Laure Mamy
email: laure.mamy@versailles.inra.fr

Pauline Vrignaud

Nathalie Cheviron

Francois Perreau

Mehdi Belkacem

Agathe Brault

Sébastien Breuil

Ghislaine Delarue

Jean Pierre Petraud

Isabelle Touton

Does soil compaction modify the fate and effect of isoproturon?

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Introduction

To study the effect of soil compaction on:

(1) The degradation of one herbicide, isoproturon (2) The ecotoxicological impact of this herbicide measured through two enzyme activities involved in C (β-glucosidase) and N (urease) cycles in soil.

Objectives Materials & Methods

Results & Discussion

Conclusion Acknowledgements

The results suggest that under soils compacted zones (due to traffic, tillage or short rotations), the persistence of pesticides should not increase and their effect should not be modified. However, further studies should be performed measuring additional biological indicators, studying the relationship between compaction and the degree of soil saturation, and studying the overall balance of the fate of pesticides (mineralization, extractability and formation of non-extractable residues).  Compaction is known not to affect microbial communities 3 probably because it reduces porosity, favoring small and habitable pores accessible to bacteria and fungi 4 .  Degradation was slightly faster in the highly compacted soil probably because it had the highest degree of saturation 2 .

 Only one main metabolite, monodesmethyl-isoproturon, was detected independently of the conditions of compaction. The formation kinetics are not significantly different (P > 0.05, Kruskal-Wallis test) 2 .

Effect of isoproturon as a function of soil compaction

Urease

 There was no significant effect of isoproturon on both enzymes activities compared to the control (P > 0.05, Mann-Whitney test) 2 .

 The lack of effect can be due to the adaptation of microorganisms following the previous applications of the herbicide in the field.

 Compaction did not modify the effect of isoproturon on β-glucosidase and urease activities (in the long term) (P > 0.05, Kruskal-Wallis test) 2 .  This is in agreement with studies showing that compaction is of little consequence on the microbial communities 3 .

The

  Authors are grateful to Dr Jérémie D. Lebrun (INRA, PESSAC) for constructive comments and to Rachid Benabdallah and Cédric Repinçay (INRA, PESSAC) for chemical analyses. National Institute for Agronomic Research Laure Mamy*, Pauline Vrignaud, Nathalie Cheviron, François Perreau, Mehdi Belkacem, Agathe Brault, Sébastien Breuil, Ghislaine Delarue, Jean-Pierre Pétraud, Isabelle Touton, Christian Mougin, Véronique Chaplain Undisturbed soil cylinders were sampled in the 2-4 cm layer of La Cage experimental site (INRA, Versailles), under intensive agriculture practices. Soil: Loam, 1.69% organic matter, pH H 2 O = 7.3 50 mm Soil samples were prepared at three levels of compaction (bulk density, ρ, in g cm -3 ):  No: ρ = 1.33  0.16  Moderate (100 kPa): ρ = 1.45  0.02  High (800 kPa): ρ = 1.57  0.13 Piston 20 mm Cylinder Soil Pressure La Cage (INRA, Versailles) Samples were then incubated at 18 ± 1°C in darkness for 63 days. Each jar contained a vial with 10 mL of water to maintain a constant relative humidity. 1 µg isoproturon / g dry soil 10 mL H 2 O 500 mL glass jar At 0-2-7-14-28-63 days:  Degradation of isoproturon (IPU) Soil extraction with CH 3 OH  HPLC/UV for IPU and its main metabolites in soil: monodesmethyl-IPU and didesmethyl-IPU.  β-glucosidase and urease activities Addition of substrates to soil samples  Quantitative determination of the reaction product with spectrophotometer.

Figure 1 .

 1 Figure 1. Degradation kinetics of isoproturon (a) and formation kinetics of monodesmethylisoproturon (b) as a function of soil compaction: ( ) No compaction, ( ) Moderate compaction, ( ) High compaction. For isoproturon, lines are adjustments with first-order kinetics.

Figure 2 .

 2 Figure 2. β-glucosidase (a) and urease* (b) activities as a function of soil compaction: ( ) No compaction, ( ) Moderate compaction, ( ) High compaction; ( ) Control (Isoproturon-free not compacted soil). From Mamy et al., 2010 2 .

From


Marina Briand

Linh D Thai

Flavien Bourdreux

Nicolas Vanthuyne

Xavier Moreau

Emmanuel Magnier

Elsa Anselmi

Guillaume Dagousset

Remote Radical Trifluoromethylation: A Unified Approach to the Selective Synthesis of γ-Trifluoromethyl α,β-Unsaturated Carbonyl Compounds

Site-selective trifluoromethylation of silyl dienol ethers derived from α,β-unsaturated aldehydes, ketones, and amides was achieved for the first t ime i n t he r emote γ p osition. T his photoredox catalyzed process is quite general to compounds bearing many functionalities and is applicab le to the late-stage functionalization of b iorelevant molecules. The use of S-perfluoroalkyl s ulfoximines a s •R F radical sources enab les the generalization of the reaction to other perfluoroalkyl groups ( R F = CF 2 H, C 4 F 9 ). Importantly, an unprecedented enantioselective C(sp 3 )-H perfluoroalkylation p rocess is disclosed.

T he incorporation of a CF 3 group into organic molecules imparts profound changes in their physicochemical and biological properties. As a result, the number of bioactive molecules with a trifluoromethyl or perfluoroalkyl group has increased exponentially in the past 20 years. 1 Undoubtedly, this fact accounts for the increasing number of methods which have recently been reported for the trifluoromethylation of various organic scaffolds. 2 Among them, the synthesis of α-CF 3 carbonyl compounds from the corresponding enolate equivalents (silyl enol ether, enol acetate, metal enolate, enamine) has been thoroughly investigated, under either electrophilic 3 or radical-based 4 conditions (Scheme 1a). Surprisingly, despite these extensive studies, the corresponding vinylogous trifluoromethylation of α,β-unsaturated carbonyl compounds in the γ position remains almost unprecedented. Such γ-functionalization of vinylogous dienolate-type substrates is indeed highly challenging, in terms of both site selectivity (both α and γ sites are reactive) and enantioselectivity (the γ site is located in a more distal position). To the best of our knowledge, a single example was described on a very peculiar skeleton: Umemoto and co-workers reported the electrophilic trifluoromethylation of a bicyclic silyl dienol ether, leading to a γ-CF 3 enone with a sulfonium as reagent. [START_REF] Umemoto | Power-Variable Electrophilic Trifluoromethylating Agents. S-, Se-, and Te-(Trifluoromethyl)dibenzothio-, -seleno-, and -tellurophenium Salt System[END_REF] We initially tried to extend the scope of this methodology on more classical substrates. With standard linear silyl dienol ethers as well with steroid derivatives, many unidentified fluorinated byproducts were produced and the transformation occurred with a very low yield (see Supporting Information (SI) for details). This may be due to the poor Scheme 1. State-of-the-Art nucleophilic character of silyl dienol ethers 6 combined with the difficulty to access a strong CF 3 + electrophile. 7 Consequently, the γ-trifluoromethylation of α,β-unsaturated carbonyl compounds still faces many major unsolved challenges: (i) No versatile trifluoromethylation protocol for the synthesis of γ-CF 3 enals or γ-CF 3 α,β-unsaturated amides has been reported so far; (ii) the trifluoromethylation process should occur with high regioselectivity for the γ position, as well as high E-diastereoselectivity; (iii) A highly ambitious enantioselective version is still unknown to date. Instead of using a classical electrophilic pathway, we reasoned that a completely unexplored radical approach could fundamentally bring solutions to all these issues.

Considering the mild reaction conditions provided by photoredox catalysis 8 and the ability of silyl dienol ethers to efficiently trap radicals in the γ position, 9 a photocatalyzed trifluoromethylation method is expected to selectively afford the desired γ-CF 3 adduct for all kinds of α,β-unsaturated carbonyl compounds (Scheme 1b). Herein, we report an unprecedented methodology for the general and unified synthesis of γ-CF 3 α,β-unsaturated aldehydes, ketones, and amides under mild photoredox-catalyzed conditions. Importantly, preliminary results on an unknown enantioselective organocatalytic/photoredox dual catalytic protocol are also disclosed for the first time.

We initially chose triisopropylsilyl (TIPS) dienol ether 1a derived from (E)-2-dodecenal as the model substrate. Radical trifluoromethylation of 1a under photoredox-catalyzed conditions with Umemoto's reagent 2a afforded the expected product 3a in 69% NMR yield with complete site selectivity (entry 1). Other CF 3 sources 2b-2f were then tried (entries 2-6). While Togni's reagent 2b and CF 3 I 2f were inefficient, sulfoximine-based reagents 2c-2e, readily produced in multigram scale, 10 were quite promising. 11 Notably, N-tosyl S-CF 3 sulfoximine 2c compared to reagent 2a showed an equally high level of efficiency. Moreover, sulfoximines bearing other perfluoroalkyl groups are readily available which offers an advantage over other reagents. Reagent 2c was therefore selected for the further optimization of the process. Screening other parameters (additives, solvent, stoichiometry, concentration) led to the optimal conditions providing 3a in 68% isolated yield after 18 h of irradiation (entry 7, see SI for more details). In addition, a one-pot two-step synthesis of γ-CF 3dodecenal 3a from (E)-2-dodecenal could also be performed, with almost no erosion of the overall yield (entry 10). It is also worth noting that 3a was obtained in all cases as one single E isomer, even though substrate 1a was engaged as a mixture of diastereomers. Other silylated groups were also tested with no impact on site selectivity, and the TIPS group was selected for stability reasons.

Once our optimal conditions were determined, we turned our attention to the application scope of this new methodology (Scheme 2). Various α-unbranched γ-CF 3 enals 3a-3h bearing a large array of functional groups (alkene, ester, nitrile, epoxy, Br, phthalimido) were efficiently prepared. α-Aryl and α-alkyl substrates were also successfully engaged in this photoredoxmediated protocol, leading to the corresponding trifluoromethylated enals 3i-3m in up to 72% yield. In some cases, the isolated yields were lower than the corresponding 19 F NMR yields; this decrease in yield could be attributed to either the high volatility of the fluorinated enals or the difficulty in separating them from triisopropylsilanol (TIPSOH), produced as a byproduct during the process. Nonetheless, it is worth noting that both α-substituted and α-unsubstituted enals were formed with almost perfect site selectivity (γ/α > 98:2 in all cases).

To demonstrate the synthetic utility of this novel photocatalysed process, an experiment on 5 mmol of substrate 1a was performed using continuous-flow techniques. With a flow rate of 0.5 mL•min -1 (residence time of 20 min), 575 mg of γ-CF 3 enal 3a could be isolated, showing the simplicity to scale up the process. With these first results for enals in hand, we next attempted to apply our method for the synthesis of other γ-CF 3 carbonyl compounds. Pleasingly, various γ-CF 3 enones 3n-3s and γ-CF 3 α,β-unsaturated imides 3t-3v were successfully produced in good yields. 12,13 Once again this mild photocatalyzed process was perfectly compatible with many functionalities (ester, nitrile, nitro).

Having established the general and versatile character of our new methodology to access γ-CF 3 α,β-unsaturated compounds, we then turned our attention to the introduction of other relevant fluoroalkyl moieties (R F ). 14 We were pleased to see that S-perfluorobutyl sulfoximine 2g and S-difluoromethyl sulfoximine 2h (Hu's reagent) [START_REF] Zhang | N-Tosyl-S-difluoromethyl-Sphenylsulfoximine: A New Difluoromethylation Reagent for S-, N-, and C-Nucleophiles[END_REF] readily reacted under our optimized photoredox conditions: the corresponding compounds 4-5 were isolated in up to 74% yield with equally high γ-selectivity. Furthermore, ethyl bromodifluoroacetate smoothly reacted with silyl dienol ethers 1k,n, furnishing the desired γ-difluoroacetylated enal 6k and enone 6n, respectively. A key feature of photocatalyzed methodologies consists of the late-stage functionalization of complex molecules, a very useful tool in modern drug discovery. [START_REF] Börgel | Late-Stage Functionalization[END_REF] Pleasingly, compounds 1w-1ab derived from L-tyrosine, (R)-(-)-myrtenal, 4cholesten-3-one, Locostatin, Metaxalone, and Crotamiton were successfully transformed into the corresponding γ-R F α,βunsaturated compounds.

As both light and photocatalyst were needed for the reaction (see Table 1, entries 8-9), a mechanism involving a radical pathway was assumed. To verify this hypothesis, the redox potential of 2c was measured using cyclic voltammetry. The found value (-1.73 V vs SCE) indicated that 2c may be reduced by the excited state of Ir(ppy) 3 (E 1/2 red = -1.73 V vs SCE), following an oxidative quenching photoredox cycle. This was confirmed by Stern-Volmer luminescence quenching experiments which showed that Ir*(ppy) 3 was efficiently quenched by sulfoximine 2c (see SI for more details). Based on these observations, we propose a mechanism in which the perfluoroalkyl radical •R F , generated by one-electron reduction from the corresponding sulfoximine, adds onto substrate 1 in a γ-selective manner, leading to the stabilized allylic radical intermediate A (Scheme 3). The latter is then oxidized by Ir IV , regenerating the ground-state photocatalyst Ir(ppy) 3 together with the formation of the corresponding carbocation B, which rapidly evolves into the desired product 3-6. The measured quantum yield Φ = 0.25 suggested that an alternative radical chain mechanism (generation of •R F from reduction of 2 by intermediate A) was not the major pathway operating in this process. It is worth noting that, for most of these new γ-R F α,βunsaturated compounds 3-6, the perfluoroalkyl group is attached to a stereogenic carbon atom. Given the importance of chiral fluorinated molecules, [START_REF] Yang | Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions[END_REF] we next sought to examine the possibility of controlling the enantioselectivity of our new perfluoroalkylation process under a dual photoredox/organocatalytic system. However, if photoredox/enamine dual catalysis has been widely used for enantioselective αfunctionalization of aldehydes, [START_REF] Zou | Iminium and Enamine Catalysis in Enantioselective Photochemical Reactions[END_REF] including α-perfluoroalkylation, 4d,e the analogous photoredox/dienamine dual catalysis remains largely unexplored and much more challenging. 19 Initial attempts with 2-phenyl-2-pentenal as the model substrate and sulfoximine 2g as the •C 4 F 9 source failed to give any product. However, by switching to C 4 F 9 I as the radical source and by adapting the reaction conditions (see SI for complete optimization table), we were delighted to see that the corresponding γ-C 4 F 9 enal 4k, subsequently transformed into ester 8a in order to avoid any partial racemization, was produced with a high level of enantioselectivity (86% ee, Scheme 4). The absolute(S) configuration of the major enantiomer was assigned by comparison of the experimental ECD (electronic circular dichroism) spectra with DFT calculations (see SI for more details). A similar reaction with CF 3 I led to product 8b with an erosion of enantioselectivity (53% ee), most probably due to the smaller size of the CF 3 radical. However, this represents the first example of a catalytic enantioselective C-H remote perfluoroalkylation reaction.

In conclusion, we have developed a unified approach for the synthesis of γ-R F α,β-unsaturated compounds. The key characteristics of this mild photoredox methodology are as follows: (i) it occurs with perfect E-diastereoselectivity and very high γ regioselectivity; (ii) it is applicable to a wide range of functionalized enals, enones, and α,β-unsaturated amides, including many complex biorelevant molecules; (iii) it is compatible with a series of perfluoroalkyl groups (R F = CF 3 , CF 2 H, C 4 F 9 , CF 2 CO 2 Et). Importantly, an enantioselective version was achieved for the first time by using a dual photoredox/dienamine catalytic system. Further developments in the field of remote organocatalytic functionalizations are currently underway and will be reported in due course. ■ dr, diastereomeric ratio; ECD, electronic circular dichroism; EDA, electron donor-acceptor; ee, enantiomeric excess; NHC, N-heterocyclic carbene; SCE, saturated calomel electrode

Scheme 2 .

 2 Scheme 2. Reaction Scope for the γ-Trifluoromethylation/γ-Perfluoroalkylation of α,β-Unsaturated Carbonyls a

  Scheme 3. Proposed Mechanism

Table 1 .

 1 Optimization Studies for the γ-Trifluoromethylation of Silyl Dienol Ether 1a a

	Entry	CF 3 source	Solvent	Additive	Yield (%) b
	1	2a	CH 2 Cl 2	K 2 HPO 4	69
	2	2b	CH 2 Cl 2	K 2 HPO 4	3
	3	2c	CH 2 Cl 2	K 2 HPO 4	65
	4	2d	CH 2 Cl 2	K 2 HPO 4	51
	5	2e	CH 2 Cl 2	K 2 HPO 4	23
	6	2f	CH 2 Cl 2	K 2 HPO 4	6
	7 c,d	2c	CH 2 Cl 2 /MeCN	-	77 (68) e
	8 d,f	2c	CH 2 Cl 2 /MeCN	-	-
	9 c,d,g	2c	CH 2 Cl 2 /MeCN	-	-
	10 h	2c	CH 2 Cl 2 /MeCN	-	60

a General conditions: 1a (0.15 mmol), 2 (0.225 mmol), Ir(ppy) 3 (0.003 mmol), additive (0.3 mmol) in 1.5 mL of solvent irradiated with 5 W blue LEDs at rt for 18 h. b Yields determined by 19 F NMR spectroscopy using PhOCF 3 as an internal standard. c With 4 mol % of Ir(ppy) 3 . d In 3 mL of solvent. e Yield into brackets refers to chromatographically pure product. f Without Ir(ppy) 3 g Without irradiation. h Two-step one-pot procedure from (E)-2-dodecenal. See SI for more details.


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  Extracellular proteome of the fungus Trametes versicolor -insights into the development of tools for ecotoxicity assessment in soils Nathalie Cheviron, Achref Aloui, Christelle Marrauld, Kévin Varandas, Didier Chevret, Christian Mougin To cite this version: Nathalie Cheviron, Achref Aloui, Christelle Marrauld, Kévin Varandas, Didier Chevret, et al.. Extracellular proteome of the fungus Trametes versicolor -insights into the development of tools for ecotoxicity assessment in soils. European Meeting Oxizymes, Sep 2012, Marseille, France. 2012

•

  Results confirm the relevance of our approach • Results in protein expression, synthesis and activity vary in same ways in batchs and soils cosms • The lack of information concerning sequences of fungal proteins in databases limits the use of secretion profiles as biomarkers • It remains necessary to improve the extraction of soil proteins and RNAs RESULTS of BATCH EXPERIMENTS METHODOLOGY RESULTS of INCUBATIONS in SOIL COSMS • 2D gels: evolution of the protein expression with Copper or xylidine exposition of T. versicolor Modified proteins of fungal secretome (LC-MS/MS Orbitrap), (NI : unidentified) • basidiomycete T. versicolor ATCC 32745 (Lebrun et al. (2010).• Luvisol, silti loam pH 7,4-sand 27%, clay 17%, loam 56%-OM 1

UR251 Physico-chimie et Ecotoxicologie des SolS d'Agrosystèmes Contaminés, INRA, Versailles

Plateforme PAPPSO, Unité MICALIS, INRA, Jouy en Josas

ABSTRACT

The development of relevant and sensitive tools to assess the ecotoxicity of soils contaminated by chemicals is an actual key challenge. Actual approaches are mainly based on the expression of the genetic potentialities of microbial communities, or on the measurement of the resulting enzymatic activities. Because multiple levels of regulation exist between these two endpoints, genomic studies to not reflect the functional biodiversity really expressed into the soils, and enzymatic activities measurements can be submitted to interferences, thus disturbing their interpretation. Other endpoints are studied, such as profiles of secreted proteins. Fungal proteomics is well expanding and may provide interesting developments for our purpose. Because of the complexity of the soil ecosystem, our studies were targeted on the extracellular proteome of the basidiomycete Trametes versicolor, a well-known strain that can be easily inoculated into the soil. Here, our objectives were to study the proteome secreted by Trametes exposed to soil pollutants: an organic compound (Xylidine) or a metal (copper) in a two-step approach based on the use of pure liquid culture and spiked soil. We aimed at identifying secretion profiles specific to each pollutant. Our results obtained in liquid cultures showed global patterns of protein secretion quite similar in response to pollutants, but some differences were noticed. Protein analysis by mass spectrometry has identified 46 well separated proteins, being essentially oxidases. Among these, two laccase isoforms were specifically induced either by Xylidine or copper. By contrast, numerous spots remained unidentified. Data analysis revealed three groups of protein whose secretion was 1) stimulated by Xylidine, 2) suppressed by the pollutant, and 3) overexpressed by copper. These proteomic results are in agreement with our transcriptomic and functional responses. In spiked soils inoculated with the fungus, we revealed specific pathways in functional response to pollutants. Proteomic and transcriptomic approaches are in progress.

These preliminary results are promising and encourage us to continue our approach in soils.

Acknowledgements

Achref Aloui thanks the région Ile-de-France and the DIM Astrea for his postdoctoral funding. The authors are also grateful to L.. Rajou (Plateforme de Biochimie des Protéines, IJBP, INRA Versailles) for his help in performing 2D experiments.


Nicolas Vanthuyne

Maxime Baudillon

Thomas Cauchy

Narcis Avarvari
email: narcis.avarvari@univ-angers.fr

Flavia Pop
email: flavia.pop@univ-angers.fr

Configurationally stable dithia[7]helicene and dithia-quasi[8]circulene fused dithiolones †

Dithia- [7]helicene and quasi [8]circulene have been formed on the 1,3-dithiol-2-one ring by oxidative dehydrocyclisation of bis-naphthothiophenyl-1,3-dithiol-2-one. Quasi-circulenes are easily obtained at room temperature by successive dehydrocyclisations regardless the amount of oxidation reagent whereas selectivity towards helicene, involving a single dehydrocyclisation, has been achieved only at low temperature. DFT calculations suggest a mechanism via a dication intermediate rather than a mono-cation for the formation of the quasi-circulenes whereas the helicene should be formed via a radical cation intermediate. While dithia [7]helicene is known to give stable stereoisomers, here the unsubstituted dithiaquasi[8]circulene shows unprecedented configurational stability of the enantiomers, with a theoretically estimated enantiomerisation energy barrier of 30.4 kcal mol -1 , in excellent agreement with the experimentally determined value of 29.8 kcal mol -1 . The enantiomers of both helicene and quasi-circulene have been separated by chiral chromatography and their absolute configuration assigned from the calculated CD spectra.

Introduction

[n]Helicenes are aromatic compounds with inherent chirality built of n ortho-fused aromatic rings along a helical axis. They have long been known for their high specific optical rotation, strong absorption and emission of circularly polarized luminescence and have been recently intensively used for molecular recognition and chiral induction, as chiroptical switches or found applications in catalysis, chiral photonics and spintronics. [START_REF] Shen | Helicenes: Synthesis and Applications[END_REF][START_REF] Gingras | One hundred years of helicene chemistry. Part 3: applications and properties of carbohelicenes[END_REF][START_REF] Yang | Circularly polarized light detection by a chiral organic semiconductor transistor[END_REF] Their chiroptical properties arise from the inherent chirality coupled with the nonplanar π-delocalization on the whole polycyclic aromatic system. The introduction of heteroatoms into the fused helical polycyclic system, providing hetero-helicenes, offers new synthetic opportunities together with the possibility to tune their electronic and optoelectronic properties. [START_REF] Dhaibi | Enantioenriched Helicenes and Helicenoids Containing Main-Group Elements[END_REF] Similarly to [n]helicenes, [n]circulenes are formed of n ortho-fused rings except they have a cyclic disposition around a central ring with n sides. Removal of a CHvCH vinylene unit from one ring of the parent [n]circulenes (as highlighted in Chart 1) gives quasi[n]circulenes. Such cyclic structures are formed when the terminal positions of the helicene are connected by a σ bond, and have been used in the synthetic pathway of circulenes. Wynberg et al. [START_REF] Dopper | Dehydrogenation of heterohelicenes by a Scholl type reaction. Dehydrohelicenes[END_REF] have referred them as "dehydrohelicenes" because they were obtained by dehydrogenation of the corresponding [n]helicenes through a Scholl reaction (in the presence of Friedel-Craft catalysts), their results indicating a limitation of the dehydrogenation reaction to hetero- [5] and - [6]helicenes. Recently, Itami et al. [START_REF] Kawasumi | A grossly warped nanographene and the consequences of multiple odd-membered-ring defects[END_REF][START_REF] Qiu | Negatively Curved Nanographene with Heptagonal and[END_REF] and Wu et al. 8 have shown that quasi-circulenes can be formed from [6] and [7]helicenes, respectively. This family of polycyclic aromatic systems represents an emerging and unexplored class of materials with structures similar to either helicenes or circulenes. Depending on their composition and substitution scheme they can adopt flat, twisted or saddle-like topologies. 9 As shown by Rajca et al., 10 heptathia [8]circulenes have flat geometry whereas an increasing number of phenyl rings in the helix structure of hetero-quasi [8]circulenes induces a proportional distortion of the geometry (Fig. S1,ESI †).

Chart 1 Structures of carbo- [6]helicene, [7]circulene and quasi [7] circulene.

We report herein the synthesis, crystalline structures and chiroptical properties of unprecedented dithia [7]helicene and dithia-quasi [8]circulenes to which a 1,3-dithiol-2-one unit is fused, together with DFT calculations shedding light on mechanistic issues and supporting the chiroptical properties. As mentioned above, the presence of the dithiolone unit opens ways towards both TTFs and metal-dithiolene complexes, whereas that of the heteroatoms has the benefit to bring chemical versatility, tune the electronic properties and improve intermolecular interactions in the solid state.

Synthesis and redox properties

The key intermediate bis-naphtho-thiophene-1,3-dithiol-2-one 4 has been obtained following the synthetic route shown in Scheme 1. The starting material 2-bromonaphtho[2,1-b]-thiophene 2a has been obtained in accordance with described procedures [START_REF] Rungtaweevoranit | A facile two-step synthesis of thiophene end-capped aromatic systems[END_REF][25][START_REF] Clarke | Substitiution reaction of naphtho[2,1-b]thiophen[END_REF] and easily crystallized to give suitable single crystals for X-ray diffraction (Fig. S2 †). The di-naphthothiophene-ethyne 3 has been synthesized in only one step by the cross-coupling of 2 with calcium carbide as acetylene source 27 in the presence of palladium catalyst and a base. The yields of the cross-coupling reactions have been massively improved by using the 2-iodonaphtho[2,1-b]-thiophene 2b instead of 2a. Further, the 1,3-dithiol-2-one 4, bearing two naphthothiophene units, was obtained by a radical chain process, adapted from the work of Gareau et al., [START_REF] Gareau | Simple Method for the Preparation of 1,3-Dithiol-2-one and 1,3-Dithiol-2-thione[END_REF] using 3 and diisopropyl xanthogen disulphide in the presence of azobis(isobutyronitrile) (AIBN). The structure of the 1,3-dithiol-2-one 4 was confirmed by X-ray diffraction analysis on single crystals obtained by evaporation from halogenated solvents (Fig. S3 †).

The desired helicene and quasi-circulene molecules have been obtained as racemates by oxidative dehydrocyclisation Accordingly, the methyl substituted all-hydrocarbon quasi [8] circulene (QC, Fig. 1, bottom right) has a saddle-like geometry, its [7]helicene moiety being a highly distorted helix. In such compounds the distortion of the geometry of the π-system has been found to be directly responsible of the stereochemical stability. On the other hand, hetero-quasi [8]circulenes, formed of three five-member rings and four phenyls, are less distorted when unsubstituted (tAQCs in Fig. 1 and S1, † torsion angles of 26-33°) and racemize at room temperature (calculated enantiomerisation energy of about 6 kcal mol -1 ), 11 whereas the presence of substituents in the terminal positions (tAQC and TdAQC with R′ = OMe, Fig. 1 and S1 †) highly distorts their geometries and makes possible the separation of the enantiomers (calculated enantiomerisation energy between 38.5 and 42.8 kcal mol -1 ). [START_REF] Lousen | Compressing a Non-Planar Aromatic Heterocyclic [7]Helicene to a Planar Hetero[END_REF] Quasi-circulenes are still rare and, in spite of lower stereochemical stability than their helicene counterparts, show peculiar topologies, yet they have never been used in electroactive materials.

In this respect, the introduction of helical chirality in precursors providing chiral conducting and photoactive materials [START_REF] Pop | Main-Group-Based Electro-and Photoactive Chiral Materials[END_REF] opens new avenues towards the observation of synergistic phenomena involving chirality and conductivity, such as the electrical magnetochiral anisotropy effect (eMChA), [START_REF] Pop | Electrical magnetochiral anisotropy in a bulk chiral molecular conductor[END_REF] or chirality and light emission, such as circularly polarized luminescence (CPL). [START_REF] Dhaibi | Enantioenriched Helicenes and Helicenoids Containing Main-Group Elements[END_REF][START_REF] Pop | Main-Group-Based Electro-and Photoactive Chiral Materials[END_REF] Two of the most valuable families of chiral electroactive precursors are those of tetrathiafulvalenes (TTF) [START_REF] Avarvari | Strategies towards chiral molecular conductors[END_REF][START_REF] Mroweh | Search of Chiral Molecular Superconductors: κ-[(S,S)-DM-BEDT-TTF] 2 ClO 4 Revisited[END_REF] and metal dithiolene complexes, [START_REF] Pop | Chiral metal-dithiolene complexes[END_REF][START_REF] Branzea | Localization versus Delocalization in Chiral Single Component Conductors of Gold Bis(dithiolene) Complexes[END_REF] which we have been recently used in combination with helicene backbones into helicene-TTF [START_REF] Biet | Ethylenedithio-Tetrathiafulvalene-Helicenes: Electroactive Helical Precursors with Switchable Chiroptical Properties[END_REF] and helicene-metal-dithiolene complexes, [START_REF] Biet | Triplet state CPL active helicene-dithiolene platinum bipyridine complexes[END_REF] showing redox switchable chiroptical and CPL properties, respectively. Note that TTF and dithiolene ligands are closely related since they usually have 1,3-dithiol-2ones as common synthetic precursors, [START_REF] Yamada | New Trends in the Synthesis of π-Electron Donors for Molecular Conductors and Superconductors[END_REF][START_REF] Rovira | Bis(ethylenethio)tetrathiafulvalene (BET-TTF) and Related Dissymmetrical Electron Donors: From the Molecule to Functional Molecular Materials and Devices (OFETs)[END_REF][START_REF] Kato | Conducting Metal Dithiolene Complexes: Structural and Electronic Properties[END_REF] therefore the straightforward access to the latter represents a crucial step towards the former. from molecule 4. The first choice of oxidation agent was FeCl 3 . Thus, dithia-quasi [8]circulene 1-dTQC-Cl was quantitatively obtained when up to 10 equivalents of solid FeCl 3 were added on top of a chloroform solution of 4 independently of the reaction time (Table 1, entries 1 and 2). Similar electrophilic substitution has been previously reported when solid FeCl 3 was used as oxidation reagent for the dehydrocyclisation reaction. [START_REF] Ferguson | Photochemical and oxidative cyclisation of tetraphenylpyrroles[END_REF] If the oxidation agent is added as nitromethane solution, 1-dTQC is quantitatively obtained after only one hour of reaction (Table 1, entry 3). With only one equivalent of the oxidation agent in a mixture of chloroform and nitromethane, the reaction is not complete but does show the formation of the dithia [7]helicene 1-dTH together with its corresponding quasi [8]circulene (Table 1, entry 4). Thus, using FeCl 3 as oxidation agent one can selectively obtain either the dithia-quasi [8]circulene 1-dTQC and its chlorinated equivalent 1-dTQC-Cl but not the dithia [7]helicene 1-dTH. The latter has been successfully synthesized by intramolecular dehydrocyclisation with the hypervalent iodine(III) reagent phenyliodine bis(trifluoroacetate) (PIFA). In this respect, two sets of conditions have been tried at low temperature (Table 1, entries 5-7). The reaction does not provide the desired product when only PIFA alone is used, instead it has been obtained with activated PIFA-BF 3 •Et 2 O (boron trifluoride diethyl etherate), similarly to previously reported procedures. [START_REF] Kita | Non-phenolic oxidative coupling of phenol ether derivatives using phenyliodine(III) bis(trifluoroacetate)[END_REF] Selectivity towards the dithia [7]helicene 1-dTH over the dithia-quasi [8]circulene 1-dTQC was achieved when controlling the amount of the oxidizing reagent (Table 1,entry 7). With 1.2 equivalents of reagent the reaction is not complete affording 1-dTH in 45% yield and no formation of 1-dTQC. Note that, rather surprisingly, complete selectivity towards monoaza- [7]helicene was recently reported by Ema et al. [START_REF] Maeda | Facile Synthesis of Azahelicenes and Diaza[8]circulenes through the Intramolecular Scholl Reaction[END_REF] when using up to 10 equivalents of FeCl 3 , whereas the presence of methoxy substituents induced selective formation of the monoaza-quasi [8]circulene in the same reaction conditions. In their work the selectivity towards the quasi-circulene was favoured by higher spin density at the terminal benzene rings of the radical cation form induced by the nature of the substituents. In our case the dithia-quasi [8] circulene 1-dTQC could not be obtained by sequential oxidative dehydrocyclisation passing through the helicenic form as described for thiadiaza-quasi [8]circulenes TdAQC derivatives (Fig. 1), which have been obtained with only one equivalent of oxidizing reagent (chloranil-BF 3 •Et 2 O). [START_REF] Lousen | Compressing a Non-Planar Aromatic Heterocyclic [7]Helicene to a Planar Hetero[END_REF] In fact, dithia [7]helicene 1-dTH treated with an excess of FeCl 3 over long reaction time or with chloranil (tetrachloro-1,4-benzoquinone)-BF 3 •Et 2 O could not be further cyclized to the corresponding quasi [8]circulene (Table S1 †). These results suggest that the reaction cannot be done stepwise using FeCl 3 or chloranil as oxidants and the formation of quasi-circulene from 4 points towards a mechanism which does not involve a helicene intermediate. We thus hypothesize that if the starting material 4 is oxidized to dication, it undergoes cyclization between the terminal benzene rings followed by a very fast second cyclization between the thiophene units to provide the quasi [8]circu-Scheme 1 Synthetic pathways for dithia [7]helicene 1-dTH and the corresponding dithia-quasi [8]circulenes 1-dTQC and 1-dTQC-Cl. (Fig. 2 and S18 †). The electron donor character of the precursor and derivatives is rather similar, with oxidation potential values around 1.4 V vs. SCE, but only dithia [7]helicene 1-dTH and quasi [8]circulene 1-dTQC show reversible redox character. At high scan rates partial reversibility of the oxidized form of 4 is observed whereas the recorded CVs at low scan rates (50 and 100 mV s -1 ) are irreversible indicating a high reactivity of the radical cation form. On the contrary, the CVs of 1-dTH at different scan rates are the same suggesting a higher stability of the mono-oxidized form of the helicene compared to 4. This result is in accordance with our observations on the chemical oxidation of the helicene and the difficulty to form the quasi [8]circulene from the corresponding helicene.

Solid state characterization

Single crystals of the racemic forms of dithia [7]helicene 1-dTH and of quasi [8]circulene 1-dTQC have been obtained by evaporation from halogenated solvents such as dichloromethane and chloroform (Fig. 3). Poorer crystallographic data have been obtained for 1-dTQC-Cl therefore it is not included in the discussion, nevertheless the data was suitable to confirm the structure (Fig. S11-S14 †). Dithia [7]helicene 1-dTH crystallizes in the triclinic system, P1 ˉspace group, with two independent molecules in the unit cell (A and B of M and P helicity, respectively). The stacking of the molecules is directed by S⋯S interaction along the b and a axes. Within the stack molecules alternate in a head-to-tail fashion, with a small overlap taking place only between the S rich parts of the molecules (donor part) and with a lateral shift with respect to each other of 1.470 Å and 1.641 Å for A and B, respectively (Fig. S4 †). The result of this arrangement gives a segregation of the 1,3-dithiol-2-one unit and the carbon based helicene side within the packing (Fig. S5 and S6 †). The small The electrochemical properties of the precursor and final products have been investigated using cyclic voltammetry

In helicenes and quasi-circulenes the values of the internal torsion angles of each of the constituting rings (A to D for [7] helicenes and quasi [8]circulenes) and their sums are a good indicator of the degree of helical twist (Table 2). Equivalent helicenes with a ring of five atoms instead of the phenyl ring A have a smaller sum of the internal torsion angles (between 56.9 to 61.9°) than the sum in the dithia [7]helicene 1-dTH (ca. 76°) thus suggesting a more important helical twist and a higher stability of the stereoisomers of the latter. 32 In dithia [7] helicene 1-dTH the twist is high around A, B and B′ rings whereas in quasi [8]circulene 1-dTQC it is less important around rings B and B′. Quasi [8]circulene shows significant distortion of planarity of rings A, C and C′ and high inter-planar angle of the D and D′ rings of ca. 61°and 64°(ca. 35°for 1-dTH) suggesting a high degree of helical twist imposed by the D-D′ covalent bond. All-hydrocarbon quasi [8]circulene (QC, Fig. 1), in which the B and B′ rings are phenyls, present similar characteristics with smaller torsions angles of these rings and high angle of ca. 79°between the planes of rings D and D′. 8 Moreover, the degree of torsion of the helicenic unit of quasi-circulenes described in here, seen only through the twist around ring A, is comparable to previously reported double dioxa [7]helicene (values between 28.6°and 31.8°) [START_REF] Chang | Furan-containing double tetraoxa[7]helicene and its radical cation[END_REF] which is about 10°superior to 1-dTH (ca. 18°, Fig. S15, ESI †).

Mechanistic issues

Density functional theory (DFT) calculations have been performed in order to rationalize the formation of the quasi [8]circulene 1-dTQC via a cationic reaction mechanism (the computational methodology is detailed in the ESI †). Thus, the precursor 4 and dithia [7]helicene 1-dTH have been optimized as neutral species, radical cations (4-cat and 1-dTH-cat), dihydroradical cations (4′-cat and 1-dTH′-cat), dications (4-dicat and 1-dTH-dicat), dihydro-dications (4′-dicat and 1-dTH′-dicat), and tetrahydro-dications (4″-dicat) forms. The different dications have been considered in their singlet state since, for example, the optimization of 4-dicat as both singlet and triplet states indicates that the latter is higher in energy by 7.17 kcal mol -1 than the former. The higher stability of the singlet state of the dications is not surprising when considering the extent of the Fig. 4 Intermolecular lateral interactions between molecules A and B, S th ⋯S dithiolene (grey) in the structure of dithia [7]helicene 1-dTH. Fig. 5 View along the a axis of the intermolecular interactions (Å) between molecules of type A and molecules of type B, S th ⋯S dithiolene (grey) and S dithiolene ⋯S dithiolene (green) in the structure of dithia [7]helicene 1-dTH.

overlap is due to steric crowdedness of the helicene rings and is being directed by intermolecular interactions between the S atoms of both types (thiophene and dithiolene). In the bc plane all S atoms interact laterally by S th ⋯S dithiolene short contacts of 3.390-3.579 Å resulting in the formation of infinite layers of alternate -A-B-molecules (Fig. 4). Other notable small distances between the stacks of A and stacks of B consist in C-H⋯π inter-stack interactions of the helicene parts of the molecules (Fig. S7 †). In the stack, along the a axis, these layers show S dithiolene ⋯S dithiolene distances of 3.773, 4.045 Å and S th ⋯S dithiolene of 3.940, 4.079 Å between the type A molecules and, respectively, of 4.009, 4.015 Å and of 3.857, 4.038 Å between the type B molecules (Fig. 5).

Racemic quasi [8]circulene 1-dTQC crystallizes in the monoclinic system, P2 1 /c space group, with the asymmetric unit formed by one independent molecule. In the stack 1-dTQC molecules are disposed in a head-to-tail manner along a and interact along c through S dithiolene ⋯S dithiolene (green) contacts (Fig. S8-S10 †). Molecules of alternating layers are tilted with respect to each other of about 48.8° and stack via short lateral interactions S th ⋯S dithiolene (grey) and S dithiolene ⋯S dithiolene (green) of about 3.409, 3.492 and 3.392 Å, respectively (Fig. 6). bution in the HOMO of 4-dicat points towards a favourable formation of the first C-C bond between the terminal phenyl rings that would provide the dihydro-intermediate 4′-circ-dicat, which does not converge upon geometry optimization but leads to a second C-C bond formation between the thiophene rings to give the tetrahydro-intermediate 4″-dicat. Then, dehydrogenation takes place to afford the desired quasi [8]circulene 1-dTQC (Fig. 7, middle). Furthermore, the possibility to obtain the circulene from the helicene via a radical cation intermediate has been considered. The SOMO topology of 1-dTH-cat (Fig. S19 †) clearly shows that the thermal ring closure towards 1-dTH′-cat is not favourable, thus excluding the formation of quasi [8]circulene 1-dTQC from the radical cation of the helicene via the dihydro-radical cation form. Moreover, the 1-dTHdicat seems to be the proper intermediate for the formation of the quasi [8]circulene from 1-dTH, which, although is not converging, leads directly to 1-dTH′-dicat (Fig. 7, bottom). These results allow us to hypothesize that under our experimental conditions dithia [7]helicene 1-dTH could be formed from 4 via the radical cation route only, whereas quasi [8]circulene 1-dTQC could be produced from both 4 and 1-dTH via the dication route. Moreover, the electronic density of the HOMO of 1-dTQC (Table S7 †) explains the selectivity of the double electrophilic substitution of chlorine on the outer positions to afford de 1-dTQC-Cl circulene.

Enantiomerisation energy barriers and enantiomer resolution

The enantiomerisation barriers for 1-dTH and 1-dTQC were estimated by DFT calculations and experimentally determined by first-order kinetics measurements (details in the ESI †). As seen in Fig. 8 the calculated energy barrier is higher for the helicene than the corresponding quasi-circulene. The isomerization barriers of dithia [7]helicenes have been estimated at 36.8 and 36.9 kcal mol -1 for 1-dTH-Cl and 1-dTH, respectively. These values are in perfect agreement with the experimentally determined one at 37.0 kcal mol -1 for 1-dTH. 1-dTH-Cl and 1- Table 2 Values of the torsion angles (°) for each of the constituting rings, together with the dihedral angle (°) of the terminal rings in dithia [7]helicene 1-dTH, quasi [8]circulenes 1-dTQC, and in all-hydrocarbon quasi [8]circulene QC 8

Ring

Torsion angles (°) QC (Fig. 1 conjugation between the two naphthothiophene moieties illustrated by the shape of the HOMO of 4-dicat (Fig. 7). The SOMO topology of 4-cat suggests the formation of helicene via the 4′cat-cis intermediary through a disrotatory ring closure (Fig. 7, top). A dication route is not plausible for the access to helicene as suggested by the absence of electronic density in the HOMO of 4-dicat on the carbon atoms of the thiophene rings involved in the ring closure. On the contrary, the electron density distri-within the unsubstituted dihetero [7]helicene series with O, ON, N and S heteroatoms. In the case of diaza [7]helicene dAH substitution on the N atoms induces a slightly higher barrier which still remains inferior to dithia [7]helicene, whereas substituents on the two extremities of the helix have, as expected, greater influence (Fig. 1, Table 3 and Table S4 †). 34 The stereochemical stability of unsubstituted 1-dTH is the highest amongst simple dihetero-and trihetero- [7]helicenes reported to date at the exception of π-extended double dioxa [7]helicene and triple dioxa [7]helicene which attain values of 50.5 kcal mol -1 , 33 51.9 and 77.4 kcal mol -1 , [START_REF] Zhou | New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene synthesis of fluorescent hetero[8]circulene analogues with tunable solubilities and optical properties[END_REF] respectively. In the trihetero [7]helicene series replacing one N with S and the methyl substituent with methoxy induces an increase of the barrier up to 32.9 kcal mol -1 for TdAH-OMe,H 12 vs. tAH-Me,H 11 (25.5 kcal mol -1 ). Similar to helicenes, twisted C s -symmetry of the transition state has been predicted for dithia-quasi [8]circulene 1-dTQC and the calculated enantiomerisation energy is of 30.4 kcal mol -1 , suggesting a lower stereostability than the 1-dTH but still high enough to allow the separation of the enantiomers. The experimentally determined value for 1-dTQC of 29.8 kcal mol -1 is in perfect agreement with the calculations. Thus, the dithia-quasi [8]circulenes reported in this work have the highest stereostability amongst reported unsubstituted quasi-circulenes. Enantiomers of both 1-dTH and 1-dTQC have been separated by chiral HPLC with chiral stationary phases (Chiralpak IE and (S,S)-Whelk-O1) and mixtures of hexane/dichloromethane as mobile phases (ESI for details †). As predicted by the theory and confirmed experimentally, the enantiomerisation energies are high enough to allow separation of the enantiomers which show mirror image circular dichroism (CD) Fig. 7 Proposed reaction mechanism for helicene 1-dTH and quasi-circulene 1-dTQC, together with the optimized orbitals for the radical cation and dication of 4 and dihydro-dication of 1-dTH. In red are highlighted the cyclized dihydro-and tetrahydro-radical cation and dication intermediates.

Fig. 8 Isomerisation process from M to P enantiomer together with the calculated relative Gibbs free energy (kcal mol -1 ) for 1-dTH (left) and 1-dTQC (right) (the computational methodology is detailed in the ESI †).

dTH-Br (Fig. 1) have been included in the theoretical study for comparison purposes. As expected, a substituent in the external position of the helix does not induce any effect on the barrier, whereas if inserted at the two extremities of the helix the impact is highly significant (Table 3, calculated enantiomerisation barriers for both dithia [7]helicene and dithia-quasi [8]circulenes with Cl external substituent and Br at the extremities of the helix). The enantiomerisation energy estimated by DFT calculations indicates for 1-dTH the highest barrier spectra (Fig. 9). The absolute configuration of the enantiomers was deduced by comparison with the calculated CD spectra. For both 1-dTH and 1-dTQC the first eluted fraction corresponds to M and the second one to P enantiomers (black and red curves respectively) and the relation between the absolute configuration and the optical rotation follows the general trend observed in helicenes. Thus, M enantiomers are levorotatory for both 1-dTH and 1-dTQC, with specific optical rotation values of -1050 and -700 deg mL g S5 andS6 †). In both cases, the first eluted fraction shows a first negative Cotton effect at low energy, 407 nm for 1-dTH and 405 nm for 1-dTQC, in contrast to what was observed when comparing other [7]helicene and quasi- [8]circulenes tAH-Me,H and tAQC-OMe,H. In that particular case the helicene showed a positive Cotton effect at low energy whereas the circulene was negative for the same enantiomer. 11,[START_REF] Matsuo | Thermal racemisation of hepta-, octa-, and nonahelicene : Kinetic results, reaction path and experimental proofs that the racemisation of hexa-and heptahelicene does not involve an intramolecular double diels-alder reaction[END_REF] Moreover, in our case the CD intensities of 1-dTH and 1-dTQC are comparable whereas azahepta [8]circulene recently reported [START_REF] Maeda | Facile Synthesis of Azahelicenes and Diaza[8]circulenes through the Intramolecular Scholl Reaction[END_REF] present much weaker Cotton effects than their helicenic equivalents.

-1 dm -1 ([α] 25 D in CH 2 Cl 2 ) (Tables
Thus, the first two low energy bands, arising at 407/ 393 nm (1-dTH) and 405/383 nm (1-dTQC) and calculated at 399/370 nm (1-dTH) and 394/357 nm (1-dTQC), correspond to almost pure HOMO→LUMO and HOMO-1→LUMO transitions (Tables S8 andS9 †). In the high energy area, the stronger Cotton effects predicted by theory correspond, for example, to excitations at 273 nm (experimental at 279 nm) for 1-dTH and 294 nm (experimental at 296 nm) for 1-dTQC, which are described predominantly by HOMO→LUMO+6 and HOMO→LUMO+4 transitions, respectively (Tables S8 and S9 †). Whereas for helicene the predicted spectra are reproducing the experimental ones in terms of rotational strength, for circulene the stronger experimental CD signal at 252 nm would be predominantly a HOMO-4→LUMO+1 transition, calculated as well at 252 nm, but less intense. Note the non-negligible involvement of the dithiolene ring in all these CD active transitions, according to the participation of the dithiolene atoms to the corresponding molecular orbitals, witnessing its conjugation with the helical backbone.

Table 3 Estimated and experimentally (in brackets) determined enantiomerisation energies of [7]helicene and their corresponding quasi [8]circulenes (in greensynthesized molecules, in greycalculated molecules for comparison) a Substituent Cl is situated at the exterior of the helix (see Fig. 1). b Substituent Br at the extremities of the helix (see Fig. 1). c Not reported previously, values calculated by DFT in this work for comparison reason. Within this work, unprecedented dithia [7]helicene and dithiaquasi [8]circulenes decorated with 1,3-dithio-2-one have been synthesized through an elegant method involving a one step simple and double oxidative dehydrocyclisation of a bisnaphtho-thiophene-1,3-dithiol-2-one precursor. A selectivity towards quasi [8]circulene has been observed with FeCl 3 oxidant whereas the helicene has been preferentially obtained at low temperature with PIFA-BF 3 •Et 2 O oxidant. DFT calculations suggest a mechanism through a radical cation intermediate for the synthesis of dithia [7]helicene and dication in the case of dithia-quasi [8]circulene. Theoretical simulations estimate enantiomerisation barriers of 36.9 kcal mol -1 for 1-dTH and 30.4 kcal mol -1 for 1-dQC in excellent agreement with the experimentally determined values of 37.0 and 29.8 kcal mol -1 , respectively. Thus, dithia [7]helicene and dithia-quasi [8]circulene have the highest stereostability amongst simple dihetero-and trihetero- [7]helicenes and unsubstituted quasi-circulenes, respectively. Enantiomers of both helicene and quasi-circulenes show stereostability at room temperature and have been successfully separated by chiral chromatography. Importantly, the 1,3-dithio-2-one motif should further give straightforward access to TTF and metaldithiolene complexes, fused in the middle of the helical unit, which are valuable precursors for conducting materials with helical chirality.

Fig. 1

 1 Fig. 1 Examples of Hetero-[7]Helicenes et Quasi[8]Circulenes; those described in this work are highlighted with the blue rectangle.

Fig. 2

 2 Fig. 2 Cyclic voltammetry of 4 (1.24 mM), 1-dTH (1.24 mM) and 1-dTQC (1.04 mM) using TBAPF 6 electrolyte (100 mM solution in dichloromethane) at different scan rates.

Fig. 3

 3 Fig.3Top and side view of dithia[7]helicene 1-dTH (M) (left), dithia-quasi[8]circulenes 1-dTQC (P) (right) in the crystal structures of the racemic forms of the two compounds.

lene 1 -

 1 dTQC. Nonetheless, the dehydrocyclisation of 1-dTH to afford the corresponding quasi-circulene 1-dTQC could be performed with DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone), which is a stronger oxidizing reagent (TableS1†).

Fig. 6

 6 Fig. 6 Tilt angle (°) and intermolecular lateral interactions (Å) between molecule of alternating layers together with S th ⋯S dithiolene (grey) and S dithiolene ⋯S dithiolene (green) in the structure of quasi[8]circulene 1-dTQC.

Fig. 9

 9 Fig. 9 CD spectra (black first and red second eluted fractions) of 1-dTH and 1-dTQC 0.19 mM in dichloromethane, together with the DFT calculated CD spectra of the M enantiomers (dotted black).

Table 1

 1 Oxidative dehydrocyclisation conditions of bis-naphtho-thiophene-1,3-dithiol-2-one 4

		Oxidant	Eq.	Solvent	Reaction time	Product
	1	Solid FeCl 3	Excess	CHCl 3	60 h (rt)	1-dTQC-Cl (quant.)
	2	Solid FeCl 3	10	CHCl 3	3 h (rt)	1-dTQC-Cl (quant.)
	3	Solution of FeCl 3 /CH 3 NO 2	10	CHCl 3 /CH 3 NO 2	1 h (rt)	1-dTQC (quant.)
	4	Solution of FeCl 3 /CH 3 NO 2	1	CHCl 3 /CH 3 NO 2	up to 80 h (rt)	4 + 1-dTQC + 1-dTH
	5	PIFA	1	CH 2 Cl 2	0.5 h (-78 °C), 1 h (rt)	4
	6	PIFA-BF 3 •Et 2 O	Excess	CH 2 Cl 2	0.5 h (-78 °C)	1-dTQC (quant.)
	7	PIFA-BF 3 •Et 2 O	1.2	CH 2 Cl 2	1 h (-78 °C)	4 + 1-dTH (45%)

  )

	A	18.23	18.19	32.47	63.9
	B	17.42	20.68	1.13	3.1
	B′	18.65	15.41	9.25	6.2
	C	10.61	12.17	25.61	48
	C′	11.42	10.41	32.49	47.3
	Total	76.33	76.86	101.95 (20.39)	168.5
	(average)	(15.26)	(15.37)		(33.7)
	D			29.42	16.3
	D′			27.61	23.5
	D-D′			81.40	91.7
		Helical curvature a (°)
	D-D′	35.77	35.00	61.17	79.2

a Interplanar angle (angle between the planes of the terminal cycles).


R Assila
email: rym.assila@im2np.fr

Belhadj Mefteh¹

N Dehaese¹

R Vauché¹

J Gaubert¹

Estimation de l'atténuation du corps humain en tant que canal de propagation des communications HBC standardisées

Les communications via le corps humain (HBC pour Human Body Communication), dont la fréquence porteuse standardisée est 21MHz (standard IEEE 802.15.6), offrent potentiellement des conditions de propagation plus favorables que les technologies sans fil habituelles telles que le Zigbee, ou le Bluetooth. Cependant, en raison de leur sensibilité à l'environnement proche, l'atténuation du signal ne peut être déterminée à l'aide d'appareils de mesure standards car ces derniers modifient le chemin de propagation. Par conséquent, pour effectuer la mesure de cette atténuation dans des conditions proches de celles obtenues avec de potentiels dispositifs commerciaux, un émetteur-récepteur compact, alimenté sur batterie et capable d'estimer de manière autonome les tensions émise et reçue, est proposé dans cet article. Un prototype sur circuit-imprimé de ce dernier, construit autour d'un microcontrôleur et de composants discrets, a permis de mesurer une atténuation en tension comprise entre 40 et 50 dB pour des communications sur le corps humain allant de 20 cm à 1 m.

Introduction

Les communications sur le corps humain (HBC) sont définies comme une couche physique possible (PHY) du standard IEEE 802.15.6 dédié aux réseaux sans fil fonctionnant à proximité du corps humain (WBAN). Cette couche PHY exploite une bande de fréquence centrée sur 21 MHz et permet d'établir une liaison via le corps humain avec un débit maximal de 1,3125 Mbits/s [START_REF]IEEE standard for Local and metropolitan area network -Part 15.6: Wirless Body Area Networks[END_REF].

Contrairement aux communications sans fil standard (Zigbee, Bluetooth) qui utilisent l'air comme canal de propagation, les HBC marque un véritable changement de paradigme puisqu'il propose d'utiliser le corps humain comme milieu de propagation en remplaçant les antennes par des électrodes. Dès lors, pour assurer la sécurité des personnes et limiter les interférences avec les signaux électriques biologiques, de même qu'avec d'autres dispositifs, le champ électrique produit par une électrode HBC mesurée à 30 m en espace libre ne doit en aucun cas dépasser 30 μV/m (réglementation FCC [START_REF]FCC 96-326: Guidelines for Evaluating the Environmental Effects of Radiofrequency Radiation[END_REF]) en plus d'être conforme à la réglementation locale [START_REF]IEEE standard for Local and metropolitan area network -Part 15.6: Wirless Body Area Networks[END_REF].

Les communications HBC, sont principalement associées à deux types de couplage avec le corps comme le montre sur la Figure 1. Le premier est le couplage galvanique (CG-HBC) [START_REF] Callejón | Distributed Circuit Modeling of Galvanic and Capacitive Coupling for Intrabody Communication[END_REF], [START_REF] Seyedi | An Empirical Comparison of Limb Joint Effects on Capacitive and Galvanic Coupled Intra-Body Communications[END_REF] Concernant le mode de transmission CC-HBC, il est possible de trouver dans la littérature [START_REF] Wegmueller | Signal Transmission by Galvanic Coupling Through the Human Body[END_REF]- [START_REF] Bae | The Signal Transmission Mechanism on the Surface of Human Body for Body Channel Communication[END_REF] une atténuation autour de 21MHz comprise entre 22dB et 62dB comme indiqué sur la figure 2. Cette disparité s'explique par la forte dépendance de l'atténuation introduite par le corps humain (« path-loss ») à l'environnement de mesure (distance inter-électrode, présence de couplage parasite via la mise à la terre des appareils, utilisation ou non de baluns, etc.). Par conséquent, pour estimer l'atténuation du signal dans le mode CC-HBC dans des conditions proches de celles obtenues avec de potentiels dispositifs commerciaux, un système de mesure ad hoc, ayant un facteur de forme proche de ces potentiels dispositifs commerciaux, est proposé.

L'article est organisé de la manière suivante. Tout d'abord, l'architecture du système de mesure proposé est présentée dans la section 2. Puis, dans la section 3, l'algorithme de Goertzel permettant l'estimation du niveau des signaux est décrit et le choix des paramètres associés est détaillé. Enfin, les résultats expérimentaux obtenus avec le système développé sont présentés dans la section 4. L'émetteur et le récepteur proposé ont chacun été mis en oeuvre sur un circuit-imprimé (PCB) de dimensions 5x5 cm. Concernant l'électrode en contact avec le corps humain, une électrode médicale standard (diamètre 8 mm) fixée sur le côté "Bottom" du PCB est utilisée (Figure 3). L'électrode de masse est quant à elle constituée du plan de masse situé sur le côté "Top" du PCB. En considérant que le condensateur est complètement chargé après un temps égal à 5τ (où τ = RonC est la constante de temps du circuit ainsi formé), la condition pour avoir un temps de charge suffisamment rapide s'exprime comme suit :

5τ < 𝑇 𝑒𝑐ℎ 2 (1) qui conduit à : C < 𝑇 𝑒𝑐ℎ 2×5×𝑅 𝑜𝑛 (2)
où, Tech est la période d'échantillonnage. Etant donné que la valeur typique de Ron pour le commutateur utilisé est de 6,5 Ω, il apparaît également que C doit être inférieur à 32 nF.

Pendant la phase de maintien (PWML = 1), la tension stockée est connectée à l'entrée de l'ADC et il est possible de supposer que le condensateur se décharge à un courant constant Ileak égal au courant de fuite de l'entrée de l'ADC comme indiqué sur la Figure 5.(b) (Ileak = 0,6 µA suivant la fiche technique du DSPIC). Ainsi, la condition sur C pour que la décharge du condensateur soit inférieure au quantum q durant le temps de conversion de l'ADC (Tc) est :

Algorithme de Goertzel

L'algorithme de Goertzel [START_REF] Couraud | Real-Time Impedance Characterization Method for RFID-Type Backscatter Communication Devices[END_REF] réalise la transformée de Fourier discrète d'un signal v[n] à une fréquence unique. Il permet donc d'estimer l'amplitude du spectre du signal à une fréquence particulière f0. Cet algorithme est défini par un nombre restreint d'opérations mathématiques et peut-être aisément implantée dans un µC. L'atténuation en tension subie par le signal se propageant sur le corps humain peut alors être déterminée à l'aide du rapport des estimations de l'amplitude en V des signaux reçu et émis obtenu grâce à cet algorithme implémenté côté récepteur et côté émetteur.

L'estimation de l'amplitude Ag du spectre d'un signal v(t) à une fréquence f0 s'écrit selon l'algorithme :

𝐴𝑔 = √𝑔[𝑁] 2 +𝑔[𝑁-1] 2 -2𝑔[𝑁]𝑔[𝑁-1] 𝑐𝑜𝑠(𝛼) 𝑁 2 (4)
où le paramètre α est défini par :

α = 2𝜋𝑓 0 𝑓 𝑒𝑐ℎ (5)
avec fech la fréquence d'échantillonnage du signal v(t), f0 la fréquence d'intérêt et où la séquence g[n] est calculée à partir de N échantillons de la tension v[n] tel que :

𝑔[1] = 𝑣[1] (6) 𝑔[2] = 𝑣[2] + 2 cos(𝛼). 𝑔[1] (7) 𝑔[𝑛] = 𝑣[𝑛] + 2 𝑐𝑜𝑠(𝛼). 𝑔[𝑛 -1] -𝑔[𝑛 -2](8)
La fréquence d'échantillonnage fech et le nombre d'échantillons N sur lequel appliquer l'algorithme de Goertzel doivent être judicieusement choisis [START_REF] Couraud | Real-Time Impedance Characterization Method for RFID-Type Backscatter Communication Devices[END_REF]. Un moyen de garantir que 2q/p ne soit pas un entier est alors de considérer un nombre impair pour 4q/p. Pour cela, il est possible de choisir p égal à 4 et q égal à un nombre impair.

Pour déterminer q, il faut maintenant prendre en compte la fréquence d'échantillonnage maximale du DSPIC qui est ici de 500 kbps. Or, un entier impair q permettant d'obtenir une fréquence d'échantillonnage finie légèrement inférieur à 500 kHz étant 175, la fréquence d'échantillonnage est donc de 480 kHz.

Enfin, la convergence entre la série de Fourier et l'algorithme de Goertzel étant p périodique pour un signal non-bruité, il est judicieux d'appliquer l'algorithme sur un multiple entier r de p tel que : 𝑁 = 𝑟 × 𝑝 . (13) où N est le nombre total d'échantillons. Pour assurer la stabilisation de l'algorithme, r est ici pris égale à 10. En conséquence, N est ici égal à 40.

Résultats de Mesure

La Figure 6 montre les quatre scénarios retenus pour la mesure de l'atténuation subie par le signal lors d'une transmission CC-HBC réalisée à travers le corps humain (TX1-RX1, TX1-RX2, TX1-RX3 et TX1-RX4). Chaque scénario correspond à une distance inter-électrodes différente (respectivement 20 cm, 40 cm, 60 cm et 100 cm environ).

Les valeurs mesurées de l'atténuation subie par le signal dans les différents scénarios sont résumées sur la Figure 7. Les résultats montrent que l'atténuation en tension est de l'ordre de 40 dB pour la distance la plus courte (TX1-RX1 ~ 20 cm). L'atténuation se détériore ensuite sensiblement pour la configuration TX1-RX2 (distance ~40 cm) puis de manière moins marquée pour les configurations TX1-RX3 (~60 cm) et TX1-RX4 (~100 cm). Pour cette dernière, une atténuation de 50 dB a été obtenue.

Conclusion

Les communications sur le corps-humain pourraient présenter un bilan de propagation plus favorables vis-à-vis des communications sans fil usuelles (Bluetooth, Zigbee). Néanmoins, leur sensibilité à l'environnement proche rend difficile, lorsque les appareils de mesure usuels sont utilisés, l'estimation de l'atténuation que subirait le signal avec des potentiels produits commerciaux à venir. C'est pourquoi, un prototype d'émetteur et de récepteur CC-HBC sur circuit-imprimé, ayant un facteur de forme proche de ces produits et permettant d'estimer l'atténuation, a été proposé dans cette article. Les premiers résultats obtenus avec ce prototype indiquent une atténuation comprise entre 40 dB et 50 dB selon la position des électrodes. Néanmoins, ces résultats sont maintenant à consolider en procédant à des tests sur différents sujets et pour des scénarios plus variés.

  où 4 électrodes appliquées sur le corps (2 coté émetteur et 2 côté récepteur) sont utilisées pour transmettre et recevoir le signal en mode différentiel (pas d'électrode reliée à la masse). Le second est le couplage capacitif (CC-HBC) [3][6] où une seule des 2 électrodes (coté émetteur et côté récepteur) est en contact avec le corps, l'autre étant reliée à la masse. La propagation du signal est alors similaire à celle d'une ligne de transmission : le chemin aller se faisant via le corps humain et le chemin retour se faisant via l'environnement proche (exemple l'air) par l'intermédiaire des électrodes de masse.

Figure 1 .

 1 Figure 1. Les deux types de communications couplées au corps : le couplage galvanique (a), le couplage capacitif (b) [5]

Figure 2 . 7 ] 2 .

 272 Figure 2. Comparaison entre les mesures de la perte de trajet du corps humain trouvées dans [7] 2. Conception de l'émetteur-récepteur proposé 2.a. Architecture du système de mesure proposé Le système proposé pour la mesure de l'atténuation (« path-loss ») subie par le signal lors de son passage à travers le corps humain est illustré sur la Figure 3. Il est basé sur un émetteur et un récepteur compact, chacun étant alimenté sur batterie et construit autour d'un microcontrôleur (µC) DSPIC de chez Microchip. Coté émetteur (TX), comme indiqué sur la Figure 4.(a) le microcontrôleur est configuré pour générer un signal carré de 21 MHz qui est ensuite filtré par un résonateur parallèle de type LC, associé à un montage amplificateur non-inverseur, afin de ne conserver que le fondamental (le gain global de l'ensemble filtre et amplificateur est ici réglé à 1). Le fondamental à 21MHz est ensuite transmis au corps via l'électrode. Afin d'estimer l'amplitude du signal transmis, l'algorithme de Goertzel détaillé dans la section suivante est utilisé. Pour cela, le signal est sous-échantillonné (à 480 ksps) à l'aide d'un échantillonneur-bloqueur (S&H : Sample & Hold) « externe » contrôlé par un signal de 480 kHz généré par le périphérique de modulation de largeur d'impulsion PWM du µC comme indiqué sur la Figure 4.(b) (la fonction S&H intégrée au µC présentant une bande passante trop faible pour pouvoir être utilisée ici). Pendant la phase d'échantillonnage, PWML est égal à 0 ce qui permet d'injecter le fondamental à 21 MHz dans la capacité de stockage C. Pendant la phase de maintien, PWML est égal à 1 et la tension stockée dans C est connectée à l'entrée du convertisseur analogiquenumérique (ADC). Lors de cette phase, la conversion analogique-numérique est réalisée. Enfin, un écran OLED piloté par le µC permet d'afficher l'amplitude (en dBV) de la composante à 21 MHz du signal émis obtenue au préalable à l'aide de l'algorithme de Goertzel et notée Ag. L'architecture de récepteur proposée (Figure 4.(c)) est similaire à celle de l'émetteur. Toutefois, le signal est ici reçu au niveau de l'électrode puis filtré et amplifié à l'aide d'un résonateur LC et d'un amplificateur non-inverseur, l'ensemble présentant un gain fixé à ~ 30 dB. Le signal obtenu est ensuite échantillonné par un circuit S&H externe semblable à celui de l'émetteur puis traité par le µC afin d'afficher l'amplitude en dBV de la composante à 21 MHz du signal reçu. Connaissant l'amplitude du

Figure 3 .Figure 4 .

 34 Figure 3. Système de mesure de l'atténuation du corps humain

  est le temps nécessaire à la conversion analogiquenumérique (égale à 0,5 µs d'après la fiche technique DSPIC) et q est le quantum qui est égal à Vref/2 N (Vref = 3,3 V et N = 10 bits). Par conséquent, C doit être supérieur à 93 pF.En pratique, il a été constaté lors de mesures que la valeur optimale du condensateur est de 120 pF, ce qui remplit les conditions (2) et (3).

Figure 5 .

 5 Figure 5. Circuit équivalent de l'échantillonneurbloqueur externe pendant : la phase de d'échantillonnage (a), la phase de maintien (b).

  Tout d'abord, fech peut s'exprimer en fonction de la fréquence d'intérêt f0 comme suit : un entier supérieur ou égal à 3 et q est un entier supérieur ou égal à 1. De plus, en injectant (9) dans (5), α peut s'écrire comme suit : q doivent être choisis de sorte que α ne soit pas un multiple de π. Selon (5), cela signifie que 2f0 ne doit pas être un multiple de fech ou selon (10), que 2q/p ne soit pas un entier.Par ailleurs, il est à noter que la fréquence de cadencement du µC (Fosc) a été choisie comme un multiple de f0 tel que : ce qui conduit à Fosc = 84 MHz puisque f0 est égal à 21 MHz. En associant (9) et (11), on obtient l'équation suivante :

Figure 6 .Figure 7 .

 67 Figure 6. Emplacement des électrodes pour les différents scénarios testés