Synthesis and electronic properties of π-extended flavins

Article abstract of DOI:10.1039/c5ob01418b

Flavin derivatives with an extended π-conjugation were synthesized in moderate to good yields from aryl bromides via a Buchwald-Hartwig palladium catalyzed amination protocol, followed by condensation of the corresponding aromatic amines with violuric acid. The electronic properties of the new compounds were investigated by absorption and emission spectroscopy, cyclic voltammetry, density functional theory (DFT) and time dependent density functional theory (TDDFT). The compounds absorb up to 550 nm and show strong luminescence. The photoluminescence quantum yields _PL measured in dichloromethane reach 80% and in PMMA (poly(methyl methacrylate)) 77%, respectively, at ambient temperature. The electrochemical redox behaviour of π-extended flavins follows the mechanism previously described for the parent flavin.

Full text of DOI:10.1039/c5ob01418b

Organic &
Biomolecular Chemistry
View Article Online
View Journal
PAPER
Synthesis and electronic properties of π-extended
flavins†
Cite this: DOI: 10.1039/c5ob01418b
a,b
b
a
a
a
c
L. N. Mataranga-Popa, I. Torje, T. Ghosh, M. J. Leitl, A. Späth, M. L. Novianti,
c
a
R. D. Webster* and B. König*
Flavin derivatives with an extended π-conjugation were synthesized in moderate to good yields from aryl
bromides via a Buchwald–Hartwig palladium catalyzed amination protocol, followed by condensation of the
corresponding aromatic amines with violuric acid. The electronic properties of the new compounds were
investigated by absorption and emission spectroscopy, cyclic voltammetry, density functional theory (DFT)
and time dependent density functional theory (TDDFT). The compounds absorb up to 550 nm and show
strong luminescence. The photoluminescence quantum yields ϕPL measured in dichloromethane reach 80%
and in PMMA (poly(methyl methacrylate)) 77%, respectively, at ambient temperature. The electrochemical
redox behaviour of π-extended flavins follows the mechanism previously described for the parent flavin.
Received 12th July 2015,
Accepted 14th August 2015
DOI: 10.1039/c5ob01418b
www.rsc.org/obc
Flavins are the prosthetic group of flavoproteins and universal π-system. An extended conjugation length is expected to shift
1
–3
redox cofactors in biology.
They play an important role in the absorption maxima to a longer wavelength and affect the
light, oxygen, and voltage-sensitive (LOV) domains sensitive for extinction coefficient and redox properties of the chromo-
4
30,31
blue light excitation. However, flavins have also found many phore.
We report here the synthesis and electronic pro-
5
–11
12–14
applications in photocatalysis
or as photosensitizers
perties of three new flavins with extended aromatic π-systems.
in singlet oxygen generation for synthesis or in photodynamic
1
3,15,16
17
disinfection.
bonding,
The local environment,
hydrogen
1
8,19
20
21,22
π–π stacking or metal coordination
to the
Results and discussion
2
3
chromophore and the type and position of substituents
Synthesis
determine the redox potentials and the photophysical pro-
perties of flavin derivatives. Donor–acceptor systems, in which
flavins are covalently linked to other chromophores showing
3
2
The synthesis of new π-system extended flavins 3a, 3b and 3c
was accomplished by the condensation of violuric acid 1
with the corresponding amines 2a–c as starting materials. The
3
3
2
4,25
different absorptions have been synthesized
photo-voltaic devices, molecular switching or molecular logic
and used in
3
4
26
amines were obtained via a Buchwald–Hartwig amination in
good to very good yields. The subsequent condensation of
amines 2a–2c with violuric acid 1 in boiling acetic acid easily
furnished multi-gram quantities of flavins 3a–c in moderate to
good yields (Scheme 1).
The structures of flavins 3a–3c were determined by NMR
spectroscopy and confirmed by high resolution mass spectro-
metry and elemental analysis. The electronic properties of
flavin derivatives 3a–3c were investigated by absorption and
emission spectroscopy (Table 1), cyclic voltammetry, DFT and
TDDFT calculations (Fig. 1). Furthermore, the fluorescence
quantum yields of the chromophores were determined with an
integrating sphere accessory.
2
6,27
gates.
acceptors in photoinduced electron transfer (PET)
known to bind different metal ions inducing a positive shift
Oxidized forms of flavin derivatives act as electron
2
8,29
and are
2
9
in their one-electron reduction potentials and long-lived
charge-separation.
2
9
A less explored option to modify the optical and electronic
properties of flavins is the extension of their aromatic
a
University of Regensburg, Universitatsstraße 31, 93053 Regensburg, Germany.
E-mail: burkhard.koenig@chemie.uni-regensburg.de
b
Babes-Bolyai University Cluj-Napoca, Faculty of Chemistry and Chemical
Engineering, Arany Janos Str. 11, Cluj-Napoca, 400428 Romania
c
Division of Chemistry & Biological Chemistry, School of Physical and Mathematical
Theoretical calculations
Sciences, Nanyang Technological University, 21 Nanyang Link, 637371 Singapore.
E-mail: Webster@ntu.edu.sg
Computational investigations are particularly useful for under-
standing trends observed in the electrochemical and photo-
physical properties of molecular materials. Thus, density
functional theory (DFT) and time dependent density func-
†
Electronic supplementary information (ESI) available: Detailed experimental
1
13
procedures, copies of H and C NMR spectra of compounds 2a–2c and 3a–3c;
and selected molecular orbitals for compounds 3a–3c. See DOI: 10.1039/
c5ob01418b
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
TDDFT calculations revealed that transitions between these
frontier orbitals determine the lowest excited singlet state S1.
The corresponding transition energies amount to 2.47 eV (3a),
2.44 eV (3b), and 2.85 eV (3c). This is in agreement with the
experimental results (see below) which show that the emission
energies of compounds 3a and 3b are similar, whereas the
emission of compound 3c is clearly blue-shifted. This trend is
also seen in the absorption spectra.
Electronic properties
The UV-visible absorption and emission spectral data of the
flavins in two different organic solvents and in a polymer
matrix (PMMA = poly(methyl methacrylate)) are summarized
in Table 1. The absorption and emission spectra of flavin
derivatives 3a, 3b, 3c, and butyl flavin derivative 4 recorded in
DMSO are displayed in Fig. 2a and b. All new derivatives show
a complex absorption profile characteristic for the presence of
multiple chromophores. The flavins exhibit intense absorption
bands in the range of 306–543 nm. The S
4
1
0
→ S
40 nm, characteristic for the parent flavin 4, is red shifted by
5 nm for compound 3c, 52 nm for 3b, and 57 nm for 3a,
decreased
Scheme 1 Synthesis of the flavins 3a–3c. Reaction conditions: amines HOMO–LUMO gap. Furthermore, the absorption bands in the
1
band around
respectively, in DMSO solution, indicating
a
2
a–2c (1.2 eq.), violuric acid 1 (1 eq.), acetic acid, reflux, 19 h. For com-
range 306–400 nm show a vibrational fine structure character-
parison, the structure of the parent flavin 4 is shown.
istic for the isolated naphthalene, anthracene and pyrene
3
5
chromophore. However, the molar extinction coefficient of
anthracene derivative 3b is significantly higher than those
observed for pyrene 3a and naphthalene 3c. A likely reason for
tional (TDDFT) calculations were performed to gain additional this is the extended linear conjugated system.
understanding of the electronic structures of the π-expanded
flavins (3a, 3b, and 3c).
Compounds 3a and 3b show an intense orange emission
under daylight irradiation, while 3c emits in the green.
The emission spectrum of 3c shows a vibrational structure,
Interestingly, the contour curves of the lowest unoccupied
molecular orbitals (LUMOs) look similar for all three investi- similar to that of butyl flavin (4), with a spacing of the
−
1
gated compounds being largely unaffected by the π-extension vibrational satellites amounting to about 1000 cm . This
Fig. 1). Also, the LUMO energies are similar ranging from energy spacing corresponds to the characteristic stretching
2.88 eV to −2.96 eV. In contrast to this, the highest occupied modes of isoalloxazines. Furthermore, the structured emission
(
−
molecular orbitals (HOMOs) are delocalized over large parts of indicates that the emission is originating from a localized π–π*
the molecule for all investigated compounds (Fig. 1). Conse- transition. In contrast, the emissions of 3a and 3b are broad
quently, the HOMO energies vary in a wider energy range from and do not exhibit any structure indicating that the emission
−5.70 eV to −6.11 eV.
originates from a state with some charge transfer character.
Table 1 Selected photophysical properties of flavins 3a–3c and 4 measured at ambient and liquid nitrogen temperature, respectively. λabs.max is the
peak wavelength of the absorption spectrum, λem.max is the peak wavelength of the emission spectrum, τ the emission decay time, and ΦPL the
photoluminescence quantum yield. PMMA: poly(methyl methacrylate)
τ (300 K)/τ
(77 K) [ns]
ΦPL (300 K)/ΦPL
(77 K) [%]
Compound
Solvent polymer
λabs.max [nm]
λem.max (300 K) [nm]
3a
3b
3c
4
DCM
339, 355, 503, 543
340, 357, 500, 530
610
628
580
585
605
628
511, 544 (sh)
516, 545 (sh)
518 (sh), 539
498, 526 (sh)
60/80
46/57
50/74
24/70
53/65
28/35
80/≈100
13/33
77/80
14
DMSO
PMMA
DCM
DMSO
PMMA
DCM
DMSO
PMMA
DMSO
9/15
11/11
361, 384, 505, 542
357, 386, 495, 526
7/16
6/6
306, 462, 490
306, 457, 486
2/11
11/11
—
343, 443, 470
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Organic & Biomolecular Chemistry
Paper
Fig. 1 HOMOs and LUMOs of compounds 3a, 3b, and 3c. The plots result from DFT calculations performed on the B3LYP/6-31G** level of theory.
The iso-contour value was set to 0.03. Further molecular orbitals and the corresponding energies are displayed in the ESI.†
the isoalloxazine part. In addition, the emission maxima show
a clear dependence on the polarity of the solvent, which is
typical for charge transfer transitions. In the case of 3a, in
3
6
DCM (ET(30) = 41.1) the emission peaks at 610 nm whereas
3
6
it is red shifted by 18 nm in DMSO (ET(30) = 45.0) to 628 nm.
Compound 3b exhibits a similar red shift of 20 nm from
5
3
85 nm to 605 nm when we go from DCM to DMSO. For flavin
c a corresponding shift from 511 nm to 516 nm is observed.
The emission quantum yields of the new compounds 3a–3c
vary with solvent and temperature. In solution at T = 300 K the
emission quantum yields are between 24 and 80% in DCM, 13
and 53% in DMSO and 13 and 77% in PMMA. The corres-
ponding ΦPL values at nitrogen temperature increase, which
may be explained by a decrease of non-radiative deactivations
on cooling. The life times at 300 K of the excited states of the
three compounds are in the range of 2 to 9 ns in DMSO and
6
–11 ns in PMMA. The values increase only slightly when
decreasing the temperature from 300 K to 77 K; in PMMA the
same values are observed for both temperatures. We assume
that the radiative emission at 300 K and 77 K originates from
the singlet excited state being involved without the triplet state
involvement.
Redox properties
The voltammetric behaviour and reduction mechanism of
compounds 3a, 3b and 3c in DMSO can be interpreted based
on the mechanism for the closely related riboflavin, which has
Fig. 2 (a) UV-Vis and (b) emission spectra of 1.0 × 10− M solutions of
3
4
a (black line), 3b (red line), 3c (blue line) and 4 (green line) in DMSO at
300 K (λexc = 450 nm).
3
7–39
been studied in detail previously.
The variable scan rate cyclic voltammograms of compound
3a shown in Fig. 3 appear most similar to those obtained for
This assignment is also supported by the TDDFT calculation riboflavin and can be interpreted based on the mechanism in
3
9
0
(
Fig. 1), which predicts that the S
1
state is of partial charge Scheme 2. Compound 3a (Fl ) is initially reduced at E
f(1)
by
ox
•
−
transfer character for 3a and 3b due to HOMO orbitals deloca- one-electron to form the radical anion (Flrad ). The radical
lized over the entire molecule and LUMO orbitals localized on anion reacts quickly with another flavin by proton transfer to
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
•
form the neutral radical (FlradH ) via eqn (1) plus the deproto-
nated flavin (Flox−). Because Flrad
H
•
is easier to reduce
than Flox, it is immediately further reduced at the electrode
−
0
surface by one-electron to form FlredH at E f(3). Therefore, the
first voltammetric process (wave 1) observed at ∼−1.0 V vs.
+
Fc/Fc actually involves two one-electron transfers interspaced
with a proton transfer reaction. When the scan direction is
+
reversed at approximately −1.5 V vs. Fc/Fc , two oxidative
peaks are observed. The first oxidative peak at ∼−1.0 V vs.
+
•−
Fc/Fc (wave 2) is due to the one-electron oxidation of Flrad back
to the starting material, Fl , while the second electron transfer
ox
+
at −0.7 V vs. Fc/Fc is due to the one-electron oxidation of
−
•
Flred
H to FlradH (wave 3). If the equilibrium in eqn (1) in
3
9
Scheme 2 favours the back reaction (as it does for riboflavin),
then any Flrad
•
H
that deprotonates on the voltammetric
timescale will also undergo further one-electron oxidation
in wave 3 to regenerate the starting material. As the scan rate
−1
is increased up to 20 V s , the initial reduction process at
+
∼
−1.0 V vs. Fc/Fc becomes more chemically reversible shown
ox red
by how the i /ip ratio approaches unity, due to the proton
p
•
−
transfer step between Flrad and Flox being outrun; hence
the reduction process changes to a chemically reversible one-
electron transfer.
When the voltammetric scan is extended to more negative
Fig. 3 Variable scan rate CVs of 2 mM 3a in DMSO with 0.2 M
n-Bu
4 6
NPF
, recorded at a 1 mm Pt electrode at 22(±2) °C. The current potentials, additional reduction processes are detected at
−0.5
+
+
data were scaled by multiplying by ν
.
∼−1.7 V vs. Fc/Fc (wave 4) and ∼−2.0 V vs. Fc/Fc (wave 5) for
compound 3a. Wave 4 is associated with the one-electron
−
reduction of Flox that is formed from the Flox reacting with
•
−
0
Flrad (E ), and wave 5 is associated with the further one-
f(4)
•
−
2−
0
electron reduction of Flrad to form Flred (E f(5)). When the
forward potential scan is extended all the way past wave 5, on
the reverse scan it can be observed that the oxidative wave 3 is
larger than when the forward scan is only extended just past
−
wave 1. The reason for wave 3 appearing larger is because Flred
H
(
which undergoes oxidation in wave 3) can also be formed via
2−
−
−
Flred reacting with Flox to form FlredH (plus Flox ) (eqn (2)).
The voltammetric responses observed for compounds 3b
and 3c appear somewhat different from 3a, but they can be
interpreted based on exactly the same mechanism as for com-
pound 3a; the subtle differences in the voltammetric waves
can be accounted for by varying equilibrium constants for the
homogeneous reactions given in Scheme 2. For example, at
relatively slow scan rates the first voltammetric reduction
process of 3b and 3c appears to be fully chemically reversible
implying a simple chemically reversible electron transfer reac-
tion (only waves 1 and 2 are observed), and the process
remains chemically reversible as the scan rate is increased up
to 20 V s− . The reason for the high chemical reversibility
1
•
−
likely relates to the radical anion (Flrad ) formed in the initial
0
electron transfer step at E
undergoing a slow homogeneous
f(1)
reaction with Flox (eqn (1)), so on the short voltammetric time-
•
−
scale Flrad survives fully at the electrode surface and is able
to be converted back to Flox when the scan direction is
reversed (Fig. 4 and 5).
When the scan is extended to more negative potentials,
compounds 3b and 3c show an additional process at ∼−1.8 V
Scheme 2 General electrochemical reduction mechanism for flavins in
DMSO.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Organic & Biomolecular Chemistry
Paper
+
vs. Fc/Fc (wave 5) which is associated with the further one-
•
−
2−
0
electron reduction of Flrad to form Flred (E f(5)). Wave 5
appears more clearly than was observed during the reduction
•
−
of compound 3a because more Flrad exists at the electrode
surface in higher amounts (due to the slower proton transfer
reaction with Flox). Similarly, the reduction process associated
0
with wave 4 (E f(4)) is not observed during the reduction of 3b
and 3c because Flox− does not have time to form via the proton
•
−
transfer reaction between Flrad and Flox. The peak shape of
the wave 5 reduction process is “sharp” and this is likely due
to some adsorption of the dianion onto the electrode surface.
−
2•−
The reason that wave 4 (reduction of FlredH to Flrad ) is not
observed for compounds 3b and 3c may arise either due to
lower acidity of the N–H proton of the starting materials or
due to lower basicity of their corresponding anion radicals
•
−
(
Flrad ).
When then voltammetric scanning direction was switched
+
•−
2−
at −2.2 V vs. Fc/Fc after first reducing Flrad to Flred , no
reverse peak was detected associated with the oxidation of
2
−
•−
Flred back to Flrad regardless of the scan rate, indicating
that the dianion is only very short-lived for compounds 3b and
3
c. Similarly, when the potential was first scanned to −2.2 V
+
vs. Fc/Fc , on the reverse scan only wave 2 was observed at slow
Fig. 4 Variable scan rate CVs of 2 mM 3b in DMSO with 0.2 M scan rates. However, as the scan rate is increased, wave 3
n-Bu NPF
, recorded at a 1 mm Pt electrode at 22(±2) °C. The current becomes more pronounced and wave 2 diminishes in size. A
data were scaled by multiplying by ν
4
6
−0.5
.
reason for this apparently anomalous behaviour can be based
on the equilibrium reactions that exist between the different
•
−
species in Scheme 2 favouring the reformation of Flrad . For
example, when the dianion is formed, it immediately under-
goes a proton transfer reaction with the starting material to
−
−
−
form Flred
H
plus Flox (Scheme 2, eqn (2)). Flred
H
then
−
undergoes another reaction with Fl
of Flrad (Scheme 2, eqn (3)). Therefore, at slow scan rates,
to form two molecules
ox
•
−
2
−
•−
Flred has time to convert all the way back to Flrad so only
wave 2 is observed, while at faster scan rates, there is only
2
−
−
time for Flred to convert to Flred
H and so wave 3 is mainly
observed.
Experimental part
Computational procedures
DFT and TDDFT calculations were performed using Gaussian
4
0
0
9. For all calculations (geometry optimizations and TDDFT
4
1,42
energy calculations), B3LYP
combination with the 6-31G** basis set.
was used as the functional in
4
3,44
As the starting
geometry, manually drawn structures were used. For all com-
pounds, the structure was optimized prior to TDDFT energy
calculations.
General procedure for the syntheses of compounds 3a–c (GP1)
A mixture of amines 2a–c (1 eq.), violuric acid 1 (1.2 eq.) and
100 mL of glacial acetic acid was added to a round bottom
flask and refluxed for 24 h. Acetic acid was removed
under reduced pressure, giving a purple solid residue. The
residue was purified by flash chromatography on silica gel
Fig. 5 Variable scan rate CVs of 2 mM 3c in DMSO with 0.2 M
n-Bu NPF , recorded at a 1 mm Pt electrode at 22(±2) °C. The current
data were scaled by multiplying by ν
4
6
−0.5
.
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
(chloroform/methanol 50 : 1) to yield flavins 3a–c as yellow or 130.14 (Cquat), 130.65 (Cquat), 132.98 (Cquat), 133.50 (Cquat),
red solids.
133.70 (C ), 140.59 (Cquat), 141.53 (Cquat), 147.61 (Cquat).
quat
IR (ν, cm− ): 2967 (w), 1638 (s), 1473 (m), 1412 (s), 1202 (m).
1
9
-Butylpyreno[4,5-g]pteridine-11,13(9H,12H)-dione (3a)
UV-Vis (CH
2
Cl
2
):
λ
max (ε)
= 262 (18 440), 306 (8170),
This compound was synthesized according to GP1 and after 315 (8350), 434 (5280), 462 (8210), 490 (7080). MS (ES-MS) m/z:
+
purification by flash chromatography on silica gel (chloro- 321 (M + H). MS(HRMS/ESI) m/z: calc. For C18
H
16
N
4
O
2
+
form/methanol 50 : 1), 3a (224 mg, 47%) was obtained as a red (M + H ): 321.1273, found 321.1350.
solid. R (chloroform/methanol 10 : 1): 0.44.
f
1
M.p. 300 °C (decomp). H-NMR (300 MHz, CF
3
COOD,
δ ppm): 1.43 (t, J = 6 Hz, 3 H), 1.92 (m, 2 H), 2.76 (m, 2 H), 6.19 Conclusions
(
9
(
(
1
(
1
1
t, J = 6 Hz, 2 H), 8.76 (m, 4 H), 9.05 (d, J = 9 Hz, H), 9.24 (d, J =
1
3
Flavin derivatives 3a–c were obtained from the condensation
of naphthyl-, anthranyl- or pyrenyl-amines 2a–c with violuric
acid. Extending the π-system of the parent flavin by annulation
of benzene, the naphthalene or pyrene unit changes the elec-
tronic and redox properties of the chromophore significantly.
The chromophore absorption shifts bathochromic and
all three compounds show intensive emission with quantum
yields of up to 80%. The reduction mechanism of the
expanded flavins in DMSO as observed in cyclic voltammetry
experiments can be interpreted analogously to the previously
investigated parent flavin, with the subtle differences in the
voltammetric behaviour due to varying equilibrium constants
for the homogeneous reactions following electron transfer.
Hz, H), 9.45 (d, J = 9 Hz, H), 9.99 (d, J = 9 Hz, H). C-NMR
COOD, δ ppm): 11.69 (CH ), 18.91 (CH ), 30.47
CH ), 59.46 (CH ), 109.07 (CH), 112.82 (Cquat), 116.57 (Cquat),
300 MHz, CF
3
3
2
2
2
20.32 (CH), 124.93 (CH), 125.64 (CH), 126.94 (CH), 127.45
CH), 129.21 (Cquat), 129.45 (CH), 129.93 (CH), 130.26 (Cquat),
32.11 (Cquat), 132.36 (Cquat), 133.21 (Cquat), 136.86 (Cquat),
40.18 (Cquat), 141.75 (Cquat), 144.86 (Cquat), 150.12 (Cquat).
−
1
IR (ν, cm ): 2961 (m), 1652 (s), 1460 (m), 1426 (m), 1400 (m),
1
3
(
191 (m). UV-Vis (CH Cl ): λmax(ε) = 281 (17 100), 340 (8480),
2 2
55 (8250), 503 (3740), 543 (4370). MS (ES-MS) m/z: 395
+
+
M + H). MS(HRMS/ESI) m/z: calc. For C24
H
18
N
4
O
2
(M + H):
3
95.143, found 395.150. Anal. calcd for C H N O ·0.5H O:
2
4
18
4
2
2
C 71.45, H 4.75, N 13.89, found: C 71.02, H 4.60, N 13.91.
5
-Butylanthra[1,2-g]pteridine-1,3(2H,5H)-dione (3b)
Acknowledgements
The compound was synthesized according to GP1 and after
purification by flash chromatography on silica gel (chloro-
form/methanol 50 : 1), 3b (224 mg, 58%) was obtained as a red
We thank M. Hansen for helping with the graphical abstract.
solid. R
M.p. 320 °C (decomp). H-NMR (300 MHz, CF
δ ppm): 1.69 (t, J = 6 Hz, 3 H), 2.36 (m, 2 H), 2.71 (m, 2 H), 5.57
t, J = 9 Hz, 2 H), 8.44 (m, 3 H), 8.85 (dd, J = 6 Hz, 2 H), 9.31 (s,
f
(chloroform/methanol 10 : 1): 0.20.
1
3
COOD,
Notes and references
(
1 J. P. Beardmore, L. M. Antill and J. R. Woodward, Angew.
Chem., Int. Ed., 2015, 54, 8494–8497.
2 E. Jortzik, L. Wang, J. Ma and K. Becker, in Flavins and
Flavoproteins, ed. S. Weber and E. Schleicher, Springer,
New York, 2014, vol. 1146, ch. 7, pp. 113–157.
1
3
H), 9.50 (d, J = 9 Hz, H), 10.47 (s, H). C-NMR (300 MHz,
CF COOD, δ ppm): 12.06 (CH ), 19.36 (CH ), 29.81 (CH ),
3
3
2
2
5
2
1.32 (CH ), 109.06 (CH), 112.81 (Cquat), 116.56 (CH), 120.32
(CH), 126.00 (CH), 127.22 (CH), 129.23 (Cquat), 129.74 (CH),
1
29.90 (Cquat), 130.49 (Cquat), 132.10 (CH), 143.96 (CH), 135.35
3 M. Lee, J. Hong, D.-H. Seo, D. H. Nam, K. T. Nam, K. Kang
and C. B. Park, Angew. Chem., Int. Ed., 2013, 52, 8322–8328.
4 K. S. Conrad, C. C. Manahan and B. R. Crane, Nat. Chem.
Biol., 2014, 10, 801–809.
(Cquat), 136.78 (Cquat), 140.06 (Cquat), 143.76 (Cquat), 150.15
−
1
(C
quat), 150.49 (Cquat). IR (ν, cm ): 2958 (m), 1647 (s), 1518
(m), 1496 (m), 1448 (m), 1244 (m). UV-Vis (CH Cl ): λmax(ε) =
2
2
2
95 (27 210), 361 (6900), 505 (5940), 542 (7210). MS (ES-MS)
5 V. Mojr, E. Svobodova, K. Strakova, T. Nevesely, J. Chudoba,
H. Dvorakova and R. Cibulka, Chem. Commun., 2015, 51,
12036–12039.
+
18 4 2
m/z: 371 (M + H). MS (HRMS/ESI) m/z: calc. For C22H N O
+
(M + H): 371.1503, found 371.1506.
6
S. K. B. König and R. Cibulka, Chemical Photocatalysis, ed.
B. König, de Gruyter, Berlin, 2013, pp. 45–66.
3
2
7
-Butylnaphto[1,2-g]pteridine-9,11(7H,10H)-dione (3c)
The compound was synthesized according to GP1 and after
purification by recrystallization from chloroform, 3c (173 mg,
7 J. Daďová, S. Kümmel, C. Feldmeier, J. Cibulková,
R. Pažout, J. Maixner, R. M. Gschwind, B. König and
R. Cibulka, Chem. – Eur. J., 2013, 19, 1066–1075.
8 T. Ghosh, T. Slanina and B. Konig, Chem. Sci., 2015, 6,
2027–2034.
4
6%) was obtained as an orange solid. R
methanol 10 : 1): 0.38.
M.p. 280 °C (decomp). H-NMR (300 MHz, CF
ppm): 1.80 (t, J = 6 Hz, 3 H), 2.47 (m, 2 H), 2.82 (m, 2 H), 5.74
f
(chloroform/
1
3
COOD, δ
9 R. Lechner, S. Kummel and B. Konig, Photochem. Photobiol.
Sci., 2010, 9, 1367–1377.
(
6
1
t, J = 6 Hz, 2 H), 8.85 (m, 4 H), 9.55 (d, J = 9 Hz, H), 10.1 (d, J =
1
3
Hz, H). C-NMR (300 MHz, CF
3
COOD, δ ppm): 12.16 (CH
3
), 10 U. Megerle, M. Wenninger, R.-J. Kutta, R. Lechner,
9.48 (CH ), 29.92 (CH ), 51.41 (CH
2
2
2
), 109.18 (CH), 112.93
B. Konig, B. Dick and E. Riedle, Phys. Chem. Chem. Phys.,
2011, 13, 8869–8880.
(CH), 116.68 (CH), 120.44 (CH), 125.40 (CH), 129.00 (CH),
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Organic & Biomolecular Chemistry
Paper
1
1 B. Muhldorf and R. Wolf, Chem. Commun., 2015, 51, 8425–
428.
and D. Trauner, Curr. Opin. Neurobiol., 2009, 19, 544–
552.
8
1
2 D. R. Cardoso, S. H. Libardi and L. H. Skibsted, Food 31 C. M. Marian, S. Nakagawa, V. Rai-Constapel, B. Karasulu
Funct., 2012, 3, 487–502.
3 B. G. Solheim, Transfus. Apher. Sci., 2008, 39, 75–82.
4 R. Yin, T. Dai, P. Avci, A. E. S. Jorge, W. C. M. A. de Melo,
and W. Thiel, J. Phys. Chem. B, 2014, 118, 1743–1753.
32 H. Lettre and M.-E. Fernholz, Ber. Dtsch. Chem. Ges. B,
1940, 436–441.
1
1
D. Vecchio, Y.-Y. Huang, A. Gupta and M. R. Hamblin, 33 A. Rosler and W. Pfleiderer, Helv. Chim. Acta, 1997, 80,
Curr. Opin. Pharmacol., 2013, 13, 731–762. 1869–1881.
5 J. Glaeser, A. M. Nuss, B. A. Berghoff and G. Klug, in 34 J. Louie and J. F. Hartwig, Tetrahedron Lett., 1995, 36, 3609–
1
Advances in Microbial Physiology, ed. K. P. Robert, Academic
Press, 2011, vol. 58, pp. 141–173.
6 M. Insińska-Rak and M. Sikorski, Chem. – Eur. J., 2014, 20,
3612.
35 D. Kumar and K. R. J. Thomas, J. Photochem. Photobiol., A,
2011, 218, 162–173.
1
1
1
1
2
2
1
5280–15291.
36 C. Reichardt, Angew. Chem., Int. Ed. Engl., 1979, 18,
98–110.
37 H. Lettre and M. Fernholz, Ber. Dtsch Chem. Ges. B, 1940, 436.
7 M. Prongjit, J. Sucharitakul, B. A. Palfey and P. Chaiyen,
Biochemistry, 2013, 52, 1437–1445.
8 T. Akiyama, F. Simeno, M. Murakami and F. Yoneda, J. Am. 38 A. Niemz, J. Imbriglio and V. M. Rotello, J. Am. Chem. Soc.,
Chem. Soc., 1992, 114, 6613–6620. 1997, 119, 887–892.
9 B. D. Zoltowski, A. I. Nash and K. H. Gardner, Biochemistry, 39 S. L. J. Tan and R. D. Webster, J. Am. Chem. Soc., 2012, 134,
011, 50, 8771–8779. 5954–5964.
0 V. Nandwana, I. Samuel, G. Cooke and V. M. Rotello, Acc. 40 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
2
Chem. Res., 2013, 46, 1000–1009.
1 S. Gozem, E. Mirzakulova, I. Schapiro, F. Melaccio,
K. D. Glusac and M. Olivucci, Angew. Chem., Int. Ed., 2014,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato,
X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng,
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao,
H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta,
F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers,
K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand,
K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene,
J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador,
J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas,
J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaus-
sian 09, Revision D.01, Gaussian, Inc., Wallingford CT,
2009.
5
3, 9870–9875.
2 M. Szymański, A. Maciejewski and R. P. Steer, Chem. Phys.,
988, 124, 143–154.
3 S. Sayin, G. Uysal Akkuş, R. Cibulka, I. Stibor and
M. Yilmaz, Helv. Chim. Acta, 2011, 94, 481–486.
2
2
2
2
1
4 Y.-M. Legrand, M. Gray, G. Cooke and V. M. Rotello, J. Am.
Chem. Soc., 2003, 125, 15789–15795.
5 R. F. Pauszek, G. Kodali, S. T. Caldwell, B. Fitzpatrick,
N. Y. Zainalabdeen, G. Cooke, V. M. Rotello and
R. J. Stanley, J. Phys. Chem. B, 2013, 117, 15684–15694.
6 F. L. Carter, R. F. Siatkowski and J. Wohltjen, Molecular
Electronic Devices, Elsevier, Amsterdam, The Netherlands,
2
1
988.
2
2
2
7 J. Jortner and M. A. Ratner, Molecular Electronics, Blackwell,
Oxford, 1997.
8 L. Crovetto and S. E. Braslavsky, J. Phys. Chem. A, 2006, 110, 41 F. Weigend and R. Ahlrichs, Phys. Chem. Chem. Phys., 2005,
307–7315. 7, 3297–3305.
9 F. Tanaka, H. Chosrowjan, S. Taniguchi, N. Mataga, 42 A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652.
K. Sato, Y. Nishina and K. Shiga, J. Phys. Chem. B, 2007, 43 W. J. Hehre, R. Ditchfield and J. A. Pople, J. Chem. Phys.,
7
1
11, 5694–5699.
0 Modified flavins with bathochromic absorption may be 44 J. D. Dill and J. A. Pople, J. Chem. Phys., 1975, 62, 2921–
of interest for neurobiology. R. H. Kramer, D. L. Fortin 2923.
1972, 56, 2257–2261.
3
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.