Solvatofluorochromic , non-centrosymmetric π-expanded diketopyrrolopyrrole

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Introduction
Current methods for fluorescence imaging rely on classical dyes such as fluorescein, rhodamines and coumarins. 1The advent of new luminescent probes is growing in the literature ranging from organic chromophores, 1 quantum dots, 2 carbon dots, 3 organic nanodots, 4 fluorescent organic nanoparticles, 5 etc. Notwithstanding new options, it is clear that organic chromophores, due to their tunability and possibility to attach to sensing units, continue to prevail in real-world applications. 6Among various targets, non-centrosymmetric π-conjugated systems, whose fluorescence is dependent on solvent polarity, are one of the most important tributes. 7The subtle interplay between centrosymmetric and non-centrosymmetric structures has been recently revealed by a few breakthrough approaches showing that (a) quadrupolar molecules can display solvato-fluorochromism due to symmetry breaking in the excitedstate 8 and (b) the emission properties of dipolar fluorophores in aqueous media can be significantly altered by replacing the donor amino substituent with a very polar one. 9pplication of diketopyrrolopyrroles (DPPs, 1,4-diketo-2H, 5H-pyrrolo[4,3-c]pyrroles) began as red-pigments of unprecedented light-fastness. 10In recent decades however, applications of DPPs have been reinvented as they have found new uses in diverse areas of applications such as optoelectronics and molecular electronics.DPPs' derivatives have been widely employed in fields such as dye-sensitized solar cells, 11 light emitting diodes, 12 organic field effect transistors 13 and aboveall, bulk-heterojunction solar cells. 14,15Certain attention has also been focused on its inversed analoguepyrrolo [3,2-b]  pyrrole-2,5(1H,4H)-dione (iDPP). 16Although replacing phenyl substituents 17 with five-membered heterocycles and their π-expanded analogues offers some opportunities in modulating the absorption and emission properties, 11c,18 the most significant change in optical properties has been achieved by expanding the DPP-core via fusion with other aromatics/dyes.Four strategies towards making such compounds have been recently revealed respectively by Zumbusch, 19 Shimizu,20a,c Würthner 20b and the Gryko group. 21Two-photon absorbing properties of DPPs have rarely been studied despite the fact that their electron-poor core seems to be an excellent starting point for the construction of D-A-D or A-D architectures, important for generating large two-photon absorption crosssections.18e,f,21b,22 Herein we would like to present a strategy towards non-centrosymmetric π-expanded diketopyrrolopyrroles.

Design and synthesis
The C 2 -symmetry of diketopyrrolopyrroles and their N-alkylated derivatives makes it difficult to design analogous dyes lacking this symmetry.Our recently reported two-step route of the DPP chromophore expansion is not exceptional in this regard. 21Double alkylation of DPP pigments with 2-bromoacetaldehyde diethyl acetal and the subsequent treatment of the intermediate diacetals with acid always led to the centrosymmetric double-cyclized products.This was also the case when ketonesphenacyl bromideswere used as alkylating agents.21b Mixed-alkylation of DPP with 2-bromoacetaldehyde diethyl acetal and n-alkyl bromide is one of the several possible strategies to synthesize non-symmetric analogues, 23 however, due to different reactivities of the two alkylating agents, the desired non-symmetrically substituted product may be obtained in low yields.Our strategy towards D-A type π-expanded diketopyrrolopyrroles is based on the use of mild conditions in the final ring-closure step.We expected that after the alkylation of DPP 1 with 1-bromo-3,3-dimethylbutan-2-one, instead of previously used bromoacetaldehyde acetal or phenacyl bromides, 21 diketone 2 would be obtained (Scheme 1).We have decided to use 1-bromo-3,3-dimethylbutan-2-one in order to ensure that the final donor-acceptor dye would possess the moderately reactive t-BuCO group rather than the chemically unstable CHO functionality.
Pigment 1, possessing electron-rich 3,4-dimethoxyphenyl substituents, was prepared according to the literature procedure 21a via the condensation of diisopropyl succinate with 3,4dimethoxybenzonitrile in the presence of sodium tert-amylate (Scheme 1).The alkylation reaction of DPP 1 with commercially available 1-bromo-3,3-dimethylbutan-2-one was performed under similar conditions as developed for the alkylation with 2-bromoacetaldehyde diethyl acetal: at 120 °C in DMF, using potassium carbonate as a base and tetrabutylammonium bisulfate (TBAHS) as a phase-transfer catalyst (Scheme 1). 21As previously noted, 21b in contrast to bromoacetaldehyde acetal, bromoketones react much faster and the reaction is finished within 2 hours (acetal required at least 16 h).
Diketone 2 was obtained in moderate yield (43%, Scheme 1).It was well soluble in chlorinated and aromatic solvents and strongly fluorescent in solutions.It is noteworthy that product 2 also exhibited intense fluorescence in the solidstate under UV irradiation.
Dye 2 was added to the reaction with triflic acid (TfOH) at 60 °C in chloroform and the progress was controlled using TLC.When the conversion of the starting material was complete (about 3 h), the main product was purified by silica gel chromatography.NMR spectra revealed that non-centrosymmetric dye 3 was formed exclusively (Scheme 1).
X-ray quality crystals have been obtained for dye 3. Crystallographic analysis fully confirmed the structure (Fig. 1).The four-fused ring system is almost planar (deviations from the calculated plane less than 0.1 Å).Hence the presence of short hydrogen bonding between carbonyl oxygen and the benzene Scheme 1 Synthesis of dye 3. hydrogen atom (distance: 2.39 Å, Fig. 1) does not cause a significant deformation of the polycyclic system, as was also observed in the case of a bis-fused DPP derivative (O⋯H distance 2.45 Å, highest deviations from planarity: 0.34 Å). 21b The plane of the benzene ring in the 3,4-dimethoxyphenyl substituent is twisted by 34.5°relative to the polycyclic system.This torsion angle is similar to the corresponding angles in nonfused N,N-dialkyl DPPs. 24In the tetragonal crystal lattice, molecules of 3 form dimers through π-π interactions, see Fig. S1.† The distance between the chromophores (3.73 Å) is noticeably longer than in the case of the bis-cyclized DPP derivative (3.48 Å), 21b which is due to the presence of the bulky tert-butyl groups.

Optical properties
The maxima of absorption (λabs) and emission (λem) for 2 are similar to those reported for previously described DPPs having 3,4-dimethoxyphenyl at 3 and 6 positions and 2,2-diethoxyethyl substituents at the nitrogen atoms, 21 which indicates negligible perturbation by the nature of the N-substituents (Table 1).In chloroform, mono-fused DPP 3 has an absorption ∼590 nm and an emission at ∼620 nm, which results in a Stokes shift of about 800 cm −1 (Fig. 2, Table 1).The absorption maximum of compound 3 is only 6 nm hypsochromically shifted versus its double-fused analogue 4 (Fig. 3, 587 nm vs. 593 nm), 21a whereas emission is even bathochromically shifted (619 nm vs. 597 nm).The Stokes shift, which in the case of centrosymmetric and rigid π-expanded DPPs is typically very small (90-230 cm −1 ), 21a,b increases for compound 3 in CHCl 3 to 880 cm −1 (see Table 1).These results are associated with the fact that the rigid and centrosymmetric chromophore in 4 is replaced by the more flexible, non-symmetric, push-pull system of compound 3.The molar absorption coefficient of 3 is 27 000, only slightly higher than that before cyclization (compound 2), but significantly lower than that of the biscyclized compound 4 (110 000 M −1 cm −1 ).21a,b Absorption and emission (fluorescence) spectra of compound 3 in n-hexane are presented in Fig. S2.† The Stokes shift in this solvent is relatively small, ∼450 cm −1 .Freezing of the matrix to 5 K does not lead to noticeable sharpening of the fluorescence spectrum.The fluorescence quantum yield of 3 in n-hexane is 0.56, whereas the decay time of this emission is 8.37 ns (see the ESI †).
Whereas absorption does not undergo notable changes from non-polar solvents to MeCN and MeOH, the emission quantum yield drastically decreases from 0.66-0.82 in hydrocarbon solvents to 0.12 in MeOH (Table 1).Simultaneously, the emission maximum is slightly bathochromically shifted by 14 nm, when moving from non-polar pentane to polar methanol.The slight red-shift of emission seems to be related more to inhomogeneous broadening with the loss of a fine structure in more polar solvents (starting from CHCl 3 ).The slight redshift cannot explain the decrease in quantum yield as it does for a push-pull system (only 4 nm from toluene to methanol).
Two-photon absorption (2PA) measurements of both of the new compounds 2 and 3 were performed using the two-photon excited fluorescence (TPEF) method (see the ESI †).Non-fused 2 possesses a moderate 2PA cross-section located around 700 nm (Table 2) resulting most probably from its quadrupolar structure.Interestingly, the new π-expanded DPP 3 possessing a dimethoxyphenyl unit has a larger maximum 2PA crosssection than centrosymmetric compound 4 studied previously (Table 2).20b Its 2PA response is also slightly higher than that of the centrosymmetric derivative 2 and does not show a clear maximum.In addition, the 2PA maximum (≤740 nm) of 3 is located at much shorter wavelengths than the doubled wavelength of the one-photon absorption maximum (1176 nm, see   Fig. 4).This is an interesting and unusual result, because such an effect is typically observed for centrosymmetric chromophores, for which one-photon allowed excitations are twophoton forbidden and vice versa, whereas for non-symmetric dyes both processes obey the same quantum selection rules and 2PA is usually recorded at approximately twice the wavelength of the 1PA maximum.Therefore, under the two-photon excitation, non-symmetric compound 3 behaves more like a centrosymmetric chromophore.

Calculations
Calculated excitation energies, oscillator strengths and 2PA cross-sections are listed in Table 3.We note that the strongest oscillator strength in 1PA is found for the S 1 state, and this    transition is almost dark in 2PA.In contrast to this, the S 5 state exhibits a large 2PA cross-section.At the same time, this state is dark in 1PA.However, for the other states we do not find such a strong alternation between one-and two-photon absorption.Indeed the S 2 state shows weak activity in both processes, i.e., 1PA and 2PA whereas the S 3 state shows reasonable 1PA and 2PA activities, in good agreement with the experimental data (Fig. 4).Evaluating the orbital transitions involved in the excitation to the S 1 state, we note that this state is dominated by the HOMO-LUMO transition.Both the HOMO and the LUMO are located mainly on the DPP backbone (see Fig. 5).These parts of the HOMO are gerade with respect to the inversion center of the backbone while the corresponding contributions to the LUMO are ungerade.Hence the orbitals show pseudo-centrosymmetry explaining the strong 1PA and weak 2PA character of the states.In contrast to the S 1 state, higher electronic states S i (in particular S 3 and S 5 ) involve different molecular orbital transitions.Fig. 5 shows the molecular orbitals involved in the S1, S3 and S5 states.While the S3 state is dominated by the HOMO > LUMO+1 transition, the S5 state involves the HOMO−6 > LUMO, HOMO > LUMO+5 and HOMO > LUMO+3-transitions.By evaluating the shape of the orbitals, we note that the HOMO−6 and the HOMO are tendentially gerade with regard to the inversion center of the DPP-backbone (as 3 is not a centrosymmetric molecule, the orbitals cannot be gerade or ungerade in the whole molecule but parts of them can show a local pseudosymmetric behavior).Also the LUMO+3 and the LUMO+5 are pseudo-gerade while the LUMO is pseudo-ungerade.The LUMO+1 cannot be classified as either gerade or ungerade as it is mostly located on the isoquinoline moiety.This explains why the S3 state shows both 1PA and 2PA activities while the S1 state is only active in 1PA and the S5 state only in 2PA.Both states have charge-transfer character.The result of such transitions is to change the dipole moment of a molecule in the excited state, and it promotes a greater cross-section for two-photon transitions. 25

Conclusions
In summary, we have proven that cascade processes leading to π-expanded diketopyrrolopyrroles can be controlled to lead to a donor-acceptor type product.The resulting heterocycle possesses four conjugated rings and lacks a center of symmetry.However, 1PA and 2PA measurements revealed that the final dye simultaneously exhibits photophysical characteristics of both symmetric and non-symmetric chromophores.This behavior is in agreement with the results of DFT calculations, and can be explained by analysis of the symmetry of the molecular orbitals in this molecule.This provides a synthetic entry to bright, red-emitting two-photon fluorophores.The other notable finding is that breaking the overall symmetry of a molecule does not necessarily extinguish the symmetry completely.Some molecular properties and excited states still can show "pseudosymmetric behavior".This study is complemen-tary to the investigation of solvatofluorochromism for centrosymmetric bis(thienyl)DPPs 18d and at the same time it offers opportunities in fluorescence imaging.

Optical studies
One-photon absorption spectra were measured with a Perkin Elmer Lambda 35 UV/VIS spectrometer.Fluorescence spectra at room and at 5 K were measured with the aid of a home-built set-up equipped with a liquid helium optical cryostat, a McPherson 207 monochromator, an EMI 9659 photomultiplier and an electronic card inserted into a PC.The excitation source was a Coherent Verdi-V5 (532 nm) and a Coherent 700 dye laser (with the simplified optics for a cw operation at 568.5 nm).
Fluorescence decay curves were monitored with the aid of a "time correlated" single photon counting technique (in inverted time mode).The system composed of a mode-locked Coherent Mira-HP laser pumped by a Verdi 18 laser, an APE Pulse selector reducing the repetition of Mira laser pulses to 2 MHz, and a frequency doubling crystal.Fluorescence photons, dispersed with a McPherson 207 monochromator, were detected with a HMP-100-50 hybrid detector and a SPC-150 module inserted into a PC, both from Becker&Hickl GmbH.
Two-photon absorption cross-sections of 10 −4 M solutions were measured relative to fluorescein in 0.01 M aqueous NaOH for 700-800 nm, 26 using the well-established method described by Xu and Webb 26b and the appropriate solventrelated refractive index corrections. 27The reference values between 700 and 715 nm for fluorescein were taken from the literature. 28The quadratic dependence of the fluorescence intensity on the excitation power was checked for each sample and all wavelengths.To span the 700-980 nm range, a Nd:YLFpumped S2 Ti:sapphire oscillator was used generating 150 fs pulses at a 76 MHz rate.To span the 1000-1400 nm range, an OPO (PP-BBO) was added to the setup to collect and modulate the output signal of the Ti:sapphire oscillator.

Computational studies
To simplify the computational treatment, the two t-butyl groups in molecule 3 have been replaced by methyl groups.The t-butyl groups are not expected to influence the absorption properties of the molecule, but to increase the computational complexity because of the increases in the number of atoms and increases in the conformational freedom.The modified structure will be referred to as molecule 3a.The structure of 3a has been optimized using the B3LYP density functional 29 and the TZVP basis set 30 using the TURBOMOLE suite of programs. 31Two-photon absorption calculations have been carried out using DALTON 32 using the CAM-BL3LYP density functional 33 and the aug-cc-pVDZ basis set from the Dunning family of basis sets.
34 D. T. G. thanks the National Science Centre of the Republic of Poland (MAESTRO-2012/06/A/ST5/00216) and the Global Research Laboratory Program (2014K1A1A2064569) through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning, Korea.This work was partially supported by the European Commission (TOPBIO ITN) and BASF-Schweiz.MBD gratefully acknowledges financial support from Conseil Régional d'Aquitaine (chaire d'accueil grant and fellowship to VH).D. H. F. acknowledge support from the Research Council of Norway through a Centre of Excellence Grant (Grant No. 179568/V30) and from the Norwegian Supercomputing Program (Grant No. NN4654 K).We also thank Eli M. Espinoza (UC Riverside) and Kenneth Ruud (University of Tromsø).

Table 2
Two-photon absorption data

Table 3
Results of calculations of two-photon absorption for compound 3