Two-photon absorption properties of push-pull oxazolones derivatives

Article abstract of DOI:10.1016/j.dyepig.2012.06.005

New fluorescent oxazolone derivatives with high two-photon absorption cross-section were synthesized. Electron donor (phenyl, dimethylaniline and furanyl) and acceptor (nitrobenzene and ethenyl-phenyl-benzimidazol) groups have been appended to the methyle

Full text of DOI:10.1016/j.dyepig.2012.06.005

Dyes and Pigments 95 (2012) 713e722
Contents lists available at SciVerse ScienceDirect
Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
Two-photon absorption properties of pushepull oxazolones derivatives
Catarina A.B. Rodrigues , Inês F.A. Mariz , Ermelinda M.S. Maçôas *, Carlos A.M. Afonso a,
José M.G. Martinho
a
a
b
b,
b
Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
Centro de Química-Física Molecular and IN-Institute of Nanoscience and Nanothecnology, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 April 2012
Received in revised form
New fluorescent oxazolone derivatives with high two-photon absorption cross-section were synthesized.
Electron donor (phenyl, dimethylaniline and furanyl) and acceptor (nitrobenzene and ethenyl-phenyl-
benzimidazol) groups have been appended to the methylene end of 4-(methylidene)-2-phenyl-1,3-
12 June 2012
oxazol-5(4H)-one in order to produce an highly conjugated
p-system with pushepull geometry. The
Accepted 13 June 2012
Available online 10 July 2012
linear and nonlinear optical properties of the oxazolones have been determined. The compounds with
a high charge transfer from the substituent group to the oxazolone ring have relatively high two-photon
absorption cross-sections (80e100 GM). The best performing nonlinear fluorophore being the benzi-
midazol derivative with a two-photon absorption cross-section of 80 GM and a relatively high emission
Keywords:
Two-photon absorption
Fluorescence
quantum yield,
f
¼ 0.31.
Oxazolone
Ó 2012 Elsevier Ltd. All rights reserved.
Solvatochromism
Nonlinear emission
Push-pull
1
. Introduction
circumvented in the solid phase because the photochemical
decomposition due to ring-opening is strongly inhibited. In addi-
tion, the emission quantum yields of oxazolones with an exocyclic
double bond at position 4 (Fig. 1b), also known as unsaturated
oxazolones, are usually low. One of the factors determinant of the
low quantum yield is the Z to Eꢀ geometrical isomerization.
Encapsulation in the solid matrix prevents geometrical isomeriza-
tion, thus increasing the radiative quantum yield. An interesting
application of oxazolones in solid phase (dispersed in solegel and
polymer matrices) is that of optical pH sensors [22e24].
Two-photon absorbing fluorophores are compounds that emit
light after absorbing simultaneously two photons that promote the
transition of an electron from a lower energy level to a higher level.
The absorbed photons are up-converted into emitted photons with
twice the energy. These type of compounds have attracted high
interest in the last decade due totheir photochemical properties and
subsequent wide range of applications such as microfabrication,
data storage, photodynamic therapy, optical power limiting and
sensors [1,2]. Many compounds with two-photon absorption (TPA)
have been described in the literature [1,2]. Optimization of the TPA
cross-section generally requires molecular structures of high
complexity employing long synthetic procedures [1,2].
With introduction of an exocyclic double bond at position 4 of
the ring (Fig. 1b) the oxazolone gains a new reactivity in this
position that allows the construction of interesting molecular
structures [25e33]. This double bond also creates a highly
Oxazol-5-(4H)-ones (hereafter referred to as oxazolones) are
small and simple molecules that have the general structure pre-
sented in Fig. 1a. Due to their numerous reactive sites, oxazolones
have a wide range of applications in chemistry and biology [3,4].
Oxazolones are valuable precursors in the synthesis of non-natural
aminoacids [5] and biological active heterocyclic molecules [3]
which led to a great interest on different types of transformations
to access highly substituted scaffolds [6e21].
conjugated
p-system and subsequently new photophysical
behaviour that makes oxazolones suitable for applications in
photonics and electronics. Since the late 70’s this conjugated
system attracted the attention of several scientists and the influ-
ence of aryl substituents in the absorption and fluorescence of
oxazolones have been extensively studied [34e37]. In 1995 the
first observation of nonlinear optical behaviour of oxazolones
trough second harmonic generation (SHG) [38] was reported.
Since then a huge amount of studies regarding spectroscopy and
nonlinear properties of oxazolones have been described [39e44].
One of these studies mentioned that oxazolones might show TPA
characteristics [42].
One of the main issues regarding application of oxazolones is
related to their poor photochemical stability. This issue can be
*
Corresponding author. Tel.: þ351 218419218.
E-mail address: ermelinda.macoas@ist.utl.pt (E.M.S. Maçôas).
0143-7208/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.dyepig.2012.06.005

714
C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
Varian Inc. Palo Alto CA, USA, equipped with an ESI source. High
Resolution mass spectra were obtained in a Finnigan FT/MS 2001
DT, FT-ICR/MS mass spectrometer, operating at EI positive mode.
The linear absorption spectra were recorded on a Shimadzu UV-
3101PC UVeviseNIR spectrophotometer. The emission spectra
were recorded on a Horiba Jobin Yvon Fluorolog 3-22 Spectroflu-
orimeter. The solvatochromic shifts have been determined in
spectroscopic grade solvents without further purification, degass-
ing or drying. The solvents were chosen so has to span a wide range
of dielectric constants without a significant change of the refractive
index. In order of increasing dielectric constant, the solvents used
were: benzene (Bz), toluene (Tol), chloroform (CF), diethyl ether
Fig. 1. a) General structure of oxazol-5-(4H)-ones and their reactive sites a, b) general
structure of unsaturated oxazol-5-(4H)-ones.
Herein, we present the study of TPA properties of a set of
pushepull compounds based on 4-(methylidene)-2-phenyl-1,3-
oxazol-5(4H)-one easily synthesised by the well-known Erlen-
meyer method [45,46]. The goal of this study is to understand the
(
(
(
DE), methyl acetate (MA), ethyl acetate (EA), tetrahydrofuran
THF), dichloromethane (DCM), acetone (Ac), dimethylformamide
DMF), acetonitrile (ACN) and dimethylsulfoxide (DMSO).
The two-photon absorption spectra were measured by two-
photophysics of a set of oxazolone derivatives with D-
A arrangements in order to gain insight on the design of oxazolone
derivatives with high two-photon absorption cross-section ( ) and
acceptable fluorescence quantum yields ( ). These are properties
p-A and A-p-
photon excited fluorescence using Rhodamine 6G (fluorescence
quantum yield of 0.93,
lem ¼ 500e600 nm) [50] as a standard to
s
2
account for collection efficiency and pulse characteristics. A
modified setup that follows closely the one described by Xu and
Webb [51] was used. In order to select a narrow bandwidth of
emission wavelengths an H20Vis Jobin Yvon monochromator was
placed at the entrance of a PMC-100-4 photomultiplyer tube
f
that potentiate their application as labels in bioimaging, and as
nonlinearly activated optical sensors. The nonlinearity of interac-
tion with light is particularly advantageous when working in bio-
logical samples due to the intrinsic reduction of out of focus
photobleaching and photodamage, and the greater penetration
depth of the longer wavelengths used in multiphoton excitation
(
Becker and Hickl GmbH). The excitation source was a Ti:Sapphire
laser (Tsunami BB, Spectra-Physics, 710e990 nm, 1.7 W, 100 s,
2 Mz). In general, solutions of 10 M concentration in tetrahy-
8
m
[47]. In addition, the up-converted emission signal, usually in the
drofuran (THF) were used. The TPA cross-sections of more chal-
lenging derivatives with low TPA values were evaluated in
visible range, is very efficiently separated from scattered excitation
light in the infrared range. The main problem of multiphoton
excitation relates to the high excitation powers required due to the
2e0.7 mM concentrated THF solutions. The two-photon absorption
cross-section was calculated from the relation:
low probability of the nonlinear absorption process (typically
s
2
ꢀ
51
ꢀ46
4
ꢀ
ꢁ
ꢀ
ꢁ
values are w10 e10
cm s while linear absorption cross-
F2
Cn
Cn
f s
2
F2
2
s
2
¼
(1)
sections are
s
1
w 10ꢀ19e10ꢀ16 cm ), which causes significant
f
ox
ref
bleaching in the focal plane. The unwanted bleaching can be
reduced by designing more efficient nonlinear fluorophores.
Indeed, commercially available fluorophores used in bioimaging,
which simultaneously show a high degree of selectivity toward
specific cell organelles and biologically relevant molecules, have
where F2 stands for fluorescence intensity,
f
is the one-photon
excited fluorescence quantum yield, n refers to the refractive
index of the solution, C is the concentration, and ox and ref are
relative to the oxazolone derivatives and the Rhodamine 6G refer-
ence, respectively. The emission intensity dependence of the exci-
tation power was checked to be quadratic at the excitation
maximum for all the molecules studied.
The photostability of selected derivatives was tested under
excitation with the spectrofluorimeter lamp (450 W Xe) through
a slit width of 15 nm. The same conditions were used to study the
photoisomerization.
ꢀ
50
4
very low
s
2
values (<20 GM, 1 GM ¼ 10
cm s), with record high
values around 200 GM reported for a few fluorophores [48]. The
two-photon absorption is the most relevant nonlinear absorption
process because it is a low order process and for stable fluorescent
molecules it usually occurs under irradiation through the NIR
optical window of biological samples.
2
. Experimental and computational details
2.3. Synthesis
2.1. Material
The general method of synthesis of oxazol-5-(4H)-ones as been
All the reagents used were purchased from Aldrich or Merck and
reported elsewhere [45,46] and it can be described as follows: all
the reagents (aldehyde (1 eq.), hippuric acid (1.1eq.), sodium
acetate (1 eq.) and acetic anhydride (2 eq.) were placed in a flask
were used without further purification. The aldehyde used to
synthesise compound VI was prepared accordingly to the described
method [49]. The reaction evolution was followed by TLC using
silica Merck Kieselgel 60 F254 plates, and revealed by ultraviolet
light at 254 nm and 325 nm or stain solutions of phosphomo-
lybdenum acid in ethanol.
ꢁ
and stirred under 100e120 C during 2 h. The mixture changed
colour upon fusion of all the reagents. After cooling down to room
temperature some methanol was added, the solid was filtered and
washed with methanol. If further purification was needed some of
the compounds were recrystallized in a suitable solvent. Details of
the characterization of the oxazolone derivatives by NMR, IR,
elemental analysis, melting point determination and mass spec-
trometry are given in the following sub-sections and additional
structural spectra can be found in supplementary material.
2
.2. Instrumentation
The compounds were characterized by NMR, in a Bruker Avance
II 400 Ultrashield Plus, by elemental analysis performed at the
Universidade Nova de Lisboa services, by infrared spectroscopy in
a Shimadzu IRAffinity-1 FTIR spectrometer, using KBr platelets, by
measuring the melting point in a Stuart SMP10 apparatus and by
mass spectrometry in a quadrupole ion trap mass spectrometer
2.3.1. (4Z)-4-Benzylidene-2-phenyloxazol-5(4H)-one (I)
Light yellow solid, yield: 64% (washed with methanol). M.p.:
ꢁ
1
166e167 C. H NMR (CDCl3, 400 MHz)
d
(ppm): 8.21 (td, J ¼ 8.4,

C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
715
1
.7 Hz, 4H, 4ꢂ CHAr), 7.66e7.58 (m, 1H, 1ꢂ CHAr), 7.58e7.40 (m, 5H,
J ¼ 7.1 Hz, 2H, 2ꢂ CHAr), 7.61e7.42 (m, 6H, 5ꢂ CHAr þ eC¼CHe), 7.16
(d, J ¼ 11.8 Hz,1H, eC¼CHe), 7.07 (d, J ¼ 15.3 Hz,1H, eC¼CHe), 6.68
13
5
1
1
1
8
C
ꢂ CHAr), 7.26 (s, J ¼ 1.4 Hz, 1H). C NMR (CDCl3, 101 MHz)
67.64, 163.54, 133.52, 133.37, 133.27, 132.48, 131.79, 131.22, 128.95,
28.92, 128.39, 125.58. IR (KBr) : 1793.8, 1768.72, 1653, 1595.13,
552.7, 1489.05, 1448.54, 1327.03, 1317.38, 1296.16, 1163.08, 983.7,
d (ppm)
13
(d, J ¼ 8.8 Hz, 2H, 2ꢂ CHAr), 3.05 (s, 6H, eN(CH
3 2
) ). C NMR (CDCl3,
n
101 MHz)
131.32, 130.61, 130.52, 129.29, 128.21, 127.87, 126.54, 124.46, 119.22,
112.36, 40.59 (N(CH ). IR (KBr) : 3035.96, 2897.08, 2858.51,
d (ppm) 167.74, 160.95, 152.09, 146.18, 135.52, 132.90,
ꢀ
1
66.04, 767.67, 698.23, 686.66, 551.64 cm . HRMS calc for
3
)
2
n
16
H
11NO
2
: 249.078430, found: 249.077825. MS (ESIþ) m/z calc for
1770.65, 1641.42, 1608.63, 1589.34, 1575.84, 1550.77, 1523.76,
1490.97, 1450.47, 1371.39, 1325.1, 1300.02, 1276.88, 1224.8, 1163.08,
þ
þ
[C
16
H
11NO
2
þH] : 250.07, found: 282.1 [M þ MeOH þ Na] , 250.1
: % N, 5.62, % C, 77.10, %
þ
ꢀ1
[
M þ H] . Elemental Anal. Calcd. C16
H11NO
2
968.27, 867.97, 806.25, 723 14, 694.37 cm . MS (ESIþ) m/z calc for
þ
þ
H, 4.45. Found: %N, 5.55; %C, 76.92; %H, 4.73.
[C20
18
H N
2
O
2
þ1]: 319.17, found: 351.2 [M þ Na] , 319.2 [M þ H]
2
.3.6. (4Z)-4-(4-((E)-2-(1H-benzo[d]imidazol-2-yl)vinyl)
benzylidene)-2-phenyloxazol-5(4H)-one (VI)
Light orange solid, yield: 52% (washed with methanol). M.p.:
2
.3.2. (4Z)-4-(4-nitrobenzylidene)-2-phenyloxazol-5(4H)-one (II)
Yellow solid, yield: 66% (washed with methanol). M.p.:
ꢁ
1
2
8
42e244 C (decomposition). H NMR (CDCl
3
, 400 MHz) d (ppm)
ꢁ
1
2
33 C (decomposition). H NMR (DMSO, 400 MHz) d (ppm) 8.38 (d,
.35 (dd, J ¼ 22.1, 8.7 Hz, 4H, 4ꢂ CHAr), 8.22 (d, J ¼ 7.6 Hz, 2H, 2ꢂ
J ¼ 8.3 Hz, 2H), 8.16 (d, J ¼ 7.3 Hz, 2H), 7.84 (d, J ¼ 8.3 Hz, 2H),
CHAr), 7.68 (t, J ¼ 7.2 Hz, 1H, 1ꢂ CHAr), 7.58 (t, J ¼ 7.7 Hz, 2H, 2ꢂ
13
7.79e7.61 (m, 4H), 7.57 (dd, J ¼ 5.9, 3.2 Hz, 2H), 7.39 (t, J ¼ 8.2 Hz,
CHAr), 7.24 (s, 1H, eC¼CHe). C NMR (CDCl
66.75, 165.66, 148.31, 139.39, 136.31, 134.26, 132.75, 129.17, 128.83,
27.56, 124.95, 123.96. IR (KBr), : 3103.46, 3066.82, 3043.67,
797.66, 1761.01, 1654.92, 1641.42, 1598.99, 1579.7, 1556.55, 1519.91,
489.05, 1452.4, 1413.82, 1361.74, 1344.38, 1325.1, 1296.16, 1240.23,
224.8, 1163.08, 1109.07, 1093.64, 1070.49, 1001.06, 979.84, 894.97,
83.4, 867.97, 862.18, 848.68, 823.6, 777.31, 763.81, 746.45, 700.16,
3
, 101 MHz) d (ppm)
1
3
2
2
H), 7.21 (dd, J ¼ 6.0, 3.1 Hz, 2H). C NMR (DMSO,101 MHz)
d (ppm)
1
1
1
1
07.05, 167.35, 163.52, 151.04, 138.84, 134.22, 134.18, 133.87, 133.65,
n
1
(
1
33.33, 130.40, 129.85, 128.49, 128.02, 125.58, 122.83, 120.10. IR
KBr) : 3066.82, 3034.03, 2995.45, 1788.01, 1762.94, 1637.56,
597.06, 1560.41, 1419.61, 1325.1, 1313.52, 1298.09, 1163.08, 983.7,
n
1
ꢀ
1
7
00.16 cm . MS (ESIþ) m/z calc for [C25
H
17
N
3
O
2
þ1]: 392.42,
found: 424.3 [M þ MeOH] , 392.2 [M þ H] , Elemental Anal. Calcd.
for C25 .2H O: % N, 9.83, % C, 70.25, % H, 4.95. Found: %N,
.74; %C, 69.79; %H, 5.40.
8
6
2
þ
þ
ꢀ
1
84.73, 669.3 cm
MS (ESIþ) m/z calc for [C16H10N2O4þ1]:
H
17
N
3
O
2
2
95.26, found: 349.2 [M þ MeOH þ Na]þ, 295.1 [M þ H]þ.
9
Elemental Anal. Calcd. for C16H10N2O4: % N, 9.52, % C, 65.31, % H,
3
.43. Found: %N, 9.23; %C, 65.28; %H, 3.64.
2.4. Computational methods
2
5
.3.3. (4Z)-4-(furan-2-ylmethylidene)-2-phenyloxazol-
(4H)-one (III)
Calculations were done using Gaussian03 [52]. Ground state
geometry optimizations were performed in vaccum at the B3LYP/6-
Brownish yellow solid, yield: 52% (washed with methanol).
3
1þþg(2d,2p) level, and frequency calculations were used to
ꢁ
1
M.p.: 171e173 C. H NMR (CDCl3, 400 MHz)
d (ppm) 8.14 (d,
ensure that a global minimum was reached. TDDFT calculations
were done at the same level of approximation to estimate the
FranckeCondon transition energies and the corresponding coeffi-
cients, transition dipole moments and oscillator strengths. The
J ¼ 7.5 Hz, 2H, 2ꢂ CHAr), 7.67 (s, 1H, 1 ꢂCHAr), 7.63e7.42 (m, 4H, 4
1
3
xCHAr), 7.16 (s, 1H, eC¼CHe), 6.65 (s, 1H, 1ꢂ CHAr). C NMR
CDCl3,101 MHz) (ppm) 167.21, 163.10, 150.61, 146.77, 133.35,
(
d
130.50, 129.02, 128.38, 125.65, 120.28, 118.42, 113.92. IR (KBr)
n:
Onsager radius was calculated from the computed ground state
3
1
012.81, 3039.81, 3062.96, 1789.94, 1753.29, 1649.14, 1629.85,
598.99, 1558.48, 1490.97, 1465.9, 1452.4, 1328.95, 1296.16, 1232.51,
3
molecular volume (Vmol ¼ 4
p
a /3) using an increased density of
points (keyword volume ¼ tight) in the Monte Carlo integration as
1157.29, 1024.2, 989.48, 941.26, 883.4, 862.18, 758.02, 700.16,
implemented in Gaussian03.
ꢀ
1
6
84.73, 592.15 cm . MS (ESIþ) m/z calc for [C14
H
9
NO
3
þ1]: 240.06
þ
þ
found: 294.1 [M þ MeOH þ Na] , 273.1 [M þ MeOH] , 240.1
3. Discussion
þ
[
%
M þ H] . Elemental Anal. Calcd. for C14
9 3
H NO % N, 5.86, % C, 70.29,
H, 3.79. Found: %N, 5.73; %C, 70.19; %H, 3.88.
A set of derivatives of 4-(methylidene)-2-phenyl-1,3-oxazol-
5(4H)-one have been studied with different electron donor and
2
5
.3.4. (4Z)-4-[4-(dimethylamino)benzylidene]-2-phenyloxazol-
(4H)-one (IV)
acceptor substituents on the methylidene end (see Fig. 2). We
anticipate that depending on the donor(D)/acceptor (A) strength of
the substituents, the 2-phenyl-1,3-oxazol-5(4H)-one can act as an
electron acceptor by accommodating an excess charge on the
carbonyl group or as an electron donor with a charge deficient
benzene ring. Derivatives II and VI are substituted with 4-
nitrophenyl and 4[(E)-2-(1H-benzimidazol-2-yl)ethenyl] phenyl,
Bright orange needles. Yield: 45% (recristalized from ethyl ace-
ꢁ
1
tate).M.p.: 218e219 C. H NMR (CDCl3, 400 MHz)
d (ppm) 8.14 (d,
J ¼ 6.9 Hz, 4H, 4ꢂ CHAr), 7.65e7.42 (m, 3H, 3ꢂCHAr), 7.20 (s,
1
H,eCHeC ¼ ), 6.75 (d, J ¼ 8.8 Hz, 2H, 2ꢂ CHAr), 3.09 (s, 6H,
13
3 2
eN(CH ) ). C NMR (CDCl3, 101 MHz) d (ppm) 168.55, 160.58,
1
1
3
1
52.16, 134.86, 133.35, 132.30, 128.79, 128.33, 127.77, 126.34, 121.82,
11.82, 40.11 (N(CH ). IR (KBr) : 3080.32, 3035.96, 3022.45,
005.1, 1784.15, 1762.94, 1647.21, 1606.7, 1595.13, 1581.63, 1568.13,
529.55, 1490.97, 1448.54, 1375.25, 1323.17, 1296.16, 1195.87,
which are typical electron acceptor groups in an A-p-A arrange-
3
)
2
n
ment. Derivatives III, IV and V are substituted with furan-2-yl, and
4-(dimethylamino)phenyl either directly attached to the methylene
end or separated by an ethylene bridge. These two molecules have
ꢀ
1
1161.15, 1126.43, 856.39, 813.96 cm . HRMS calcd. for C18
H
16
N
2
O
2
:
a D-p-A arrangement. Compound I was prepared for the sake of
2
92.120629, found: 292.120841. MS (ESIþ) m/z calc for
completeness of the series. The asymmetric polarization induced
by the presence of electron donor and electron acceptor groups in
þ
þ
[
C
18
H
16
N
2
O
2
þ1]: 293.12, found: 315.1 [M þ Na] , 293.1 [M þ H] .
Elemental Anal. Calcd. for C18 : % N, 9.88, % C, 73.95, % H,
.52. Found: %N, 9.32; %C, 73.93; %H, 5.30.
H
16
N
2
O
2
these
p
-electron conjugated molecules entails an extensive delo-
-electron distribution, which is expected to favor
5
calization of the
p
their nonlinear interaction with light.
2.3.5. (4Z)-4-((E)-3-(4-(dimethylamino)phenyl)allylidene)-2-
Table 1 summarizes relevant photophysical properties of the
phenyloxazol-5(4H)-one (V)
compounds, namely the maximum wavelength (lmax) of one- and
Dark red solid, yield: 55% (recrystallized from toluene), M.p.:
two-photon absorption (OPA and TPA), the maximumwavelength of
one-photon induced emission (OPE), the fluorescence emission
ꢁ
1
2
36 C (decomposition). H NMR (CDCl3, 400 MHz)
d
(ppm) 8.12 (d,

716
C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
efficient for oxazolones IV, V and VI. Photostability tests show that,
oxazolones IV, V and VI, unlike many of the previously studied
oxazolone molecules [43], are stable at room temperature under
excitation at maximum absorption wavelength (see supporting
information). Excitation in the UV (330 nm) leads to very fast
decomposition. Similarly, oxazolones I, II and III are photolabile
under irradiation at the maximum absorption wavelength, which
corresponds to excitation in the UV.
For all molecules, in the ground state the phenyloxazolone
moiety and the substituent ring lay on the same plane. The
extended conjugation in compounds IV and V leads to a nearly
planar arrangement between the dimethylamine and the benzyl
ꢁ
ring of the dimethylaniline group (z4 off from planarity). The
CeN bond distance is calculated to be 1.37 Å for both compounds,
laying in between the typical bond distances between an aromatic
2
3
carbon and an sp (1.355 Å) and sp (1.394 Å) nitrogen atom of an
amine group [54]. With the exception of oxazolones I and III, all the
studied molecules show a HOMO / LUMO transition with an
appreciable charge transfer character, as shown in the isodensity
surface of the frontier molecular orbital in Fig. 3. The charge is
transferred from the phenyloxazolone moiety to the nitrophenyl
group in compound II, while for compounds IV, V and VI, the
charge is transferred in the reverse direction, from the dimethyla-
mino or the benzimidazole groups to the phenyloxazolone
terminus. Table 2 shows calculated properties relevant to UVeVis
absorption such as, transition energies, oscillator strength and
transition dipole moments for the two lowest energy transitions.
The molecular plane is the xy plane, with the y axis nearly aligned
with the O]C..N molecular axis, and the positive direction of the
x axis being towards the substituent group. Comparison of the
experimental and calculated maximum absorption wavelength
allows us to verify the accuracy of the calculations. The average
difference between the theoretical and experimental values is less
the 0.1 eV, which is acceptable, specially taking into consideration
Fig. 2. 4-(methylidene)-2-phenyl-1,3-oxazol-5(4H)-one derivatives.
quantumyield (
in GM units where 1 GM ¼ 10
2
f), and the two-photon absorption cross-section (s ,
ꢀ
50
ꢀ4 ꢀ1
photons cm s ). On the last
column of Table 1 the values for the effective two-photon absorption
cross-section are shown. These values, which are the product of the
emission quantum yields with the TPA cross-sections, reflect the
two-photon induced brightness of the molecules.
0 1
Based on the energy of the S / S transition, the molecules in
Table 1 can be separated into two sets: oxazolones I, II and III with
higher energy transitions (360e390 nm) and oxazolones IV, V and
VI with lower energy transitions (430e490 nm). This observation
suggests that electronic delocalization in the ground state is more
Table 1
a
Photophysical properties of substituted 4-(methylidene)-2-phenyl-1,3-oxazol-5(4H)-one solution in tetrahydrofuran.
OPA
max (nm)
OPE
max (nm)
TPA
max (nm)
b
s
2
fb (GM)
Comp.
Substituent (R1)
l
l
l
s
2
(GM)
f
I
363
379
389
465
488
424
416
460
454
525
614
537
740
760
780
895
950
880
3
0.001
0.003
0.011
0.012
0.240
0.440
II
36
40
87
<0.001
0.0003
0.003
0.004
0.31
III
IV
V
105
80
VI
25.81
a
OPA, OPE and TPA stand for one-photon absorption, one-photon emission and two-photon absorption, respectively.
b
Two-photon absorption cross-section measured by two-photon induced emission using Rhodamine 6G in methanol as a standard ([50]) with quantum yield of 0.94 ([53]);
50
ꢀ4 ꢀ1
s . The estimated error limits for
1
GM ¼ 10ꢀ photons cm
s
2
are ꢃ20% and for
f
are less than ꢃ10%.

C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
717
E-isomer taking place via a triplet state [56,57] Indeed, at room
temperature, molecules I, II and III undergo isomerization when
excited at their corresponding absorption maxima. As an illustra-
tive example, Fig. 4 shows the excitation and emission spectra of
the Z and E-isomers of molecule II. Excitation of the Z-isomer
during 30 min at 379 nm leads to a red-shift of the absorption
maximum by 15 nm due to the formation of the E-isomer, in good
0 1
agreement with the calculation that predict the S / S transition
of the E-isomer to be shifted by 6 nm to lower energies, compared
to the Z-isomer. Discrimination between the two isomers is more
clear in emission, where emission of E-isomer appears red-shifted
by about 70 nm (lmax z 530 nm) from that of the Z-isomer.
No isomerization was observed for molecules IV, V and VI upon
excitation at their corresponding absorption maxima for more than
2
h. The absence of isomerization in these molecules can be under-
stood on the basis of energetic considerations. As described above,
oxazolones IV, V and VI have absorption maxima in the visible while
oxazolones I, II and III have absorption maxima at considerably
higher energies. Furthermore, we have observed that for molecule I
decreasing the temperature up to 77 K increases the emission
quantum yield. Even though isomerization is not expected at these
low temperatures due to a solvent caging effect, the increased
fluorescence quantumyield suggests that the triplet sate involved in
the isomerization at higher temperatures is an activated state that is
not efficiently populated at 77 K. Such an activated triplet is pre-
dicted for compounds I and II to be T
3 1
laying 3e17 nm above S . In IV,
V and VI the T triplets appears at 40e60 nm above S .
3
1
However, the absence of isomerization alone does not explain
the low fluorescence quantum yields observed for compounds IV
(f
¼ 0.003) and V ( ¼ 0.004), because the isomerization process
f
was not observed in these molecules. Alternative, another non-
radiative decay processes must be effective for these molecules.
Indeed both molecules contain a dimethylamino donor (D) group
and the oxazolone acceptor (A) group which are adequate to induce
an efficient non-radiative decay channel due to formation of
a twisted intramolecular charge transfer excited state. This process
has been extensively studied in the analogous prototypical mole-
cule of (4-dimethylamino)benzonitrile [58]. Further evidence of the
intramolecular charge transfer from the dimethylamino group to
the oxazolone ring come from the solvatochromic shifts in solvents
of different polarity. We have studied the solvatochromic effect on
the absorption and emission of oxazolones IV, V and VI using a set
of solvents with increasing dielectric constant (from ε ¼ 2.28 in Bz
to ε ¼ 48.9 in DMSO) and approximately constant refractive indexes
Fig. 3. Isodensity surfaces of the frontier molecular orbital of the oxazolone
derivatives.
that the calculations were performed in vacuum. Nevertheless, it
should be pointed out that the accuracy of the calculations is
consistently worse for the molecules with a charge transfer excited
state (II, IV, V and VI). Indeed, the limited accuracy in describing
delocalized excited states (charge transfer states, valence state of
(from n ¼ 1.50 in Bz to n ¼ 1.34 in ACN). Fig. 5 shows the sovato-
chromic effect on the absorption and emission spectra of oxazo-
lones IV, V and VI for a reduced set of solvents.
molecules with extended
p systems, Rydberg states) are known
Both the absorption and emission spectrum of oxazolone IV and
V show a modest red-shift with increasing orientation polarization
function (eq. (2)) whereas for oxazolone VI only in emission are
appreciable solvatochromic shifts observed. The difference in the
trend observed in the absorption spectra is readily understood on
the basis of their respective ground state static dipole moment. The
shift for the absorption and emission maxima are shown to be
related to the ground and excited state dipole moments [59]:
shortfalls in the performance of TDDFT calculations [55].
3.1. Quantum yield
Except for compound VI with
f
¼ 0.31, all compounds listed in
Table 1 have a relatively low fluorescence quantum yields. The low
quantum yields can be understood on the basis of an efficient
nonradiative deactivation channel of the excess energy. Measure-
ments of fluorescence lifetime of molecules I, VI and V confirm that
the emission quantum yield is essentially determined by the non-
radiative processes. The average fluorescence lifetime increases
from a few picoseconds (3e10 ps) in I and IV to z 0.9 ns in VI,
which gives nonradiative decay rates decreasing in the order of
À
Á
2
ðε ꢀ 1Þ
n ꢀ 1
D
f ¼
ꢀ
(2)
(3)
2
2ε þ 1 2n
þ 1
¼ ꢀ 2
!
!
m
11
!
Dn
~
m
00ð
ꢀ
m
00Þ
D
f þ c
abs
3
hca
1
1
10
8 ꢀ1
3
ꢂ 10 (I), 9.5 ꢂ 10 (IV) and 8.4 ꢂ 10 s (V). This nonradiative
deactivation is well documented for molecule I and other ethynyl
oxazolone derivatives as resulting from geometrical isomerization
from the lowest energy isomer (the Z-isomer) to the less stable
ꢀ
ꢁ
Dnem ¼ ꢀ 2
m
m
ꢀ
m
D
f þ c
(4)
!
!
!
~
1
1
11
00
3
hca

718
C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
Table 2
UVeVis absorption properties (experimental in THF and calculated at TD-DFT level in vacuo).
Comp.
Exp.
lmax (nm)
Calc.
Transition
Oscillator strength
Transition dipole moment
m
f0
Orbitals
Coefficients
energies (nm)
x
y
z
I
363
379
378
0.8577
0.0003
0.8716
0.0002
ꢀ3.2480
0.0000
3.4246
ꢀ0.0003
ꢀ0.3346
0.0000
0.0000
HOMO / LUMO
HOMO-4 / LUMO
HOMO / LUMO
HOMO-4 / LUMO
HOMO-4 / LUMOþ1
HOMO / LUMO
HOMO-3 / LUMO
HOMO / LUMO
HOMO / LUMOþ1
HOMO-1 / LUMO
HOMO-5/LUMO
HOMO / LUMO
HOMO-1 / LUMO
HOMO/LUMOþ1
HOMO / LUMOþ4
HOMO-5 / LUMO
HOMO/LUMO
0.61913
0.69305
0.62602
0.67373
0.12908
0.60329
0.69322
0.62070
0.48699
0.46746
0.10523
0.60939
0.52610
ꢀ0.41181
ꢀ0.10420
ꢀ0.10153
0.64260
0.63839
0.23413
ꢀ0.11188
3
25
409
43
ꢀ0.0523
II
ꢀ0.1190
0.0000
3
0.0001
ꢀ0.0434
III
IV
389
465
398
24
434
20
0.7979
0.0003
0.9410
0.1496
ꢀ3.1420
0.0006
3.6550
ꢀ1.2502
0.7640
0.0000
0.0000
ꢀ0.0580
0.0074
ꢀ0.0087
3
ꢀ0.2873
3
0.1102
V
488
424
467
53
1.3992
0.1563
4.6302
ꢀ1.3398
ꢀ0.2026
ꢀ0.1514
0.0090
ꢀ0.0049
3
VI
490
96
1.4255
0.1821
4.7916
ꢀ1.4881
ꢀ0.1390
ꢀ0.4018
0.0000
0.0000
3
HOMO-1 / LUMO
HOMO-2 / LUMO
HOMO / LUMOþ1
!
!
m
00
where
m
and
are the static dipole moment of the excited and
(Bz and Tol) have been excluded from the correlation for two main
reasons: i) both Bz and Tol have a large polarizability, and thus the
dispersion contribution cannot be neglected as assumed in the
derivation of eqs. (3) and (4); ii) the fluorescence of the compounds
seems to indicate the formation of a charge transfer complex with
the solvent (please see the fluorescence spectra of compounds IV, V
and VI in Fig. 5). In order to evaluate if the excited state for
absorption and emission is the same in each molecule, the excited
state dipole moments can also be calculated from the slope of the
11
ground state, respectively.
The ground state dipole moments calculated for oxazolones IV
and V are 7.54 and 8.89 D, while that estimated for oxazolone VI is
considerably lower (2.02 D). Consequently, the absorption spec-
trum of oxazolones IV and V are more sensitive to solvent polarity.
The fact that the emission spectra of the three molecules show
a noticeable red-shift with increasing solvent polarity indicates that
their excited states have quite large dipole moments. Indeed, the
excited state dipole moment estimated on the basis of the slope of
Dn
~
em as a function of Df (eq. (4)), again assuming collinear dipole
the
D
~
n
as a function of
D
f (eq. (3)) assuming that the ground state
moments and using the calculated ground state dipole moment.
This approach gives excited state dipole moments of 14 ꢃ 1, 16 ꢃ 1
and 15.4 ꢃ 0.9 D for oxazolones IV, V, and VI, respectively. Since
both approaches give, within our experimental error, equal excited
state dipole moments, we can conclude that the same excited state
is involved in absorption and emission. It should be noted that for
compound VI the dipole moment of the ground and excited state
abs
and the excited state dipole moments are co-linear and using the
calculated Onsager radius are 13 ꢃ 3, 14 ꢃ 4 and 13 ꢃ 5 D for
oxazolones IV, V and VI (Table 3 shows a list of the parameters used
in the calculations). In the fitting procedure the less polar solvents
are anti-parallel, as indicated by the negative
f in Table 3.
Once it was established that the emissive state is populated via
D
~
n
= f and positive
D
abs
em
=
Dn D
~
direct excitation from the ground state we can safely use the Stokes
shifts to evaluate the dipole moment change exclusively based on
experimental data using the LipperteMataga equation:
2
hca3
D
~
n
¼
ð
m
ꢀ
m
00Þ2Df þ c
(5)
SS
11
where
Dn
~
refers to the change in the stokes shift. The plot of the
SS
Stokes shift versus the orientation polarization function,
Df, is
shown in Fig. 6. It is noteworthy that in this figure the Bz and Tol
points obey the linear correlation though they have not been
considered in the fitting due to difficulty in discriminating the
position of the absorption maxima corresponding to the uncom-
plexed molecules. This probably occurs because the Stokes shift is
essentially determined by the emission shift and the emission
maxima coincides with emission from the uncomplexed molecules.
The ratio between eqs. (3) and (4) allows us to estimate the ground
state dipole moment from the solvatochromic shifts. This gives
ground state dipole moments (5 ꢃ 3 D (IV), 5 ꢃ 4 D (V) and 1.5 ꢃ 0.6
D (VI)) in good agreement with those obtained from the electronic
structure calculations (7.5 D (IV), 8.9 D (V) and 2.0 (VI) D. Eq. (5)
Fig. 4. Excitation and emission spectra of Z and E-isomers of molecule II. The exci-
tation and emission spectra of the Z-isomer were recorded before irradiation by col-
lecting emission at
The excitation spectrum of the E-isomer was recorded after 30 min of irradiation at
79 nm collecting emission at
l
em ¼ 460 nm and upon excitation at
l
exc ¼ 379 nm, respectively.
3
l
em ¼ 520 nm, while its emission spectrum was ob-
tained by deconvolution of the emission spectra of the photostationary state in the E
and Z isomer components.

C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
719
Fig. 5. Solvatochromic effects on the linear absorption and emission spectra of oxazolones IV, V and VI. The solvent abbreviations correspond to: Bz, benzene; EA, ethyl acetate; THF,
tetrahydrofuran; DMF, dimethylformamide; DCM, dichloromethane and DMSO, dimethylsulfoxide.
allows us to estimate the difference between the permanent dipole
moments to be 7.0 ꢃ 0.7 D (IV), 7.8 ꢃ 0.6 D (V) and 15 ꢃ 1 D (VI).
Note that the difference between the static dipole moments for VI
section have either strong donor groups (IV and V) or a relatively
mild acceptor substituent (VI), which transfer electron density to
the oxazolone ring upon excitation. These three derivatives have at
(
Dmss ¼ 15 ꢃ 1 D) is higher that the excited state dipole moment
2
least one order of magnitude high effective TPA cross-section (s .f)
(m
11 ¼ 13.7 ꢃ 0.9 D) because the ground and excited state dipole
than the other studied derivatives (Table 1). The linear (OPA) and
two-photon (TPA) absorption and fluorescence of oxazolones IV, V
and VI in THF are shown in Fig. 7. The emission spectra are insen-
sitive to the nature of the excitation process. As discussed above,
the broad and unstructured emission bands are characteristic of
intramolecular charge transfer in the excited state. As a result of the
charge transfer nature of the FranckeCondon excited state, mole-
cules IV, V and VI have the higher TPA cross-sections (87, 105 and
80 GM, respectively). For oxazolones IV and V the TPA spectra can
be overlapped with the OPA spectra using for the TPA spectra an
energy scale factor that is exactly twice the wavelength of the OPA
spectra. In contrast, oxazolone VI has two TPA maxima (740 and
moments are anti-parallel. The charge transfer character of the
/ S electronic transition is stronger for the VI derivative.
Fig. 6 shows that the magnitude of the Stokes shifts increases
S
0
1
from oxazolone IV to V and VI implying that there is an extensive
structural rearrangement of the solvent molecules from the
FranckeCondon geometry reached upon absorption to attain the
relaxed emissive charge transfer state. This structural relaxation
implies a solute-solvent coupling that could lead to an effective
nonradiative energy relaxation, and for low emission quantum
yield. The reason for oxazolone VI to have a much higher quantum
yield than oxazolones IV and V remains unclear.
880 nm) underneath the apparently unstructured OPA absorption
centered at 424 nm.
3.2. Two-photon absorption
For polar unsymmetrical molecules with either parallel or
antiparallel dipole moments, the two-photon absorption cross-
section is generally well described within the framework of
a two-level system as follows [60]:
Compound I, with a phenyl substituent is the one with the
lowest TPA cross-section (3 GM). All the other derivatives have TPA
cross-section ranging from z40 to 100 GM (Table 1), which are
comparable with those of commercial TPA dyes. Derivatives II and
III, with TPA cross-sections of z40 GM, have exceedingly low
emission quantum yields to be of any use as fluorescent labels in
D-imaging. Alternatively, nonlinear absorption materials with low
emission quantum yields have been used in optical power limiting
applications. The oxazolone derivatives with the higher TPA cross-
4
2ð2 LÞ
p
2
2
s
2ð
n
Þ ¼
ð
m
ꢀ
m
00Þ
m
gð2
n
Þ
(6)
11
10
2
5
ðhcnÞ
3
2
where L is the Lorentzian local field factor (L¼(n þ2)/3),
transition dipole moment and g(2
m
10 is the
n
) is the normalized TPA line
Table 3
Measured spectroscopic data and calculated parameters relevant for the estimation of permanent dipole moments from solvatochromic effects are listed together with the
estimated dipole moments and TPA cross-sections.
4
a
b
c
d
Comp.
S
0
/ S
1
ε
max ꢂ 10
ꢀ1
(cm /M )
a
calc (Å)
Dnabs
(cm
/
D
)
f
Dnem
(cm
/
D
)
f
DnSS
(cm
/
D
)
f
DmSS (D)
m
11 (D)
s
2 SS
s
2 TPEF
ꢀ
1
ꢀ1
ꢀ1
ꢀ1
exp (nm)
(GM)
(GM)
VI
V
VI
465
488
424
5.41
4.74
4.75
4.52
4.59
4.87
ꢀ4138
ꢀ4270
1978
ꢀ9504
ꢀ10586
ꢀ18035
5366
6315
20013
7.0 ꢃ 0.7
7.8 ꢃ 0.6
15 ꢃ 1
12 ꢃ 6
13 ꢃ 5
14 ꢃ 3
75
85
287
87
105
80
a
Dmss is the permanent dipole moment change calculated from DnSS
m
/D
f and equation (5).
b
c
11 is the excited state dipole moment extracted from DnSS
/D
f and Dnem f according to equations (4) and (5).
/D
s
2 SS is the TPA cross-section calculated according to equation (7) with an estimated error of ꢃ20%.
d
s
2 TPEF is the measured absorption cross-section with an estimated error of ꢃ20%.

720
C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
3
4
s
2ð
n
Þ ¼ 1
2 ln10
p
10 L ε10ð
nÞð
m
m
ꢀ 00Þ
(7)
2
11
N hc n2
2
~
5
n
A
10
2
1
In deriving this equation it was assumed that
approximated by [60]:
m
0gð2
n
Þ can be
ꢂ
ꢃ
3
ꢂ
ꢃ
3 ꢂ 10 ln10hcε ~
n
n
1
0
2
1
2
m
0gð2
n
Þ ¼
m
g ~
n
¼
(8)
10
10
3
2
ð2
p
Þ N ~
n
L
A
10
Thus, the dipole moment differences extracted from the Stokes
shifts can be used to estimate two-photon absorption cross-section
for this set of oxazolones. This approach was applied only to
molecules IV, V and VI due to their higher TPA cross-section.
Molecules II and III have exceedingly low emission quantum
yields to allow for an accurate analysis of the solvatochromic shifts
and molecule I has both low emission quantum yields and low TPA
cross-section. The values obtained for the oxazolones VI and V
using the spectroscopic data in Table 3 were 75 and 85 GM, which
are in good agreement with the experimentally determined values
of 87 and 105 GM. These values show that, even though increasing
the conjugation length is a well-known strategy to increase the TPA
cross-section [1], this effect is quite modest for the two dimethy-
laniline derivatives in this study. The experimental maximum ob-
tained for oxazolone VI (80 GM) is equal to those of oxazolones IV
and V. Conversely, the estimated value for the TPA of oxazolone VI
on the basis of the linear spectroscopic properties is significantly
higher than the measured one (287 GM). This discrepancy cannot
be accounted for based on the approximation of the two-photon
absorption line shape by that of the one-photon absorption.
Comparison of the TPA and OPA spectra in Fig. 7 shows that the
strongest band in the TPA spectra is considerably narrower than the
strongest OPA band. The maximum of the normalized line shape
function for the TPA is roughly three times higher than that of the
OPA band. Thus a more accurate prediction of the TPA cross-section
for oxazolone VI based on the TPA line shape function would
actually be larger than the value on Table 3.
Fig. 6. Stokes shift as a function of the solvent orientation polarization showing the
fitting of the experimental data points to eq. (5) (straight line). For each compound. the
two experimental points with
Df close to zero correspond to Bz and Tol and have not
been considered in the fitting to eq. (5).
shape function. Assuming that the TPA line shape can be approxi-
mated by the OPA line shape it is possible to describe the TPA cross-
section based on linear spectroscopic properties such as the dipole
moment change, the extinction coefficient and the frequency of the
maximum of the OPA band, as follows [60]:
Similar discrepancies have been reported before by Rebane et al.
and explained in terms of a molecular point dipole that is displaced
from the center of the molecule [61], which is obviously the case for
the studied oxazolone derivatives. The measured two-photon
absorption cross-section does not depend on the exact location of
the dipole moment due to the fact that the radiation wavelength is
much larger than the molecular dimensions, thus the TPA cross-
section is well defined by
a point dipole approximation.
Conversely the solvatochromic shifts do depend on interaction of
the solute molecule with its immediate surroundings so that
a displacement of the molecular dipole from the center of the
molecule would lead to increased interaction energy. Thus, the
dipole moments estimated from the solvatochromic shift could be
overestimated leading also to an overestimation of the TPA cross-
section. In the IV and V derivatives, the overestimation of the
dipole moments seem to cancel out in the dipole moment differ-
ence, while in derivative VI the overestimation remains due to the
fact that the ground state dipole moment is in fact small.
The additional shorter wavelength band in the TPA spectrum of
oxazolone VI (740 nm) is assigned to a biphotonic transition to
a higher energy singlet state. An S
calculation to lay 93 nm above in energy from the S
2
state is predicted by the TD-DFT
state (Table 2).
1
This prediction agrees well with the 70 nm estimated from the
difference between the band maxima observed in TPA spectrum
OPA
S1
OPA
S2
TPA
TPA
(
1
l
e
l
¼
l
S1 /2e
lS2 /2). The dominant transition is a HOMO-
/ LUMO transition that involves also some degree of charge
transfer from the benzimidazole unit to the oxazolone terminus.
The much weaker oscillator strength associated with this transition
Fig. 7. Linear absorption and emission spectra and two-photon absorption spectra of
oxazolones IV V and VI in THF.

C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
721
(
(
S
almost one order of magnitude lower than the S
see Table 2)) precludes its observation in the OPA spectra. Similar
/ S transitions are observed in the TPA spectrum of oxazolones
0
/ S
1
transition
[3] Fisk JS, Mosey RA, Tepe JJ. The diverse chemistry of oxazol-5-(4H)-ones. Chem
Soc Rev 2007;36(9):1432e40.
[4] Alba ANR, Rios R. Oxazolones in organocatalysis, new tricks for an old reagent.
0
2
Chem Asian J 2011;6(3):720e34.
V (730 nm), but with much weaker TPA cross-sections (14 GM).
The benzoimidazol derivative (VI) is by far the best performing
molecule as a two-photon activated fluorophore, given the much
higher quantum yield (Table 1). The effective TPA cross-section for
oxazolone VI (25 GM) is almost two orders of magnitude higher
that of oxazolones IV and V (0.24 and 0.44 GM, respectively). The
value of the effective TPA cross-section of oxazolone VI is compa-
rable to commercially available fluorophores like Fluorescein
[5] Mosey RA, Fisk JS, Tepe JJ. Stereoselective syntheses of quaternary substituted
alpha-amino acids using oxazol-5-(4H)-ones. Tetrahedron-Asymmetry 2008;
19(24):2755e62.
[
6] Aleman J, Milelli A, Cabrera S, Reyes E, Jorgensen KA. Asymmetric 1,4-Addition
of oxazolones to Nitroalkenes by Bifunctional cinchona Alkaloid Thiourea
organocatalysts: synthesis of alpha, alpha-disubstituted alpha-amino acids.
Chem Eur J 2008;14(35):10958e66.
[
7] Cabrera S, Reyes E, Aleman J, Milelli A, Kobbelgaard S, Jorgensen KA. Orga-
nocatalytic asymmetric synthesis of alpha, alpha-disubstituted alpha-amino
acids and derivatives. J Am Chem Soc 2008;130(36):12031e7.
[
[
8] Uraguchi D, Ueki Y, Ooi T. Chiral Tetraaminophosphonium Carboxylate-
catalyzed direct Mannich-type reaction. J Am Chem Soc 2008;130(43):14088.
9] Dong SX, Liu XH, Chen XH, Mei F, Zhang YL, Gao B, et al. Chiral Bisguanidine-
catalyzed inverse-electron-demand Hetero-Diels-Alder reaction of Chalcones
with azlactones. J Am Chem Soc 2010;132(31):10650e1.
(
60 GM), Rhodamine 6G (120 GM) or Rhodamine B (135 GM).
4
. Conclusions
[
[
[
10] Liu XD, Deng LJ, Jiang XX, Yan WJ, Liu CL, Wang R. Asymmetric Aza-Mannich
addition of oxazolones to N-Tosyl Aldimines: synthesis of Chiral alpha-
disubstituted alpha, beta-Diamino acids. Org Lett 2010;12(4):876e9.
11] Weber M, Jautze S, Frey W, Peters R. Bispalladacycle-catalyzed bronsted acid/
base-promoted asymmetric Tandem azlactone formation-Michael addition.
J Am Chem Soc 2010;132(35):12222e5.
A set of pushepull molecules with either D-p-A or A-p-A
arrangements have been synthesized based on the 2-phenyl-1,3-
oxazol-5(4H)-one unit aiming at preparing stable oxazolone
based fluorophores with appreciable nonlinear excitation. Their
linear and nonlinear photophysical properties relevant to evalua-
tion of the two-photon absorption cross-section have been char-
acterized. The TPA cross-sections were estimated using two
different approaches: (1) from the two-photon excited fluorescence
and (2) calculated within a two-level approximation from the
transition dipole moments and the changes between the perma-
nent dipole moment extracted from linear spectroscopic data.
Electronic structure allowed for a deeper insight into the nature of
the relevant electronic transitions. The highest TPA cross-sections
were estimated between 80 and 100 GM either for oxazolone
derivatives with strong electron donating groups (dimethylamine)
or mild electron accepting groups (benzoimidazol) that actually
behave as electron donors with respect to the oxazolone ring. Thus,
in this set of molecules the nonlinear interaction is favored by an
efficient charge transfer from the substituent group to the oxazo-
lone ring. Nevertheless, the dimethylamine and furanyl derivatives
have extremely low quantum yields thus precluding their use as
nonlinear fluorophores. Alternatively their nonlinear response
could be relevant in optical power limiting applications. The best
performing nonlinear fluorophore was the benzoimidazol deriva-
tive with a TPA cross-section of 80 GM and an emission quantum
yield of 0.31. The results from this study will guide our future work
12] Yang X, Lu GJ, Birman VB. Benzotetramisole-catalyzed dynamic kinetic reso-
lution of azlactones. Org Lett 2010;12(4):892e5.
[13] Alba ANR, Calbet T, Font-Bardia M, Moyano A, Rios R. Alkylation of oxazolones
and related heterocycles through an S(N)1 reaction. Eur Org Chem
011;(11):2053e6.
J
2
[
14] De CK, Mittal N, Seidel D. A dual-catalysis approach to the asymmetric steglich
rearrangement and catalytic enantioselective addition of o-acylated azlac-
tones to isoquinolines. J Am Chem Soc 2011;133(42):16802e5.
[15] Di Giacomo M, Serra M, Brusasca M, Colombo L. Stereoselective Pd-catalyzed
synthesis of quaternary alpha-D-C-Mannosyl-(S)-amino acids. J Org Chem
2011;76(13):5247e57.
[16] Dong SX, Liu XH, Zhang YL, Lin LL, Feng XM. Asymmetric synthesis of 3, 4-
Diaminochroman-2-ones promoted by guanidine and bisguanidium salt.
Org Lett 2011;13(19):5060e3.
[17] Lu GJ, Birman VB. Dynamic kinetic resolution of azlactones catalyzed by Chiral
Bronsted acids. Org Lett 2011;13(3):356e8.
[
18] Melhado AD, Amarante GW, Wang ZJ, Luparia M, Toste FD. Gold(I)-Catalyzed
Diastereo- and enantioselective 1,3-Dipolar cycloaddition and Mannich
reactions of azlactones. J Am Chem Soc 2011;133(10):3517e27.
[19] Terada M, Nii H. Highly Stereoselective 4þ2 cycloaddition of azlactones to
beta, gamma-unsaturated alpha-Ketoesters catalyzed by an axially Chiral
Guanidine base. Chem Eur J 2011;17(6):1760e3.
[
20] Truppo MD, Hughes G. Development of an improved immobilized CAL-B for
the Enzymatic resolution of a key intermediate to Odanacatib. Org Proc Res
Dev 2011;15(5):1033e5.
[
21] Ying Y, Chai Z, Wang HF, Li P, Zheng CW, Zhao G, et al. Bifunctional cinchona
alkaloids-catalyzed asymmetric 4þ2 cycloaddition reaction of beta, gamma-
unsaturated alpha-keto esters with oxazolones. Tetrahedron 2011;67(19):
3337e42.
_
[22] Ertekin K, Alp S, Karapire C, Yenigül B, Henden E, Içli S. Fluorescence emission
on the oxazolone derivatives as
a two-photon absorption
studies of an azlactone derivative embedded in polymer films: an optical
fluorophores.
sensor for pH measurements.
37(2e3):155e61.
J Photochem Photobiol A: Chem 2000;
1
[
[
23] Ertekin K, Alp S, Yalcin I. Determination of pK(a) values of azlactone dyes in
non-aqueous media. Dyes Pigment 2005;65(1):33e8.
24] Ertekin K, Karapire C, Alp S, Yenigül B, Içli S. Photophysical and photochemical
characteristics of an azlactone dye in sol-gel matrix; a new fluorescent pH
indicator. Dyes Pigment 2003;56(2):125e33.
Acknowledgment
The authors thank the FCT-Fundação para a Ciência e a Tecnlogia
for financial support (project PTDC/CTM-POL/114367/2009, PhD
grant: SFRH/BD/48145/2008 and post-doc grant: SFRH/BPD/75782/
[
25] Wu LX, Burgess K. Syntheses of highly fluorescent GFP-chromophore
analogues. J Am Chem Soc 2008;130(12):4089e96.
[26] Misra NC, Ila H. 4-Bis(methylthio)methylene-2-phenyloxazol-5-one: versatile
template for synthesis of 2-Phenyl-4,5-functionalized Oxazoles. J Org Chem
2
011)
2010;75(15):5195e202.
[
27] Amareshwar V, Mishra NC, Ila H. 2-Phenyl-4-bis(methylthio)methyleneox-
azol-5-one: versatile template for diversity oriented synthesis of heterocycles.
Org & Biomol Chem. 2011;9(16):5793e801.
Appendix A. Supplementary material
Supplementary material associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.dyepig.
[28] Baud MGJ, Leiser T, Meyer-Almes FJ, Fuchter MJ. New synthetic strategies
towards psammaplin A, access to natural product analogues for biological
evaluation. Org & Biomol Chem. 2011;9(3):659e62.
2
012.06.005.
[
29] Genady AR, Nakamura H. Amphiphilic allylation of arylidene-1,3-oxazol-5(4H)-one
using bis-pi-allylpalladium complexes: an approach to synthesis of cyclohexyl and
cyclohexenyl alpha-amino acids. Org Biomol Chem 2011;9(20):7180e9.
References
[30] Jiang H, Gschwend B, Albrecht L, Hansen SG, Jorgensen KA. Asymmetric Tri-
enamine catalysis for the construction of structurally rigid cyclic alpha, alpha-
disubstituted amino acid derivatives. Chem Eur J 2011;17(33):9032e6.
[31] Kaur H, Heapy AM, Brimble MA. The synthesis of dehydrotryptophan and
dehydrotryptophan-containing peptides. Org Biomol Chem 2011;9(17):
5897e907.
[
[
1] He GS, Tan L-S, Zheng Q, Prasad PN. Multiphoton absorbing materials:
molecular designs, characterization, and applications. Chem Rev 2008;108:
1245e330.
2] Pawlicki M, Collins HA, Denning RG, Anderson HL. Two-photon absorption
and the design of two-photon dyes. Angew Chem Int Ed 2009;48(18):
[32] Trost BM, Morris PJ. Palladium-catalyzed Diastereo- and enantioselective
synthesis of substituted Cyclopentanes through a dynamic kinetic asymmetric
3244e66.

722
C.A.B. Rodrigues et al. / Dyes and Pigments 95 (2012) 713e722
formal 3þ2 -Cycloaddition of Vinyl Cyclopropanes and Alkylidene azlactones.
Angew Chem Int Ed 2011;50(27):6167e70.
[47] König K. Multiphoton microscopy in life sciences. J Microsc 2000;200(2):
83e104.
[
[
[
[
[
[
[
[
[
[
33] Wang SL, Ding J, Jiang B, Gao Y, Tu SJ. Microwave-assisted solvent-dependent
reaction: chemoselective synthesis of Quinoxalin-2(1H)-ones, Benzo d imid-
azoles and Dipeptides. Acs Comb Sci 2011;13(5):572e7.
34] Krasovitskii BM, Lysova IV, Afanasiadi LS. Synthesis and spectral-
Luminescence properties of 2-aryloxazole-5-ones. Khimiya Geter-
otsiklicheskikh Soedinenii 1978;(2):158e60.
35] Krasovitskii BM, Lysova IV, Afanasiadi LS. Synthesis and spectral-lumine
scence properties of 2- aryl- 4- benzylide ne-5-oxazolones. Chem Heterocyc
Comp 1980;16(7):701e3.
36] Krasovitskii BM, Lysova IV, Afanasiadi LS, Stryukov MB, Knyazhanskii MI,
Vinetskaya YM. Luminescence properties of compounds containing both 2,5-
diaryloxazole and 5-oxazole units. J Appl Spectrosc 1980;33(3):930e3.
37] Krasovitskii BM, Lysova IV, Afanasiadi LS, Surov YN. Luminophores of the
azlactone Series with Difluoromethylsulfonyl groups. Khimiya Geter-
otsiklicheskikh Soedinenii 1981;(12):1600e3.
[48] Diaspro A, Chirico G, Collini M. Two-photon fluorescence excitation and
related techniques in biological microscopy. Quarter Rev Biophys 2005;
38(02):97e166.
[49] Huang ZL, Li N, Lei H, Qiu ZR, Wang HZ, Zhong ZP, et al. Two-photon induced
blue fluorescent emission of heterocycle-based organic molecule. Chem
Commun 2002;(20):2400e1.
[50] Makarov NS, Drobizhev M, Rebane A. Two-photon absorption standards in the
550-1600 nm excitation wavelength range. Opt Express 2008;16(6):4029e47.
[51] Xu C, Webb WW. Measurement of two-photon excitation cross sections of
molecular fluorophores with data from 690 to 1050 nm. J Opt Soc Am B Opt
Phys 1996;13(3):481e91.
[52] Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al.
Gaussian 03 RC. Wallingford CT: Gaussian, Inc.; 2004.
[53] Magde D, Wong R, Seybold PG. Fluorescence quantum yields and their rela-
tion to lifetimes of rhodamine 6G and fluorescein in nine solvents: Improved
absolute standards for quantum yields. Photochem and Photology 2002;
75(4):327e34.
[54] Allen FH, Kennard O, Watson DG, Brammer L, Orpen AG, Taylor R. Tables of
bond lengths determined by X-ray and neutron-diffraction .1. Bond lengths in
organic-compounds. J Chem Soc-Perkin Trans 1987;2(12):S1e19.
[55] Dreuw A, Head-Gordon M. Single-reference ab initio methods for the calcu-
lation of excited states of large molecules. Chem Rev 2005;105(11):4009e37.
[56] Ullman EF, Baumann N. Unsaturated Lactone Photochemistry - Effect of
wavelength and Sensitizer structure on selective population of specific
excited states. J Am Chem Soc 1970;92(20):5892.
[57] Icli S, Doroshenko AO, Alp S, Abmanova NA, Egorova SI, Astley ST. Structure
and luminescent properties of the 4-arylidene-2-aryl-5-oxazolones(a-
zlactones) in solution and crystalline state. Spectrosc Lett 1999;32(4):553e69.
[58] Grabowski ZR, Rotkiewicz K, Rettig W. Structural changes accompanying
intramolecular electron transfer: focus on twisted intramolecular charge-
transfer states and structures. Chem Rev 2003;103(10):3899e4031.
[59] Lakowicz JR. Principles of fluorescence spectroscopy. 3rd ed. Singapore:
Springer US; 2006.
38] Kitazawa M, Higuchi R, Takasashi M, Wada T, Sasabe H. Novel molecular
design for 2nd-Harmonic generation - Azlactone derivatives. J Phys Chem
1995;99(40):14784e92.
39] Diaz JL, Villacampa B, Lopez-Calahorra F, Velasco D. Experimental and theoretical
study of a new class of acceptor group in chromophores for nonlinear optics: 2-
substituted 4-methylene-4H-oxazol-5-ones. Chem Mat 2002;14(5):2240e51.
40] Song HC, Wen H, Li WM. Study on the second-order optical behavior of 4-
(
substituted-benzylidene)-2-phenyl-4H-oxazol-5-one. Spectrochim Acta A-
Mol Biomol Spectrosc 2004;60(7):1587e91.
41] Smokal V, Czaplicki R, Derkowska B, Krupka O, Kolendo A, Sahraoui B.
Synthesis and study of nonlinear optical properties of oxazolone containing
polymers. Synth Met 2007;157(18e20):708e12.
42] Murthy YLN, Christopher V, Prasad UV, Bisht PB, Ramanaih DV, Kalanoor BS,
et al. Synthesis and study of nonlinear optical properties of 4-substituted
benzylidene-2-phenyl oxazol-5-ones by Z-scan technique. Synth Met 2010;
160(5e6):535e9.
[
43] Derkowska B, Krupka O, Smokal V, Sahraoui B. Optical properties of oxazalone
derivatives with and without DNA-CTMA. Opt Mater 2011;33(9):1429e33.
44] Sun YF, Cui YP. The synthesis, structure and spectroscopic properties of novel
oxazolone-, pyrazolone- and pyrazoline-containing heterocycle chromo-
phores. Dyes Pigment 2009;81(1):27e34.
[
[60] Drobizhev M, Meng FQ, Rebane A, Stepanenko Y, Nickel E, Spangler CW.
Strong two-photon absorption in new asymmetrically substituted porphyrins:
Interference between charge-transfer and intermediate-resonance pathways.
J Phys Chem B 2006;110(20):9802e14.
[45] Buck
JS,
Ide
WS.
Azlactone
of
alpha-benzoylamino-beta-(3,4-
dimethoxyphenyl)-acrylic acid 2-phenyl-4-(3 ’, 4 ’-dimethoxybenzal)- oxa-
zolone. Org Synth 1933;13:8e9.
46] Acheson RM, Booth DA, Brettle R, Harris AM. The synthesis of some acylgly-
cines and related Oxazolones. J Chem Soc 1960;(SEP):3457e61.
[61] Rebane A, Drobizhev M, Makarov NS, Beuerman E, Haley JE, Douglas MK, et al.
Relation between two-photon absorption and dipolar properties in a series of
Fluorenyl-based chromophores with electron donating or electron with-
drawing substituents. J Phys Chem A 2011;115(17):4255e62.
[