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Synthesis and biological evaluation of new penta- and heptacyclic indolo- and quinolinocarbazole ring systems obtained via Pd0 catalysed reductive N-heteroannulation Marie Laronze-Cochard,a Fabien Cochard,a Etienne Daras,a Amélie Lansiaux,b Bertrand Brassart,c Enguerran Vanquelef,a,d Elise Prost,e,f Jean-Marc Nuzillard,e Brigitte Baldeyrou,b Jean-François Goosens,g Olivier Lozach,h Laurent Meijer,h Jean-François Riou,i Eric Henon,*j and Janos Sapi*a

a Université de Reims-Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR 6229, Groupe BSMA, UFR de Pharmacie, 51 rue Cognacq-Jay, F-51096 Reims, Cedex, France. Fax: +33(0)326918029; email: [email protected] b Laboratoire de Pharmacologie Antitumorale, INSERM U-837, Centre Oscar Lambret, Université Nord de France, Institut de Recherches sur le Cancer de Lille, IMPRT, 1 Place de Verdun, F-59045 Lille, Cedex, France c Université de Reims-Champagne-Ardenne, CNRS UMR 6237, IFR 53 Biomolécules, UFR des Sciences Exactes et Naturelles, BP 1039, F-51687 Reims, Cedex 2, France

d Université de Picardie Jules Verne, Laboratoire des Glucides, CNRS UMR 6219, Equipe THERA, Faculté de Pharmacie, 1 rue des Louvels, F-80037 Amiens, Cedex 1, France e Université de Reims-Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR 6229, Groupe IS, UFR des Sciences Exactes et Naturelles, Bat. 18., BP 1039, F-51687 Reims, Cedex 2, France f Université Paris Descartes, Synthèse et Structure de Molécules d'Intérêt Pharmacologique, CNRS UMR 8638, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l’Observatoire, F-75270 Paris, Cedex 06, France g Université de Lille 2, EA 4034, Laboratoire de Chimie Analytique, Faculté des Sciences Pharmaceutiques et Biologiques, 3 rue du Professeur Laguesse, BP 83, F-59006 Lille, Cedex, France h CNRS, Protein Phosphorylation & Human Disease Group, USR3151, Station Biologique, BP 74, F-29682 Roscoff, France i Régulation et Dynamique des Génomes, INSERM U565, CNRS UMR 5153, USM 503, Muséum National d’Histoire Naturelle, 43 rue Cuvier, CP26, F-75231 Paris Cedex 5, France j Université de Reims-Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR 6229, Groupe BSMA, UFR des Sciences Exactes et Naturelles, Bat. 18., BP 1039, F-51687 Reims, Cedex 2, France. Fax: +33(0)326918497; email: [email protected]

Table of contents Computational study of the key intermediate 8a S1 – S4 Synthesis and analytical data of 6b, 6c, 8b, 8c, 17a S4 – S6 Biological evaluation of 11, 13, 14, 16b, 17a-b, 18 S6 – S9 References S10 Copies of NMR Spectra of 6b-c, 8a-c, 10, 11, 12, 13, 14, 16b, 17a-b, 18 S11 – S59 Computational data of 8a S60 – S77

Computational study of the key intermediate 8a The NMR spectra of 8a have provided evidence for the existence of several stable isomers, even at high temperature (180°C). Thus, collaterally with the experimental work, computations were performed to help in the understanding of these experimental results. The details of the quantum mechanical calculations are reported in the experimental section. Geometry variations of 8a were considered by examining the internal rotation involving the nitrophenyl groups and the ester group. Four conformers were found (Figure 2) with the ethyl backbone lying in the plane of symmetry of the carbazole tricyclic structure. Due to steric hindrance the carbazole and nitrophenyl groups are non-planar with rotation dihedral angles varying between 67 and 89°. The H...O distance between the carbazole NH group and an ester oxygen atom was found to be short (about 2 Å) in the four isomers showing a significant interaction. The S and A notations have been reserved for the structures with the two nitro functions being on the same side (syn) or on opposite sides (anti) of the carbazole structure, respectively. The * notation refers to geometries with the ester carbonyl group directed in the opposite direction of the NH function. ZPE corrected energies obtained at several levels of theory are reported in Table 4. In the most stable isomer (A) the two nitro groups are on opposite sides and the ester carbonyl group is directed toward the NH function. From that, it seems that favourable van der Waals (VDW) contact between the ethyl function and the neighbouring nitrophenyl group combined with the anti arrangement contribute to the structure stabilisation. Isomers S and A* are very close in energy and are less stable than A by 2.2-2.5 kcal.mol-1.

Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is (c) The Royal Society of Chemistry 2010

Table 4. (8a) ZPE corrected relative energies (given in kcal.mol-1)

A S A* S*

gas/B3LYP/6-31G**

0.0 2.2 2.5 4.1

gas/B3LYP/6-311++G(2d,p) //B3LYP/6-31G** a

0.0 1.5 1.5 3.2

PCM/B3LYP/6-31G** b 0.0

(0.0)

1.9

(0.9)

2.4

(1.1)

3.8

(2.4)

a single point B3LYP/6-311++G(2d,p) using B3LYP/6-31G** geometry and ZPE b Gibbs free energy value in brackets

It is interesting to note that these conformers generate distinct magnetic environments for CH3, CH2 and NH protons what could explain the separated signals observed experimentally. To achieve a deeper interpretation of these NMR data, chemical shifts were subsequently computed for all stable conformers relative to the absolute shielding constants of TMS. The results are reported in Table 5.

Table 5. Selected experimental 1H chemical shifts (in ppm) for rotamers of 8a and calculated values at the B3LYP/6-311++G(2d,p)//B3LYP/6-31G** level of theory

A S A* S*

CH2 4.18 4.16 4.47 4.49 CH3 1.07 0.98 1.40 1.39 NH 11.29 11.24 9.86 9.73

Exp. CH2 4.08a 4.76 Exp. CH3 0.88a 1.65 Exp. NH 10.60a 10.40 10.15

a Experimental major peak

Though DFT can lead to NMR properties with reasonable accuracy, it is known that calculated δ values can lie within 0.5 ppm of the experimental value. Thus, only relative shifts will be considered hereafter. Several signals were indeed predicted for CH3, as well as for CH2 and NH functions. They result from different magnetically environments in A, S, A* and S*. In order to compare with experimental values two questions have been addressed. Firstly, what are the Boltzmann weightings if a thermal equilibrium process occurs under experimental conditions (453K, overnight)? Another question is how slow interconversion (between these conformers) has to be in order to see separate peaks rather than an averaged peak on the NMR time scale? A critical element in assessing these features was the barrier height between each of the isomers. Therefore, transition states were searched for pathways between A, A*, S and S* conformers. Several saddle points were found for both the syn/anti interconversion and the ester rotation. The vibrational analysis of each of them gave a low imaginary frequency (about 30i-40i) whose animation was consistent with the desired rotation. Significant barriers to rotation have been found resulting from steric hindrance. The activation potential energies vary between 6.3 and 20.9 kcal.mol−1 for the co-called atropoisomers (relatively stable rotamers). Energy profiles for the rotation pathways are presented in Figure 4.


Figure 4. Toluene PCM HF-DFT(B3LYP/6-31G**) potential energy profiles for rotational pathways between hindered rotamers of 8a.

A and S stand for anti and syn arrangements; the * notation refers to the spatial orientation of ester; values include the ZPE correction (Gibbs free energy values are in brackets)

The anti/syn interconversion rotational barrier (TS3 and TS4, 18.7-21.3 kcal.mol-1) is higher than that needed for the ester conformational change (TS1 and TS2, 6.3-8.9 kcal.mol-1). A very similar barrier (18.3 kcal.mol-1) was obtained (both experimentally and theoretically) for the rotational change of biphenyl derivatives and found to allow interconversion37 at 363K on the NMR time scale. Thus, the equilibrium process is likely to occur under our experimental conditions (453K, overnight). According to energy values in Table 4. the resulting Boltzmann distribution is such that only A, S and A* are expected to have populations. However, although S* was found to be energetically higher whatever the DFT level of theory considered (about 4 kcal.mol-1 above A), it can not be completely excluded that 8a is in S* state because the energy levels spacing is within the precision of DFT. Based on an equilibrium distribution of A, S and A*, and on the assumption (see below) that no exchange arises on the NMR time scale between conformers at 293K, two well-separated 1H NMR signals have been predicted for both CH3 (δ = 1.0 and 1.4 ppm) and CH2 protons (δ = 4.2 and 4.5 ppm), in very good agreement with experimental findings. The predicted separation may then originate from the two isomer classes (A,S) and (A*). Hence, from DFT simulations, the observed separation could be ascribed to the orientation of the ester carbonyl function and consequently to the ethyl position relative to the neighbouring nitrophenyl group. Isomers differing only by the anti or syn spatial arrangement would not result in separated signals for CH3 and CH2 groups. Agreement with experimental data was not as good for NH proton since only two distinct chemical shifts have been predicted (δ = 11.2-11.3, and 9.86 ppm). We next considered the possibility of the effects of conformational exchange between (A,S) and A* on the NMR spectrum. The condition for slow conformational change on the NMR time scale is that the conversion rate (kex) must be much slower than the difference in resonance frequency (Δν) between the two exchanging conformers: kex

< πΔν/√2.38 Based on the CH2 signals observed at δ = 4.08 and 4.76 ppm, the resulting upper limit to allow interconversion between the conformers is then: kex = 453 s-1. Applying the Eyring equation39 to unimolecular reaction at T = 293K provided an estimate of the corresponding expected lower limit for the rotational activation free energy: ΔG‡ = 13.6 kcal.mol-1. This value does not agree favourably with our smaller free energy barrier connecting A and A* (7.7-8.8 kcal.mol-1). However, non covalent interactions seem to play a crucial role in the predicted structure and NMR properties of 8a. It is known that DFT methods do not properly describe these effects. That is the reason why the use


of other correlation methods such as MP2, MP4 or CCSD(T) would be needed to get a better estimate of activation energy properties, but the examination of compound 8a would be computationally prohibitive.

Computational experiments Calculations were performed using the GAUSSIAN 03 packages.47 The structures were fully optimised at the HF-DFT (B3LYP)48,49,50,51 level of theory using the analytical gradients and the 6-31G** basis set (thus, adding one set of d polarization functions on the carbon, oxygen and nitrogen atoms, and one set of p polarization functions on the hydrogen atom). The properties of similar cyclic structures have suitably been obtained using this hybrid DFT functional.52 Stationary points were obtained using both the gas-phase model and the Polarized Continuum Model (PCM).53,54,55 In the latter case, the structures (minima and first order saddle points) were fully optimised in the field of toluene using the solvent accessible surface (SAS). Comparison with the gas-phase results have indicated that there is no significant solvent effect on the structures nor on the relative energies, and it is not surprising owing to its small dielectric constant (ε = 2.4). Vibrational frequencies were determined within the harmonic approximation, at the same level of theory (vacuum and PCM). All transition states were characterized by one imaginary frequency (first order saddle points on the potential energy surface (PES)) associated with the desired reaction pathway. Special care was taken to determine the ground state multiplicity (singlet or triplet state) by using the unrestricted approach for all stationary points (including transition states). The singlet spin state was always found to be energetically more stable than the triplet state. The resulting spin-contamination in the unrestricted electronic structure calculations was zero. Chemical shifts were subsequently predicted at the B3LYP/6-311++G(2d,p)//B3LYP/6-31G** level using the GIAO method56,57 and relative to the absolute shielding constants of TMS obtained at the same level of theory. Starting from A, A*, S and S*, conformations were probed by performing rotations of the ethyl group about the single O-CH2 and the single Csp2-O bonds of the ester group. Two supplementary conformations were found for each of the four previous molecules. In these geometry variations the methyl group moved away from the carbazole plane of symmetry. For each of the four atropoisomers, energy differences between the three conformers did not exceed 0.5 kcal.mol-1. Calculated chemical shifts for the methyl protons (or methylene protons) wer not found to be equivalent because of different chemical environments in these three molecular structures. But barrier to methyl rotation is known to be low (1-3 kcal.mol-1) and moreover, a fast population equilibration process was expected between the three minima, owing to the predicted low activation barrier. For example, the energy was found to increase by no more than 1 kcal.mol-1 as the H3C-C(H2)-O-C dihedral angle was scanned from its value in A to its value in A'. Therefore, in order to compare with our experimental values, the chemical shifts of the methyl protons (or of the methylene protons, or of the NH proton) were averaged over all three conformers. In order to keep the computational CPU time to reasonable limits the gas phase formalism was applied for all NMR calculations.

Synthesis of carbazole derivatives General procedure for the preparation of tetrahydrocarbazoles (6b,c) by microwave irradiation

To a solution of the diastereomerically pure tetramolecular condensation product 3b or 3c in CH2Cl2 was added silicagel. After concentration under reduced pressure the residue was heated in open reaction vessel under microwave irradiation (Procedure A: Normalab Normatron 112® apparatus (1000 W); Procedure B: CEM Discover® apparatus). Purification of the crude solid by column chromatography on silica gel afforded the corresponding tetrahydrocarbazoles 6b or 6c as a mixture of diastereomers.

2,4-Diphenyl-1-ethoxycarbonyl-9H-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid (6b), mixture of five diastereomers (d1/d2/d3/d4/d5)

Procedure A: starting from 3b (130 mg, 0.25 mmol) mixed with silicagel (1.5 g); Irradiation: Normalab Normatron 112® (1000 W, 20 min); Purification gave two fractions of 6b diastereomers. The less polar one (eluent: CH2Cl2→CH2Cl2/CH3OH 99.5/0.5), a white foam (40 mg, 37%) was obtained as mixture of three inseparable diastereomers (d1,d2,d3) (1H NMR ratio of d1/d2/d3: 23/23/6), while the more polar one, (eluent: CH2Cl2/CH3OH 90/10) corresponding to a mixture of two inseparable diastereomers (1H NMR ratio of d4/d5 : 28/20), was isolated as a white solid (37 mg, 34%). Procedure B: starting from 3b (69 mg, 0.13 mmol) mixed with silicagel (175 mg); Irradiation: CEM Discover®, (150°C for 85 min then at 200°C for 15 min); Purification gave carbazole 8b (eluent: cyclohexane→cyclohexane/CH2Cl2 50/50) as a yellow solid (5 mg, 10%) and the corresponding tetrahydrocarbazoles 6b as a mixture of five diastereomers. This mixture was then repurified by column chromatography affording two fractions of 6b diastereomers. The less polar one (eluent: CH2Cl2→CH2Cl2/CH3OH 99.5/0.5), a white foam (9 mg, 15%) was obtained as mixture of three inseparable diastereomers (d1,d2,d3) (1H NMR ratio of d1/d2/d3: 23/23/6). The more polar fraction (eluent: CH2Cl2/CH3OH 90/10) corresponded to a mixture of two inseparable diastereomers (1H NMR ratio of d4/d5: 28/20), isolated as a white solid (41 mg, 71%).

6b(d1,d2,d3) mixture of three inseparable diastereomers: White foam; νmax (film)/cm-1 3410, 3030, 2936, 1734, 1454,


1265, 1155 and 1038; δH(300 MHz; CDCl3; Me4Si) 1.22 (3 × 3 H, t, J 7.1, 3 × CO2CH2CH3)d1,d2,d3, 3.25 (1 H, dd, J 5.1 and 12.2, 3-H)d1, 3.47 (1 H, dd, J 5.1 and 12.0, 3-H)d2, 3.60–3.71 (1 H, m, 3-H)d3, 3.87–4.09 (6 H, m, 3 × 1-H and 3 × 2-H)d1,d2,d3, 4.11–4.26 (3 × 2 H, m, 3 × CO2CH2CH3)d1,d2,d3, 4.30 (1 H, d, J 5.1, 4-H)d2, 4.54 (1 H, d, J 5.1, 4-H)d1, 4.66 (1 H, d, J 5.2, 4-H)d3, 6.68–7.30 (3 × 14 H, m)d1,d2,d3, 8.22 (1 H, s, NH)d2, 8.27 (1 H, s, NH)d1 and 8.32 (1 H, s, NH)d3; δC(75 MHz; CDCl3; Me4Si) (the intensities of d3 isomer signals are too low and can not be reported) 14.1 (2 × CO2CH2CH3)d1,d2, 39.2 (2-CH)d2, 39.5 (2-CH)d1, 40.9 (2 × 4-CH)d1,d2, 49.1 (1-CH)d1, 49.4 (1-CH)d2, 52.1 (3-CH)d2, 52.4 (3-CH)d1, 61.8 (2 × CO2CH2CH3)d1,d2, 110.8 (8-CH), 110.9 (8-CH), 112.0 (4a-C)d2, 112.1 (4a-C)d1, 118.7, 118.9, 119.7, 119.8, 122.5 (2 × CH)d1,d2, 126.0 (4b-C)d1, 126.1 (4b-C)d2, 127.2 (2 × CH), 127.3, 127.5, 128.0, 128.1, 128.3 (2 × CH), 128.5, 128.6, 129.0, 129.0 (9a-C)d2, 129.1 (9a-C)d1, 129.3, 136.4 (8a-C)d2, 136.5 (8a-C)d1, 138.8d2, 139.2d1, 141.1, 141.5, 165.7 (CO2H)d1, 166.2 (CO2H)d2 and 170.8 (2 × CO2CH2CH3)d1,d2; m/z (EI) 439 (M+ 23%), 421 (21), 218 (100); HRMS: calcd. for C28H25NO4 439.1784, found 439.1782.

6b(d4,d5) mixture of two inseparable diastereomers: White solid; νmax (film)/cm-1 3404, 3034, 2993, 2934, 1719, 1454, 1265, 1155 and 1030; δH(300 MHz; CDCl3; Me4Si) 1.09–1.29 (2 × 3 H, m, 2 × CO2CH2CH3)d4,d5, 3.29 (1 H, br s, 3-H)d5, 3.50 (1 H, br d, J 5.9, 3-H)d4, 3.80–4.05 (2 × 2 H, m, 2 × 1-H and 2 × 2-H)d4,d5, 4.07–4.25 (2 × 2 H, m, 2 × CO2CH2CH3)d4,d5, 4.48 (1 H, br s, 4-H)d5, 4.65 (1 H, br s, 4-H)d4, 6.78–7.40 (2 × 14 H, m)d4,d5, 8.23 (1 H, s, NH)d4 and 8.55 (1 H, br s, NH)d5; δC(75 MHz; CDCl3; Me4Si) (the intensities of some of the d5 isomer signals are too low and can not be reported) 14.1 (2 × CO2CH2CH3)d4,d5, 39.3 (2-CH)d4, 41.1 (4-CH)d4, 49.3 (1-CH)d4, 51.8 (3-CH)d4, 61.6 (CO2CH2CH3)d5, 61.7 (CO2CH2CH3)d4, 110.8 (8-CH)d4, 112.3 (4a-C)d4, 118.8d4, 119.5d5, 119.7d4, 122.0d5, 122.3d4, 126.3 (4b-C)d4, 126.5d5, 126.8d5, 126.9d4, 128.0d4, 128.2d4, 128.9d5, 129.0d4, 129.5(9a-C)d4, 136.5 (8a-C)d4, 140.2, 140.3, 142.5, 143.4 and 171.3 (2 × CO2CH2CH3 and 2 × CO2H)d4,d5; m/z (EI) 439 (M+ 15%), 218 (100); HRMS calcd. for C28H25NO4 439.1784, found 439.1785. 2,4-Diphenyl-9-methyl-1,2,3,4-tetrahydro-carbazole-3-carboxylic acid (6c), mixture of two inseparable diastereomers (d1/d2) Procedure A: starting from 3c (105 mg, 0.23 mmol) mixed with silicagel (1.5 g); Irradiation: Normalab Normatron 112® (1000 W, 60 min); Purification (eluent: cyclohexane/ethylacetate 90/10→ 70/30) gave 6c(d1,d2) as mixture of two inseparable diastereomers (1H NMR ratio of d1/d2: 68/32) as a white solid (61 mg, 71%); νmax (KBr)/cm-1 3428 , 3028, 2922, 1711 and 1472; δH(300 MHz; CDCl3; Me4Si) 2.82 (1 H, dd, J 10.7 and 16.4, 1b-H)d1, 3.14–3.32 (3 H, m, 1a-Hd1, 3-Hd2, 1b-Hd2), 3.37–3.69 (4 H, m, 3-Hd1, 2-Hd2, 2-Hd1, 1a-Hd2), 3.64 (3 H, s, Me)d1, 3.73 (3 H, s, Me)d2, 4.57 (1 H, d, J 4.3, 4-H)d2, 4.76 (1 H, d, J 5.4, 4-H)d1 and 6.80–7.41 (2 × 14 H, m)d1,d2; δC(75 MHz; CDCl3; Me4Si) 25.7 (2 × CH, 1a-CH and 1b-CH)d2, 29.2 (Me)d1, 29.3 (Me)d2, 31.4 (2 × CH, 1a-CH and 1b-CH)d1, 37.6 (2-CH)d1, 38.5 (2-CH)d2, 40.6 (4-CH)d2, 41.6 (4-CH)d1, 51.6 (3-CH)d1, 53.9 (3-CH)d2, 108.6 (2 × 8-CH)d1,d2, 108.8 (4a-C)d2, 109.6 (4a-C)d1, 118.5, 118.9, 119.1, 120.9, 121.2, 126.0 (4b-C)d1, 126.5, 126.6 (4b-C)d2, 126.7, 126.9, 127.4, 127.8, 128.0, 128.3, 128.4, 128.6, 128.7, 128.8, 135.1d1, 135.8d2, 137.5d1, 137.6d2, 140.8d1, 141.8d2, 143.8d2, 144.4d1, 176.8 (CO2H)d1 and 177.6 (CO2H)d2; m/z (EI) 381 (M+ 6%), 232 (100); HRMS calcd. for C26H23NO2 381.1729, found 381.1763.

General procedure for the preparation of carbazoles (8a-c) by microwave irradiation

To a solution of the diastereomerically pure tetramolecular condensation product 3a, 3b or 3c in CH2Cl2 was added silicagel. After concentration under reduced pressure the residue was heated under microwave irradiation in open reaction vessel. Procedure A: Normalab Normatron 112® apparatus (1000 W); Procedure B: CEM Discover® apparatus. Purification of the crude solid by column chromatography on silica gel afforded the corresponding carbazoles 8a, 8b or 8c. 2,4-Diphenyl-1-ethoxycarbonyl-9H-carbazole (8b) Procedure A: starting from 3b (174 mg, 0.33 mmol) mixed with silicagel (1.5 g); Irradiation: Normalab Normatron 112® (1000 W, 60 min); Purification (eluent: cyclohexane/CH2Cl2: 60/40→30/70) gave 8b (50 mg, 38%), as a yellow cristalline powder and a mixture of two inseparable diastereomers of 6b(d4,d5) (eluent: CH2Cl2/CH3OH: 90/10), as a white solid (25 mg, 17%). Procedure B: starting from 3b (81 mg, 0.15 mmol) mixed with silicagel (243 mg); Irradiation: CEM Discover® (210°C for 25 min then 220°C for 45 min); Purification by column chromatography gave 8b (25 mg, 41%) (eluent: cyclohexane/CH2Cl2: 60/40→30/70) as a yellow powder and 6b(d4,d5) as mixture of two inseparable diastereomers (eluent: CH2Cl2/CH3OH: 90/10) in form of a white solid (18 mg, 26%). 8b: Yellow cristalline powder; mp 204–205°C; νmax (KBr)/cm-1 3424, 1674, 1271, 1215 and 1150; δH(300 MHz; CDCl3; Me4Si) 0.88 (3 H, t, J 7.1, CO2CH2CH3), 4.12 (2 H, q, J 7.1, CO2CH2CH3), 7.01 (1 H, t, J 7.8, 6-H), 7.09 (1 H, s, 3-H), 7.30–7.41 (6 H, m), 7.43–7.58 (5 H, m), 7.59–7.70 (2 H, m) and 10.15 (1 H, s, NH); δC(75 MHz; CDCl3; Me4Si) 13.3 (CO2CH2CH3), 60.6 (CO2CH2CH3), 109.8, 110.9 (8-CH), 119.5 (6-CH), 120.9 (4a-C), 122.1 (4b-C), 122.3, 124.1, 126.2, 126.7, 127.6, 128.1, 128.5, 128.9, 129.0, 140.2, 140.9, 141.3, 141.8, 143.1 and 168.6 (CO2CH2CH3); m/z (EI) 391 (M+ 59%), 345 (100); HRMS calcd. for C27H21NO2 391.1572, found 391.1569. 2,4-Diphenyl-9-methylcarbazole (8c)


Procedure A: starting from 3c (119 mg, 0.26 mmol) mixed with silicagel (1.2 g); Irradiation: Normalab Normatron 112® (1000 W, 230 min); Purification (eluent: cyclohexane/ethyl acetate: 90/10→ 80/20) gave 8c (16 mg, 19%) as a yellow powder and 6c (78 mg, 80%), as a white solid (mixture of diastereomers) (eluent: cyclohexane/ethyl acetate: 70/30). 8c: Yellowish foam; νmax (film)/cm-1 3050, 2936, 1597, 1466, 1408 and 1323; δH(300 MHz; CDCl3; Me4Si) 3.84 (3 H, s, Me), 6.86–6.95 (1 H, m, 6-H), 7.22–7.35 (4 H, m), 7.35–7.50 (6 H, m), 7.52 (1 H, d, J 1.4, 1-H), 7.60 (2 H, d, J 7.2) and 7.69 (2 H, d, J 7.2); δC(75 MHz; CDCl3; Me4Si) 29.2 (Me), 105.9 (1-CH), 108.2 (8-CH), 118.7 (6-CH), 119.5 (4a-C), 120.3 (3-CH), 122.2 (4b-C), 122.3, 125.6, 127.1, 127.5, 127.6, 128.4, 128.8, 129.2, 137.9, 138.9, 141.3, 141.7, 141.9 and 142.0; m/z (EI) 333 (M+ 100); HRMS calcd. for C25H19N 333.1517, found: 333.1514.

Preparation of 5,14-Bis[2-(N,N-dimethylamino)ethyl]-indolo[2,3-c]quinolino[4,3-a]carbazole (17a) (n = 1)

According to General Procedure: Starting from 14 (80 mg, 0.22 mmol) reacted with NaH 60% (53 mg, 1.32 mmol), 2-chloroethyldimethylamine hydrochloride (series a (n = 1)) (194 mg, 1.32 mmol), Na2CO3 (190 mg, 1.79 mmol), TBAI (8 mg, 0.022 mmol) in DMF (10 mL); Heating: 90°C for 3 h; Extraction: sat. aq. K2CO3 (10 mL) and ethyl acetate (10 mL × 3); Purification (eluent: CH2Cl2/CH3OH: 93/7→ CH2Cl2/CH3OH: 90/10) gave the amorphous yellow solid 17a (n = 1) (46 mg, 41%). νmax (KBr)/cm-1 2919, 2763, 1581, 1456, 1446, 1373, 1325 and 1134; δH(300 MHz; DMSO-d6) 1.49 (6 H, s, N(Me)2), 1.51–1.69 (2 H, m, 2'-CH2), 2.36 (6 H, s, N(Me)2), 2.97 (2 H, t, J 7.1, 2"-CH2), 4.68–4.83 (2 H, m, 1'-CH2), 5.11 (2 H, t, J 7.1, 1''-CH2), 7.53 (1 H, t, J 8.0, 11-H), 7.56 (1 H, t, J 8.0, 8-H), 7.69 (1 H, t, J 8.0, 12-H), 7.71 (1 H, t, J 8.0, 7-H), 7.79–7.92 (2 H, m, 3-H and 2-H), 7.98 (2 H, d, J 8.0, 13-H), 8.09 (1 H, d, J 8.0, 6-H), 8.26 (1 H, dd, J 1.4 and 7.4, 1-H), 8.77 (1 H, dd, J 1.4 and 7.4, 4-H), 8.97 (1 H, d, J 8.0, 10-H), 9.03 (1 H, d, J 8.0, 9-H) and 10.29 (1 H, s, 15-H); δC(75 MHz; DMSO-d6) 44.8 (N(Me)2), 45.6 (1"-CH2), 45.9 (N(Me)2), 46.2 (1'-CH2), 55.7 (2'-CH2), 57.7 (2"-CH2), 110.6 (13-CH), 113.0 (14b-C), 113.5 (6-CH), 116.2 (9c-C), 119.7 (4b-C), 120.3 (11-CH), 121.2 (8-CH), 121.5 (9d-C), 122.0 (4a-C), 122.5 (9b-C), 122.9 (10-CH), 123.8 (9-CH), 124.4 (9a-C), 125.8 (12-CH), 126.3 (3-CH), 126.7 (7-CH), 127.4 (4-CH), 128.5 (1-CH and 2-CH), 132.0 (14a-C), 132.4 (4c-C), 141.5 (13a-C), 143.4 (16a-C), 145.5 (5a-C) and 147.6 (15-CH); m/z (ESI+) 500 (M + H)+; m/z (EI) 500 (M+ + 1, 67%), 499 (M+ 100%), 285 (57), 284 (55), 267 (96), 236 (85); HRMS calcd. for C33H33N5 499.2736, found 499.2721.

Biological evaluations In vitro kinase assays Buffers Buffer A: 10 mM MgCl2, 1 mM EGTA, 1 mM DTT, 25 mM Tris–HCl pH 7.5, 50 μg heparin/mL. Buffer C: 60 mM β-glycerophosphate, 30 mM p-nitrophenylphosphate, 25 mM Mops (pH 7.2), 5 mM EGTA, 15 mM MgCl2, 1 mM DTT, 0.1 mM sodium vanadate, 1 mM phenylphosphate. Kinase preparations and assays Kinase activities were assayed in Buffer A or C, at 30°C, at a final ATP concentration of 15 μM. Blank values were subtracted and activities expressed in % of the maximal activity, i.e. in the absence of inhibitors. Controls were performed with appropriate dilutions of DMSO. CDK-5/p25 (human, recombinant) was prepared as previously described.10a,58 Its kinase activity was assayed in buffer C, with 1 mg histone H1 /mL, in the presence of 15 μM [γ-33P] ATP (3,000 Ci/mmol; 10 mCi/mL) in a final volume of 30 μL. After 30 min incubation at 30°C, 25 μL aliquots of supernatant were spotted onto 2.5 × 3 cm pieces of Whatman P81 phosphocellulose paper, and, 20 s later, the filters were washed five times (for at least 5 min each time) in a solution of 10 mL phosphoric acid/liter of water. The wet filters were counted in the presence of 1 mL ACS (Amersham) scintillation fluid. GSK-3αβ (porcine brain, native) was assayed, as described for CDK-5/p25 but in Buffer A and using a GSK-3β specific substrate (GS-1: YRRAAVPPSPSLSRHSSPHQSpEDEEE) (Sp stands for phosphorylated serine).59 GS-1 was synthesized by Millegen (Labege, France). DYRK-1A (rat, recombinant, expressed in Escherichia coli as a GST fusion protein) was purified by affinity chromatography on glutathione–agarose and assayed as described for CDK-5/p25 using myelin basic peptide Woodtide (KKISGRLSPIMTEQ) (1 mg/mL) as a substrate.


Compound 13 DYRK1A IC50 = 20 µM; CDK5 IC50 = 0,93 µM;

GSK3 IC50 = 1,2 µM

0

50

100

0,01 0,1 1 10 100

Concentration (µM)

Kin

ase

activ

ity (%

of a

vera

ge m

axim

al a

ctiv

ity)

Figure 5. Kinase inhibition of 13.

FRET melting experiments Compounds (16b, 17a, 17b, 18) were evaluated for their ability to bind and stabilize a telomeric G-quadruplex structure by a fluorescence resonance energy transfer (FRET) assay using the 21-mer d[(GGGTTA)3GGG] oligonucleotide end-labeled with a fluorescent donor–acceptor pair (F21D), alone or in the presence of tested compounds (5, 10 and 20 μM). FRET experiments were performed on a Light Cycler real-time PCR instrument (Roche, Basel, Switzerland) as described previously60 in a buffer containing 0.2 μM F21D, 10 mM cacodylate, (pH = 8.0), 0.1 M LiCl, and 5 mM KCl. Excitation wavelength was 470 nm, and emission of fluorescein was recorded at 530 nm. The resulting ΔTm values provide an indication of the stability of a ligand–quadruplex complex.

Compounds Conc.[µM] Tm [°C] ΔTm [°C]

DMSO - 60.18 0.00

BRACO-19 5 87.92 27.74

5 64.22 4.04

10 68.45 8.27 18

20 70.93 10.75


Figure 6. Stabilisation (ΔTm for the F21D telomeric G-quadruplex at 0.2 μM) for compound 18 (5, 10 and 20 μM).

DNA binding measurements Calf thymus DNA (CT-DNA, Pharmacia) was deproteinised with sodium dodecyl sulfate (protein content <0.2%) and extensively dialysed against 1 mM sodium cacodylate buffered solution pH 7.0. The concentrations of DNA were determined from their molar extinction coefficients of 6600 M-1cm-1. Synthesized compounds, as well as camptothecin and etoposide (Sigma), were dissolved as 10 mM solutions in DMSO. Further dilutions were made in the appropriate aqueous buffer.

Figure 7. DNA and compounds interactions:

A Absorption and B CD DNA titration of compounds 11, 14, 17a, 17b and 18 in BPE buffer for absorption and cacodylate buffer for CD DNA titration. Aliquots of a concentrated calf thymus DNA solution (CT-DNA) were added to 1 ml of a drug solution (20 µM for the

absorbance and 50 µM for the CD measurements). The drug/DNA ratios increased from 0 to 1 only for compounds17a, 17b and 18

Fluorescence spectrometry and apparent binding studies Fluorescence titration data were recorded at room temperature using SPEX fluorometer Fluorolog. Excitation was at 380 nm and fluorescence emission was monitored over the range 380 to 520 nm. Samples used for titration experiments were prepared separately at a constant drug concentration of 1 µM, and DNA concentrations ranging from 0.001 to 1 mM. Fluorescence titration data were fitted directly to get binding constants using a fitting function incorporated into Prism 3.0 (Graph Pad Prism software). Absorption spectrometry and melting temperature studies Absorption spectra and melting curves were measured using an Uvikon 943 spectrophotometer coupled to a Neslab RTE111 cryostat. Typically, 20 µM of the various drugs were prepared in 1mL of BPE buffer [6 mM Na2HPO4, 2 mM NaH2PO4, 1 mM EDTA, pH 7.1] in the presence or absence of 20 µM of base pairs of CT-DNA and transferred in a quartz cuve of 10 mm pathlength. The spectrum were recorded from 230 nm to 500 nm and are referenced against a


cuve containing the same DNA concentration in the same buffer. To perform the melting temperature measurement, 20 µM of CT-DNA or poly(dAdT)2 were incubated alone (control Tm) or with increasing concentration of the tested compounds in 1 mL of BPE buffer thus resulting in a drug/base pair ratio of 0.05, 0.1, 0.25, 0.5. The samples were transferred in quartz cells and the absorbance at 260 nm was measured every min over the range of 20 to 100°C with an increment of 1°C per min using the Uvikon 943 spectrophotometer thermostated with a Neslab RTE111 cryostat. The Tm values were obtained from first-derived plots. Topoisomerases inhibition The experimental procedure has been previously detailed.61 Supercoiled Puc 19 plasmid DNA (130 ng) was incubated with 4 units of human topoisomerase I (TopoGen) at 37°C for 45 min in 20 µL of relaxation buffer (50 mM tris(hydroxymethyl) aminomethane (pH 7.8), 50 mM KCl, 10 mM MgCl2, 1 mM dithiothreitol, 1 mM EDTA and 1 mM ATP) in the presence of graded concentrations (from 0.5 to 20 µM) of the tested compounds. The reactions were terminated by addition of SDS to 0.25% and proteinase K to 250 µg/mL and incubation at 50°C for a further 30 min. 3 µL of the electrophoresis dye mixture were then added to DNA samples which were then separated by electrophoresis in a 1% agarose gel containing (topoisomerase DNA cleavage gel) or not (inhibition of the relaxation of DNA) ethidium bromide (1 µg/mL) at room temperature for 2 h at 120 V. Gels run without ethidium bromide were then stained using a bath containing ethidium bromide. Both gels were finally washed and photographed under UV light.

Figure 8. Inhibition of the topoisomerase I activity.

A: Effects of novel derivatives on the relaxation of plasmid DNA by human topoisomerase I. Native supercoiled pLAZ (130 ng, lane DNA) was incubated with 4 units topo1 in the absence (lane Topo I) or presence of tested compounds 17a, 17b and 18 at the indicated concentration (1 to 20 µM). Camptothecin (CPT) and rebeccamycin (Reb) were used at 20 µM. A DNA samples were separated by electrophoresis on a 1% agarose gel which was stained with ethidium bromide after DNA migration.

B: DNA samples were separated by electrophoresis on an 1% agarose gel containing 1 µg/mL ethidium bromide. Gels were photographed under UV light.

Nck, nicked; Sc, supercoiled; Rel, relaxed; topo, topoisomer products


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48 C. Lee, W. Yang and R. G. Parr, Phys. Rev. B: Condens. Matter Mater. Phys., 1988, 37, 785–789. 49 B. Miehlich, A. Savin, H. Stoll and H. Preuss, Chem. Phys. Lett., 1989, 157, 200–206. 50 S. H. Vosko, L. Wilk and M. Nusair, Can. J. Phys., 1980, 58, 1200–1211. 51 A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652. 52 D. Leroux, ChemBioChem, 2004, 5, 644–649. 53 S. Miertus, E. Scrocco and J. Tomasi, Chem. Phys., 1981, 55, 117–129. 54 M. Cossi, G. Scalmani, N. Rega and V. J. Barone, Chem. Phys., 2002, 117, 43–54. 55 R. Cammi, B. Mennucci and J. Tomasi, J. Phys. Chem. A, 2000, 104, 5631–5637. 56 R. Ditchfield, Mol. Phys., 1974, 27, 789–807. 57 K. Wolinski, J. F. Hilton and P. Pulay, J. Am. Chem. Soc., 1990, 112, 8251–8260. 58 S. Bach, M. Knockaert, O. Lozach, J. Reinhardt, B. Baratte, S. Schmidt, S. P. Coburn, L. Tang, T. Jiang, D. C. Liang, H. Galons,

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60 B. Brassart, D. Gomez, A. De Cian, R. Paterski, A. Montagnac, K. H. Qui, N. Temime-Smaali, C. Trentesaux, J.-L. Mergny, F. Guéritte and J.-F. Riou, Mol. Pharmacol., 2007, 72, 631–640.

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Copies of NMR spectra of 6b-c, 8a-c, 10, 11, 12, 13, 14, 16b, 17a-b, 18


8a A computational data (toluene PCM), B3LYP/6-31G** Energy: -1655.80002935 a.u. ZPE corrected Energy: -1655.385430 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z -------------------------------------------------------------------------------- 1 6 0 1.034499 -0.322968 -0.055007 2 6 0 0.974256 1.079864 -0.235172 3 6 0 -0.309147 1.668511 -0.179687 4 6 0 -1.507239 0.926517 0.040525 5 6 0 -1.411908 -0.457401 0.217730 6 6 0 -0.144926 -1.049169 0.163977 7 6 0 2.117830 1.990210 -0.478026 8 7 0 -0.637267 2.989867 -0.337188 9 6 0 -2.596244 -1.303210 0.546947 10 1 0 -0.065405 -2.120977 0.310787 11 6 0 -3.097853 -2.335173 -0.265399 12 6 0 -4.144282 -3.164433 0.141484 13 6 0 -4.737294 -2.962130 1.382520 14 6 0 -4.267208 -1.941866 2.211589 15 6 0 -3.208742 -1.134801 1.798956 16 7 0 -2.559637 -2.579435 -1.617946 17 1 0 -4.477580 -3.947696 -0.527637 18 1 0 -5.558924 -3.596323 1.698690 19 1 0 -4.717581 -1.779061 3.185869 20 1 0 -2.829173 -0.358394 2.454909 21 8 0 -2.674435 -3.719251 -2.071836 22 8 0 -2.049202 -1.637329 -2.219318 23 6 0 2.267873 -1.165449 -0.187318 24 6 0 2.349480 -1.994765 -1.316284 25 6 0 3.421842 -2.863426 -1.516784 26 6 0 4.456455 -2.926720 -0.583843 27 6 0 4.409525 -2.112482 0.543241 28 6 0 3.325163 -1.257314 0.733475 29 1 0 1.547780 -1.945064 -2.045998 30 1 0 3.444917 -3.489986 -2.403120 31 1 0 5.292466 -3.603177 -0.728242 32 1 0 5.196261 -2.125919 1.286842 33 7 0 3.347183 -0.435190 1.953187 34 8 0 3.322469 1.394482 -0.480076 35 8 0 1.995346 3.197189 -0.662032 36 6 0 4.463644 2.266617 -0.690044 37 6 0 5.714527 1.418029 -0.576846 38 1 0 4.365081 2.736137 -1.673433 39 1 0 4.435056 3.061016 0.060926

40 1 0 6.597161 2.048743 -0.721621 41 1 0 5.777809 0.952087 0.409865 42 1 0 5.726102 0.631056 -1.336157 43 6 0 -2.008316 3.150826 -0.243518 44 6 0 -2.766742 4.317763 -0.355295 45 6 0 -4.148665 4.202061 -0.237170 46 6 0 -4.758576 2.955039 -0.016371 47 6 0 -3.997409 1.795563 0.097074 48 6 0 -2.601654 1.881651 -0.010115 49 1 0 -2.294127 5.278955 -0.531993 50 1 0 -4.765621 5.091796 -0.320769 51 1 0 -5.839533 2.896211 0.064525 52 1 0 -4.482468 0.840554 0.263474 53 1 0 0.074321 3.685233 -0.519299 54 8 0 2.277558 -0.035558 2.406544 55 8 0 4.446787 -0.205776 2.464489 ---------------------------------------------------------------------


8a S computational data (toluene PCM), B3LYP/6-31G** Energy: - 1655.79659575 a.u. ZPE corrected Energy: -1655.382423 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------ 1 6 0 1.213482 -0.262408 -0.416342 2 6 0 1.045065 1.133304 -0.286756 3 6 0 -0.282969 1.609313 -0.247394 4 6 0 -1.424558 0.759333 -0.335306 5 6 0 -1.223197 -0.621217 -0.447882 6 6 0 0.091865 -1.099641 -0.508313 7 6 0 2.130818 2.131810 -0.158855 8 7 0 -0.709616 2.907475 -0.144904 9 6 0 -2.346350 -1.592390 -0.611457 10 1 0 0.250926 -2.167925 -0.609502 11 6 0 -3.265114 -1.954506 0.389457 12 6 0 -4.314853 -2.842051 0.152408 13 6 0 -4.459419 -3.417729 -1.105638 14 6 0 -3.557980 -3.089584 -2.118423 15 6 0 -2.525192 -2.186512 -1.870524 16 7 0 -3.149051 -1.432794 1.766017 17 1 0 -4.994007 -3.070372 0.964140 18 1 0 -5.267527 -4.117924 -1.289949 19 1 0 -3.660594 -3.530191 -3.105317 20 1 0 -1.839377 -1.915336 -2.666471 21 8 0 -4.178416 -1.399216 2.442285 22 8 0 -2.038969 -1.089263 2.160602 23 6 0 2.539858 -0.944258 -0.582703 24 6 0 2.996169 -1.171175 -1.889533 25 6 0 4.165916 -1.883410 -2.147585 26 6 0 4.908669 -2.416910 -1.093221 27 6 0 4.469641 -2.232172 0.212840 28 6 0 3.306835 -1.499111 0.454756 29 1 0 2.412090 -0.773094 -2.712986 30 1 0 4.491097 -2.028377 -3.173392 31 1 0 5.817960 -2.977270 -1.284552 32 1 0 5.007353 -2.643554 1.057668 33 7 0 2.932962 -1.317400 1.868784 34 8 0 3.369668 1.612906 -0.167585 35 8 0 1.933387 3.338639 -0.057946 36 6 0 4.457775 2.558361 -0.030371 37 6 0 5.750786 1.766951 -0.048033 38 1 0 4.402777 3.278493 -0.852504 39 1 0 4.324477 3.112201 0.903425

40 1 0 6.601722 2.449283 0.040103 41 1 0 5.788394 1.060383 0.785418 42 1 0 5.852999 1.204755 -0.980336 43 6 0 -2.092412 2.952060 -0.168000 44 6 0 -2.937802 4.060876 -0.099035 45 6 0 -4.308999 3.830690 -0.160030

46 6 0 -4.823778 2.529250 -0.288708 47 6 0 -3.976539 1.427384 -0.355003 48 6 0 -2.589682 1.626866 -0.290924 49 1 0 -2.538074 5.065553 -0.002483 50 1 0 -4.992271 4.673099 -0.107834 51 1 0 -5.898168 2.381658 -0.334570 52 1 0 -4.392123 0.431040 -0.454385 53 1 0 -0.049699 3.669244 -0.060680 54 8 0 2.230565 -0.354196 2.164131 55 8 0 3.367986 -2.139041 2.678312 ---------------------------------------------------------------------


8a A* computational data (toluene PCM), B3LYP/6-31G** Energy: - 1655.79568188 a.u. ZPE corrected Energy: -1655.381605 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z -------------------------------------------------------------------------------- 1 6 0 1.132964 -0.642720 -0.082392 2 6 0 1.223316 0.765009 -0.190704 3 6 0 0.014588 1.488249 -0.088854 4 6 0 -1.251543 0.857648 0.105979 5 6 0 -1.304997 -0.536451 0.204503 6 6 0 -0.111250 -1.257666 0.104389 7 6 0 2.540172 1.416745 -0.383240 8 7 0 -0.192683 2.845088 -0.164306 9 6 0 -2.573074 -1.265405 0.504375 10 1 0 -0.143602 -2.338629 0.188702 11 6 0 -3.230795 -2.135611 -0.381938 12 6 0 -4.359588 -2.867565 -0.009779 13 6 0 -4.876112 -2.726805 1.273215 14 6 0 -4.249220 -1.866935 2.177102 15 6 0 -3.112211 -1.156986 1.796063 16 7 0 -2.773520 -2.300967 -1.775507 17 1 0 -4.813865 -3.528543 -0.737058 18 1 0 -5.760034 -3.284769 1.564127 19 1 0 -4.639244 -1.754679 3.184008 20 1 0 -2.613246 -0.506894 2.507158 21 8 0 -3.066250 -3.354742 -2.342949 22 8 0 -2.148441 -1.379419 -2.294705 23 6 0 2.288833 -1.581279 -0.268497 24 6 0 2.331714 -2.289881 -1.477959 25 6 0 3.323103 -3.233621 -1.744493 26 6 0 4.308352 -3.500332 -0.795143 27 6 0 4.290961 -2.817914 0.416691 28 6 0 3.290712 -1.881205 0.671574 29 1 0 1.566973 -2.082995 -2.219596 30 1 0 3.320988 -3.758976 -2.694706 31 1 0 5.083067 -4.234278 -0.991494 32 1 0 5.039065 -2.994194 1.178512 33 7 0 3.338525 -1.212401 1.982676 34 8 0 2.453354 2.775037 -0.499071 35 8 0 3.611584 0.845979 -0.441987 36 6 0 3.715164 3.465950 -0.674052 37 6 0 3.417680 4.949994 -0.765602 38 1 0 4.364469 3.226798 0.172784

39 1 0 4.198728 3.086156 -1.578526 40 1 0 4.350677 5.505456 -0.899998 41 1 0 2.766639 5.170754 -1.616982 42 1 0 2.936744 5.313113 0.147804 43 6 0 -1.540985 3.131192 -0.037977 44 6 0 -2.183716 4.370156 -0.066274 45 6 0 -3.568905 4.380157 0.070423 46 6 0 -4.292836 3.185850 0.227982 47 6 0 -3.645259 1.954263 0.257784 48 6 0 -2.249283 1.913682 0.129840 49 1 0 -1.623839 5.291679 -0.193625 50 1 0 -4.098155 5.328157 0.051566 51 1 0 -5.373237 3.225515 0.325771 52 1 0 -4.217168 1.041244 0.376483 53 1 0 0.559164 3.499896 -0.307380 54 8 0 2.353590 -0.571787 2.348277 55 8 0 4.361529 -1.344811 2.655974 ---------------------------------------------------------------------


8a S* computational data (toluene PCM), B3LYP/6-31G** Energy: - 1655.79337846 a.u. ZPE corrected Energy: -1655.379427 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.312723 -0.579774 -0.436078 2 6 0 1.254417 0.828264 -0.349390 3 6 0 -0.030291 1.409718 -0.302006 4 6 0 -1.231456 0.639191 -0.353602 5 6 0 -1.138213 -0.755510 -0.428663 6 6 0 0.133868 -1.335288 -0.488390 7 6 0 2.508621 1.615890 -0.291694 8 7 0 -0.376723 2.738072 -0.234159 9 6 0 -2.335343 -1.640549 -0.555088 10 1 0 0.212444 -2.415049 -0.555212 11 6 0 -3.254056 -1.926677 0.470303 12 6 0 -4.369088 -2.740061 0.266868 13 6 0 -4.583675 -3.315338 -0.981251 14 6 0 -3.685865 -3.060452 -2.018167 15 6 0 -2.586055 -2.231141 -1.803475 16 7 0 -3.071781 -1.397231 1.836844 17 1 0 -5.043403 -2.911453 1.096377 18 1 0 -5.443254 -3.958285 -1.139434 19 1 0 -3.842723 -3.501364 -2.997767 20 1 0 -1.901109 -2.017573 -2.617479 21 8 0 -4.078265 -1.302051 2.541238 22 8 0 -1.934949 -1.106387 2.196098 23 6 0 2.589904 -1.352858 -0.593029 24 6 0 2.950650 -1.732274 -1.894438 25 6 0 4.064957 -2.528717 -2.148305 26 6 0 4.847903 -2.994599 -1.091840 27 6 0 4.501914 -2.659840 0.211729 28 6 0 3.391113 -1.849282 0.449644 29 1 0 2.338424 -1.380900 -2.718614 30 1 0 4.317173 -2.788127 -3.172112 31 1 0 5.717346 -3.616320 -1.278661 32 1 0 5.073936 -3.012275 1.060220 33 7 0 3.109788 -1.527808 1.859077 34 8 0 2.291034 2.954149 -0.127326 35 8 0 3.631748 1.162169 -0.382553 36 6 0 3.484271 3.771272 -0.040326 37 6 0 3.044463 5.209680 0.151555 38 1 0 4.091858 3.411975 0.794912

39 1 0 4.068419 3.637157 -0.955350 40 1 0 3.923444 5.856668 0.228899 41 1 0 2.443540 5.556423 -0.694906 42 1 0 2.458349 5.323399 1.068396 43 6 0 -1.753843 2.873568 -0.242886 44 6 0 -2.522447 4.037914 -0.195256 45 6 0 -3.906571 3.898120 -0.235634 46 6 0 -4.506746 2.630546 -0.323777 47 6 0 -3.734576 1.473680 -0.368491 48 6 0 -2.336791 1.582324 -0.323278 49 1 0 -2.056798 5.016621 -0.130558 50 1 0 -4.532022 4.785039 -0.199459 51 1 0 -5.588928 2.552827 -0.355273 52 1 0 -4.216704 0.505218 -0.437444 53 1 0 0.308389 3.472830 -0.160567 54 8 0 2.380569 -0.570055 2.105776 55 8 0 3.632851 -2.239686 2.719454 ---------------------------------------------------------------------


TS1 computational data (toluene PCM), B3LYP/6-31G** Energy: -1655.78500157 a.u. ZPE corrected Energy: -1655.371505 a.u. Imaginary frequency: 67i ----------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ----------------------------------------------------------------------- 1 6 0 -2.300019 2.024403 -0.151841 2 6 0 -1.342909 0.933247 -0.066940 3 6 0 -0.077099 1.479264 -0.414844 4 7 0 -0.232107 2.826461 -0.678334 5 6 0 -1.564455 3.177723 -0.535781 6 6 0 -1.426215 -0.438130 0.229670 7 6 0 -0.262159 -1.205433 0.162928 8 6 0 0.983164 -0.654056 -0.182960 9 6 0 1.088036 0.710497 -0.481047 10 6 0 -3.685616 2.139520 0.034622 11 6 0 -4.296186 3.375836 -0.151299 12 6 0 -3.545666 4.504508 -0.523154 13 6 0 -2.170766 4.421541 -0.721400 14 6 0 2.159816 -1.565225 -0.320026 15 6 0 2.158337 -2.481471 -1.383278 16 6 0 3.232496 -3.338644 -1.614905 17 6 0 4.358947 -3.290022 -0.792629 18 6 0 4.396036 -2.389482 0.266210 19 6 0 3.301709 -1.555503 0.500710 20 6 0 2.384145 1.334780 -0.923348 21 8 0 2.775923 1.376673 -2.069966 22 6 0 -2.693276 -1.072064 0.698933 23 6 0 -3.391521 -2.078059 0.008790 24 6 0 -4.512845 -2.713376 0.544926 25 6 0 -4.985407 -2.331111 1.795186 26 6 0 -4.320548 -1.328964 2.504679 27 6 0 -3.189032 -0.720685 1.964862 28 7 0 -2.990924 -2.499852 -1.347808 29 8 0 -2.430780 -1.679142 -2.069721 30 7 0 3.384888 -0.697440 1.697483 31 8 0 4.511454 -0.344153 2.057824 32 8 0 3.047489 1.862158 0.122988 33 6 0 4.343348 2.456403 -0.161480 34 6 0 4.876094 3.015160 1.142699 35 8 0 -3.266907 -3.653855 -1.681560 36 8 0 2.344467 -0.413897 2.281040 37 1 0 -0.309601 -2.261778 0.406520 38 1 0 -4.997009 -3.489922 -0.033867 39 1 0 -5.864177 -2.812613 2.211391 40 1 0 -4.675519 -1.027495 3.485379 41 1 0 -2.658434 0.038754 2.529701 42 1 0 1.296452 -2.497134 -2.042412 43 1 0 3.192472 -4.036107 -2.445824 44 1 0 5.201877 -3.949762 -0.970361 45 1 0 5.249966 -2.325970 0.928955 46 1 0 4.993748 1.678984 -0.573218 47 1 0 4.215735 3.224976 -0.929970 48 1 0 5.866908 3.450540 0.979467 49 1 0 4.217069 3.796182 1.532761 50 1 0 4.959028 2.222307 1.889918 51 1 0 -1.590937 5.291711 -1.014175 52 1 0 -4.045861 5.458298 -0.661707 53 1 0 -5.368245 3.470609 -0.009682 54 1 0 -4.277990 1.277046 0.317342 55 1 0 0.497890 3.440970 -1.000133 ---------------------------------------------------------------------

TS2 computational data (toluene PCM), B3LYP/6-31G** Energy: -1655.78166394 a.u. ZPE corrected Energy: -1655.368281 a.u. Imaginary frequency: 60i ------------------------------------------------------------------------ Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------ 1 6 0 -2.398852 1.648269 -0.442929 2 6 0 -1.267218 0.736057 -0.449385 3 6 0 -0.098557 1.543319 -0.456555 4 7 0 -0.476033 2.871729 -0.433659 5 6 0 -1.857803 2.962281 -0.432492 6 6 0 -1.115408 -0.663381 -0.466814 7 6 0 0.174579 -1.189272 -0.533205 8 6 0 1.327712 -0.380119 -0.550289 9 6 0 1.195678 1.013630 -0.511640 10 6 0 -3.793776 1.496132 -0.464147 11 6 0 -4.601877 2.628336 -0.465575 12 6 0 -4.042029 3.917273 -0.447656 13 6 0 -2.663165 4.102458 -0.432015 14 6 0 2.664456 -1.029864 -0.694092 15 6 0 3.426930 -0.775146 -1.846163 16 6 0 4.636871 -1.426161 -2.082235 17 6 0 5.113255 -2.377372 -1.179720 18 6 0 4.379035 -2.659455 -0.032345 19 6 0 3.186128 -1.977625 0.205340 20 6 0 2.374988 1.945915 -0.544639 21 8 0 2.917240 2.340596 -1.557967 22 6 0 -2.270699 -1.608058 -0.517337 23 6 0 -3.214654 -1.804761 0.507059 24 6 0 -4.287711 -2.686270 0.374365 25 6 0 -4.432218 -3.426129 -0.794621 26 6 0 -3.506783 -3.265614 -1.826004 27 6 0 -2.452203 -2.364952 -1.686102 28 7 0 -3.104662 -1.106998 1.804318 29 8 0 -1.989723 -0.764388 2.183713 30 7 0 2.521727 -2.266020 1.491505 31 8 0 2.635513 -3.409750 1.937699 32 8 0 2.735309 2.324382 0.693523 33 6 0 3.876299 3.217936 0.783215 34 6 0 4.115890 3.499492 2.252990 35 8 0 -4.148212 -0.934645 2.437718 36 8 0 1.930705 -1.348358 2.051876 37 1 0 0.296530 -2.267169 -0.562707 38 1 0 -4.984260 -2.781365 1.197800 39 1 0 -5.258339 -4.122309 -0.895453 40 1 0 -3.608227 -3.834787 -2.744945 41 1 0 -1.748948 -2.223431 -2.500172 42 1 0 3.052879 -0.052426 -2.561971 43 1 0 5.199902 -1.197032 -2.981749 44 1 0 6.049711 -2.894044 -1.363179 45 1 0 4.715344 -3.388522 0.694452 46 1 0 4.734234 2.733288 0.307663 47 1 0 3.657100 4.127843 0.215515 48 1 0 4.975318 4.167499 2.365677 49 1 0 3.244595 3.978764 2.707804 50 1 0 4.322171 2.574709 2.798227 51 1 0 -2.228861 5.097668 -0.422118 52 1 0 -4.695106 4.784774 -0.447100 53 1 0 -5.681206 2.514797 -0.478781 54 1 0 -4.245776 0.511272 -0.480280 55 1 0 0.155837 3.655274 -0.458367 ---------------------------------------------------------------------


TS3 computational data (toluene PCM), B3LYP/6-31G** Energy: -1655.76758964 a.u. ZPE corrected Energy: -1655.352685 a.u. Imaginary frequency: 31i ------------------------------------------------------------------------ Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------ 1 6 0 -0.876486 -0.004996 0.429665 2 6 0 -0.655301 1.342003 0.079959 3 6 0 0.696969 1.734456 -0.024511 4 6 0 1.829216 0.869374 0.158946 5 6 0 1.552083 -0.530738 0.236262 6 6 0 0.212977 -0.875169 0.506702 7 6 0 -1.693582 2.377840 -0.132648 8 7 0 1.133326 3.010920 -0.252725 9 6 0 2.522193 -1.641506 -0.000849 10 1 0 -0.021495 -1.889845 0.786046 11 6 0 2.165111 -3.006125 -0.171967 12 6 0 3.099739 -4.036608 -0.243233 13 6 0 4.460664 -3.750329 -0.261042 14 6 0 4.853814 -2.415973 -0.240317 15 6 0 3.904356 -1.406149 -0.112020 16 7 0 0.790366 -3.486635 -0.444706 17 1 0 2.740032 -5.055821 -0.327848 18 1 0 5.187924 -4.552378 -0.329182 19 1 0 5.903143 -2.149083 -0.318294 20 1 0 4.246779 -0.389372 -0.128943 21 8 0 0.310892 -4.308357 0.338881 22 8 0 0.254402 -3.088340 -1.471801 23 6 0 -2.194955 -0.612594 0.806827 24 6 0 -2.393256 -0.909569 2.163054 25 6 0 -3.549385 -1.542422 2.618674 26 6 0 -4.552115 -1.899544 1.718389 27 6 0 -4.390250 -1.611090 0.367180 28 6 0 -3.225914 -0.983873 -0.072967 29 1 0 -1.616505 -0.632032 2.868139 30 1 0 -3.661564 -1.756955 3.677020 31 1 0 -5.452109 -2.399427 2.061035 32 1 0 -5.148793 -1.864508 -0.362145 33 7 0 -3.137602 -0.704977 -1.516455 34 8 0 -2.954975 1.927958 -0.039194 35 8 0 -1.446744 3.555883 -0.375175 36 6 0 -4.000860 2.909920 -0.264194 37 6 0 -5.332412 2.192844 -0.162703 38 1 0 -3.896543 3.704150 0.481019 39 1 0 -3.847382 3.357765 -1.250002 40 1 0 -6.143572 2.906329 -0.337999 41 1 0 -5.403708 1.396282 -0.907845 42 1 0 -5.468754 1.754935 0.830105 43 6 0 2.495754 3.075791 -0.092196 44 6 0 3.300517 4.216750 -0.132178 45 6 0 4.639670 4.079846 0.207291 46 6 0 5.141304 2.834430 0.616380 47 6 0 4.334416 1.701795 0.632101 48 6 0 2.989372 1.772820 0.209148 49 1 0 2.876608 5.181856 -0.391642 50 1 0 5.291335 4.948037 0.192369 51 1 0 6.172155 2.752457 0.946124 52 1 0 4.754226 0.790852 1.036255 53 1 0 0.470934 3.767296 -0.376407 54 8 0 -2.030585 -0.510286 -2.008192 55 8 0 -4.193890 -0.688459 -2.155658

------------------------------------------------------------

TS4 computational data (toluene PCM), B3LYP/6-31G** Energy: -1655.76270545 a.u. ZPE corrected Energy: -1655.348300 a.u. Imaginary frequency: 32i ----------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------ 1 6 0 -1.060882 -0.030055 0.503580 2 6 0 -0.694609 1.290563 0.186508 3 6 0 0.688508 1.538079 0.078340 4 6 0 1.711976 0.539940 0.237489 5 6 0 1.281994 -0.823396 0.279070 6 6 0 -0.084936 -1.024002 0.552897 7 6 0 -1.742118 2.325599 0.012121 8 7 0 1.284024 2.758198 -0.121329 9 6 0 2.119628 -2.026862 -0.006575 10 1 0 -0.433398 -2.011450 0.811648 11 6 0 1.605435 -3.334555 -0.220360 12 6 0 2.413489 -4.462724 -0.341905 13 6 0 3.797966 -4.334900 -0.369728 14 6 0 4.343020 -3.056283 -0.308197 15 6 0 3.518625 -1.948640 -0.130744 16 7 0 0.181636 -3.642398 -0.489248 17 1 0 1.937174 -5.429693 -0.457532 18 1 0 4.426851 -5.212306 -0.476890 19 1 0 5.415279 -2.909556 -0.392802 20 1 0 3.977577 -0.978585 -0.118624 21 8 0 -0.378053 -4.439842 0.265002 22 8 0 -0.319796 -3.136282 -1.486394 23 6 0 -2.453106 -0.460759 0.859866 24 6 0 -2.763779 -0.548379 2.224039 25 6 0 -3.993849 -1.028897 2.668732 26 6 0 -4.951140 -1.457534 1.749673 27 6 0 -4.665596 -1.401821 0.390478 28 6 0 -3.434208 -0.909197 -0.041502 29 1 0 -2.017159 -0.227197 2.943126 30 1 0 -4.199404 -1.072435 3.734021 31 1 0 -5.910908 -1.835997 2.085790 32 1 0 -5.377005 -1.733612 -0.354341 33 7 0 -3.223384 -0.860938 -1.499534 34 8 0 -1.247063 3.539097 -0.373229 35 8 0 -2.931549 2.152954 0.185229 36 6 0 -2.238523 4.574235 -0.590894 37 6 0 -1.506049 5.828822 -1.024757 38 1 0 -2.942582 4.224820 -1.351015 39 1 0 -2.799458 4.722686 0.336278 40 1 0 -2.227207 6.630638 -1.209414 41 1 0 -0.812692 6.171132 -0.250101 42 1 0 -0.944476 5.657652 -1.947833 43 6 0 2.644265 2.653406 0.040282 44 6 0 3.583066 3.687493 0.027749 45 6 0 4.893224 3.379732 0.369338 46 6 0 5.234896 2.073856 0.753629 47 6 0 4.294544 1.049135 0.740494 48 6 0 2.972189 1.294461 0.311700 49 1 0 3.284095 4.703506 -0.211512 50 1 0 5.646569 4.161376 0.375854 51 1 0 6.245347 1.858886 1.086482 52 1 0 4.594033 0.083993 1.125589 53 1 0 0.747604 3.601760 -0.250029 54 8 0 -2.268516 -0.217987 -1.930733 55 8 0 -4.028819 -1.462137 -2.211857

------------------------------------------------------------


8a A computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79952097 a.u. ZPE corrected Energy: -1655.384904 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z -------------------------------------------------------------------------------- 1 6 0 1.033566 -0.321357 -0.055216 2 6 0 0.973123 1.081432 -0.235138 3 6 0 -0.310428 1.669771 -0.180359 4 6 0 -1.508534 0.927521 0.039128 5 6 0 -1.412775 -0.456281 0.217159 6 6 0 -0.145670 -1.047734 0.163890 7 6 0 2.116655 1.992231 -0.476625 8 7 0 -0.638653 2.991002 -0.338152 9 6 0 -2.596705 -1.302379 0.546580 10 1 0 -0.065873 -2.119495 0.310877 11 6 0 -3.093943 -2.338843 -0.262612 12 6 0 -4.140100 -3.168157 0.144669 13 6 0 -4.737349 -2.961316 1.382928 14 6 0 -4.271549 -1.936617 2.208965 15 6 0 -3.213268 -1.129546 1.796070 16 7 0 -2.550564 -2.588921 -1.612314 17 1 0 -4.469520 -3.955111 -0.522058 18 1 0 -5.558809 -3.595658 1.699355 19 1 0 -4.724991 -1.770325 3.181257 20 1 0 -2.836856 -0.349688 2.449740 21 8 0 -2.659333 -3.732043 -2.059127 22 8 0 -2.042282 -1.648257 -2.217448 23 6 0 2.266675 -1.163980 -0.188914 24 6 0 2.347090 -1.992427 -1.318678 25 6 0 3.418762 -2.861633 -1.520311 26 6 0 4.453767 -2.926233 -0.587882 27 6 0 4.407961 -2.112832 0.539881 28 6 0 3.324250 -1.257182 0.731264 29 1 0 1.544907 -1.941820 -2.047810 30 1 0 3.440743 -3.487625 -2.407094 31 1 0 5.289298 -3.603155 -0.733125 32 1 0 5.194946 -2.127090 1.283218 33 7 0 3.347209 -0.436041 1.951904 34 8 0 3.321679 1.397074 -0.476695 35 8 0 1.993921 3.199039 -0.661021 36 6 0 4.462479 2.270520 -0.682891 37 6 0 5.713906 1.422851 -0.568531 38 1 0 4.365530 2.741627 -1.665690

39 1 0 4.431712 3.063585 0.069380 40 1 0 6.596245 2.054691 -0.710272 41 1 0 5.775548 0.955243 0.417478 42 1 0 5.727747 0.637239 -1.329264 43 6 0 -2.009696 3.151694 -0.245665 44 6 0 -2.768189 4.318490 -0.358440 45 6 0 -4.150202 4.202603 -0.242085 46 6 0 -4.760190 2.955478 -0.022124 47 6 0 -3.998974 1.796162 0.092403 48 6 0 -2.603085 1.882432 -0.012759 49 1 0 -2.295428 5.279662 -0.534776 50 1 0 -4.767202 5.092214 -0.326711 51 1 0 -5.841289 2.896415 0.056859 52 1 0 -4.484128 0.841005 0.257661 53 1 0 0.073002 3.686519 -0.519538 54 8 0 2.277873 -0.036775 2.405896 55 8 0 4.447267 -0.207607 2.462420 ---------------------------------------------------------------------


8a S computational data (gas-phase), B3LYP/6-31G** Energy: -1655.79557605 a.u. ZPE corrected Energy: -1655.381397 a.u. ------------------------------------------------------------------------------ Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------ 1 6 0 1.214406 -0.260144 -0.420679 2 6 0 1.044496 1.135434 -0.291686 3 6 0 -0.284087 1.610150 -0.253267 4 6 0 -1.424791 0.758689 -0.339679 5 6 0 -1.221771 -0.621759 -0.450105 6 6 0 0.093832 -1.098760 -0.511404 7 6 0 2.129004 2.134707 -0.160801 8 7 0 -0.712114 2.907759 -0.152000 9 6 0 -2.343550 -1.595149 -0.609391 10 1 0 0.254026 -2.167029 -0.611091 11 6 0 -3.261671 -1.953521 0.393287 12 6 0 -4.309428 -2.844466 0.161112 13 6 0 -4.452665 -3.427482 -1.093754 14 6 0 -3.551937 -3.102997 -2.108319 15 6 0 -2.521066 -2.196486 -1.865280 16 7 0 -3.147328 -1.423289 1.767266 17 1 0 -4.988217 -3.069078 0.974214 18 1 0 -5.259408 -4.130320 -1.274148 19 1 0 -3.653708 -3.549085 -3.092887 20 1 0 -1.835620 -1.928060 -2.662503 21 8 0 -4.178131 -1.384939 2.440631 22 8 0 -2.037478 -1.078528 2.160621 23 6 0 2.541667 -0.939692 -0.589011 24 6 0 3.002597 -1.155372 -1.896167 25 6 0 4.173564 -1.864902 -2.156030 26 6 0 4.912704 -2.407022 -1.103526 27 6 0 4.469125 -2.233106 0.202556 28 6 0 3.305401 -1.502400 0.446334 29 1 0 2.420993 -0.750610 -2.718156 30 1 0 4.502479 -2.001147 -3.181900 31 1 0 5.822791 -2.965697 -1.296224 32 1 0 5.003707 -2.651141 1.046137 33 7 0 2.927373 -1.330418 1.861046 34 8 0 3.368114 1.615639 -0.154756 35 8 0 1.931012 3.342037 -0.068570 36 6 0 4.454061 2.561898 -0.008393 37 6 0 5.747217 1.770433 -0.003497 38 1 0 4.410479 3.277300 -0.835384

39 1 0 4.308173 3.121166 0.920227 40 1 0 6.596944 2.453330 0.091990 41 1 0 5.773263 1.069317 0.834968 42 1 0 5.862058 1.202215 -0.930728 43 6 0 -2.095035 2.950666 -0.173479 44 6 0 -2.941519 4.058568 -0.104167 45 6 0 -4.312483 3.826779 -0.163265 46 6 0 -4.825949 2.524707 -0.290632 47 6 0 -3.977585 1.423801 -0.357348 48 6 0 -2.590873 1.624883 -0.295028 49 1 0 -2.542759 5.063649 -0.007993 50 1 0 -4.996690 4.668350 -0.110024 51 1 0 -5.900241 2.375827 -0.334275 52 1 0 -4.392269 0.426925 -0.454975 53 1 0 -0.053377 3.670500 -0.067590 54 8 0 2.225663 -0.368188 2.160167 55 8 0 3.359554 -2.158460 2.665140 ---------------------------------------------------------------------


8a A*computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79506589 a.u. ZPE corrected Energy: -1655.380977 a.u. ------------------------------------------------------------------------------ Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------ 1 6 0 1.130110 -0.646198 -0.084614 2 6 0 1.223207 0.761090 -0.196391 3 6 0 0.016253 1.487098 -0.094511 4 6 0 -1.251111 0.859802 0.102259 5 6 0 -1.307414 -0.533971 0.204112 6 6 0 -0.115310 -1.257894 0.104933 7 6 0 2.541039 1.409387 -0.393615 8 7 0 -0.188039 2.844347 -0.172689 9 6 0 -2.576568 -1.259651 0.506980 10 1 0 -0.149714 -2.338510 0.192624 11 6 0 -3.234706 -2.133242 -0.375535 12 6 0 -4.364460 -2.862178 -0.000672 13 6 0 -4.881560 -2.714729 1.281359 14 6 0 -4.254191 -1.851379 2.181609 15 6 0 -3.116192 -1.144516 1.797945 16 7 0 -2.776414 -2.306120 -1.768132 17 1 0 -4.818607 -3.526302 -0.725189 18 1 0 -5.766194 -3.270517 1.574382 19 1 0 -4.644420 -1.734084 3.187886 20 1 0 -2.616604 -0.491857 2.506249 21 8 0 -3.067433 -3.363757 -2.328955 22 8 0 -2.152481 -1.386582 -2.291946 23 6 0 2.283919 -1.587948 -0.266853 24 6 0 2.322305 -2.306384 -1.470642 25 6 0 3.312063 -3.253192 -1.732360 26 6 0 4.300093 -3.512755 -0.783952 27 6 0 4.287156 -2.820363 0.422324 28 6 0 3.288381 -1.881011 0.672611 29 1 0 1.555728 -2.104682 -2.211828 30 1 0 3.306456 -3.786276 -2.678250 31 1 0 5.073743 -4.248805 -0.976670 32 1 0 5.037593 -2.990676 1.183248 33 7 0 3.340680 -1.201581 1.978327 34 8 0 2.458925 2.769267 -0.497094 35 8 0 3.609721 0.835296 -0.465539 36 6 0 3.722729 3.455746 -0.673454 37 6 0 3.431821 4.942155 -0.746880 38 1 0 4.376680 3.204503 0.166234

39 1 0 4.198407 3.083532 -1.585265 40 1 0 4.366671 5.494646 -0.880853 41 1 0 2.776598 5.175428 -1.591759 42 1 0 2.958099 5.297171 0.173446 43 6 0 -1.535442 3.133746 -0.046040 44 6 0 -2.175483 4.374066 -0.076240 45 6 0 -3.560615 4.387506 0.060693 46 6 0 -4.287183 3.195118 0.220288 47 6 0 -3.642305 1.962138 0.252131 48 6 0 -2.246476 1.918116 0.124277 49 1 0 -1.613481 5.294054 -0.205452 50 1 0 -4.087764 5.336661 0.040144 51 1 0 -5.367535 3.237319 0.317694 52 1 0 -4.216238 1.050546 0.372038 53 1 0 0.565733 3.497216 -0.314339 54 8 0 2.354820 -0.562131 2.343767 55 8 0 4.367811 -1.324500 2.646586 ---------------------------------------------------------------------


8a S* computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79237598 a.u. ZPE corrected Energy: -1655.378428 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.310021 -0.589045 -0.442868 2 6 0 1.252488 0.819597 -0.369097 3 6 0 -0.031350 1.402204 -0.321675 4 6 0 -1.233437 0.632636 -0.364657 5 6 0 -1.141390 -0.762804 -0.427606 6 6 0 0.130253 -1.344007 -0.484618 7 6 0 2.507291 1.607553 -0.327599 8 7 0 -0.375943 2.731603 -0.263740 9 6 0 -2.338793 -1.649081 -0.540768 10 1 0 0.207883 -2.424553 -0.538614 11 6 0 -3.258665 -1.917023 0.488298 12 6 0 -4.373693 -2.733350 0.298093 13 6 0 -4.586987 -3.330642 -0.939934 14 6 0 -3.687973 -3.094253 -1.980170 15 6 0 -2.588321 -2.261439 -1.778951 16 7 0 -3.077804 -1.363561 1.845987 17 1 0 -5.048958 -2.889299 1.129913 18 1 0 -5.446595 -3.976089 -1.087655 19 1 0 -3.843903 -3.552250 -2.952103 20 1 0 -1.902448 -2.062002 -2.595776 21 8 0 -4.086872 -1.247600 2.543118 22 8 0 -1.940093 -1.075482 2.203858 23 6 0 2.586214 -1.365651 -0.590139 24 6 0 2.935337 -1.780215 -1.884052 25 6 0 4.047979 -2.582392 -2.126679 26 6 0 4.840596 -3.019522 -1.065221 27 6 0 4.505604 -2.650677 0.232063 28 6 0 3.397040 -1.833886 0.458171 29 1 0 2.315494 -1.450921 -2.711660 30 1 0 4.291468 -2.868545 -3.145498 31 1 0 5.708965 -3.645421 -1.242960 32 1 0 5.084546 -2.981105 1.084763 33 7 0 3.128684 -1.476412 1.861968 34 8 0 2.292585 2.942220 -0.133005 35 8 0 3.628023 1.156891 -0.454342 36 6 0 3.487272 3.757459 -0.051867 37 6 0 3.051670 5.190084 0.187446 38 1 0 4.113085 3.377075 0.760167

39 1 0 4.051208 3.647637 -0.982765 40 1 0 3.932194 5.835039 0.264641 41 1 0 2.433952 5.559662 -0.637095 42 1 0 2.483879 5.278261 1.118437 43 6 0 -1.752853 2.868472 -0.268359 44 6 0 -2.520035 4.033927 -0.225411 45 6 0 -3.904412 3.895578 -0.260560 46 6 0 -4.506315 2.628248 -0.339390 47 6 0 -3.735599 1.470280 -0.379315 48 6 0 -2.337566 1.577377 -0.338608 49 1 0 -2.052975 5.012400 -0.167582 50 1 0 -4.528782 4.783373 -0.227147 51 1 0 -5.588675 2.551533 -0.366455 52 1 0 -4.219230 0.502055 -0.440170 53 1 0 0.310104 3.465009 -0.185488 54 8 0 2.416817 -0.501171 2.090341 55 8 0 3.645535 -2.177337 2.734328 ---------------------------------------------------------------------


8a A' computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79944349 a.u. ZPE corrected Energy: -1655.384591 a.u. -------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z -------------------------------------------------------------------------------- 1 6 0 1.040736 -0.416823 -0.119328 2 6 0 1.033949 0.983902 -0.324831 3 6 0 -0.221206 1.627344 -0.246890 4 6 0 -1.443322 0.940231 0.015469 5 6 0 -1.401131 -0.443515 0.214107 6 6 0 -0.161624 -1.089257 0.140309 7 6 0 2.209928 1.836642 -0.615298 8 7 0 -0.497207 2.958719 -0.418768 9 6 0 -2.610517 -1.233714 0.587428 10 1 0 -0.122749 -2.160627 0.305476 11 6 0 -3.172127 -2.259068 -0.193103 12 6 0 -4.240344 -3.038453 0.253414 13 6 0 -4.795064 -2.789898 1.503774 14 6 0 -4.264943 -1.774557 2.302145 15 6 0 -3.185332 -1.018258 1.850111 16 7 0 -2.675636 -2.548986 -1.552798 17 1 0 -4.619970 -3.819922 -0.392760 18 1 0 -5.633461 -3.384696 1.851053 19 1 0 -4.684851 -1.576250 3.283463 20 1 0 -2.759138 -0.246522 2.482543 21 8 0 -2.839939 -3.693243 -1.979274 22 8 0 -2.148661 -1.637000 -2.185178 23 6 0 2.238221 -1.308897 -0.257412 24 6 0 2.273288 -2.155715 -1.375356 25 6 0 3.311347 -3.064553 -1.578933 26 6 0 4.358331 -3.149925 -0.661838 27 6 0 4.357304 -2.319548 0.454415 28 6 0 3.305183 -1.426199 0.650017 29 1 0 1.463354 -2.087465 -2.094434 30 1 0 3.298338 -3.704095 -2.456187 31 1 0 5.168772 -3.856095 -0.809966 32 1 0 5.154333 -2.349742 1.186474 33 7 0 3.369783 -0.595252 1.862622 34 8 0 3.377464 1.171572 -0.661789 35 8 0 2.138273 3.046875 -0.804800 36 6 0 4.575131 1.951353 -0.920526 37 6 0 5.124768 2.559944 0.359493 38 1 0 4.339086 2.717243 -1.662103

39 1 0 5.269779 1.227287 -1.351829 40 1 0 6.077676 3.057037 0.149231 41 1 0 4.432180 3.303208 0.761204 42 1 0 5.294858 1.787652 1.114533 43 6 0 -1.857376 3.179197 -0.293327 44 6 0 -2.568491 4.375465 -0.405146 45 6 0 -3.950566 4.320520 -0.250698 46 6 0 -4.606742 3.104137 0.005444 47 6 0 -3.892461 1.915172 0.118726 48 6 0 -2.497510 1.940169 -0.024153 49 1 0 -2.060486 5.312838 -0.609420 50 1 0 -4.531378 5.234330 -0.333612 51 1 0 -5.686856 3.092623 0.113642 52 1 0 -4.412615 0.983948 0.311706 53 1 0 0.237828 3.621272 -0.627657 54 8 0 2.322561 -0.136243 2.311809 55 8 0 4.480318 -0.417909 2.370877 ---------------------------------------------------------------------


8a S' computational data (gas-phase), B3LYP/6-31G** Energy: -1655.79638262 a.u. ZPE corrected Energy: -1655.381824 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------ 1 6 0 1.171249 -0.489572 -0.457489 2 6 0 1.089415 0.923403 -0.461684 3 6 0 -0.208427 1.481470 -0.427236 4 6 0 -1.401205 0.700831 -0.390039 5 6 0 -1.285576 -0.693290 -0.375835 6 6 0 -0.005075 -1.255466 -0.433987 7 6 0 2.226692 1.872178 -0.505586 8 7 0 -0.555247 2.806913 -0.448490 9 6 0 -2.470359 -1.602969 -0.405685 10 1 0 0.086252 -2.335992 -0.423202 11 6 0 -3.361246 -1.819311 0.660293 12 6 0 -4.470701 -2.657098 0.546966 13 6 0 -4.707080 -3.329285 -0.647738 14 6 0 -3.836469 -3.145856 -1.722231 15 6 0 -2.742563 -2.290603 -1.598658 16 7 0 -3.152236 -1.186220 1.978674 17 1 0 -5.123470 -2.770233 1.403324 18 1 0 -5.562435 -3.991090 -0.735608 19 1 0 -4.010893 -3.662208 -2.661234 20 1 0 -2.080548 -2.131494 -2.443544 21 8 0 -4.144616 -1.039491 2.693739 22 8 0 -2.008792 -0.868613 2.289984 23 6 0 2.436165 -1.286608 -0.583021 24 6 0 2.638906 -1.976826 -1.787722 25 6 0 3.750526 -2.792530 -1.996491 26 6 0 4.707623 -2.940819 -0.993825 27 6 0 4.542614 -2.263940 0.210414 28 6 0 3.419795 -1.461897 0.406309 29 1 0 1.903035 -1.855996 -2.575911 30 1 0 3.866324 -3.308860 -2.944646 31 1 0 5.574763 -3.575579 -1.143938 32 1 0 5.266460 -2.343799 1.011424 33 7 0 3.319352 -0.789007 1.712632 34 8 0 3.437442 1.287198 -0.499236 35 8 0 2.090114 3.090648 -0.551572 36 6 0 4.596156 2.163376 -0.517484 37 6 0 4.954030 2.637899 0.881747 38 1 0 4.388745 3.001350 -1.186134

39 1 0 5.385905 1.541855 -0.945206 40 1 0 5.884787 3.213907 0.845704 41 1 0 4.168080 3.281457 1.283410 42 1 0 5.096874 1.788393 1.554764 43 6 0 -1.932697 2.935346 -0.429622 44 6 0 -2.707621 4.096329 -0.447388 45 6 0 -4.091266 3.947618 -0.435536 46 6 0 -4.686357 2.674628 -0.408938 47 6 0 -3.908859 1.520771 -0.389852 48 6 0 -2.511202 1.638462 -0.396189 49 1 0 -2.245728 5.078473 -0.469666 50 1 0 -4.721204 4.832068 -0.447003 51 1 0 -5.768529 2.590786 -0.400374 52 1 0 -4.386611 0.547828 -0.369308 53 1 0 0.150198 3.530935 -0.479119 54 8 0 2.210786 -0.436845 2.102487 55 8 0 4.365830 -0.629277 2.347800 ---------------------------------------------------------------------


8a A'* computational data (gas-phase), B3LYP/6-31G** Energy: -1655.79489858 a.u. ZPE corrected Energy: -1655.380561 a.u. -------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.118566 -0.569793 -0.019966 2 6 0 1.184657 0.842415 -0.081298 3 6 0 -0.040537 1.539434 0.007910 4 6 0 -1.299455 0.879755 0.145111 5 6 0 -1.328356 -0.517469 0.200124 6 6 0 -0.118302 -1.212723 0.112753 7 6 0 2.492625 1.524586 -0.219637 8 7 0 -0.271755 2.893743 -0.031428 9 6 0 -2.588920 -1.279312 0.443623 10 1 0 -0.131907 -2.296131 0.164181 11 6 0 -3.197448 -2.145822 -0.480552 12 6 0 -4.319159 -2.911941 -0.159397 13 6 0 -4.878823 -2.810412 1.109120 14 6 0 -4.301755 -1.954872 2.049584 15 6 0 -3.170947 -1.210486 1.719381 16 7 0 -2.692996 -2.271371 -1.862227 17 1 0 -4.733784 -3.568133 -0.914203 18 1 0 -5.757365 -3.395494 1.360475 19 1 0 -4.725449 -1.873107 3.045789 20 1 0 -2.709895 -0.564553 2.459255 21 8 0 -2.940986 -3.320513 -2.458517 22 8 0 -2.075988 -1.323994 -2.342945 23 6 0 2.295781 -1.482289 -0.201137 24 6 0 2.377817 -2.163239 -1.424408 25 6 0 3.393170 -3.081571 -1.689857 26 6 0 4.363733 -3.349184 -0.725842 27 6 0 4.307894 -2.693318 0.499612 28 6 0 3.283781 -1.782715 0.753118 29 1 0 1.624794 -1.955050 -2.177612 30 1 0 3.421011 -3.586241 -2.650812 31 1 0 5.156943 -4.063405 -0.921178 32 1 0 5.043729 -2.870812 1.273103 33 7 0 3.289881 -1.142426 2.079400 34 8 0 2.378321 2.885835 -0.282599 35 8 0 3.574071 0.972361 -0.276019 36 6 0 3.619363 3.627677 -0.412659 37 6 0 4.056001 3.729585 -1.865216 38 1 0 4.380841 3.139194 0.197855

39 1 0 3.391009 4.609459 0.009279 40 1 0 4.951236 4.355869 -1.938049 41 1 0 4.295447 2.741107 -2.263069 42 1 0 3.271594 4.180240 -2.480489 43 6 0 -1.628298 3.151079 0.062390 44 6 0 -2.293675 4.378287 0.052293 45 6 0 -3.682344 4.358725 0.145659 46 6 0 -4.387569 3.146998 0.243172 47 6 0 -3.717514 1.927187 0.255520 48 6 0 -2.317759 1.916062 0.170669 49 1 0 -1.747871 5.313370 -0.029163 50 1 0 -4.228950 5.297006 0.139299 51 1 0 -5.471085 3.163653 0.307482 52 1 0 -4.275256 1.000637 0.327408 53 1 0 0.472535 3.564958 -0.132061 54 8 0 2.276107 -0.548572 2.445256 55 8 0 4.308644 -1.251623 2.762560 ---------------------------------------------------------------------


8a S'* computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79217818 a.u. ZPE corrected Energy: -1655.377981 a.u. -------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.291375 -0.535097 -0.379401 2 6 0 1.236958 0.866418 -0.217019 3 6 0 -0.046123 1.452009 -0.172890 4 6 0 -1.249358 0.693103 -0.298484 5 6 0 -1.160332 -0.696408 -0.444874 6 6 0 0.110707 -1.279251 -0.503052 7 6 0 2.492342 1.642417 -0.082336 8 7 0 -0.387263 2.776824 -0.043509 9 6 0 -2.355161 -1.570348 -0.643907 10 1 0 0.186109 -2.354504 -0.624167 11 6 0 -3.317317 -1.875724 0.334886 12 6 0 -4.426598 -2.677387 0.065757 13 6 0 -4.591246 -3.222225 -1.203562 14 6 0 -3.649439 -2.948380 -2.195526 15 6 0 -2.555939 -2.130380 -1.915383 16 7 0 -3.189081 -1.382125 1.721240 17 1 0 -5.135811 -2.864716 0.862162 18 1 0 -5.446451 -3.856488 -1.412580 19 1 0 -3.767027 -3.365280 -3.191050 20 1 0 -1.836536 -1.901084 -2.694678 21 8 0 -4.226675 -1.277948 2.377116 22 8 0 -2.064183 -1.129259 2.140752 23 6 0 2.568036 -1.307789 -0.542471 24 6 0 2.962885 -1.621742 -1.851489 25 6 0 4.078401 -2.413247 -2.115396 26 6 0 4.827640 -2.940449 -1.063374 27 6 0 4.447238 -2.671084 0.245835 28 6 0 3.336108 -1.864460 0.494461 29 1 0 2.376677 -1.222925 -2.673047 30 1 0 4.357826 -2.620950 -3.143976 31 1 0 5.697539 -3.559138 -1.258076 32 1 0 4.991881 -3.072470 1.090640 33 7 0 3.017016 -1.614742 1.910908 34 8 0 2.271205 2.968324 0.167830 35 8 0 3.614187 1.186598 -0.180360 36 6 0 3.452482 3.794631 0.333354 37 6 0 3.983424 4.281929 -1.005370 38 1 0 4.205482 3.217262 0.872540

39 1 0 3.115003 4.624229 0.959219 40 1 0 4.828339 4.959219 -0.842938 41 1 0 4.329873 3.440295 -1.609180 42 1 0 3.212335 4.824623 -1.560534 43 6 0 -1.762758 2.921932 -0.081477 44 6 0 -2.525867 4.087335 0.008643 45 6 0 -3.909124 3.959693 -0.076004 46 6 0 -4.513544 2.702934 -0.248465 47 6 0 -3.746882 1.544873 -0.335216 48 6 0 -2.350132 1.640866 -0.247076 49 1 0 -2.056482 5.057634 0.139401 50 1 0 -4.530490 4.847582 -0.007664 51 1 0 -5.594930 2.634252 -0.311611 52 1 0 -4.233125 0.585138 -0.467591 53 1 0 0.300665 3.499692 0.093968 54 8 0 2.298403 -0.657098 2.186794 55 8 0 3.500531 -2.382752 2.745081 ---------------------------------------------------------------------


8a A'' computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79876083 a.u. ZPE corrected Energy: -1655.384086 a.u. ------------------------------------------------------------------------------ Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------ 1 6 0 1.040742 -0.403131 0.021116 2 6 0 1.034784 1.006788 -0.122371 3 6 0 -0.227955 1.639627 -0.090664 4 6 0 -1.458785 0.936915 0.072612 5 6 0 -1.417770 -0.453315 0.218949 6 6 0 -0.171293 -1.088636 0.187778 7 6 0 2.217290 1.882042 -0.300277 8 7 0 -0.503154 2.975910 -0.221882 9 6 0 -2.639318 -1.264250 0.494395 10 1 0 -0.134931 -2.165519 0.312203 11 6 0 -3.136248 -2.278220 -0.343171 12 6 0 -4.221574 -3.078981 0.015893 13 6 0 -4.859495 -2.864752 1.232410 14 6 0 -4.395030 -1.861934 2.085574 15 6 0 -3.297916 -1.083915 1.721279 16 7 0 -2.549616 -2.533543 -1.673663 17 1 0 -4.548575 -3.849844 -0.670550 18 1 0 -5.711119 -3.476591 1.511156 19 1 0 -4.880016 -1.690529 3.041619 20 1 0 -2.923622 -0.321898 2.396822 21 8 0 -2.669151 -3.671186 -2.131511 22 8 0 -1.997009 -1.602021 -2.253692 23 6 0 2.242772 -1.291738 -0.097058 24 6 0 2.286678 -2.156209 -1.201774 25 6 0 3.331236 -3.061687 -1.388472 26 6 0 4.377543 -3.124173 -0.469321 27 6 0 4.370258 -2.272728 0.631725 28 6 0 3.310576 -1.386567 0.810986 29 1 0 1.479620 -2.103185 -1.925436 30 1 0 3.324186 -3.714998 -2.255554 31 1 0 5.193339 -3.826756 -0.604686 32 1 0 5.168737 -2.282189 1.363146 33 7 0 3.367791 -0.533324 2.008035 34 8 0 3.393564 1.232653 -0.271061 35 8 0 2.145097 3.097529 -0.451302 36 6 0 4.601685 2.030857 -0.370414 37 6 0 4.990044 2.263662 -1.821136 38 1 0 4.440213 2.973608 0.155762

39 1 0 5.347888 1.439270 0.163559 40 1 0 5.944980 2.797692 -1.865451 41 1 0 5.102874 1.314226 -2.352300 42 1 0 4.235477 2.867754 -2.330480 43 6 0 -1.869558 3.184939 -0.165919 44 6 0 -2.580953 4.381952 -0.268291 45 6 0 -3.969174 4.314844 -0.196321 46 6 0 -4.630935 3.085915 -0.030088 47 6 0 -3.916548 1.896272 0.074309 48 6 0 -2.515788 1.932956 0.013689 49 1 0 -2.068127 5.329179 -0.403285 50 1 0 -4.550263 5.228938 -0.273922 51 1 0 -5.715383 3.065240 0.014906 52 1 0 -4.441043 0.955802 0.198144 53 1 0 0.238237 3.650246 -0.358179 54 8 0 2.308289 -0.162978 2.507662 55 8 0 4.484306 -0.253117 2.450216 ---------------------------------------------------------------------


8a S'' computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79573349 a.u. ZPE corrected Energy: -1655.381191 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.174175 -0.493178 -0.323075 2 6 0 1.105067 0.919812 -0.245629 3 6 0 -0.187783 1.490930 -0.242015 4 6 0 -1.388789 0.725245 -0.312973 5 6 0 -1.287723 -0.668294 -0.376994 6 6 0 -0.011547 -1.242039 -0.402484 7 6 0 2.249537 1.858842 -0.176011 8 7 0 -0.520487 2.819586 -0.199249 9 6 0 -2.477723 -1.559260 -0.525489 10 1 0 0.067333 -2.322514 -0.449366 11 6 0 -3.426271 -1.831491 0.476005 12 6 0 -4.534895 -2.647638 0.250866 13 6 0 -4.712913 -3.239786 -0.995189 14 6 0 -3.784915 -2.999007 -2.008571 15 6 0 -2.691792 -2.166706 -1.772681 16 7 0 -3.283579 -1.284571 1.841018 17 1 0 -5.233368 -2.807368 1.062562 18 1 0 -5.568075 -3.884403 -1.169914 19 1 0 -3.913522 -3.452459 -2.986620 20 1 0 -1.984033 -1.962269 -2.569375 21 8 0 -4.310833 -1.178171 2.512591 22 8 0 -2.156993 -0.992888 2.229604 23 6 0 2.431039 -1.304850 -0.431668 24 6 0 2.640089 -2.006051 -1.629397 25 6 0 3.747141 -2.832303 -1.822020 26 6 0 4.695875 -2.977962 -0.811481 27 6 0 4.527673 -2.286195 0.384469 28 6 0 3.407545 -1.478446 0.564356 29 1 0 1.913903 -1.884355 -2.426329 30 1 0 3.866512 -3.357291 -2.764933 31 1 0 5.559759 -3.619901 -0.949379 32 1 0 5.247354 -2.360639 1.190143 33 7 0 3.302503 -0.792889 1.863225 34 8 0 3.452893 1.260754 -0.144112 35 8 0 2.125500 3.078891 -0.144075 36 6 0 4.619443 2.111968 0.002040 37 6 0 5.127702 2.584274 -1.350052 38 1 0 4.357940 2.953542 0.646163

39 1 0 5.343845 1.474663 0.512822 40 1 0 6.050251 3.158818 -1.216642 41 1 0 5.344278 1.734944 -2.004430 42 1 0 4.390330 3.227908 -1.835772 43 6 0 -1.895698 2.964301 -0.242990 44 6 0 -2.657514 4.134005 -0.229130 45 6 0 -4.041240 4.002430 -0.297967 46 6 0 -4.649177 2.737876 -0.380369 47 6 0 -3.884899 1.575161 -0.391823 48 6 0 -2.487715 1.675427 -0.318871 49 1 0 -2.185759 5.109725 -0.167004 50 1 0 -4.661185 4.893923 -0.287609 51 1 0 -5.731075 2.667590 -0.432761 52 1 0 -4.372339 0.608803 -0.455584 53 1 0 0.192342 3.534913 -0.144249 54 8 0 2.182371 -0.543221 2.297416 55 8 0 4.356850 -0.524228 2.444598 ----------------------------------


8a A''*computational data (gas-phase), B3LYP/6-31G**Energy: -1655.79504370 a.u. ZPE corrected Energy: -1655.380649 a.u. ------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.089619 -0.613332 -0.133521 2 6 0 1.179624 0.786200 -0.322684 3 6 0 -0.024334 1.518171 -0.226960 4 6 0 -1.286667 0.903949 0.034512 5 6 0 -1.340336 -0.482596 0.209479 6 6 0 -0.150765 -1.212106 0.118791 7 6 0 2.490955 1.421963 -0.590234 8 7 0 -0.230090 2.869531 -0.370439 9 6 0 -2.601390 -1.190812 0.579523 10 1 0 -0.182800 -2.286430 0.264872 11 6 0 -3.274093 -2.115429 -0.237640 12 6 0 -4.394294 -2.823230 0.200742 13 6 0 -4.887341 -2.601872 1.481675 14 6 0 -4.245264 -1.686296 2.317650 15 6 0 -3.116548 -1.001388 1.871721 16 7 0 -2.842747 -2.367701 -1.626799 17 1 0 -4.860199 -3.529251 -0.475068 18 1 0 -5.764694 -3.140973 1.823638 19 1 0 -4.616643 -1.510812 3.322596 20 1 0 -2.605511 -0.307343 2.530821 21 8 0 -3.138351 -3.457984 -2.118490 22 8 0 -2.235321 -1.477346 -2.216280 23 6 0 2.238162 -1.566335 -0.287710 24 6 0 2.240036 -2.366805 -1.439226 25 6 0 3.222407 -3.330433 -1.665365 26 6 0 4.240788 -3.523539 -0.733375 27 6 0 4.265906 -2.747450 0.420649 28 6 0 3.273622 -1.792989 0.636616 29 1 0 1.450657 -2.216710 -2.168669 30 1 0 3.187431 -3.928239 -2.571071 31 1 0 5.008952 -4.271902 -0.898638 32 1 0 5.041381 -2.863518 1.166599 33 7 0 3.367711 -1.023185 1.888356 34 8 0 2.402815 2.777078 -0.749472 35 8 0 3.553902 0.838062 -0.673082 36 6 0 3.653792 3.477330 -0.980422 37 6 0 4.365681 3.787092 0.326553 38 1 0 3.357734 4.388863 -1.505367

39 1 0 4.276518 2.867000 -1.636988 40 1 0 5.268748 4.372416 0.124313 41 1 0 3.723701 4.367408 0.995748 42 1 0 4.660149 2.864475 0.831115 43 6 0 -1.573447 3.167789 -0.224003 44 6 0 -2.212893 4.406320 -0.301534 45 6 0 -3.593976 4.429845 -0.129860 46 6 0 -4.317119 3.248782 0.109601 47 6 0 -3.672746 2.017634 0.188158 48 6 0 -2.280657 1.963948 0.027048 49 1 0 -1.653456 5.317061 -0.492545 50 1 0 -4.120694 5.377809 -0.185717 51 1 0 -5.394559 3.298240 0.232485 52 1 0 -4.244308 1.114766 0.369599 53 1 0 0.522132 3.512093 -0.559888 54 8 0 2.384704 -0.378679 2.252887 55 8 0 4.425877 -1.078871 2.516091 ----------------------------------------------------------------------------------


8a S''* computational data (gas-phase), B3LYP/6-31G** Energy: -1655.79241018 a.u. ZPE corrected Energy: -1655.378181 a.u. -------------------------------------------------------------------------------- Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z ------------------------------------------------------------------------------- 1 6 0 1.263490 -0.561260 -0.501855 2 6 0 1.202054 0.849029 -0.492851 3 6 0 -0.082158 1.429783 -0.439548 4 6 0 -1.282246 0.656079 -0.418140 5 6 0 -1.186475 -0.740485 -0.418356 6 6 0 0.085681 -1.320435 -0.479186 7 6 0 2.454051 1.642344 -0.521494 8 7 0 -0.429717 2.759480 -0.433207 9 6 0 -2.383557 -1.633653 -0.456390 10 1 0 0.166009 -2.402120 -0.482301 11 6 0 -3.273795 -1.852528 0.609651 12 6 0 -4.392539 -2.677035 0.490125 13 6 0 -4.639136 -3.333265 -0.711380 14 6 0 -3.769546 -3.147004 -1.786230 15 6 0 -2.666210 -2.304877 -1.656262 16 7 0 -3.055287 -1.235170 1.933763 17 1 0 -5.044260 -2.793000 1.346909 18 1 0 -5.501415 -3.985338 -0.804135 19 1 0 -3.951594 -3.651400 -2.730257 20 1 0 -2.004033 -2.144420 -2.500755 21 8 0 -4.045102 -1.081086 2.650722 22 8 0 -1.907380 -0.935984 2.247512 23 6 0 2.538237 -1.342178 -0.637522 24 6 0 2.844773 -1.847080 -1.910023 25 6 0 3.950884 -2.663728 -2.133495 26 6 0 4.779393 -3.026108 -1.071330 27 6 0 4.486854 -2.567729 0.207522 28 6 0 3.385692 -1.735509 0.412907 29 1 0 2.196478 -1.577103 -2.737263 30 1 0 4.160964 -3.019836 -3.137572 31 1 0 5.642743 -3.662964 -1.233890 32 1 0 5.094255 -2.839003 1.061381 33 7 0 3.166939 -1.280859 1.796716 34 8 0 2.235354 2.980191 -0.348211 35 8 0 3.568790 1.188485 -0.685354 36 6 0 3.417882 3.820246 -0.292515 37 6 0 3.997616 3.856473 1.112299 38 1 0 4.145212 3.444739 -1.014674

39 1 0 3.065784 4.804953 -0.609821 40 1 0 4.854137 4.538132 1.141257 41 1 0 3.254219 4.206491 1.834114 42 1 0 4.337204 2.862740 1.412289 43 6 0 -1.806638 2.892858 -0.408216 44 6 0 -2.576367 4.057371 -0.396474 45 6 0 -3.960657 3.914466 -0.389710 46 6 0 -4.560174 2.643534 -0.397768 47 6 0 -3.786893 1.486674 -0.407000 48 6 0 -2.388627 1.598544 -0.406621 49 1 0 -2.111196 5.038429 -0.393800 50 1 0 -4.586980 4.801446 -0.378991 51 1 0 -5.642607 2.563325 -0.393858 52 1 0 -4.268632 0.515685 -0.413223 53 1 0 0.256729 3.495841 -0.395667 54 8 0 2.497221 -0.266571 1.980010 55 8 0 3.682856 -1.943523 2.698885 ---------------------------------------------------------------------


indolo- and quinolinocarbazole ring systems obtained … · c Université de...

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Transcript of indolo- and quinolinocarbazole ring systems obtained … · c Université de...