 and 11, 12
in the presence of 1 equivalent of 9-MC sensitizer at 366 nm as determined by
HPLC.
[a] Stokes shift = 1/λabs – 1/λem. [b] See SI for details.
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Monitoring the photolysis of esters 7 and 8 by 1H NMR
confirmed the release of phenylacetic acid and the formation of
the corresponding picolyl alcohols as major products (Table 3;
for details see Experimental part). The photolysis was run in a
mixture of CD3CN / D2O (4 / 1), and the conversion of the
reaction was analysed after 2 h irradiation at 254 nm. Although
the formation of the phenylacetic acid was observed in 89% (±
5%) and 86% (± 5%) yields (not isolated) at 75% and 59%
conversions, respectively, important photobleaching of the
picolinium was showed also as merely 36% and 46% (± 5%) of
the expected hydroxymethylene derivatives were found at the
same conversions. Noteworthy, no trace of decarboxylated
product was observed within the detection limit. This observation
is in agreement with the mechanistic rational proposed by
Falvey et al. (Scheme 5) that suggests heterolytic rather than
homolytic bond cleavage as the major photolysis path.9,11
appreciable fragmentation was observed for C(3) derivatives
16a and 17a. Dyads having hexyl or dodecyl linkers (14-19b and
c) showed more efficient fragmentations, and α-methyl
substituted derivatives offered systematically cleaner and faster
conversions.
R
R
4
O
OH
Ph
3
2
O
365 nm
HO
N
N
Ph
n
N
+
n
N
O
H2O / ACN 1 / 1
pH = 7.4
OTf
OTf
14 C(4) R = H; a n = 3; b n = 6; c n = 12
15 C(4) R = Me; a n = 3; b n = 6; c n = 12
18 C(2) R = H; a n = 3; b n = 6; c n = 12
19 C(2) R = Me; a n = 3; b n = 6; c n = 12
Scheme 6. Photolysis of tethered N-carbazole picoline phenylacetates 14a-c,
15a-c, 18a-c and 18a-c.
Table 3. Photolysis of picolinium esters 7 and 8.
Ester consumed Acid formed Alcohol formed
Conditions
(%)[a]
(%)[a]
(%)[a]
2 h
CD3CN/D2O
7
8
75
67
27
2 h
59
51
27
CD3CN/D2O
[a] Calculated by 1H NMR using hexamethyldisiloxane as internal standard.
R
O
R
OH
O
hν
*
+
9-MC
OTf
N
N
H2O
Me
Me
7 R = H
8 R = Me
+ H2O
- e
O
hν
O
Figure 3: Relative time course of C(2) regioisomers photolysis at 366 nm
determined by HPLC.
R
O
R
O
+
9-MC
N
N
OTf
Me
Me
Scheme 5. The mechanism of the photofragmentation according to Falvey.9,11
Noteworthy, the photolysis of the tethered dyads showed
important concentration dependency in acetonitrile
/ TRIS
mixture (1 / 1) (See SI-Figure 11). This dependency was
attributed to the intermolecular π-π stacking interaction, and to
the formation of aggregates between the carbazole units, rather
than to inner filtering. In order to avoid aggregate formations a c
= 0.1 mM solution was used in a TRIS (20 mM) / acetonitrile (1 /
1) (pH = 7.4) mixture, where no more dependency of the
photolysis on the concentration was observed.
Figure 4: Relative time course of C(4) regioisomers photolysis at 366 nm
determined by HPLC.
When tethered dyads 14a and 18a having a propyl linker
were irradiated (366 nm), modest conversions were observed
after 2 h, whereas α-methyl substituted analogs, 15a and 19a,
offered clean and fast conversions (Figures 3 and 4). No
Finally, the most efficient dyad 15c was examined under
two-photon (TP) irradiation conditions. Two-photon excitation
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possesses several advantages over more conventional single-
photon activation conditions, such as higher spatial resolution,
and also the fact, that scattered IR photons do not produce out
of focus activation.1,21 The uncaging cross section (δu) of
phenylacetate 15c was determined directly from the
consumption of the starting material. A 45 µL sample of a 0.1
mM ACN/TRIS 1/1 solution was irradiated using mode-locked Ti-
Sapphire laser source at 730 nm wavelength (50 fs pulses at 80
MHz). The expanded beam was focused with a 32 mm lens so
that the whole of the excitation volume was contained in the
cuvette. Sample was irradiated for 4.5 h at 156 mW average
power. The loss of the cage was quantified by HPLC, and the
photolysis cross section calculated from the rate of reduction of
the fractional cage concentration, giving a high, experimentally
measured uncaging cross-section of δu = 0.16 GM, a remarkably
high value for a non-optimized structure.
Two conformations with energy minima on the potential
energy surfaces have been found for compound 7, hereafter
named as extended and folded (SI-Figure 13). In the extended
conformation dihedral angles α, β, γ and δ are close to 180°. In
the folded conformation β is –89.4°, resulting in a more compact
arrangement. Noteworthy, the phenyl group is orthogonal to the
plan of the ester in both conformations (ε is close to 90°).
Remarkably both conformations have similar stability in
acetonitrile suggesting that they coexist in the medium.
The absorption spectra of compounds 7-12 were
calculated from the extended and folded conformations,
respectively, using TD-DFT method (Figure 5). The calculated
spectra show similar characteristics to the experimental ones,
and the calculated lowest-energy electronic transitions correlate
well with experimental values. The absorption spectrum of 7 in
the folded conformation is dominated by several very weak
bands around 300 nm that originate from electronic mono-
excitations between orbitals localized on both aromatic rings and
thus can be characterized as a π-π* charge transfer.
Conformational analysis
In all calculated structures the electron-transfer impacted
significantly the geometry of picolinium acceptor resulting
generally in increased bond lengths and in the formation of more
quinoidal structures. The TD-DFT optimized geometry of 7 in the
S1 state is depicted in Figure 9 (see also SI-Table 2). The most
significant changes are the rotation of the phenyl group (of the
phenylacetic ester) and the elongation of the O-CH2 bond from
1.419 (S0) to 1.502 Ǻ (S1) with an important diminution of the
torsion angle from 171° (S0) to 94.7° (S1). These changes are
controlled by the energy of the LUMO (see SI-Figure 14) and
result in a π-stacked face-to-face arrangement of the picolinium
and the phenyl rings, and also, a weakening of the O-CH2 bond.
Similar geometric changes were found between the calculated
structures for the S0 to S1 transitions of 14a and 14c,
respectively (Figure 9).
Conformational analysis of compounds 7-12 was performed
by semi-empirical calculations using AM1 Hamiltonian allowing
the generation of the potential energy surfaces (SI-Figures 12
and 13). All conformation energy minima were optimized at the
highest DFT level. In the following, results obtained for
compound 7 are discussed, while qualitatively similar results
were obtained for compounds 8-12 as well.
LUMO + 2
LUMO + 1
HOMO
HOMO - 3
S1-S0 (π,π*)
300 350
S7-S0 (π,π*)
S8-S0 (π,π*)
450 500
200
250
400
nm
Figure 5. Calculated absorption spectrum of compound 7 representing main
orbitals implied in the electronic excitations and Sn-S0 density plots.
Figure 6. The S1 optimized geometries of 7, 14a and 14c.
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Therefore all these weak transitions show a charge transfer
character between picolinium and phenyl rings. Two transitions
are calculated at 225 (S0àS7) and 221 nm (S0àS8) and can be
assigned to the observed 255 and 258 nm transitions in the
experimental spectrum. The S0àS7 transition involves HOMO-3
and LUMO+1 orbitals and corresponds to a picolinium-localized
excitation while the S0àS8 transition (HàL+2) is localized on the
phenyl group. The character of the lowest excited states of 7, as
charge transfer or localized states, can be determined using the
S0-Sn differences density plot as presented in Figure 2. The
spatial arrangement of the tethered donor-acceptor dyads were
considered next and is illustrated by the analysis of compounds
14a-c. Noteworthy, the aliphatic linker allows high degree of
conformational flexibility: a systematic conformational study of
such element is beyond of the scope of this study. The
conformation of compound 14a was generated by the addition of
the N-propyl-carbazole fragment to the optimized folded
geometry of 7. As was seen with the untethered picolinium
probes, two conformation minima were found, denoted as
extended and folded (SI-Figure 14). The propyl chain adopts a
trans-trans conformation in the extended and syn-pentane
conformation in the folded conformation, respectively.
Noteworthy, the carbazole and picolinium rings adopt face-to-
face orientation in the folded geometry (the N-N distance is
estimated 3.09 Å). The energy difference between the extended
and folded structures is relatively small (0.4 kJ.mol-1) suggesting
that the energetic penalty associated to the staggered
conformation of the propyl chain in the folded geometry is
compensated by a π-π interaction between the carbazole and
picolinium units.
carbazole is in the close proximity of the phenyl group in the
second most stable conformation, 14c-b.
The calculated absorption spectrum of 14a (Figure 7) is in
agreement with the experimental data (SI-Figure 4) and
presents two regions. In the 200-350 nm window the spectrum
shows three bands at 241 nm, 271 nm and around 300 nm.
These bands reproduce nicely the spectrum of 9-MC19 and
originate from the localized excitation of the carbazole. The
second region shows two weakly allowed charge transfer bands
at 385 nm and 436 nm. These transitions are dominated by the
HOMOàLUMO and HOMO-1àLUMO contributions. From the
localization of these orbitals it is obvious that both transitions
involve charge transfers from the carbazole to the picolinium
(Figure 5 and SI-Table 4).
The absorption spectrum of 14c is similar to that of 14a in the
region of 200-350 nm. Unlike the calculated absorption spectrum
of 14a, the calculated absorption spectrum of 14c shows no
charge transfer bands in the low energy region. This is probably
due to the large spatial separation between the carbazole and
picolinium units in the optimized geometries.
Conclusion
The single- and two-photon photolysis of 9-MC tethered
picolinium probes were examined by experimental and
theoretical approaches. These probes were considered
photochemically inert earlier under similar conditions. Probes
undergo tether length-dependent fragmentation: dyads with n =
12 carbon tether were photolyzed 30-40 times more efficiently at
366 nm than that of n = 3 derivatives. α-Methyl substituted
derivatives offered systematically cleaner and faster conversions.
Communication between the picolinium and carbazole
chromophores was observed experimentally and analyzed by
density functional theory (DFT) and time dependent-DFT (TD-
DFT) calculations. The most efficient dyad, 15c, was photolyzed
under TP irradiation conditions at 730 nm showing promisingly
high δu = 0.16 GM uncaging cross-section.
14a
14c-b
LUMO + 2
LUMO
9-MC tethered picolinium probes can be considered as new
“caging” group leads in which the absorption and fragmenting
elements are spatially separated, allowing much easier
optimization than that of more conventional probes in which this
two functions are intimately linked in the same heterocycle.
Further applications in neurophysiology are underway.
HOMO - 1
HOMO
200
250
300
350
400
450
500
nm
Experimental Section
The UV irradiation experiments were accomplished by irradiation of a
solution in roughly 0.1 mM concentration in an acetonitrile/TRIS buffer
1/1 solvent mixture (pH 7.4). The plot of lnA versus irradiation time
showed a linear correlation for the disappearance of the starting material,
which suggested a first order reaction, obtained by the linear least
squares methodology for a straight line. For the UV irradiation, an aliquot
(1 mL) of the solution was irradiated at approximately 366 nm by using
8W Carl Roth lamp. Between each irradiation a small aliquot (50 µL) of
the solution was removed for analysis by reverse-phase HPLC using dual
absorbance detection at 260 and 360 nm. Optical densities at 366 nm
Figure 7. Calculated absorption spectra of compound 14a (black) and 14c-b
(red), main orbitals involved in the first electronic excitations of 14a.
Several conformational minima of 14c were found on the
potential energy surface, and labelled as a-d (SI-Figure 14). In
the most stable conformation, 14c-a, the dodecyl chain adopts
an all-trans arrangement. Others, such as 14c-b, 14c-c and
14c-d display
a more folded structure. Noteworthy, the
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10.1002/chem.201801684
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were kept around 0.1 so that aggregate formation /inner-filtering of the
irradiation and spatial gradients of concentrations could be neglected,
and the progress curves were simple decaying exponentials. Dark
hydrolysis rates were measured similarly except without illumination.
One-photon quantum yields were determined by using Eq 1:
tension was 3.5 kV. The cone tension was 24 V. The temperature of the
source was 130 °C and the temperature of desolvatation was 350 °C.
Data were treated on ThermoQuest.
Characterization of the photolysis products by 1H NMR A solution of
4 µmol of picolinium esters 7 and 8, respectively, with an equal amount of
9-MC sensitizer was dissolved in about 0.5 mL of CD3CN/D2O (4/1)
solvent mixture. Hexamethyl-disiloxane was added as internal standard.
NMR spectra were recorded before irradiation, then the samples were
transferred to a quartz cuvette for the irradiation. The solutions were
irradiated at 366 nm for 2 h by using a 8 W Carl Roth lamp, then re-
transferred to an NMR tube for analysis following the irradiation. Yields
were determined by 1H NMR integration of the compound characteristic
peaks relative to the internal standard.
-1
Qu = [σ( exc)I0( exc)t90%
]
(Eq 1)
λ
λ
where σ(
is the decadic extinction coefficient of the compound at the
exc)
λ
excitation wavelength (103 times ε), t90% is the time at which 90% of the
product was converted, as determined by HPLC, and I0( exc)is the light
λ
intensity at the excitation wavelength and is measured in
einstein.cm-2.s-1.22The light intensityI0 value was determined by
potassium ferrioxalate actinometry.22,23 Briefly, a 6.0 mM potassium
ferrioxalate solution (3 mL) was irradiated for 60 s. An aliquot of the
irradiated solution (2 mL) was added to NaOAc buffer (3 mL), 0.1%
phenanthroline solution (3 mL) and 2 M KF solution (1 mL) and the
volume was completed to 25 mL by distilled water. A blank sample was
prepared the same way, except irradiation. Samples were kept 1 h in the
dark for complexation then the absorbance was measured at 510 nm.
The light intensity was calculated by using Eq 2:
TP photolysis NIR photolysis were performed by irradiation of a sample
solution (0.1 mM) in acetonitrile/TRIS buffer 1/1 solvent mixture (pH 7.4)
for 1-4 hours. Two photon uncaging cross-sections (δu) were calculated
from the fractional conversion of the cage with exposures of approx. 4
hours in a 45 microliters cuvette of 3 mm path length. The expanded
output of a MaiTai BB (Spectra-Physics) pulsed laser was focused with a
30 mm focal length lens into the cuvette. The two-photon excitation
volume was entirely contained within the cuvette volume to obviate the
need to measure the beam waist. Beam parameters were 730 nm with
150 fs pulse width at 80 MHz and 100 mW average power after the
cuvette. Samples were centrifuged if necessary to remove particles if
apparent in the transmitted beam. For reference the two-photon uncaging
cross-section for L-glutamate release from the widely used MNI-caged
glutamate determined in this way was 0.05 GM (10-50cm4s/photon). The
conversion of the product was assayed by HPLC by monitoring the
!
3 !!510
ꢀ = !"""!
(Eq 2)
510V2ϕFe
t
where V3 is the final volume after dilution (25 ml), V2 is the volume of the
aliquot taken for analysis (2 ml), ΔD510 is the difference of absorption of
the irradiated sample and the blank at 510 nm, ε510 is the extinction
coefficient of the (Fe(phen)32+) complex at 510 nm (11100 M-1cm-1), ϕFe is
the quantum yield for ferrous ion formation at the irradiation wavelength
and t is the irradiation time (s).
remaining caged compound. The two-photon uncaging cross section δ
was calculated as follows (Eq 3):
u
Electrochemical experiments were done on a voltammetry analyzer
(Autolab PGSTAT101) with [Bu4N][PF6] as the supporting electrolyte (one
chamber three electrode cell). The electrodes used were a glassy-carbon
working, a platinum auxiliary, and the potential was measured relative to
ferrocene/ferrocenium reference. The solution (1 mM for compound
studied) was purged with nitrogen for 10 min prior to recording. Values
obtained were converted to SCE by adding 0.40 V to the measured
potentials.
!!
!
!"
!
!
ꢀ! = 3.41 x conversion %
x
(
)
(Eq 3)
!!!!
!
where δ = TP uncaging cross-section (cm4.s/photon); V = sample
u
volume (45×10-3cm3); τP= pulse width;
f
=
80×106 Hz;
6.6×10-34J.sec;
n = 1.3;
λ
=
wavelength (cm);
t
=
exposure time (s);
h
=
c = 3×1010cm.s-1; P = average power (W).
Synthesis of esters 1-6
HPLC analyses were carried out on Water 515 device with a normal
inverse phase column X-Terra® MS C18 (length: 75 mm, diameter: 4.6
mm, stationary phase: 2.5 µm) using a Waters 2487 Dual Absorbance
Detector (260-360 nm) and an isocratic system of elution (MeOH-MeCN-
H2O 7-2-1 / H2O AcONH4 (10 mM) pH 4.6). The volume of injection was
10 µL.
To
a solution of the appropriate pyridylcarbinol (3.0 mmol) and
triethylamine (1.5 eq, 4.5 mmol, 627 µL) in 10 mL acetonitrile,
phenylacetyl chloride (1.5 eq, 4.5 mmol, 595 µL) was added. The
reaction mixture was stirred at rt for 16 h. Dichloromethane and water
were added, the organic phase was washed with water and brine, dried
over Na2SO4, filtered and evaporated to dryness. The crude product was
purified by column cromatography on silica gel (cyclohexane/EtOAc 4/1).
Thin-layer chromatography was performed on aluminium-backed Merck
Kieselgel 60 F254 pre-coatedplates. Proton nuclear magnetic resonance
(1H NMR) spectra and carbon nuclear magnetic resonance (13C NMR)
spectra were recorded on a Bruker 250 spectrometer (250 MHz and 63
MHz) and on a Bruker AV-500 spectrometer (500 MHz and 125 MHz).
Chemical shifts for proton sare reported in parts per million downfield
from tetramethylsilane (TMS) and are referenced to residual proton in the
NMR solvent (CDCl3: δ 7.26, CD3CN: δ 1.94). Chemical shifts for carbon
are reported in parts per million downfield from tetramethylsilane and are
referenced to the carbon resonance softhe solvent (CDCl3: δ 77.16,
CD3CN: δ 118.26). Data are represented as follows: chemical shift,
integration, multiplicity (s = singlet, d = doublet, dd = double doublet, t =
triplet, q = quadruplet, qn = quintuplet, b = broad, m = multiplet), coupling
constants in Hertz (Hz). All solvents and inorganic reagents were from
commercial sources and used without purification unless otherwise noted.
The mass analyser was an Agilent from ThermoFisher. The capillary
Pyridin-4-ylmethyl 2-phenylacetate (1)
Yellow oil (498 mg, 73%). 1H NMR (CDCl3, 250 MHz): δ 8.60 (d, J=4.7
Hz, 1H), 7.68 (td, J= 7.5 ,1.5 Hz, 1H), 7.36-7.29 (m, 5H), 7.26-7.21 (m,
2H), 5.28 (s, 2H), 3.77 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 171.0,
149.8, 145.2, 133.6, 129.4, 128.9, 127.5, 122.0, 64.6, 41.4. MS (ESI):
m/z
=
228.2 [M+H]+. HRMS (ESI): m/z calcd for [C14H13O2N+H]+
228.1019, found 228.1012.
1-(Pyridin-4-yl)ethyl 2-phenylacetate (2)
Yellow oil (565 mg, 78%). 1H NMR (CDCl3, 500 MHz): δ 8.52 (d, J=6.0
Hz, 2H), 7.34-7.30 (m, 3H), 7.30-7.25 (m, 2H), 7.12 (dm, J=6.0 Hz, 2H),
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10.1002/chem.201801684
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+
5.83 (q, J=6.5 Hz, 1H), 3.67 (s, 2H), 1.50 (d, J=7.0 Hz, 3H). 13C NMR
(CDCl3, 125 MHz): δ 170.6, 150.7, 149.9, 133.7, 129.3, 128.7, 127.4,
120.7, 71.8, 41.6, 22.0. MS (ESI): m/z = 242.2 [M+H]+. HRMS (ESI): m/z
calcd for [C15H15O2N+H]+ 242.1176, found 242.1169.
(ESI): m/z = 242.1 [M+H] HRMS (ESI): m/z calcd for [C15H16O2N+H]+
242.1176, found 242.1170.HPLC: MeOH-MeCN-H2O 7-2-1
AcONH4 10 mM 4/6, flow rate: 0.45 mL/min, RT: 5.57 min.
/ H2O
1-Methyl-4-(1-(2-phenylacetoxy)ethyl)pyridinium
trifluoromethanesulfonate (8)
Pyridin-3-ylmethyl 2-phenylacetate (3)
Pale yellow oil (quant.).1H NMR (CDCl3, 500 MHz): δ 8.69 (d, J=6.5 Hz,
2H), 7.70 (d, J=6.5 Hz, 2H), 7.37-7.27 (m, 5H), 5.90 (q, J=6.5 Hz, 1H),
4.40 (s, 3H), 3.72 (s, 2H), 1.57 (d, J=6.5 Hz, 3H). 13C NMR (CDCl3, 125
MHz): δ 170.7, 161.0, 145.9, 133.3, 129.5, 128.9, 127.6, 124.7, 70.5,
48.3, 41.1, 21.4. MS (ESI): m/z = 256.3 [M+H]+. HRMS (ESI): m/z calcd
for [C16H18O2N]+256.1332, found 256.1331. HPLC: MeOH-MeCN-H2O 7-
2-1 / H2O AcONH4 10 mM 4/6, flow rate: 0.45 mL/min, RT: 5.05 min.
Yellow oil (586 mg, 86%). 1H NMR (CDCl3, 500 MHz): δ 8.58-8.56 (m,
2H), 7.61 (dt, J=8.0, 2.0 Hz, 1H), 7.34-7.31 (m, 2H), 7.28-7.25 (m, 4H),
5.14 (s, 2H), 3.67 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 171.3, 149.6,
149.6, 136.1, 133.7, 131.7, 129.4, 128.8, 127.4, 123.6, 64.1, 41.4. MS
(ESI): m/z = 228.1 [M+H]+. HRMS (ESI): m/z calcd for [C14H13O2N+H]+
228.1019, found 228.1012.
1-(Pyridin-3-yl)ethyl 2-phenylacetate (4)
1-Methyl-3-((2-phenylacetoxy)methyl)pyridinium
trifluoromethanesulfonate (9)
Yellow oil (623 mg, 83%). 1H NMR (CDCl3, 500 MHz): δ 8.56 (d, J=2.0
Hz, 1H), 8.53 (dd, J=4.5, 1.5 Hz, 1H), 7.57 (dt, J=7.5, 2.0 Hz, 1H), 7.34-
7.28 (m, 4H), 7.25-7.23 (m, 2H), 5.91 (q, J=7.0 Hz, 1H), 3.65 (bs, 2H),
1.55 (d, J=6.5 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 170.8, 149.3,
147.9, 137.1, 133.9, 133.8, 129.4, 128.8, 127.3, 123.5, 70.7, 41.7, 22.1.
Pale yellow oil (quant.).1H NMR (CDCl3, 500 MHz): δ 8.73 (d, J=6.5 Hz,
1H), 8.68 (s, 1H), 8.22 (d, J=8.5 Hz, 1H), 7.88 (dd, J=8, 6 Hz, 1H), 7.33-
7.26 (m, 5H), 5.27 (s, 2H), 4.35 (s, 3H), 3.72 (s, 2H). 13C NMR (CDCl3,
125 MHz): δ 171.2, 144.9, 144.5, 143.9, 138.1, 133.4, 129.6, 128.9,
128.1, 127.6, 61.9, 49.0, 40.9. MS (ESI): m/z = 242.2 [M+H]+. HRMS
(ESI): m/z calcd for [C15H16O2N+H]+ 242.1176, found 242.1169.HPLC:
MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 4/6, flow rate: 0.45
mL/min, RT: 4.80 min.
MS (ESI): m/z
=
242.1 [M+H]+. HRMS (ESI): m/z calcd for
[C15H15O2N+H]+ 242.1176, found 242.1171.
Pyridin-2-ylmethyl 2-phenylacetate (5)
Yellow oil (566 mg, 81%). 1H NMR (CDCl3, 500 MHz): δ 8.58 (bd, J=4.5
Hz, 1H), 7.64 (td, J=7.5, 2.0 Hz, 1H), 7.34-7.29 (m, 4H), 7.28-7.25 (m,
1H), 7.21 (d, J=8.0 Hz, 1H), 7.18-7.20 (m, 1H), 5.25 (s, 2H), 3.72 (s, 2H).
13C NMR (CDCl3, 125 MHz): δ 171.2, 155.7, 149.3, 137.0, 133.8, 129.4,
128.7, 127.2, 122.9, 121.7, 67.0, 41.3. MS (ESI): m/z = 228.1 [M+H]+.
HRMS (ESI): m/z calcd for [C14H13O2N+H]+ 228.1019, found 228.1013.
1-Methyl-3-(1-(2-phenylacetoxy)ethyl)pyridinium
trifluoromethanesulfonate (10)
Pale yellow oil (quant.).1H NMR (CDCl3, 500 MHz): δ 8.72 (d, J=6.0 Hz,
1H), 8.60 (s, 1H), 8.17 (d, J=8.5 Hz, 1H), 7.87 (dd, J=8.0, 6.0 Hz, 1H),
7.32-7.23 (m, 5H), 5.94 (q, J=6.5 Hz, 1H), 4.32 (s, 3H), 3.69 (s, 2H), 1.58
(d, J=6.5 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 170.7, 144.9, 143.3,
143.2, 142.3, 133.5, 129.5, 128.9, 128.3, 127.6, 69.1, 49.0, 41.2, 21.5.
1-(Pyridin-2-yl)ethyl 2-phenylacetate (6)
MS (ESI): m/z
=
256.2 [M+H]+. HRMS (ESI): m/z calcd for
[C16H18O2N+H]+ 256.1332, found 256.1323. HPLC: MeOH-MeCN-H2O 7-
Yellow oil (543 mg, 75%). 1H NMR (CDCl3, 500 MHz): δ 8.58 (d, J=4.0
Hz, 1H), 7.61 (t, J=7.5 Hz, 1H), 7.24-7.34 (m, 4H), 7.20-7.16 (m, 2H),
5.92 (q, J=6.5 Hz, 1H), 3.69 (d, J=2.5 Hz, 2H), 1.58 (d, J=6.5 Hz, 3H).
13C NMR (CDCl3, 125 MHz): δ 170.9, 160.3, 149.2, 137.1, 134.0, 129.4,
128.7, 127.2, 122.8, 120.4, 73.4, 41.6, 20.8. MS (ESI): m/z = 242.1
[M+H]+. HRMS (ESI): m/z calcd for [C15H15O2N+H]+ 242.1176, found
242.1169.
2-1 / H2O AcONH4 10 mM 4/6, flow rate: 0.45 mL/min, RT: 4.19 min.
1-Methyl-2-((2-phenylacetoxy)methyl)pyridinium
trifluoromethanesulfonate (11)
Pale yellow oil (quant.).1H NMR (CDCl3, 500 MHz): δ 8.77 (d, J=6.0 Hz,
1H), 8.27 (td, J=8.0, 1.5 Hz, 1H), 7.81 (d, J=8 Hz, 2H), 7.32-7.22 (m, 5H),
5.40 (s, 2H), 4.22 (s, 3H), 3.73 (s, 2H). 13C NMR (CDCl3, 125 MHz):
170.8, 151.7, 147.5, 145.7, 133.0, 129.5, 128.9, 128.1, 127.7, 127.5,
61.2, 45.9, 40.7. MS (ESI): m/z = 242.1 [M+H]+HRMS (ESI): m/z calcd for
[C15H16O2N+H]+ 242.1176, found 242.1170.HPLC: MeOH-MeCN-H2O 7-
2-1 / H2O AcONH4 10 mM 4/6, flow rate: 0.45 mL/min, RT: 4.03 min.
N-Methylation of esters 1-6
To a solution of compounds 1-6 (0.20 mmol, for 1,3,5: 45 mg, for 2,4,6:
48 mg) in dry dichloromethane (1 mL) is added methyl trifluoromethane-
sulfonate (1.0 eq, 0.20 mmol, 23 µL). The mixture is allowed to stir at rt
for 1 h (TLC shows no sign of starting material), under argon and
protected from light. The solvent is evaporated and the product obtained
is used without further purification. CAUTION: methyl trifluoromethane-
sulfonate is a powerful methylating agent, handle with extreme care in a
well ventilated hood.
1-Methyl-2-(1-(2-phenylacetoxy)ethyl)pyridinium
trifluoromethanesulfonate (12)
Pale yellow oil (quant.).1H NMR (CDCl3, 500 MHz): δ 8.83 (d, J=5.5 Hz,
1H), 8.31 (td, J=8.0, 1 Hz, 1H), 7.87–7.84 (m, 1H), 7.72 (dd, J=8.0, 1.5
Hz, 1H), 7.33-7.26 (m, 3H), 7.22-7.20 (m, 2H), 6.00 (q, J=6.5 Hz, 1H),
4.29 (s, 3H), 3.67 (s, 2H), 1.63 (d, J=7.0 Hz, 3H). 13C NMR (CDCl3, 125
MHz): δ 171.1, 157.3, 147.5, 146.2, 132.7, 129.4, 129.0, 127.8, 127.4,
125.4, 67.3, 46.4, 40.9, 19.7. MS (ESI): m/z = 256.3 [M+H]+. HPLC:
MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 4/6, flow rate: 0.45
mL/min, RT: 4.55 min.
1-Methyl-4-((2-phenylacetoxy)methyl)pyridinium
trifluoromethanesulfonate (7)
Pale yellow oil (quant.).1H NMR (CDCl3, 500 MHz): δ 8.70 (d, J=6.5 Hz,
2H), 7.74 (d, J=6.5 Hz, 2H), 7.36-7.33 (m, 2H), 7.30-7.28 (m, 3H), 5.31 (s,
2H), 4.36 (s, 3H), 3.77 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 170.9,
156.2, 145.4, 133.2, 129.5, 129.0, 127.8, 125.4, 63.3, 48.5, 41.0. MS
This article is protected by copyright. All rights reserved.

10.1002/chem.201801684
Chemistry - A European Journal
FULL PAPER
N-Alkylation of carbazole
12-(9H-Carbazol-9-yl)dodecyl trifluoromethanesulfonate (13c)
To a solution of carbazole (10.0mmol, 1.67 g) in DMF (25 mL), NaH
(60% dispersion in mineral oil, 1.5 eq, 15.0mmol, 600 mg) was added at
0°C. After 30 min stirring, 1.5 eq of alkyl bromide was added (15.00 mmol,
Colourless oil (870 mg, quant).1H NMR (CDCl3, 500 MHz): δ 8.11 (d,
J=7.5 Hz, 2H), 7.47 (ddd, J=9.5, 7.0, 1.5 Hz, 2H), 7.41 (d, J=8 Hz, 2H),
7.25 (ddd, 7.5, 7.0, 1.2 Hz, 2H), 4.53 (t, J=6.5 Hz, 2H), 4.31 (t, J=7 Hz,
2H), 1.91-1.79 (m, 4H), 1.44-1.25 (m, 16H).
3-bromopropanol:
1.34
mL;
6-bromohexanol:
2.72
g;
12-
bromododecanol: 3.98 g) and the mixture was stirred at rt for 24 h. The
mixture was poured onto water and extracted by DCM. The organic
phase was washed with water and brine, dried over Na2SO4, filtered and
evaporated to dryness. The crude product was purified by column
cromatography on silica gel (cyclohexane/EtOAc 4/1).
Synthesis of carbazole-linked esters 14-19
To a solution of the ester (1-6) (0.25 mmol) in 1.0 mL DCM, a solution of
the triflate (13a-c) (1.0 eq, 0.25 mmol) in DCM (0.5 mL) was added, and
the mixture was stirred at rt for 4 h under argon, while protected from
light. After evaporation to dryness, if necessary, the crude product was
purified by column cromatography on silica gel (DCM/MeOH 95/5).
During work-up, purification and upon storing the products were carefully
protected from light.
3-(9H-Carbazol-9-yl)propanol
White solid (1.36 g, 60%). 1H NMR (CDCl3, 250 MHz): δ 8.16 (d, J=7.3
Hz, 2H), 7.56-7.46 (m, 4H), 7.30 (ddd, J=7.3, 5.3, 2.2 Hz, 2H), 4.46 (t,
J=6.6 Hz, 2H), 3.57 (t, J=6.6 Hz, 2H), 2.10 (qn, J=6.6 Hz, 2H), 1.80 (s,
1H). 13C NMR (CDCl3, 125 MHz): δ 140.5, 125.8, 122.9, 120.4, 119.0,
108.7, 59.6, 39.2, 31.4.
1-(3-(9H-Carbazol-9-yl)propyl)-4-((2-
phenylacetoxy)methyl)pyridinium trifluoromethanesulfonate (14a)
Yellow oil (121 mg, 83%). 1H NMR (CD3CN, 500 MHz): δ 8.25 (d, J=7.0
Hz, 2H), 8.01 (d, J=7.5 Hz, 2H), 7.52 (d, J=8.0 Hz, 2H), 7.48 (ddd, J=8.0,
7.0, 1.2 Hz, 2H), 7.43 (d, J=6.5 Hz, 2H), 7.39-7.35 (m, 2H), 7.34-7.30 (m,
3H), 7.21 (ddd, J=8.0, 7.0, 1.2 Hz, 2H), 5.18 (s, 2H), 4.52 (t, J=7.0 Hz,
2H), 4.51 (t, J=7.0 Hz, 2H), 3.80 (s, 2H), 2.56 (qn, J=7.0 Hz, 2H). 13C
NMR (CD3CN, 125 MHz): δ 171.7, 157.1, 144.2, 140.8, 134.9, 130.4,
129.5, 128.2, 127.0, 125.4, 123.6, 121.2, 120.3, 110.0, 63.9, 60.1, 41.1,
40.7, 30.0. MS (ESI): m/z = 435.2 [M+H]+. HRMS (ESI): m/z calcd for
[C29H27O2N2+H]+ 435.2067, found 435.2078. HPLC: MeOH-MeCN-H2O
7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT: 3.34 min.
6-(9H-Carbazol-9-yl)hexanol
White solid (1.70 g, 64%). 1H NMR (CDCl3, 500 MHz): δ 8.08 (d, J=7.5
Hz, 2H), 7.44 (td, J=8.0, 1.5 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 7.21 (td,
J=8.0, 1.0 Hz, 2H), 4.27 (t, J=7.0 Hz, 2H), 3.55 (t, J=6.5 Hz, 2H), 1.86 (qn,
J=7.5 Hz, 2H), 1.49 (qn, J=7.0 Hz, 2H), 1.39-1.33 (m, 4H). 13C NMR
(CDCl3, 125 MHz): δ 140.5, 125.7, 122.9, 120.5, 118.9, 108.7, 62.8, 43.1,
32.7, 29.0, 27.2, 25.6.
12-(9H-Carbazol-9-yl)dodecanol
White solid (2.53 g, 72 %). 1H NMR (CDCl3, 500 MHz): δ 8.07 (d, J=8.0
Hz, 2H), 7.42 (td, J=8.0, 1.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 2H), 7.19 (td,
J=8.0, 1.0 Hz, 2H), 4.22 (t, J=7.5 Hz, 2H), 3.56 (t, J=6.5 Hz, 2H), 1.81 (qn,
J=7.0 Hz, 2H), 1.50 (qn, J=7.0 Hz, 2H), 1.36-1.18 (m, 16H). 13C NMR
(CDCl3, 125 MHz): δ 140.5, 125.6, 122.9, 120.4, 118.7, 108.7, 63.0, 43.1,
32.8, 29.7-29.5 (6C), 29.0, 27.4, 25.8.
1-(6-(9H-Carbazol-9-yl)hexyl)-4-((2-phenylacetoxy)methyl)pyridinium
trifluoromethanesulfonate (14b)
Yellow oil (136 mg, 87%). 1H NMR (CDCl3, 500 MHz): δ 8.50 (d, J=6.5
Hz, 2H), 7.99 (d, J=8 Hz, 2H), 7.53 (d, J=7 Hz, 2H), 7.39 (ddd, J=8.0, 7.0,
1.0 Hz, 2H), 7.32-7.22 (m, 7H), 7.15 (ddd, J=8.0, 7.0, 1.0 Hz, 2H), 5.07 (s,
2H), 4.27 (t, J=7.5 Hz, 2H), 4.19 (d, J=7.0 Hz, 2H), 3.69 (s, 2H), 1.75-
1.66 (m, 4H), 1.28-1.24 (m, 2H), 1.20-1.16 (m, 2H). 13C NMR (CDCl3,
125 MHz): δ 170.7, 156.0, 144.2, 140.3, 133.1, 129.4, 128.9, 127.7,
125.9, 125.3, 122.7, 120.4, 119.0, 108.9, 63.1, 61.5, 42.7, 40.9, 31.2,
28.5, 26.4, 25.4. MS (ESI): m/z = 477.3 [M+H]+. HRMS (ESI): m/z calcd
for [C32H33O2N2+H]+ 477.2537, found 477.2529. HPLC: MeOH-MeCN-
H2O 7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT: 5.66 min.
Synthesis of compounds 13a-c
To a solution of the appropriate alcohol (1.80 mmol, 3-(9H-carbazol-9-
yl)propanol: 406 mg, 6-(9H-carbazol-9-yl)hexanol: 481 mg, 12-(9H-
carbazol-9-yl)dodecanol: 633 mg) and pyridine (1.0 eq, 1.80 mmol, 146
µL) in DCM (10 mL), trifluoromethanesulfonic anhydride (1.0 eq, 1.80
mmol, 303 µL) was added at 0°C. The mixture was stirred at rt for 2 h,
then was poured onto water. The organic phase was washed with water
and brine, dried over Na2SO4, filtered and evaporated to dryness. The
crude product obtained was used directly for the next reaction step.
1-(12-(9H-Carbazol-9-yl)dodecyl)-4-((2-
phenylacetoxy)methyl)pyridinium trifluoromethanesulfonate (14c)
Yellow oil (142 mg, 80%). 1H NMR (CDCl3, 500 MHz): δ 8.69 (d, J=6.5
Hz, 2H), 8.06 (d, J=8.0 Hz, 2H), 7.72 (d, J=7.0 Hz, 2H), 7.43 (ddd, J=8.0,
7.0, 1.5 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.34-7.30 (m, 2H), 7.29-7.25 (m,
3H), 7.19 (ddd, J=8.0, 7.0, 1.0 Hz, 2H), 5.22 (s, 2H), 4.46 (t, J=7.5 Hz,
2H), 4.25 (t, J=7.5 Hz, 2H), 3.74 (s, 2H), 1.88-1.78 (m, 4H), 1.38-1.30 (m,
2H), 1.30-1.15 (m, 14H). 13C NMR (CDCl3, 125 MHz): δ 170.8, 156.3,
144.4, 140.5, 133.1, 129.5, 128.9, 127.7, 125.7, 125.6, 122.8, 120.4,
118.8, 108.8, 63.2, 62.0, 43.1, 40.9, 31.5, 29.4-28.9 (8C), 27.3, 26.0. MS
(ESI): m/z = 561.4 [M+H]+. HRMS (ESI): m/z calcd for [C38H45O2N2+H]+
3-(9H-Carbazol-9-yl)propyl trifluoromethanesulfonate (13a)
Colourless oil (643 mg, quant).1H NMR (CDCl3, 250 MHz): δ 8.15 (d,
J=8.4 Hz, 2H), 7.53 (ddd, J=8.4, 7.5, 1.3 Hz, 2H), 7.39 (d, J=8.4 Hz, 2H),
7.31 (ddd, J=7.5, 7.5, 0.8 Hz, 2H), 4.46 (d, J=6.2 Hz, 2H), 4.44 (d, J=6.5
Hz, 2H), 2.36 (qn, J=6.4 Hz, 2H).
6-(9H-Carbazol-9-yl)hexyl trifluoromethanesulfonate (13b)
561.3476, found 561.3466. HPLC: MeOH-MeCN-H2O 7-2-1
AcONH4 10 mM 9/1, flow rate: 0.7 mL/min, RT: 5.71 min.
/ H2O
Colourless oil (719 mg, quant).1H NMR (CDCl3, 250 MHz): δ 8.13 (d,
J=7.9 Hz, 2H), 7.50 (ddd, J=7.5, 7.2, 1.0 Hz, 2H), 7.41 (d, J=7.9 Hz, 2H),
7.27 (ddd, J=7.9, 7.5, 1.0 Hz, 2H), 4.47 (t, J=6.2 Hz, 2H), 4.32 (t, J=7.0
Hz, 2H), 1.96-1.83 (m, 2H), 1.80-1.69 (m, 2H), 1.49-1.30(m, 4H).
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10.1002/chem.201801684
Chemistry - A European Journal
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1-(3-(9H-Carbazol-9-yl)propyl)-4-(1-(2-
phenylacetoxy)ethyl)pyridinium trifluoromethanesulfonate(15a)
(t, J=7 Hz, 2H), 3.64 (s, 2H), 1.77-1.68 (m, 4H), 1.28-1.18 (m, 4H). 13C
NMR (CDCl3, 125 MHz): δ 171.0, 143.8, 143.7, 143.0, 140.4, 138.1,
133.4, 129.5, 128.8, 128.1, 127.5, 125.9, 122.7, 120.4, 119.0, 108.9,
62.1, 61.8, 42.7, 40.9, 31.2, 28.6, 26.5, 25.6. MS (ESI): m/z = 477.2
[M+H]+. HRMS (ESI): m/z calcd for [C32H33O2N2+H]+ 477.2537, found
477.2521. HPLC: MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 7/3,
flow rate: 0.7 mL/min, RT: 5.50 min.
Yellow oil (137 mg, 92%). 1H NMR (CDCl3, 500 MHz): δ 8.18 (d, J=7 Hz,
2H), 7.82 (d, J=8 Hz, 2H), 7.43-7.39 (m, 4H), 7.32-7.25 (m, 2H), 7.21-
7.19 (m, 2H), 7.12 (ddd, J=8.0, 6.5, 2 Hz, 2H), 7.01 (d, J=6.5 Hz, 2H),
5.60 (q, J=7 Hz, 1H), 4.58 (t, J=7.0 Hz, 2H), 4.46 (t, J=6.5 Hz, 2H), 3.62
(s, 2H), 2.58 (qn, J=6.5 Hz, 2H), 1.31 (d, J=7.0 Hz, 3H). 13C NMR (CDCl3,
125 MHz): δ 170.3, 160.3, 143.2, 139.6, 133.1, 129.4, 128.9, 127.7,
126.5, 123.6, 122.7, 120.3, 119.7, 109.1, 69.8, 59.6, 41.1, 40.2, 29.0,
21.3. MS (ESI): m/z = 449.2 [M+H]+. HRMS (ESI): m/z calcd for
[C30H29O2N2+H]+ 449.2224, found 449.2211. HPLC: MeOH-MeCN-H2O
7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT: 3.78 min.
1-(12-(9H-Carbazol-9-yl)dodecyl)-3-((2-
phenylacetoxy)methyl)pyridinium trifluoromethanesulfonate (16c)
Yellow oil (126 mg, 71%). 1H NMR (CDCl3, 500 MHz): δ 8.70 (s, J=6.0 Hz,
1H), 8.69 (d, 1H), 8.16 (dm, J=7.5 Hz, 1H), 8.05 (d, J=8.0 Hz, 2H), 7.84
(dd, J=8.0, 6.0 Hz, 1H), 7.43 (td, J=8.0, 1.0 Hz, 2H), 7.37 (d, J=8.0 Hz,
2H), 7.30-7.22 (m, 5H), 7.19 (td, J=8.0, 1.0 Hz, 2H), 5.22 (s, 2H), 4.46 (t,
J=8.0 Hz, 2H), 4.24 (t, J=7.5 Hz, 2H), 3.69 (s, 2H), 1.86-1.78 (m, 4H),
1.38-1.30 (m, 2H), 1.30-1.16 (m, 14H). 13C NMR (CDCl3, 125 MHz): δ
171.0, 144.0, 143.8, 143.2, 140.4, 138.2, 133.4, 129.4, 128.8, 128.3,
127.4, 125.7, 122.8 120.3, 118.8, 108.8, 62.5, 61.9, 43.1, 40.9,
31.6,29.6-28.8 (7C), 27.3, 26.0. MS (ESI): m/z = 575.3 [M+H]+. HRMS
(ESI): m/z calcd for [C38H45O2N2+H]+ 561.3476, found 561.3481. HPLC:
MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 9/1, flow rate: 0.7 mL/min,
RT: 6.85 min.
1-(6-(9H-Carbazol-9-yl)hexyl)-4-((2-phenylacetoxy)ethyl)pyridinium
trifluoromethanesulfonate (15b)
Yellow oil (123 mg, 77 %). 1H NMR (CDCl3, 500 MHz): δ 8.56 (d, J=6.5
Hz, 2H), 8.05 (d, J=8 Hz, 2H), 7.59 (d, J=6 Hz, 2H), 7.45-7.28 (m, 8 H),
7.24-7.18 (m, 3H), 5.82 (q, J=7 Hz, 1H), 4.37 (t, J=7.5 Hz, 2H), 4.27 (t,
J=6.5 Hz, 2H), 3.69 (s, 2H), 1.77 (m, 4H), 1.48 (d, J=7 Hz, 3H), 1.35-1.20
(m, 4H). 13C NMR (CDCl3, 125 MHz): 170.4, 161.0, 144.5, 140.4, 133.0,
129.3, 128.9, 127.7, 125.8, 124.8, 122.8, 120.3, 118.9, 108.9, 61.5, 42.7,
41.1, 31.1, 28.5, 26.4, 25.5, 21.3. MS (ESI): m/z = 491.3 [M+H]+. HRMS
(ESI): m/z calcd for [C33H35O2N2+H]+ 491.2693, found 491.2674. HPLC:
MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min,
RT: 6.62 min.
1-(3-(9H-Carbazol-9-yl)propyl)-3-(1-(2-
phenylacetoxy)ethyl)pyridinium trifluoromethanesulfonate(17a)
Yellow oil (107 mg, 71 %). 1H NMR (CDCl3, 500 MHz): δ 8.30 (d, J=6.0
Hz, 1H), 8.22 (s, 1H), 7.86 (d, J=7.5 Hz, 2H), 7.71 (d, J=8.5 Hz, 1H),
7.42-7.37 (m, 4H), 7.27-7.19 (m, 3H), 7.18-7.12 (m, 5H), 5.54 (q, J=6.5
Hz, 1H), 4.62 (td, J=7.0, 2.5 Hz, 2H), 4.45 (td, J=6.5, 2.5 Hz, 2H), 3.60
(bs, 2H), 2.56 (qn, J=7.0 Hz, 2H), 1.31 (d, J=6.5 Hz, 3H). 13C NMR
(CDCl3, 125 MHz): δ 170.3, 142.9, 142.6, 141.5, 140.9, 139.7, 133.4,
129.4, 128.8, 127.5, 127.4, 126.4, 122.7, 120.3, 119.7, 109.1, 68.6, 60.3,
41.2, 40.1, 29.5, 21.0. MS (ESI): m/z = 449.2 [M+H]+. HRMS (ESI): m/z
calcd for [C30H29O2N2+H]+ 449.2224, found 449.2210. HPLC: MeOH-
MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT:
3.36 min.
1-(12-(9H-Carbazol-9-yl)dodecyl)-4-((2-phenylacetoxy)ethyl)-
pyridinium trifluoromethanesulfonate (15c)
Yellow oil (121 mg, 67%). 1H NMR (CDCl3, 500 MHz): δ 8.72 (d, J=7 Hz,
2H), 8.08 (d, J=8.0 Hz, 2H), 7.71 (d, J=6.5 Hz, 2H), 7.47-7.25 (m, 9H),
7.21 (td, J=8.0, 1.0 Hz, 2H), 5.88 (q, J=6.5 Hz, 1H), 4.54 (t, J=7.5, 2H),
4.28 (t, J=7.5 Hz, 2H), 3.71 (s, 2H), 1.90-1.82 (m, 4H), 1.53 (d, J=7, 3H),
1.38-1.20(m, 16H). 13C NMR (CDCl3, 125 MHz): δ 170.6, 161.2, 144.8,
140.6, 133.2, 129.4, 129.0, 127.8, 125.7, 125.0, 122.9, 120.4, 118.8,
108.8, 70.4, 62.1, 43.2, 41.3, 31.6, 29.5-29.0 (7C), 27.4, 26.1, 21.5. MS
(ESI): m/z = 575.4 [M+H]+. HRMS (ESI): m/z calcd for [C39H47O2N2+H]+
575.3632, found 575.3610. HPLC: MeOH-MeCN-H2O 7-2-1
AcONH4 10 mM 9/1, flow rate: 0.7 mL/min, RT: 6.07 min.
/
H2O
1-(6-(9H-Carbazol-9-yl)hexyl)-3-((2-phenylacetoxy)ethyl)pyridinium
trifluoromethanesulfonate (17b)
1-(3-(9H-Carbazol-9-yl)propyl)-3-((2-phenylacetoxy)methyl)-
pyridinium trifluoromethanesulfonate(16a)
Yellow oil (122 mg, 76%). 1H NMR (CDCl3, 500 MHz): δ 8.60 (d, J=6.0
Hz, 1H), 8.51 (s, 1H), 8.04 (d, J=7.5 Hz, 2H), 8.01 (d, J=8.0 Hz, 1H), 7.72
(dd, J=8.5, 6.0 Hz, 1H), 7.42 (m, 2H), 7.36 (d, J=8.0 Hz, 2H), 7.26-7.15
(m, 7H), 5.84 (q, J=6.5 Hz, 1H), 4.38 (t, J=7.5 Hz, 2H), 4.24 (t, J=7 Hz,
2H), 3.63 (s, 2H), 1.81-1.67 (m, 4H), 1.52 (d, J=6.5 Hz, 3H), 1.31-1.20 (m,
4H). 13C NMR (CDCl3, 125 MHz): δ 170.5, 143.9, 143.4, 142.3, 142.1,
140.5, 133.4, 129.4, 128.8, 128.4, 127.5, 125.9, 122.8, 120.4, 119.0,
109.0, 69.0, 62.3, 42.8, 41.3, 31.4, 28.6, 26.5, 25.6, 21.4. MS (ESI): m/z
= 491.2 [M+H]+. HRMS (ESI): m/z calcd for [C33H35O2N2+H]+ 491.2693,
found 491.2672. HPLC: MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM
7/3, flow rate: 0.7 mL/min, RT: 7.29 min.
Yellow oil (121 mg, 83%). 1H NMR (CDCl3, 500 MHz): δ 8.17 (d, J=6.0
Hz, 1H), 8.07 (s, 1H), 7.80 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.0 Hz, 1H),
7.41-7.35 (m, 4H), 7.25-7.20 (m, 2H), 7.20-7.15 (m, 3H), 7.13-7.09 (m,
3H), 4.68 (s, 2H), 4.56 (t, J=6.5 Hz, 2H), 4.42 (t, J=6.5 Hz, 2H), 3.60 (s,
2H), 2.56 (qn, J=6.0 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ 170.8,
142.33, 142.31, 141.3, 139.5, 137.1, 133.4, 129.5, 128.8, 127.5, 126.8,
126.4, 122.6, 120.2, 119.7, 109.1, 61.4, 60.1, 40.7, 40.1, 28.8. MS (ESI):
m/z
=
435.2449.2 [M+H]+. HRMS (ESI): m/z calcd for
[C29H27O2N2+H]+435.2067, found 435.2048. HPLC: MeOH-MeCN-H2O 7-
2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT: 3.00 min.
1-(12-(9H-Carbazol-9-yl)dodecyl)-3-((2-
phenylacetoxy)ethyl)pyridinium trifluoromethanesulfonate (17c)
1-(6-(9H-Carbazol-9-yl)hexyl)-3-((2-phenylacetoxy)methyl)pyridinium
trifluoromethanesulfonate (16b)
Yellow oil (125 mg, 69%). 1H NMR (CDCl3, 250 MHz): δ 8.81 (d, J=6.0
Hz, 1H), 8.19 (t, J=7.8 Hz, 1H), 8.01 (d, J=7.5 Hz, 2H), 7.81 (ddd, J=7.5,
6.2, 1.5 Hz, 1H), 7.57 (dd, J=8.0, 1.5 Hz, 1H), 7.42-7.30 (m, 4H), 7.25-
7.10 (m, 7H), 5.89 (bq, J=6.8 Hz, 1H), 4.70-4.55 (m, 1H), 4.45-4.32 (m,
1H), 4.21 (t, J=7.3 Hz, 2H), 3.61 (s, 2H), 2.04-1.70 (m, 4H), 1.61 (d,
J=6.5 Hz, 3H), 1.36-1.10 (m, 16H). 13C NMR (CDCl3, 63 MHz): δ 170.8,
Yellow oil (118 mg, 75%). 1H NMR (CDCl3, 500 MHz): δ 8.54 (s, 1H),
8.52 (d, J=6.5 Hz, 1H), 8.01 (d, J=7.5 Hz, 2H), 7.98 (d, J=8.5 Hz, 1H),
7.65 (dd, J=8.0, 6.0 Hz, 1H), 7.39 (ddd, J=8.0, 7.0, 1.0 Hz, 2H), 7.33 (d,
J=8.5 Hz, 2H), 7.24-7.15 (m, 7H), 5.1 (s, 2H), 4.32 (t, J=7.5 Hz, 2H), 4.20
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10.1002/chem.201801684
Chemistry - A European Journal
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156.7, 146.6, 146.3, 140.5, 132.5, 129.4, 129.0, 127.8, 127.7, 125.7,
125.3, 122.8, 120.4, 118.8, 108.8, 67.0, 59.0, 43.2, 41.0, 30.9, 29.5* (2C),
29.3* (2C), 29.0, 27.4, 26.4, 20.7. MS (ESI): m/z = 575.3 [M+H]+ for
[C39H47N2O2]+. HPLC: MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM
9/1, flow rate: 0.7 mL/min, RT: 7.68 min.
66.8, 55.7, 40.5, 39.3, 29.9, 19.5. MS (ESI): m/z = 449.2 [M+H]+. HRMS
(ESI): m/z calcd for [C30H29O2N2+H]+ 449.2224, found 449.2210. HPLC:
MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min,
RT: 3.95 min.
1-(6-(9H-Carbazol-9-yl)hexyl)-2-(1-(2-phenylacetoxy)ethyl)pyridinium
trifluoromethanesulfonate (19b)
1-(3-(9H-Carbazol-9-yl)propyl)-2-((2-
phenylacetoxy)methyl)pyridinium trifluoromethanesulfonate (18a)
Yellow oil (103 mg, 64%). 1H NMR (CDCl3, 250 MHz): δ 8.74 (d, J=5.3
Hz, 1H), 8.14 (td, J=8.3, 1.3 Hz, 1H), 8.03 (d, J=7.5 Hz, 2H), 7.71 (ddd,
J=7.3, 6.3, 1.3 Hz, 1H), 7.55 (dd, J=7.0, 1.3 Hz, 1H), 7.45-7.33 (m, 4H),
7.30-7.23 (m, 3H), 7.21-7.14 (m, 4H), 5.81 (q, J=6.8 Hz, 1H), 4.60-4.48
(m, 1H), 4.40-4.28 (m, 1H), 4.24 (t, J=7.0 Hz, 2H), 3.62 (s, 2H), 1.96-1.72
(m, 4H), 1.53 (d, J=6.5 Hz, 3H), 1.40-1.30 (m, 4H). 13C NMR (CDCl3, 63
MHz): δ 170.8, 156.8, 146.2, 140.4, 132.6, 129.4, 128.9, 127.8, 127.5,
125.8, 125.2, 122.8, 120.3, 118.9, 108.9, 66.9, 58.5, 42.7, 40.9, 30.5,
28.6, 26.5, 25.8, 20.5. MS (ESI): m/z = 491.2 [M+H]+. HRMS (ESI): m/z
calcd for [C33H35O2N2+H]+ 491.2693, found 491.2683. HPLC: MeOH-
MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT:
7.03 min.
Yellow oil (124 mg, 85 %). 1H NMR (CDCl3, 500 MHz): δ 8.74 (dd, J=6.0,
1.0 Hz, 1H), 7.96 (td, J=7.5, 1.0 Hz, 1H), 7.95 (d, J=8.0 Hz, 2H), 7.55
(ddd, J=8.0, 6.2, 1.4 Hz, 1H), 7.44 (d, J=8.0 Hz, 2H), 7.42 (dd, J=8.0, 1.3
Hz, 1H), 7.39 (ddd, J=8.0, 7.0, 1.0 Hz, 2H), 7.21-7.17 (m, 3H), 7.15 (ddd,
J=8.0, 7.0, 0.7 Hz, 2H), 7.02-6.99 (m, 2H), 4.81 (s, 2H), 4.50-4.40 (m,
4H), 3.36 (s, 2H), 2.43-2.36 (m, 2H). 13C NMR (CDCl3, 125 MHz): δ
170.3, 150.5, 146.1, 145.4, 140.0, 132.7, 129.3, 128.8, 128.4, 127.7,
127.6, 126.4, 122.9, 120.4, 119.7, 109.1, 60.2, 55.6, 40.3, 39.4, 29.9. MS
(ESI): m/z = 435.2 [M+H]+. HRMS (ESI): m/z calcd for [C29H27O2N2+H]+
435.2067, found 435.2048. HPLC: MeOH-MeCN-H2O 7-2-1
AcONH4 10 mM 7/3, flow rate: 0.7 mL/min, RT: 3.31 min.
/ H2O
1-(6-(9H-Carbazol-9-yl)hexyl)-2-((2-phenylacetoxy)methyl)pyridinium
trifluoromethanesulfonate (18b)
1-(12-(9H-Carbazol-9-yl)dodecyl)-2-((2-
phenylacetoxy)ethyl)pyridinium trifluoromethanesulfonate (19c)
Yellow oil (109 mg, 70 %). 1H NMR (CDCl3, 500 MHz): δ 8.74 (dd, J=6.0,
1.0 Hz, 1H), 8.11 (td, J=8.0, 1.5 Hz, 1H), 8.03 (d, J=7.5 Hz, 2H), 7.74
(ddd, J=8.0, 6.0, 1.5 Hz, 1H), 7.60 (dd, J=7.5, 1.5 Hz, 1H), 7.41 (ddd,
J=8.0, 7.0, 1.5 Hz, 2H), 7.36 (d, J=8 Hz, 2H), 7.28-7.23 (m, 3H), 7.19-
7.16 (m, 4H), 5.26 (s, 2H), 4.34 (t, J=8.0 Hz, 2H), 4.25 (t, J=7 Hz, 2H),
3.64 (s, 2H), 1.80 (qn, J=7.5 Hz, 2H), 1.65 (qn, J=8.0 Hz, 2H), 1.32-1.25
(m, 4H). 13C NMR (CDCl3, 125 MHz): δ 170.5, 151.0, 146.5, 145.5, 140.4,
132.7, 129.4, 129.0, 128.1, 127.8, 127.7, 125.9, 122.7, 120.4, 119.0,
108.9, 60.5, 58.3, 42.8, 40.8, 30.6, 28.6, 26.6, 25.9. MS (ESI): m/z =
477.3 [M+H]+. HRMS (ESI): m/z calcd for [C32H33O2N2+H]+ 477.2537,
found 477.2528. HPLC: MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM
7/3, flow rate: 0.7 mL/min, RT: 5.95 min.
Yellow oil (181 mg, quant.).1H NMR (CDCl3, 500 MHz): δ 8.94 (dd, J=6.0,
1.0 Hz, 1H), 8.24 (td, J=8.0, 1.0 Hz, 1H), 8.09 (d, J=7.5 Hz, 2H), 7.92
(ddd, J=6.0, 3.5, 1.5 Hz, 1H), 7.60 (dd, J=8.0, 1.5 Hz, 1H), 7.48-7.44 (m,
2H), 7.40 (d, J=8.5 Hz, 2H), 7.36-7.29 (m, 3H), 7.24-7.20 (m, 4H), 5.99 (q,
J=6.5 Hz, 1H), 4.78-4.72 (m, 1H), 4.52-4.46 (m, 1H), 4.29 (t, J=7.5 Hz,
2H), 3.69 (s, 2H), 2.14-2.05 (m, 1H), 1.98-1.91 (m, 1H), 1.86 (qn, J=7.5
Hz, 2H), 1.71 (d, J=6.5 Hz, 3H), 1.44-1.22 (m, 16H). 13C NMR (CDCl3,
125 MHz): δ 170.8, 156.8, 146.9, 146.1, 140.6, 132.5, 129.4, 129.1,
128.0, 127.7, 125.7, 125.1, 122.9, 120.4, 118.8, 108.8, 67.0, 59.2, 43.2,
41.1, 30.9, 29.5-29.1 (7C), 27.4, 26.4, 20.7. MS (ESI): m/z = 575.3
[M+H]+. HRMS (ESI): m/z calcd for [C39H47O2N2+H]+ 575.3632, found
575.3608. HPLC: MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 9/1,
flow rate: 0.7 mL/min, RT: 6.55 min.
1-(12-(9H-Carbazol-9-yl)dodecyl)-2-((2-
phenylacetoxy)methyl)pyridinium trifluoromethanesulfonate (18c)
Theoretical calculations
Yellow oil (132 mg, 74%). 1H NMR (CDCl3, 500 MHz): δ 8.83 (dd, J=6.0,
1.0 Hz, 1H), 8.24 (td, J=8.0, 1.5 Hz, 1H), 8.07 (d, J=7.5 Hz, 2H), 7.87 (td,
J=6.0, 1.5 Hz, 1H), 7.76 (dd, J=8.0, 1.0 Hz, 1H), 7.44 (td, J=7.0, 1.0 Hz,
2H), 7.38 (d, J=8.0 Hz, 2H), 7.33-7.23 (m, 5H), 7.20 (td, J=8.0, 1.0 Hz,
2H), 5.42 (s, 2H), 4.46 (tm, J=8.0 Hz, 2H), 4.26 (t, J=7.0 Hz, 2H), 3.72 (s,
2H), 1.84 (qn, J=9.5 Hz, 4H), 1.40-1.20 (m, 16H).13C NMR (CDCl3, 125
MHz): δ 170.6, 151.1, 146.6, 145.7, 140.5, 132.7, 129.4, 129.0, 128.3,
127.9, 127.8, 125.7, 122.9, 120.4, 118.8, 108.8, 60.7, 58.6, 43.2, 40.8,
31.0, 29-5-28.9 (7C), 27.4, 26.4. MS (ESI): m/z = 561.3 [M+H]+. HRMS
(ESI): m/z calcd for [C38H45O2N2+H]+ 561.3476, found 561.3454. HPLC:
MeOH-MeCN-H2O 7-2-1 / H2O AcONH4 10 mM 9/1, flow rate: 0.7 mL/min,
RT: 6.12 min.
The calculations have been performed with Gaussian 0916a using Density
Functional Theory (DFT) and the 6-311G(d,p) Pople basis sets and the
PBE0 functional. The first low-lying electronic singlet excited states have
been calculated using the time-dependent density functional theory (TD-
DFT) method16b to obtain theoretical absorption spectra. The calculations
(geometry optimizations, TD-DFT calculations) have been performed in
acetonitrile as in the experiment and solvent have been included in the
calculations by means of the polarizable continuum model by the integral
equation formalism (IEFPCM).16c All the geometry optimizations were led
without symmetry constraints and followed by a vibrational frequency
computation to ensure that they correspond to true energetic minima.
1-(3-(9H-Carbazol-9-yl)propyl)-2-(1-(2-
phenylacetoxy)ethyl)pyridinium trifluoromethanesulfonate (19a)
Acknowledgements
This research was supported by grants from Région Ile-de-
France – DIM Nano-K 2014 (France) Fellowship and a Marie
Curie Intra European Fellowship within the 7th European
Community Framework Program (FP7-PEOPLE-2013-IEF:
629675). Authors acknowledge also the generous financial
support of the ANR-2014-BLAN-1436-01 grant.
Yellow oil (149 mg, quant).1H NMR (CDCl3, 500 MHz): δ 8.87 (dd, J=7.5,
6 Hz, 1H), 8.03 (td, J=8.0, 1.5 Hz, 1H), 7.99 (d, J=7.5 Hz, 2H), 7.60 (m,
1H), 7.46 (d, J=8 Hz, 2H), 7.38-7.23 (m, 6H), 7.18-7.15 (m, 2H), 7.10-
7.08 (m, 2H), 4.79-4.72 (m, 2H), 4.61-4.48 (m, 2H), 4.15-4.09 (m, 1H)
3.45 (s, 2H), 2.77-2.76 (m, 1H), 2.47-2.45 (m, 1H), 0.92 (d, J=7.0 Hz, 3H).
13C NMR (CDCl3, 125 MHz): δ 170.4, 157.2, 146.2, 140.1, 132.5, 129.4,
128.9, 128.6, 127.7, 127.4, 126.4, 124.6, 122.9, 120.4, 119.7, 109.4,
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10.1002/chem.201801684
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9908. e) M. Petit, C. Tran, T. Roger, T. Gallavardin, H. Dhimane, F.
Palma-Cerda, M. Blanchard-Desce, F. C. Acher, D. Ogden, P. I. Dalko,
Org. Lett. 2012,14, 6366-6369.
Keywords: Caged compounds • Electron transfer • Redox
chemistry • Ab initio calculations • Probes • Nonlinear photonics
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hν!or!!
2!hν
Covalently linked carbazole-N-
alkyl picolinium dyads undergo
fragmentation under UV (366
nm), or, two-photon photolysis
conditions (730 nm) opening
the way for the design of a
Petra Dunkel, Anna Barosi,
Hamid
Dhimane,
François
Maurel,* and Peter I. Dalko*
Page No. – Page No.
Photoinduced Electron-Transfer
(PET) Mediated Fragmentation
of Picolinium-Derived Redox
Probes
e—
novel
class
of
“caged”
compounds.
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