X Blase

C Attaccalite

Charge-transfer excitations in molecular donor-acceptor complexes within the many-body Bethe-Salpeter approach

Keywords: numbers: 31.15.A, 33.20.Kf, 71.35.-y

We study within the perturbative many-body GW and Bethe-Salpeter approach the low lying singlet charge-transfer excitations in molecular donor-acceptor complexes associating benzene, naphtalene and anthracene derivatives with the tetracyanoethylene acceptor. Our calculations demonstrate that such techniques can reproduce the experimental data with a mean average error of 0.1-0.15 eV for the present set of dimers, in excellent agreement with the best time-dependent density functional studies with optimized range-separated functionals. The present results pave the way to the study of photoinduced charge transfer processes in photovoltaic devices with a parameter-free ab initio approach showing equivalent accuracy for finite and extended systems.

A large set of studies aiming at clarifying the processes assisting the separation of the photogenerated electronhole pairs in organic solar cells revealed the importance of charge transfer excitations at donor/acceptor interfaces. 1 From a theoretical point of view, the fundamental issue of correctly modelling, at the quantum mechanical level, the electron-hole interaction, is a long standing difficulty. In particular, while standard density functional theory 2 can accurately describe excitations with a strong spatial overlap between the involved occupied and unoccupied states, the interaction of weakly overlapping electron-hole pairs requires the development of novel functionals with a fine tuning of the local and non-local exchange and correlation contributions, 3 a strategy followed e.g. in the recent developments around the range-separated functionals. 4 In this work, we study within the many-body GW and Bethe-Salpeter (BSE) perturbation framework the charge-transfer excitation energies of ten donor/acceptor molecular complexes, associating tetracyanoethylene (TCNE) with benzene, naphtalene, anthracene and their derivatives. We show that these techniques provide results which are in excellent agreement with available experimental data. The accuracy is equivalent to that of the best time-dependent density functional theory based on optimized range-separated functionals. We emphasize in particular the importance of self-consistency when performing GW -BSE calculations starting from DFT calculations with (semi)local functionals.

The choice of such donor-acceptor complexes combining TCNE and acene derivatives is dictated by the availability of gas phase experiments in the case of benzene, toluene, o-xylene and naphtalene donors, 5 complemented by experiments in solution for anthracene and its derivatives. 6 Such experiments provide invaluable reference data for the study of the merits of the various theoretical approaches, even though experiments performed in solution complicate the comparison with theoretical calculations performed on the isolated complexes.

We adopt the geometries obtained by Stein and coworkers at the DFT-B3LYP level in their TDDFT study of the same systems using an optimized range-separated functional labeled BNL(γ=0.3) in the following. 4 To illustrate the typical geometry of such systems, and highlight their donor-acceptor character, we plot in Fig. 1 an isocontour representation of the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbital of the anthracene-TCNE complex, showing the clear localization of the HOMO (LUMO) on the anthracene donor (TCNE acceptor).

As compared to the TDDFT approach, the GW -BSE formalism proceeds in two steps. First, the quasiparticle HOMO-LUMO gap, namely the difference between the ionization energy and electronic affinity, is calculated within the GW approximation. [7][8][9][10][11][START_REF] Aulbur | Quasiparticle calculations in solids[END_REF] Traditionally, such calculations are performed non-self-consistently, namely as a "single-shot" correction to the starting DFT-LDA Kohn-Sham eigenstates, an approach labeled G 0 W 0 in the following. While this approach has been shown since the mid-eighties to yield excellent results for most extended semiconducting systems, [START_REF] Aulbur | Quasiparticle calculations in solids[END_REF] several studies [13][14][15][16] evidenced that in the case of small molecular systems, the G 0 W 0 (LDA) approximation yields too small ionization potential and HOMO-LUMO gaps. It was shown that such a problem could be cured either by starting from Hartree-Fock eigenstates, [13][14][15] or by performing a simple self-consistent update of the quasiparticle energies when building the self-energy operator, 15,16 an approach labeled GW in what follows.

In a second step, the neutral (optical) excitation energies can be obtained as the eigenvalues of the Bethe-Salpeter H e-h Hamiltonian [17][18][19][20][21] which, in the |φ e i φ h j > product basis of the non-interacting unoccupied |φ e i > and occupied |φ h j > single-particle states, is composed of three terms as follows:

H diag ij,kl = δ i,k δ j,l ε QP i -ε QP j H direct ij,kl = -< φ e i φ h j |W (r, r ′ )|φ e k φ h l > H exchange ij,kl = 2 < φ e i φ h j |V C (r, r ′ )|φ h k φ e l >
with (ε QP i ,φ e/h i ) the best single-particle eigenstates in the absence of electron-hole interaction. W (r, r ′ ) and V C (r, r ′ ) are the (statically) screened and bare Coulomb potential respectively. Following the above discussion, the ε QP i can be taken to be the G 0 W 0 (LDA) or GW quasiparticle energies. Clearly, a too small HOMO-LUMO gap in H diag will result in too small neutral excitation energies.

Our G 0 W 0 -BSE and GW -BSE calculations are performed with the Fiesta code 15 which exploits an eventempered auxiliary basis representation of the two-point operators such as V C and W , while the input DFT-LDA eigenstates are taken to be those of the Siesta DFT code 22 using a large triple-zeta plus double polarization (TZ2P) basis. In the case of the smaller complexes with benzene, toluene and o-xylene, these calculations are double-checked using the planewave basis set 23 .

We compile in Fig. 2 and Table I our calculated excitation energies within the G 0 W 0 (LDA)-BSE (yellow down triangle) and GW -BSE (black diamonds) approaches, that we compare to the experimental data (red circles) and to the TDDFT results of Stein and coworkers 4 with the B3LYP (blue up triangle) and range-separated BNL(γ=0.3) (green squares) functionals. Following the analysis by Stein and coworkers, 4 experimental data obtained in solution (light red circles) have been shifted upwards by a 0.32 eV constant that approximately accounts for the solvent induced bathochromic shift. As shown in the Table, our results as obtained with the Fiesta code and with the planewave Yambo approach (in parenthesis), are in good agreement within 0.1 eV accuracy, showing that the present results are independent of the technicalities of the various implementations.

The mean absolute error (MAE) as compared to experiments is found within the GW -BSE approach to be 0.10 eV for "gas phase" benzene, toluene, o-xylene and naphtalene complexes, and 0.13 eV averaging over all systems, including the corrected data from the ex- 2b), both TDDFT-BNL and GW -BSE results agree in overestimating the extrapolated experimental data. This may indicate that the estimation of the solvation effect is incorrectly accounted for by the rigid 0.32 eV shift. Finally, as emphasized above, an important observation is that the G 0 W 0 -BSE approach provides significantly too small excitation energy, as a result of too small a G 0 W 0 -LDA quasiparticle band gap. [START_REF]In a recent G0W0-BSE study of the benzene, toluene, oxylene and naphtalene complexes, this underestimation of the G0W0(LDA) and G0W0(LDA)-BSE quasiparticle and optical band gaps, respectively, was partly compensated by considering somehow artificially the quasiparticle gap of the "non-interacting" donor-acceptor complex, namely subtracting the electronic affinity of the isolated acceptor (TCNE) to the ionization energy of the isolated donor. Such a gap is consistently 0.5-0.6 eV smaller than that of the real interacting donor-acceptor system[END_REF] As expected, the GW -BSE results are much better than those obtained with the TDDFT-B3LYP approach. [START_REF]Even though TD-B3LYP results for anthracene and its derivatives may seem anticorrelated with experiment[END_REF] In conclusion, we have shown that GW -BSE firstprinciples many-body perturbation theory provides charge transfer excitation energies in excellent agreement with experiment, with a mean average error of the order of 0.1-0.2 eV. The present results are of equivalent accuracy as compared to the best range-separated functionals TDDFT calculations, with an approach showing equivalent merits for finite size and extended systems without any adjustable parameter. In fact the screened Coulomb potential W (r, r ′ ) through which the holes and electrons are interacting is a non-local operator with a decay in finite size or extended systems automatically adjusted through the evaluation of the dielectric properties of the system. The analysis of such interaction in donoracceptor complexes may help in the future to better understand the features of the best exchange-correlation kernels within the TDDFT framework.

FIG. 1 :

 1 FIG. 1: (Color online) Isocontour representation of the (a) HOMO and (b) LUMO states of the anthracene-TCNE complex. The contours have been set to 20% of the maximum value of the wavefunction. Blue and red contours indicate different signs of the wavefunction. The grey, white and brown atoms are carbon, hydrogen and nitrogen, respectively. The π/π * character of the wavefunctions is apparent.

FIG. 2 :

 2 FIG. 2: Experimental and theoretical first singlet excitation energies in eV. The signification of the symbols is given in (a). Experimental data are from (a) Ref. 5 for gas phase experiments on benzene, toluene, o-xylene and naphtalene donors, and (b) Ref. 6 for experiments in solution on anthracene and its derivatives. Following Stein and coworkers in Ref. 4, a constant 0.32 eV shift has been added to the experimental data in (b) to (tentatively) mimic the bathochromic shift. The B3LYP and BNL data are the theoretical TDDFT results from Ref. 4. Figures (a) and (b) are not on the same energy scale.

Acknowledgements. Computing time has been provided by the local CIMENT and national GENGI-IDRIS supercomputing centers in Grenoble and Orsay (project No. 100063), respectively.


E Abou Nakad

F Bolze

A Specht

o-Nitrobenzyl (o-NB) derivatives are the most widely applied photoremovable groups for the study of dynamic biological processes. By introducing different substituents to the benzylic position we were able to generate a fluorescence signal upon irradiation. This signal originates from the formation of a nitrosoketone by-product able to achieve a keto-enol tautomerism leading to pi-conjugated α-hydroxystilbene derivatives. These o-NB caging groups can be used to directly monitor the uncaging event by the release of a detectable fluorescent side-product.

Scheme 1 Proposed photolytic reaction for aryl substituted (1-(2nitrophenyl)ethyl) derivatives.

Introduction

Biological processes are very complex phenomena ruled by a series of precise spatio-temporal events. To reveal the intimate mechanism of these phenomena, cellular activity needs to be precisely controlled and tuned with the help of orthogonal tools. During the last decade, light has become one of the major orthogonal triggers [1][2][3][4] which was initially developed for neuroscience [1][2][3][4][5][6] and is used today in many fields of biology, such as genetics or embryology. [1][2][3][4]7 Chemical phototriggers provide the capability to rapidly cause the initiation of a wide range of dynamic biological processes. This strategy uses light irradiation to induce a photolytic reaction, leading to the release of chemically or biologically active compounds. During the last two decades, the challenge has been to overcome the dilemma that only high energy light can induce photochemical reactions. One strategy to lower the phototoxicity within the domain of the one-photon excitation process is to tailor the caging groups with extended πconjugation and introduce heteroatoms and functional groups in the ring system so that a larger dipole change can be generated when being excited. 1-4,8,9 Therefore, blue light sensitive photoremovable groups have been reported in coumarin, [10][11][12] cinnamate, [13][14][15][16][17][18] orthonitrophenethyl [19][20][21][22][23][24] and orthonitrobenzyl [25][26][27] series. o-Nitrobenzyl (o-NB) derivatives have been the most widely applied photoremovable protecting groups (PPGs) for the study of dynamic biological processes. [1][2][3][4]8,9 However, this type of PPG and the uncaging secondary product exhibit similar weak brightness leading to light induced triggering of the studied responses without the possibility of quantification of the biological effector delivery.

It would be very advantageous to monitor the uncaging event, for example by the emergence of a fluorescence signal (e.g. optical reporting). Except for cinnamate [13][14][15][16][17][18] type and thiochromone-type 28- 31 photoremovable groups, the development of optical reporters of uncaging has only attracted little attention. 32,33 Interestingly, these two PPGs have been designed to release a fluorophore as a side product. [13][14][15][16][17][18][28][29][30][31] In this work, we propose a new caging group designed to allow direct monitoring of the uncaging event by the release of an easily detectable fluorescent side product in the o-NB series by using 1-(2-nitrophenyl)-2-phenylethan-1-ol PPGs.

Results and discussion

Design

Based on the photolytic release mechanism of the o-NB PPG leading to the formation of a nitrosoketone derivative, 9 we decided to introduce benzyl substituents at the benzylic position of this class of PPGs. This new class of PPGs should lead to the formation of a nitrosoketone derivative able to achieve a keto-enol tautomerism to generate a conjugated α-hydroxystilbene derivative.

We postulate that this conjugated compound could lead to a fluorescent chromophore (Scheme 1). To achieve our goal, we selected a blue light sensitive chromophore in the o-NB series. The N,N-dimethyl-4ʹ-nitro[1,1ʹ-biphenyl]-4-amine core was selected since this chromophore showed long wavelength absorption (around 400 nm) induced by the introduction of electrondonating groups to promote internal charge transfer (ICT) and good two-photon absorption cross-sections induced by a push-pull donor-acceptor biphenyl system.

Synthesis

Substituted o-NB derivatives based on the N,N-dimethyl-4ʹnitro[1,1ʹ-biphenyl]-4-amine core were synthesized following the sequence of reactions shown in Scheme 2. Commercially available 3bromobenzaldehyde 1 was nitrated at the ortho position using a mixture of concentrated nitric and sulfuric acids leading to 5-bromo-2-nitrobenzaldehyde 2 with 70% yield. The aldehyde function of the latter was protected, using ethylene glycol, leading quantitatively to the dioxolane 3. The biphenyl derivative 4 was obtained in 75% yield after a Suzuki-Miyaura cross-coupling reaction 34 (DIC) with a catalytic amount of N,Nʹdimethylaminopyridine (DMAP) in order to get access to the pure ester 6 in 68% yield. Of note is that MPAA coupling was chosen in this study instead of a biologically relevant acid (e.g. glutamate, GABA, etc) to easily quantify the uncaging efficacy by HPLC analysis. Finally, the bromoaryl derivative 6 was used in order to increase the conjugation of this system with electron donating or electron withdrawing groups using a Suzuki-Miyaura cross-coupling reaction leading to the formation of compounds 7a-c in 46-58% yield.

Photophysical and photochemical characterization

The photophysical properties of compounds 6 and 7a-c (100 μM) were studied in a 1/1 (v/v) mixture of phosphate buffer (pH 7.4, 0.1 mM) in acetonitrile. All compounds showed a similar absorbance peak at 413 nm with an absorption coefficient of 7750 M -1 cm -1 due to the 4,4ʹ-amino-nitro-biphenyl system. Interestingly each compound shows a very weak fluorescence (in the blue-green region, Φ < 0.2%) before irradiation. The photoinduced liberation of MPAA from 6 and 7a-c was monitored by UV-visible spectroscopy and HPLC.

Photolysis was carried out by irradiation of samples (between 60 and 135 μM) at 405 nm (using a LUMOS 43 LED source from Atlas Photonics Inc.) in an acetonitrile/phosphate buffer (pH 7.4, 0.1 mM) mixture (1/1, v/v). The isosbestic points at 360 nm and 485 nm for 6 (see the ESI †), at 387 nm and 480 nm for 7a (see the ESI †) and at 370 and 495 nm for 7b (Fig. 1A) indicate that a clean photochemical reaction occurred leading to stable photoproducts. However, the absence of isosbestic points for 7c (Fig. S25 †) indicates a much complex photochemical behavior for this compound. An almost quantitative (≥95%) release of MPAA was measured by HPLC for the photo-conversion of 6 and 7a-c. The hydrolytic stability was also explored by HPLC in an acetonitrile/phosphate buffer (pH 7.4, 0.1 mM) mixture (1/1, v/v) at room temperature. No hydrolysis was observed after 24 h for 6 and 7a-c. Scheme 2 Synthesis of substituted 4'-nitro-[1,1'-biphenyl]-4-amine o-NB at the benzylic position. (i) HNO3/H2SO4, 0 °C, 3 h, 70%, (ii) ethylene glycol, toluene, 165 °C, 4 h, 100%, (iii) 4-(dimethylamino)phenyl boronic acid, K2CO3, Bu4NBr, Pd(OAc)2, ethanol/water, 160 °C, 15 min, p-TsOH, acetonitrile/water/dichloromethane, 80 °C, 3 h, 88%, (iv) bromobenzylzinc bromide, THF, -78 °C, overnight, 80%, (v) 2-(3,4-dimethoxyphenyl)acetic acid, DMAP, diisopropylcarbodiimide, dichloromethane, 0 °C, 3 h, 68% and (vi) K2CO3, ethanol/water/toluene, Pd(PPh3)4, 80 °C, 45 min for 7a dimethylamino phenyl boronic acid, 55%, for 7b 4-methoxy phenyl boronic acid, 46%, for 7c 4-nitro phenyl boronic acid, 58%. The postulated mechanism for the photo-induced liberation of a nitrosoketone derivative (adapted from the literature) should be able to achieve a keto-enol tautomerism to generate a conjugated αhydroxystilbene derivative stabilized by an intramolecular hydrogen bond between the nitrogen from the nitroso group and the H of the enol group.

In order to characterize the formation of the nitroso photoproducts (see Scheme 1) an FT-IR study was undertaken using compound 7b in acetonitrile. The IR spectra of this product before and after irradiation (Fig. S28 and S29 †) show the main differences in the 1300-1500 cm -1 region. The band at 1465 cm -1 which can be attributed to the 19a vibration of the NO2 group (according to the Wilson notation 36 ) is decreasing while a band is appearing at 1446 cm -1 (attributed to the 19b vibration of the NO group 32 ) and at 1372 cm -1 (which could be attributed to an enol form signature). 38 A weak absorption can be detected at 3175 cm -1 which could also indicate an enol O-H bond vibration.

To confirm the keto-enol tautomerism, a 1 H-NMR study was undertaken using compound 6 in deuterated acetonitrile (CD3CN) at 267 and 405 μM, respectively. After 85% and 80% cleavage respectively, the NMR spectra nicely showed the release of the MPAA (see the ESI †) together with 3 major subproducts based on the 1 H dimethyl-amino signals. More interestingly, in a concentration dependent manner, 3 new NMR signals together with 2 new signals were detected respectively between 4-5.2 ppm and 9.5-10 ppm (Fig. S31 and S32 †). The singlet at 4.1 ppm is in good agreement with the CH2 of the nitroso-keto sub-product. And the two singlets at 4.87 ppm and 5.19 ppm together with the two singlets at 9.69 ppm and 9.97 ppm are also in good agreement with the 1 H expected signals for the alkene vCH and the OH signals of the enol sub-products (cis and trans), respectively.

After having confirmed the occurrence of a keto-enol tautomerism in the uncaging sub-product, we assumed that the elongated conjugated system of the α-hydroxystilbene should induce a strong enhancement of the UV-vis absorption and emission properties. In order to study the photoinduced changes in fluorescence, emission spectra were recorded for the irradiated samples (100 μM, 405 nm) in an acetonitrile/phosphate buffer (pH 7.4, 0.1 mM) mixture (1/1, v/v). For all four compounds, the fluorescence emission is very weak before photocleavage (with a maximum at 504, 489, 575 and 480 nm for 6, 3 a, 7b and 7c respectively). After complete photoconversion, compounds 6 and 7a showed a moderate increase in their emission intensity (×40 and ×32 for 6 and 7a respectively). In contrast, for 7b an intense red shifted (526 nm) emission was observed with more than 200 times increase in the fluorescence intensity (Fig. 1B). Of note is that this emission band seems to indicate that the increase of the conjugation length of the system and substitution with strong electron donating groups are able to generate a red-shifted emission band upon photocleavage. Finally, compound 7c showed during irradiation a more complex fluorescence behavior presumably due to the photodegradation of the photolytic by-product leading first to an increase followed by a decrease in the fluorescence intensity (Table S4 †).

All photochemical and photophysical properties of compounds 6 and 7a-c are summarized in Table 1.

Table 1 Variation of the fluorescence intensity ratio and emission wavelength of derivatives 6 and 7a-c a 100 μM solutions.

b Average of 3 separate irradiation times. c Not calculated due to the high bleaching of the sub-product.

Biological evaluation of the uncaging fluorescence reporting property on HeLa cells

Since compound 7b showed the highest photoinduced fluorescence linear increase and the most red-shifted fluorescence emission upon irradiation, we decided to use this compound to evaluate the possibility to monitor the uncaging events by fluorescence recording on cell culture. For this reason, we synthesized compound 11, a PEGylated version of the o-nitrobiphenyl methoxy derivative 7b. The product was synthesized (Scheme 3) in 4 steps starting from an octaethylene glycol monomethyl ether which was reacted with tertbutyl-bromoacetate to form 8 which was then deprotected to afford compound 9. This was reacted with 5 followed by a Suzuki coupling to give 11 in 30% yield. HeLa cells were incubated for 5 min with a 1 μM solution of 11. The cells were irradiated with 365 nm light from an EL6000 lamp (see the ESI †) of a Leica SPE microscope. A confocal image was obtained each 5 min for 15 min of continuous irradiation (the experiment was stopped after 15 min due to the phototoxicity of the UV irradiation). A clear increase in the detected fluorescence intensity was observed upon irradiation (see Fig. S33 †). Of note is that the HeLa cells incubated for 35 min with a 1 μM solution of 11 showed only weak fluorescence intensity. A quantitative analysis of the fluorescence intensity was performed on 5 cells showing a linear increase in the fluorescence intensity for the first 15 min and reaching a plateau (Fig. 2). Therefore, we could follow the uncaging event of this new type of o-nitrobenzyl PPG by the increase of fluorescence signal on cells.

Conclusions

There is a great need for photoremovable groups able to generate an easy way to quantify their side-products, in particular to be able to monitor in real time the light induced concentration jump of a given biological effector. This leads us to synthesize a new class of onitrobenzyl photoremovable groups able to generate a fluorescent side-product. These compounds were designed in order to produce after the photoreaction a nitrosoketone by-product able to achieve a keto-enol tautomerism leading to a conjugated α-hydroxystilbene product. A 1,2addition of bromoaryl organozinc halides to 4ʹ-(dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3-carbaldehyde followed by Miyaura-Suzuki cross coupling reactions was used in order to synthesize biphenyl substituted (1-(2-nitrophenyl)ethyl) photoremovable groups. Interestingly each synthesized o-NB PPG shows a very weak fluorescence signal before irradiation. To be able to quantify the photorelease of carboxylic acid functions a chromophoric 3,4-dimethoxyphenylacetic acid was coupled to our o-NB PPGs. Except for the p-nitrobiphenyl derivative 7c, an almost quantitative (≥93%) release of MPAA was measured by HPLC after complete photo-conversion for each photolytic precursor of MPAA. More interestingly, all these compounds showed an interesting fluorescence signal increase induced by the photolytic reaction. In particular, the p-methoxy biphenyl derivative 7b showed a 200 times increase in the green (526 nm) emission intensity after full photocleavage. Therefore, a water-soluble version of this compound has been successfully used for in vitro cell imaging and real time monitoring of the uncaging event. Our future studies will focus on the use of this strategy for the development of more efficient visible light sensitive photoremovable groups in the o-NB series 8 in order to follow the uncaging events simultaneously by fluorescence analysis and with a physiological event (for example induced by the photorelease of a neurotransmitter). 3-Bromobenzaldehyde (16.21 mmol, 0.35 mL) was dissolved in 15 mL of 98% H2SO4. To this mixture, HNO3 (52 mmol, 3.6 mL) was added dropwise under vigorous stirring at 0 °C for 1 h and then at room temperature for 2 h. The mixture was poured into ice water and extracted with ethyl acetate, the combined organic phases were dehydrated with MgSO4 and the crude product was purified over a SiO2 column using heptane/ ethyl acetate (9/1) as the eluent. The target compound 2 was isolated as pale-yellow crystals (2.6 g, 70%, Rf = 0.31).

2-(5-Bromo-2-nitrophenyl)-1,3-dioxolane (3)

In 50 mL of anhydrous toluene, 2 (655 mg, 2.84 mmol) was dissolved and ethylene glycol (0.2 mL, 3.41 mmol) was added to a mixture with p-toluene sulfonic acid (55 mg, 0.284 mmol). The mixture was heated under reflux using a Dean-Stark apparatus. After 4 h the reaction was complete (monitored by TLC) and the solvent was evaporated. The mixture was extracted 3 times with dichloromethane and washed with water affording the target compound 3 as a light brown solid (780 mg, 100%, Rf = 0.52 AcOEt/heptane 1/9 in vol.).

3ʹ-(1,3-Dioxolan-2-yl)-N,N-dimethyl-4ʹ-nitro-[1,1ʹ-biphenyl]4-amine

In a microwave vial, 365 mg of 3 (1.33 mmol) with 264 mg of 4(dimethyl amino)phenyl boronic acid (1.6 mmol), potassium carbonate (3.6 mmol) and tetrabutylammonium bromide (1.33 mmol) were dissolved in 13 mL of ethanol and 6.5 mL of water (2/1 v/v). The mixture was degassed 2 times (freeze-thaw cycles) and then Pd(OAc)2 (30 mg, 0.133 mmol) was added and the mixture was degassed 1 more time before heating under microwave radiation at 160 °C for 15 minutes. The solvent was evaporated, and the residue was extracted with water and ethyl acetate and dried over MgSO4. The solvent was evaporated under vacuum and the biphenyl acetal product was isolated as a reddish-brown solid (418 mg, 85%, Rf = 0.46 AcOEt/heptane 1/9 in vol.). The yield obtained is estimated since the side product (15% homocoupling of boronic acid from 1 H NMR integration) has the same Rf as the target product, so in this step the product was used without further purification.

MS(ESI): [M + H]

+ (C17H19N2O4 + ) m/z calcd: 315.13, m/z found: 315.05.

4ʹ-(Dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3-carbaldehyde (4)

A solution of p-toluenesulfonic acid (2.61 g, 13.75 mmol) in acetonitrile (20 mL) and water (7 mL) was added to a solution of biphenyl aldehyde (432 mg, 1.375 mmol) in dichloromethane (8 mL). The mixture was then stirred at 80 °C under reflux for 3 h (monitored by TLC). After cooling to room temperature, the solvent was evaporated, and the residue was extracted with dichloromethane and washed with water. The crude product was purified over a column to afford the target product 4 as a bright red solid (297 mg, 88%, Rf = 0.3 AcOEt/ heptane 15/85 in vol.).

4-Bromobenzyl zinc bromide: preparation

LiCl (170 mg, 4 mmol) was added to a microwave reaction vial and dried with a flame for a few minutes in open air. This vial was allowed to cool down in a desiccator under vacuum. Air was used to back pressurize the desiccator and Zn powder (265 mg, 4 mmol) was added. The vial was heated again on a flame for a few minutes in open air and allowed to cool down in a desiccator under vacuum, and argon was added to back pressurize the desiccator. A stirring bar was added, the vial was sealed, and 3 mL of anhydrous THF was injected via the septum followed by 1,2-dibromoethane (10 µL, 0.1 mmol). The mixture was heated in a microwave oven at 85 °C for 5 minutes. TMSCl (2.5 µL, 0.02 mmol) was added to the suspension and once again it was heated at 85 °C for 5 minutes. 4-Bromobenzyl bromide (500 mg, 2 mmol) was then added as a solution in 2 mL THF and the vial was heated for 1 h at 70 °C. Iodometric titration indicated that the obtained solution of 4-bromobenzyl zinc bromide had a concentration of 0.4 M.

2-(4-Bromophenyl

)-1-(4ʹ-(dimethylamino)-4-nitro- [1,1ʹ-biphenyl]-3-yl)ethan-1-ol (5)
In 10 mL of anhydrous THF, 4 (130 mg, 0.48 mmol) was dissolved. At -78 °C, a solution of 4-bromobenzyl zinc bromide (3.6 mL, 1.44 mmol) was added dropwise and the mixture was stirred for 1 h at -78 °C and allowed to warm up to room temperature and stirred overnight. The reaction was quenched with 10% HCl and extracted with water and ethyl acetate and the crude compound was purified on a column with heptane/ AcOEt 85/15 in vol. as the eluent to afford 5 as orange-red paste (210 mg, 80%, Rf = 0.32 AcOEt/heptane 15/85 in vol.).

2-(4-Bromophenyl

)-1-(4ʹ-(dimethylamino)-4-nitro[1,1ʹ-biphenyl]-3- yl)ethyl-2-(3,4-dimethoxyphenyl)acetate (6)
In 25 mL anhydrous dichloromethane, compound 5 (450 mg, 1.02 mmol) was dissolved and 2-(3,4-dimethoxyphenyl)acetic acid (300 mg, 1.53 mmol) was added along with 4-dimethyl aminopyridine (DMAP) (7 mg, 0.051 mmol) under argon. At 0 °C, N,Nʹ-diisopropyl carbodiimide (DIC) (0.24 mL, 1.53 mmol) was added dropwise and the reaction was stirred for 1 h at 0 °C, and then for 2 h at room temperature. The reaction was monitored by HPLC. The mixture was filtered on a glass-frit funnel and the filtrate was extracted with dichloromethane and water. To remove diisopropyl urea salts, the product is dissolved in cold acetonitrile. The crude product was purified over a column with silica gel using 20/80 AcOEt/ heptane in vol. as the eluent to afford 6 as orange powder (430 mg, 68%, Rf = 0.38 AcOEt/heptane 20/80 in vol.). In a microwave vial, 52 mg of 6 (0.084 mmol) with 15 mg of 4methoxyphenyl boronic acid (0.1 mmol) and potassium carbonate (30 mg, 0.21 mmol) were dissolved in 2 mL of ethanol, 1 mL of water and 7 mL of toluene (2/1/7 in vol.). The mixture was degassed 2 times (freeze-thaw cycles) and then Pd(PPh3)4 (5 mg, 4.2 × 10 -3 mmol) was added and the mixture was degassed 1 more time before heating under microwave radiation at 80 °C for 45 minutes. The solvents were evaporated, and the residue was extracted with ethyl acetate, washed with water and dried over MgSO4. The solvent was evaporated under vacuum and the crude product was purified over a column with silica gel using 40/60 AcOEt/heptane as the eluent to afford product 7b as reddish paste (25 mg, 46%, Rf = 0.32 AcOEt/heptane 40/60 in vol.). The same procedure was followed for the synthesis of 7a (4(dimethyl amino)phenyl boronic acid) with a yield of 55% and 7c (4-nitrophenyl boronic acid) with a yield of 58%. This compound was obtained in 58% yield. To a stirred solution of octaethylene glycol monomethyl ether (250 mg, 0.65 mmol) in anhydrous THF (8 mL) was added NaH (40 mg, 1.62 mmol, 60% dispersion in mineral oil) at 0 °C. The solution was stirred for 30 minutes at 0 °C, and tertbutyl bromoacetate (0.18 mL, 1.17 mmol) was added dropwise over 2 minutes. The resulting solution was allowed to warm to room temperature and stirred for 2 h. The reaction was quenched with a saturated solution of NH4Cl, the aqueous phase was washed three times with dichloromethane, the combined organic extracts were dried over MgSO4 and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography using 100% AcOEt and then 98/2 AcOEt/MeOH (in vol.) as the eluent to afford 8 (282 mg, 87%, Rf = 0.32 AcOEt/MeOH 98/2 in vol.) as a yellowish oil. 1 H NMR (400 MHz, CDCl3): δ = 4.01 (s, 2H), 3.62-3.72 (m, 30H), 3.52-3.56 (m, 2H), 3.37 (s, 3H), 1.46 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3): δ = 168.3, 83.5, 71.6, 70.1, 69.5, 68.1, 56.9, 31.7 ppm.

2-(2-Methoxyoctaethoxy)acetic acid (9) 272 mg of 8 was dissolved in 3 mL of CH2Cl2 and 1.5 mL of CF3COOH (2/1 in vol.) and stirred for 3 h. The solvent was evaporated and the remaining CF3COOH was co-evaporated 3 times with CH2Cl2 to afford 9 in quantitative yield (240 mg, Rf = 0.33 AcOEt/MeOH 98/2 in vol.).

1 H NMR (400 MHz, CDCl3): δ = 10.1 (broad s, 1H), 4.17 (s, 2H), 3.62-3.77 (m, 30H), 3.54-3.58 (m, 2H), 3.38 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ = 173.3, 71.6, 70.1, 69.5, 68.1, 67.5, 56.9 ppm. (10) In 10 mL anhydrous dichloromethane, compound 5 (210 mg, 0.47 mmol) was dissolved and 9 (306 mg, 0.71 mmol) was added along with N,Nʹ-dimethylaminopyridine (DMAP) (7 mg, 0.026 mmol) under argon. At 0 °C, N,Nʹ-diisopropyl carbodiimide (DIC) (0.11 mL, 0.71 mmol) was added dropwise and the reaction was stirred for 1 h at 0 °C, and then for 2 h at room temperature. The reaction was monitored by HPLC. The mixture was filtered on a glass-frit funnel and the filtrate was extracted with dichloromethane and water. To remove diisopropyl urea salts, the product is dissolved in cold acetonitrile. The crude product was purified over a column with silica gel using 100% AcOEt and then 98/2 AcOEt/MeOH in vol. as the eluent to afford 10 (194 mg, 48%, Rf = 0.38 AcOEt/MeOH 98/2 in vol.) as an orange paste. In a microwave vial, 115 mg of 10 (0.135 mmol) with 25 mg of 4methoxyphenyl boronic acid (0.162 mmol) and potassium carbonate (50 mg, 0.34 mmol) were dissolved in 3 mL of ethanol, 1.5 mL of water and 10 mL of toluene (2/1/7 in vol.). The mixture was degassed 2 times (freeze-thaw cycles), then Pd(PPh3)4 (8 mg, 6.75 × 10 -3 mmol) was added and the mixture was degassed 1 more time before heating under microwave radiation at 80 °C for 45 minutes. The solvent was evaporated, and the residue was extracted with water and dichloromethane and dried over MgSO4. The solvent was evaporated under vacuum and the residue was purified over a silica gel column to afford the product 11 as reddish paste (36 mg, 30%, Rf = 0.37 AcOEt/MeOH 98/2 in vol.).

2-(4-Bromophenyl

)-1-(4ʹ-(dimethylamino)-4-nitro-[1,1ʹbiphenyl]-3- yl)ethyl-2-(2-methoxyoctaethoxy)acetate

  Laboratoire de Conception et Application de Molécules Bioactives, Equipe de Chimie et Neurobiologie Moléculaire, Université de Strasbourg, CNRS, CAMB UMR 7199, F-67000 Strasbourg, France. E-mail: specht@unistra.fr; Fax: (+33)368854306 †Electronic supplementary information (ESI) available. See DOI: 10.1039/ c8ob01330f

  between the dioxolane 3 and 4-(dimethylamino)phenylboronic acid followed by the deprotection of the dioxolane to obtain compound 4. The 2-(4bromophenyl)1-(4ʹ-(dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3yl)ethan-1-ol key intermediate 5 was obtained in 85% yield by the reaction of freshly prepared 4-bromobenzyl zinc bromide 35 with aldehyde 4. However, intermediate 5 could not be separated from 1,2-bis (4-bromophenyl)ethane obtained by homocoupling as a side product in this step. 3,4-Dimethoxyphenylacetic acid (MPAA) was then grafted to this first o-NB substituted PPG 5 using N,Nʹdiisopropyl carbodiimide

Fig. 1 1

 1 Fig. 1 1 Variation of UV absorbance (A) and fluorescence emission (B) after irradiation at 405 nm of a 55 μM solution (acetonitrile/PBS 1 : 1 in v/v) of 7b.

Fig. 2

 2 Fig. 2 Fluorescence increase as a function of irradiation time observed for HeLa cells treated with 1 μM of 11.

Scheme 3

 3 Scheme 3 Synthesis of 11: a PEGylated version of the o-nitrobiphenyl methoxy derivative. (i) NaH, tert-butylbromoacetate, THF, 0 °C, 2 h, 87%; (ii) CF3COOH/dichloromethane, 3 h, room temperature, 100%; (iii) 5, DMAP, diisopropylcarbodiimide, dichloromethane, 0 °C, 48%; (vi) 4-methoxyphenyl boronic acid, K2CO3, ethanol/toluene/water, Pd(PPh3)4, 80 °C, 45 min, 30%.

1 H

 1 NMR (400 MHz, CDCl3): δ = 7.94 (s, 1H), 7.81 (d, 3 J(H,H) = 9 Hz, 1H), 7.63 (d, 3 J(H,H) = 9 Hz, 4 J(H,H) = 2.2 Hz, 1H), 6.48 (s, 1H), 4.05 (m, 4H) ppm. 13 C NMR (100 MHz, CDCl3): δ = 147.5, 135.3, 132.7, 130.9, 127.9, 126.1, 99.1, 65.4 ppm. MS(ESI): [M + H] + (C9H8BrNO4 + ) m/z calcd: 273.96, m/z found: 273.84.

1 H

 1 NMR (400 MHz, CDCl3): δ = 8.08 (d, 3 J(H,H) = 8 Hz, 1H), 8.01 (s, 1H), 7.59 (d, 3 J(H,H) = 9.6 Hz, 4 J(H,H) = 2.2 Hz, 1H), 7.55 (d, 3 J(H,H) = 9.6 Hz, 2H), 7.48 (d, 3 J(H,H) = 9.6 Hz, 2H), 7.23 (d, 3 J(H,H) = 9.6 Hz, 2H), 6.79 (d, 3 J(H,H) = 9.6 Hz, 2H), 5.59 (d, 3 J(H,H) = 10 Hz, 1H), 3.26 (d, 3 J(H,H) = 12.4 Hz, 1H), 3.03 (s, 6H), 2.8-2.86 (dd, 2 J(H,H) = 23, 3 J(H,H) = 13.6, 1H) ppm. HRMS(ESI): [M + H] + (C22H22N2O3 + ) m/z calcd: 441.0703, m/z found: 441.0177.

  1 H NMR (400 MHz, CDCl3): δ = 8.1 (d, 3 J(H,H) = 8 Hz, 1H), 7.55 (d, 3 J(H,H) = 9.6 Hz, 4 J(H,H) = 2.2 Hz, 1H), 7.41 (d, 3 J(H, H) = 9.6 Hz, 2H), 7.38 (s, 1H), 7.23 (d, 3 J(H,H) = 9.6 Hz, 2H),7.18 (d, 3 J(H,H) = 9.6 Hz, 2H), 6.79 (d, 3 J(H,H) = 9.6 Hz, 2H),6.65-6.75 (m, 3H), 6.57 (d, 3 J(H,H) = 10 Hz, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 3.52 (s, 2H), 3.32 (d, 3 J(H,H) = 12.4 Hz, 1H), 3.16 (s, 6H), 2.9-3.01 (dd, 2 J(H,H) = 23 Hz, 3 J(H,H) = 13.6 Hz, 1H) ppm. HMMS(ESI): [M + H] + (C32H32N2O6Br + ) m/z calcd: 619.1443, m/z found: 619.1436. 1-(4ʹ-(Dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3-yl)-2(4ʹ-methoxy-[1,1ʹ-biphenyl]-4-yl)ethyl-2-(3,4-dimethoxyphenyl) acetate (7b)

1 H

 1 NMR (400 MHz, CDCl3): δ = 8.08 (d,3 J(H,H) = 8.4 Hz,1H), 7.54 (d,3 J(H,H) = 8.8 Hz, 2H), 7.52 (d,3 J(H,H) = 7.6 Hz, 1H), 7.45 (d, 3 J(H,H) = 8.4 Hz, 2H), 7.31 (s, 1H), 7.19-7.24 (m, 4H), 6.98 (d, 3 J(H,H) = 9.8 Hz, 2H), 6.67-6.72 (m, 5H), 6.63 (d, 3 J(H,H) = 8.4 Hz, 1H), 3.86 (s, 3H), 3.77 (s, 3H), 3.70 (s, 3H), 3.52 (s, 2H), 3.39 (d, 3 J(H,H) = 14 Hz, 1H), 3.05-3.11 (dd, 2 J(H,H) = 22.8 Hz, 3 J(H,H) = 15.2 Hz, 1H), 3.02 (s, 6H) ppm. HRMS(ESI): [M + H] + (C39H39N2O7 + ) m/z calcd: 647.2757, m/z found: 647.2767. 1-(4ʹ-(Dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3-yl)-2(4ʹ-(dimethylamino)-[1,1ʹ-biphenyl]-4-yl)ethyl-2-(3,4dimethoxyphenyl)acetate (7a)This compound was obtained in 55% yield. 1 H NMR (400 MHz, CDCl3): δ = 8.08 (d, 3 J(H,H) = 9.36 Hz, 1H), 7.52 (d, 3 J(H,H) = 9.6 Hz, 4 J(H,H) = 2.2 Hz, 1H), 7.46 (d, 3 J(H,H) = 7.6 Hz, 2H), 7.31 (s, 1H), 7.19-7.22 (m, 4H), 6.82 (d, 3 J(H,H) = 7.6 Hz, 2H), 6.68-6.71 (m, 5H), 6.63 (d, 3 J(H,H) = 8.8 Hz, 1H), 3.77 (s, 3H), 3.71 (s, 3H), 3.53 (s, 2H), 3.38 (d, 3 J(H,H) = 14.4 Hz, 1H), 3.05-3.11 (dd, 2 J(H,H) = 23.6 Hz, 3 J(H,H) = 13.6 Hz, 1H), 3.01 (s, 6H), 3.00 (s, 6H) ppm. HRMS(ESI): [M + H] + (C40H42N3O6 + ) m/z calcd: 660.3073, m/z found: 660.3047. 1-(4ʹ-(Dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3-yl)-2-(4ʹ-nitro-[1,1ʹ-biphenyl]-4-yl)ethyl-2-(3,4-dimethoxyphenyl)acetate (7c)

  1 H NMR (400 MHz, CDCl3): δ = 8.06 (d, 3 J(H,H) = 9.2 Hz, 1H), 7.54 (s, 1H), 7.38-7.48 (m, 4H), 7.14-7.23 (m, 3H), 6.76 (d, 3 J(H,H) = 7.6 Hz, 2H), 6.63 (d, 3 J(H,H) = 8.8 Hz, 1H), 4.06 (s, 2H), 3.49-3.72 (m, 32H), 3.34 (s, 3H), 3.31 (d,2 J(H,H) = 18.6 Hz, 1H), 3.02-3.07 (dd, 2 J(H,H) = 21.3 Hz, 3 J(H,H) = 13.6 Hz, 1H), 3.01 (s, 6H) ppm. MS(ESI): [M + H] + (C41H58N2O13 + ) m/z calcd: 865.30, m/z found: 865.43. 1-(4ʹ-(Dimethylamino)-4-nitro-[1,1ʹ-biphenyl]-3-yl)-2-(4ʹmethoxy-[1,1ʹ-biphenyl]-4-yl)ethyl-2-(2-methoxyoctaethoxy) acetate(11)

1 H

 1 NMR (400 MHz, CDCl3): δ = 8.09 (d, 3 J(H,H) = 8 Hz, 1H), 7.57 (dd, 3 J(H,H) = 10.4 Hz, 4 J(H,H) = 2.2 Hz, 1H), 7.48-7.53 (m, 5H), 7.40 (d, 3 J(H,H) = 9.6 Hz, 2H), 7.32 (d, 3 J(H,H) = 7.6 Hz, 2H), 6.97 (d, 3 J(H,H) = 7.6 Hz, 2H), 6.72-6.75 (m, 3H), 4.11 (s, 2H), 3.85 (s, 3H), 3.75 (s, 3H), 3.51-3.66 (m, 32H), 3.44 (d, 3 J(H,H) = 14 Hz, 1H), 3.12-3.19 (dd, 2 J(H,H) = 22 Hz, 3 J(H,H) = 12.7 Hz, 1H), 3.01 (s, 6H) ppm. MS(ESI): [M + H] + (C48H65N2O14 + ) m/z calcd: 893.44, m/z found: 893.57.

  1 H NMR (400 MHz, CDCl3): δ = 8.01 (d, 3 J(H,H) = 7.6 Hz,1H), 7.97 (s, 1H), 7.63 (d, 3 J(H,H) = 9.6 Hz, 4 J(H,H) = 2.2 Hz, 1H), 7.56 (d, 3 J(H,H) = 8.4 Hz, 2H), 6.79 (d, 3 J(H,H) = 9.6 Hz, 2H), 6.60 (s, 1H), 4.07 (m, 4H), 3.03 (s, 6H) ppm.

  C NMR (100 MHz, CDCl3): δ = 189.1, 151.2, 147.3, 146.3, 132.5, 129.3, 128.1, 125.9, 125.5, 124.5, 124.3, 112.4, 40.2 ppm. MS(ESI): [M + H] + (C15H15N2O3 + ) m/z calcd: 271.01, m/z found: 270.99.

	1 H NMR (400 MHz, CDCl3): δ = 10.53 (s, 1H), 8.17 (d, 3 J(H,H) = 8 Hz,
	1H), 8.07 (s, 1H), 7.86 (d, 3 J(H,H) = 7.2 Hz, 4 J(H,H) = 2.2 Hz, 1H), 7.6 (d,
	3 J(H,H) = 8 Hz, 2H), 6.79 (d, 3 J(H,H) = 9.2 Hz, 2H), 3.03 (s, 6H) ppm.

13

  1 H NMR (400 MHz, CDCl3): δ = 8.17 (d,3 J(H,H) = 8.8 Hz,2H), 7.96 (d, 3 J(H,H) = 9.6 Hz, 1H), 7.6 (d, 3 J(H,H) = 7.6 Hz, 4 J(H,H) = 2.2 Hz, 2H), 7.41 (d, 3 J(H,H) = 8.8 Hz, 1H), 7.38 (d, 3 J(H,H) = 8.8 Hz, 2H), 7.18 (d, 3 J(H,H) = 8 Hz, 2H), 7.13 (s, 1H), 7.09 (d, 3 J(H,H) = 6.8 Hz, 2H), 6.56-6.63 (m, 5H), 6.54 (d, 3 J(H,H) = 8.4 Hz, 1H), 3.67 (s, 3H), 3.58 (s, 3H), 3.43 (s, 2H), 3.28 (d, 3 J(H,H) = 13.2 Hz, 1H), 2.97-3.02 (dd, 2 J(H,H) = 23.6 Hz, 3 J(H,H) = 13.6 Hz, 1H), 2.90 (s, 6H) ppm.

	HRMS(ESI): [M + H] + (C38H36N3O8 + ) m/z calcd: 662.2502, m/z found:
	662.2502.
	tert-Butyl-2-(2-methoxyoctaethoxy)acetate (8)

Acknowledgements

This work was supported by the Université de Strasbourg (IdEx Grant to A. S.), the CNRS and a grant from the Agence Nationale de la Recherche (Contract No. ANR-13-JSJV-0009-01 to A. S.). The authors thank Laura Bom and Maurice Coppe from the faculty of chemistry (University of Strasbourg) for FT-IR and NMR spectra measurements, respectively.

Notes and references

Conflicts of interest

There are no conflicts to declare.


I Guillamón

H Suderow

J G Rodrigo

S Vieira

P Rodière

L Cario

E Navarro-Moratalla

C Martí-Gastaldo

E Coronado

Chiral charge order in the superconductor 2H-TaS 2

Keywords: numbers: 64.10.+v, 74.20.Mn, 74.55.+v, 74.70.Xa 1

We find chiral charge order in the superconductor 2H-TaS 2 using Scanning Tunneling Microscopy and Spectroscopy (STM/S) at 0.1 K. Topographic images show hexagonal atomic lattice and charge density wave (CDW) with clockwise and counterclockwise charge modulations. Tunneling spectroscopy reveals the superconducting density of states, disappearing at T c = 1.75 K and showing a wide distribution of values of the superconducting gap, centered around ∆=0.28 meV.

Since the suggestion by Anderson and Blount [START_REF] Anderson | Symmetry considerations on martensitic transformations: "Ferroelectric" metals ?[END_REF] that charge order may appear in metals and superconductors, the size and anisotropy of charge density wave (CDW) modulations are an intensely debated issue [START_REF] Kiss | Chargeorder-maximized momentum-dependent superconductivity[END_REF][START_REF] Rossnagel | Fermi surface of 2H -N bSe 2 and its implications on the charge-density-wave mechanism[END_REF]. Layered compounds, such as hexagonal bilayer stackings of dichalcogenides, named 2H, have received attention because the charge order is only partial and clean metallic behavior is ubiquitously observed. In the 2H series of TaSe 2 , TaS 2 , NbSe 2 and NbS 2 , the critical temperature of the CDW decreases from around 120 K in 2H-TaSe 2 , to 80 K in 2H-TaS 2 , down to 30 K in 2H-NbSe 2 and finally no CDW in 2H-NbS 2 [START_REF] Castro Neto | Charge density wave, superconductivity, and anomalous metallic behavior in 2d transition metal dichalcogenides[END_REF][START_REF] Suderow | Pressure induced effects on the Fermi surface of superconducting 2H-NbSe 2[END_REF]. Superconductivity coexists with CDW, with a superconducting critical temperature T c which increases from around 0.2 K in 2H-TaSe 2 up to 7.2 K and 6 K in, respectively 2H-NbSe 2 and 2H-NbS 2 . Generally it is believed that their mutual interaction is competitive, as charge order usually drives towards insulating behavior, and superconductivity towards perfect conductance. However, evidence for cooperative interactions, which actually shape the form of the gap over the Fermi surface, have been found in angular resolved photoemission [START_REF] Kiss | Chargeorder-maximized momentum-dependent superconductivity[END_REF].

CDW significantly shapes the anisotropy of the superconducting properties of the compound 2H-NbSe 2 , producing vortex cores with a star shaped cross section, instead of the tubular cores expected in a simple isotropic s-wave superconductor [START_REF] Hess | Vortex-core structure observed with a scanning tunneling microscope[END_REF][START_REF] Gygi | Angular band structure of a vortex line in a type-II superconductor[END_REF][START_REF] Hayashi | Star-shaped local density of states around vortices in a type-II superconductor[END_REF][START_REF] Guillamon | Superconducting density of states and vortex cores of 2H -N bS 2[END_REF].

The Fermi surface of all four 2H compounds (2H-TaSe 2 , 2H-TaS 2 , 2H-NbSe 2 and 2H-NbS 2 ) consists essentially of warped tubes deriving from the d electrons of the transition metal, with a strong hybridization to the p electrons of the chalcogen [START_REF] Wilson | Charge-density waves and superlattices in the metallic layered transition metal dichalcogenides[END_REF][START_REF] Corcoran | Quantum oscillations in the mixed state of the type II superconductor 2H-NbSe 2[END_REF]. Calculations find that, generally, p-electron derived bands of the chalcogens do not cross the Fermi level, with the important exception of 2H-NbSe 2 , where they form a small 3D pocket [START_REF] Johannes | Fermi-surface nesting and the origin of the charge-density wave in NbSe 2[END_REF]13].

The charge order properties have been studied in the whole series, although usually at temperatures well above liquid helium (see e.g. [START_REF] Sacks | Voltage-dependent STM image of a charge density wave[END_REF]). Only the superconducting properties of 2H-NbSe 2 and of 2H-NbS 2 have been analyzed in some detail, finding peculiar multigap superconducting behavior [START_REF] Guillamon | Superconducting density of states and vortex cores of 2H -N bS 2[END_REF][START_REF] Boaknin | Heat conduction in the vortex state of NbSe 2 : Evidence for multiband superconductivity[END_REF][START_REF] Rodrigo | STM study of multiband superconductivity in NbSe 2 using a superconducting tip[END_REF][START_REF] Fletcher | Penetration depth study of superconducting gap structure of 2H-NbSe 2[END_REF][START_REF] Noat | Signatures of multigap superconductivity in tunneling spectroscopy[END_REF][START_REF] Kacmarcik | Specific heat measurements of a superconduting 2H -N bS 2 single crystal in an external magnetic field: energy gap structure[END_REF].

On the other hand, in the related semimetallic compound 1T-TiSe 2 (the 1T trigonal arrangement of single layers produces generally semimetallic or semiconducting systems [START_REF] Bulaevskii | Superconductivity and electronic properties of layered compounds[END_REF][START_REF] Disalvo | Electronic properties and superlattice formation in the semimetal TiSe 2[END_REF]), CDW has been found with novel properties. 1T-TiSe 2 presents the hitherto unique feature of alternating sheets with a 3D helical stacking of intralayer charge modulation with the helical axis perpendicular to the layers [START_REF] Ishioka | Chiral charge-density waves[END_REF]. Domains which are mirror images of each other, and cannot be brought together with only rotation operations, are found over the surface. The question if such kind of chiral charge order can appear in a superconductor with CDW has not been addressed. Chiral symmetry is a particular example of absence of space parity, a concept of fundamental importance in BCS theory. To our knowledge, the only known superconductor where chiral symmetry is presently debated is the p-wave superconductor Sr 2 RuO 4 [START_REF] Mackenzie | The superconductivity of Sr 2 Ruo 4 and the physics of spintriplet pairing[END_REF]. In Sr 2 RuO 4 , the chiral symmetry appears due to Cooper pair wavefunction phase winding at the superconducting transition, related to the particular form of the p-wave order parameter. How superconductivity evolves out of a chiral electronic environment, however, has yet to be worked out. Here we find for the first time chiral charge order in a metallic compound, 2H-TaS 2 , which, in addition, superconducts below 1.75K. We discuss chiral properties of CDW in this material, and determine the superconducting density of states from tunneling spectroscopy. 2H-TaS 2 single crystals were synthesised using a iodine transport method. Stoichiometric amounts of the elements were sealed under vacuum in a silica tube with a small amount of Iodine (5mg/cm 3 ). The tube was then heated for a period of 15 days in a gradient furnace (≈50 • C along the tube) with the mixture located in the high temperature zone (≈ 800 • C). This synthesis yielded layered crystals some hundreds of µm size that exhibit X-ray diffraction patterns corresponding to 2H-TaS 2 . For Scanning Tunneling Microscopy (STM) measurements, we use a STM in a partially home-made dilution refrigerator set-up described in detail elsewhere [START_REF] Rodrigo | Superconducting nanostructures fabricated with the scanning tunnelling microscope[END_REF][START_REF] Suderow | Compact very low temperature scanning tunneling microscope with mechanically driven horizontal linear positioning stage[END_REF]. The set-up features the possibility to mount several very small (some tens of micron size) single crystals and change the position of the tip from one sample to the other in-situ, at low temperatures. The gold tip can be moved to a sample of gold to clean and sharpen, and the energy resolution of the set-up is of 15µeV. Scanning was made at constant current with tunneling conductances of some 0.1 µS and bias voltages usually below 10 mV. Several 2H-TaS 2 samples were glued one by one using silver epoxy on an Au substrate, and measured at 100 mK. Samples were mechanically cleaved using scotch tape prior to the experiment. After cleaving, clean atomically flat surfaces are easily found, with the exposed surface composed of hexagons of the chalcogen atomic layer.

The STM topography at constant current of 2H-TaS 2 taken at 100 mK is shown in Fig. 1a.

The hexagonal atomic S lattice is nicely observed, together with a remarkable triangular 3x3 charge modulation of wavelength 3 times the lattice constant. The Fourier transform of the whole image (right panel of Fig. 1a) shows that the CDW modulation is located at one third the in-plane reciprocal lattice wavevectors, within experimental error of ± 1%. The CDW modulation leads to hexagons spanned by 3 vectors parallel to the three symmetry axis of the hexagonal atomic lattice, repeating itself in the topography. We identify two regions with different hexagonal patterns produced by the CDW modulation, marked by white rectangles in Fig. 1. In each region, within a given hexagon, the amplitude of the charge density along the three principal CDW vectors has an angular dependence, breaking six-fold rotational symmetry. The amplitude relationship between the three modulations varies when going from the upper left corner to the lower right corner. In Fig. 1b we show representative topography profiles along the three CDW wavevectors. The CDW amplitude is highest along the red arrow direction in the upper left corner, and along the green arrow direction in the lower right corner. The hexagonal pattern spanning the CDW modulation, changes as a function of the position in the image, without any step or impurity cutting the image in two. Note that both parts cannot be transferred into each other by a simple rotation.

The angular dependence of the CDW modulation observed in the real space can be further characterized by making a detailed Fourier analysis. If we look at the Fourier transforms of the two different areas marked by rectangles in Fig. 1a, we find that the amplitude of CDW Bragg peaks decrease clockwise (in R) and counter-clockwise (in L), respectively.

The normalized amplitude relationships for, respectively, q CDW 1 (red), q CDW 2 (orange), and q CDW 3 (green), are 1-0.6-0.4 for the upper part of the image (R in Fig. 2b), and 0.6-0.8-1 for the bottom part of the image (L in Fig. 2b). This behavior is not followed by the intensity changes of the lattice Bragg peaks and evidences the presence of chiral domains in the CDW of 2H-TaS 2 .

The spatial distribution of the chiral domains can be imaged by further Fourier analysis.

We first Fourier transform the whole real space image (shown in Fig. 1a), center the resulting Fourier image at the peak corresponding to CDW's component with highest amplitude in the upper left corner domain (q CDW 1 ), filter the rest of the image out, and re-transform into real space. This gives us the real space dependence of the CDW amplitude corresponding to the wavevector q CDW 1 . We then make the same procedure for the CDW modulation corresponding to q CDW 3 which has the highest amplitude in the lower right corner domain.

Finally, we subtract both images [START_REF] Zelkjovic | STM imaging of inversionsymmetry-breaking structural distortion in the Bi-based cuprate superconductors[END_REF] obtaining the map of the relative height between both modulations (Fig. 2c). We use red color for the area where q CDW 1 has highest amplitude, and green color for the area where q CDW 3 has highest amplitude (Fig. 2c). White color is used for the boundary, where both modulations have equal amplitude. The size of the areas with different CDW modulations is rather large, of up to 10 nm, and their boundary is irregular.

The height of the atomic and CDW Fourier Bragg peaks measured in the transition metal di-chalcogenides depends always on the direction. This is the result of the complex Moiré-pattern, with very different hexagonal symmetry structures appearing in different positions, ubiquitously observed in these materials (see e.g. [START_REF] Coleman | Scanning tunneling microscopy of charge density waves in transition metal chalcogenides[END_REF][START_REF] Giambattista | Scanning tunneling microscopy of charge density waves in transition metal chalcogenides[END_REF]). Calculating precisely as described in the text and shows the difference between the amplitudes of q CDW 1 and q CDW 3 normalized by the highest value of the CDW 1 amplitude. The area where q CDW 1 has highest amplitude is marked in red, and the area where q CDW 3 is highest is marked in green. White shows the boundary, where the size of both modulations is equal.

the local density of states to obtain such patterns is a problem of great complexity. Tipsample coupling, depending on the detailed band structure of the sample, and of the form and geometry of the tip, or defects, shape considerably the measured local density of states [START_REF] Tersoff | Theory and application for the scanning tunneling microscope[END_REF][START_REF] Guillamon | Intrinsic atomic-scale modulations of the superconducting gap of 2H-NbSe 2[END_REF]. For example, Moiré patterns of 2H-NbSe 2 have been widely discussed in literature, and related to different tip-sample coupling effects. In 2H-TaS 2 , within the same image, without any change in the properties of the tip nor of the surface (i.e. without any step, defect, or surface anomaly), the Moiré patterns change its symmetry properties, in a rather complex way, as shown in Figs. 1 and2. This was first found in 1T-TiSe 2 [START_REF] Ishioka | Chiral charge-density waves[END_REF], and, to the best of our knowledge, was never observed previously in any metallic 2H dichalcogenide compound. To explain such patterns, it is needed to consider out-of-plane decoupling of the three components of the CDW, which are combined in two different ways in different areas of the surface, giving chiral CDW order [START_REF] Ishioka | Chiral charge-density waves[END_REF].

Microscopic origin of chiral charge arrangements is now under debate. Electronic interactions between planes (along c), which separate in-plane charge modulations through Coulomb interaction, can lead to a c-axis chiral modulation of the CDW [START_REF] Ishioka | Chiral charge-density waves[END_REF]. More recently, it has been shown that chiral charge order can also appear in relation to orbital order, which produces transversal polarization introducing phase shifts in the CDW [START_REF] Van Wezel | Chirality and orbital order in charge density waves[END_REF]. The charge modulation observed in 2H-TaS 2 can be simulated by assuming that the intensity of the modulations corresponding to each CDW i changes as a function of the out-of-plane stacking, or by phase shifting each component [START_REF] Ishioka | Chiral charge-density waves[END_REF][START_REF] Van Wezel | Chirality and orbital order in charge density waves[END_REF]. For example, if we sum up three CDW components with CDW i (r)= A i cos(q CDW i r) (with A i the amplitude of q CDW i ), and two different amplitude relationships in two different areas, we obtain the image shown in Fig. 3a. Qualitatively, the obtained shapes agree with the experimental image of the CDW (Fig. 3b).

All these observations, which are similar to those reported in the compound 1T-TiSe 2 [START_REF] Ishioka | Chiral charge-density waves[END_REF],

demonstrate that 2H-TaS 2 has a chiral modulation of its CDW. Note that 2H-TaS 2 is a metal which superconducts, but 1T-TiSe 2 is a semimetal, with no report of superconducting correlations at ambient pressure [START_REF] Kusmartseva | Pressure induced superconductivity in pristine 1T-TiSe 2[END_REF]. Note also that in 1T-TiSe 2 the CDW modulation is located at two times the lattice constant, whereas in 2H-TaS 2 it is located at three times the lattice constant. The three fold in-plane symmetry with clockwise and counterclockwise domains appearing in the charge order features, are, however, similar. Furthermore, in 1T-TiSe 2 , there is a c-axis modulation of the CDW [START_REF] Ishioka | Chiral charge-density waves[END_REF], with periodicity 2 times the c-axis where no CDW is observed) the three coexisting CDWs lead to a reduction of the crystal symmetry from hexagonal to orthorhombic [START_REF] Littlewood | Theory of the splitting of discommensurations in the chargedensity-wave state of 2H-TaS 2[END_REF]. In 2H-NbSe 2 , as discussed above, no chiral CDW has been reported, in spite of having been very extensively studied by many different groups. It could be that 2H-TaS 2 lies in between both cases, being sufficiently 2D to present de-coupling of CDW modulations, but not enough to show structural transition or to destroy superconductivity through a too strong destruction of the Fermi surface by the CDW gap opening.

The superconducting tunneling conductance of 2H-TaS 2 measured at 100 mK is shown in Fig. 4. The tunneling conductance remains flat until around 0.15 mV, where it starts increasing continuously until 0.4 mV, where the quasiparticle peak is located. Such a feature is found over large parts of the surface, and we could not, until now, observe changes related to the domains of the chiral CDW modulation. The behavior is instead reminiscent of the compounds 2H-NbSe 2 and 2H-NbS 2 , where a distribution of values of the superconducting gap, starting also roughly at half the maximal gap value, is found. In the latter compounds, however, two clear features are seen in the tunneling conductance, which show up as two peaks in the derivative of the corresponding density of states [START_REF] Guillamon | Superconducting density of states and vortex cores of 2H -N bS 2[END_REF][START_REF] Rodrigo | STM study of multiband superconductivity in NbSe 2 using a superconducting tip[END_REF]. These features are due to the two band superconducting properties characteristic of these compounds. Here, the derivative of the density of states (DOS, obtained by de-convoluting the temperature, as shown in Ref. [START_REF] Guillamon | Superconducting density of states and vortex cores of 2H -N bS 2[END_REF]), shows only one broad peak centered at ∆=0.28 meV (Fig. 4), which evolves until the T c =1.75 K following roughly BCS theory. The value we find for ∆ is close to, although somewhat larger, than the value expected within BCS theory, ∆=1.76k B T c =0.265 meV. Thus, the superconducting gap of 2H-TaS 2 has a significant anisotropy, and the two gap features characteristic of 2H-NbSe 2 and 2H-NbS 2 are, if they exist at all, less clearly resolved in the superconducting density of states.

Our results establish that, in 2H-TaS 2 , chiral CDW properties coexist with superconductivity. Possible consequences could be related to those found in the context of other superconductors with broken space inversion symmetry. For example, in a superconductor with broken space parity and strong spin orbit coupling (spin orbit coupling is strong in 2H-TaS 2 as discussed in Ref. [START_REF] Rossnagel | Spin-orbit splitting, Fermi-surface topology, and charge-densitywave gapping of 2H-TaSe 2[END_REF]), the two fold electronic spin degeneracy may be lifted, and spin structured Cooper pairs could appear [START_REF] Edelstein | Magnetoelectric effect in polar superconductors[END_REF][START_REF] Schnyder | Topological phases and flat surface bands in superconductors without inversion symmetry[END_REF][START_REF] Bauer | Unvoncentional superconductivity in weakly correlated, non-centrosymmetric Mo 3 Al 2[END_REF][START_REF] Gor | Superconducting 2D system with lifted spin degeneracy: Mixed singlet-triplet state[END_REF][START_REF] Samokhin | Gap structure in noncentrosymmetric superconductors[END_REF]. The form and size of the superconducting gap can be under such conditions peculiar, with nodes along some directions, but it can be also fully opened [START_REF] Mackenzie | The superconductivity of Sr 2 Ruo 4 and the physics of spintriplet pairing[END_REF][START_REF] Suderow | A nodeless superconducting gap in Sr 2 RuO 4 from tunneling spectroscopy[END_REF]. In 2H-TaS 2 , the observation of an opened somewhat anisotropic gap, similar to the ones found in related materials, shows that the influence of broken space parity in the superconducting properties is, if present, weak. Characterization of superconductivity in the other system of the series, 2H-TaSe 2 [START_REF] Rossnagel | Spin-orbit splitting, Fermi-surface topology, and charge-densitywave gapping of 2H-TaSe 2[END_REF], the observation of the vortex lattice in both compounds, and a closer look to superconductivity in related CDW In summary, we have observed a chiral CDW in a metallic and superconducting compound, 2H-TaS 2 , and provide measurements of its superconducting density of states. We could not establish an influence of broken space parity through a helical electronic structure on the superconducting density of states, but the mere presence of both phenomena in the same material, calls for more work in this and similar compounds.

We acknowledge discussions with P. Kulkarni, K. Machida, A.I. Buzdin, J. Flouquet

FIG. 1 :

 1 FIG.1: In a we show the STM topography at constant current made at 5 mV in 2H-TaS 2 at 100 mK (left panel), and its corresponding Fourier transform (right panel). White circles show Bragg peaks corresponding to the atomic S lattice, and colored circles those corresponding to the three CDW with reciprocal lattice vectors q CDW 1 (red), q CDW 2 (orange) and q CDW 3 (green). In b we show real space profiles taken along the three principal directions of the CDW modulations as marked by the arrows in a) and zoomed-up images in upper panels (corresponding to areas marked by dashed white rectangles in the top (R) and bottom parts (L) of the image). It gives a peculiar Moiré pattern where the height relationship changes from a rightwise rotating angular dependence to a leftwise rotating angular dependence in the same figure, without any defect or step observed in between.

5 FIG. 2 :

 52 FIG. 2: Fourier analysis of the CDW modulations of Fig.1. In a we show the Fourier transform of the rectangles in the top (R) and bottom (L) areas of Fig.1a. Red, orange and green circles mark the Bragg peaks corresponding to each CDW modulation direction. The intensity of the peaks decreases, respectively, clockwise (R, from red to green in b) and anticlockwise (L, from green to red in b). In b, profiles are normalized to one at the highest peak. In c we show Fourier amplitude map highlighting the spatial distribution of the dominant CDW components. The map is obtained

2 FIG. 3 :

 23 FIG. 3: In a) we show the charge modulation obtained by summing up three CDW i = A i cos(q CDW i r), using A 1 = 1, A 2 = 0.6, A 3 = 0.3 in the upper left corner's chiral domain (clockwise decrease of the amplitude of the CDW Fourier peaks as shown by the arrow), and A 1 = 0.3, A 2 = 0.6, A 3 = 1 in the lower right corner's chiral domain (counterclockwise decrease of the amplitude of the CDW Fourier peaks as shown by the arrow). These modulations give differently oriented oval shaped patterns. In between, the difference between the A i are smoothly varied as a function of the position. As the difference in A i becomes smaller, a circularly shaped pattern is visible. b) shows the CDW modulation observed in the experiment. Atomic lattice modulations are removed from the Fig.1 by Fourier transform filtering. Oval shaped patterns are observed in the two chiral domains, with more round circular patterns along the chiral domain wall. Arrows indicate main CDW modulation directions, as in Fig.1. In both figures, the color goes continously from dark blue for highest charge density to white for lowest charge density.

FIG. 4 :

 4 FIG. 4: a. Normalized tunneling conductance curve obtained in 2H-TaS 2 at 0.1 K (conductance σ at 1mV is of 1.7 µS). In b we show the derivative of the associated local density of states (DOS), which has been obtained by de-convoluting the temperature from the tunneling conductance. The derivative has a peak at ∆ =0.28 meV. In c we show the temperature dependence of ∆ (red cicles) and expectation from BCS theory (black line) with T c =1.75 K.

  and F. Guinea. The Laboratorio de Bajas Temperaturas is associated to the ICMM of the CSIC. This work was supported by the Spanish MICINN (Consolider Ingenio Molecular Nanoscience CSD2007-00010 program and FIS2008-00454 and by ACI-2009-0905), by the Comunidad de Madrid through program Nanobiomagnet, and by NES program of the ESF.