Tosyl­ate salts of the anti­cancer drug lapatinib

Two tosyl­ate salts of an anti­cancer drug lapatinib, viz. a mono­tosyl­ate [systematic name: ({5-[4-({3-chloro-4-[(3-fluoro­phen­yl)meth­oxy]phen­yl}amino)­quinazolin-6-yl]furan-2-yl}meth­yl)[2-(methyl­sulfon­yl)eth­yl]aza­nium 4-methyl­benzene­sulfonate], C₂₉H₂₇ClFN₄O₄S⁺·C₇H₇O₃S^-, (I), and a di­tosyl­ate [systematic name: 4-({3-chloro-4-[(3-fluoro­phen­yl)meth­oxy]phen­yl}amino)-6-]5-({[2-(methyl­sulfon­yl)eth­yl]aza­nium­yl}meth­yl)furan-2-yl[quinazolin-1-ium bis­(4-methyl­benzene­sulfonate)], C₂₉H₂₈ClFN₄O₄S²⁺·2C₇H₇O₃S^-, (II), were ob­tained during crystallization attempts for polymorphism. In both structures, the lapatinib cation is in a distorted U-like conformation and the tosyl­ate anion is clamped between the aniline N atom and methyl­amine N atom through N-H...O hydrogen bonds, forming an R₂²(15) ring motif. The 4-ani­­lino­quinazoline ring system is essentially planar in (I), while it is twisted in (II), controlled by an intra­molecular C-H...N inter­action. In (I), alternating cations and anions are linked by N-H...O hydrogen bonds into C₂²(6) chains. These chains are linked by cations in a helical manner. The presence of the additional tosyl­ate anion in (II) results in the formation of one-dimensional tapes of fused hydrogen-bonded rings through N-H...O and C-H...O inter­actions. These studies augment our understanding of the role of nonbonded inter­actions in the solid state, which is useful for correlation to the physicochemical properties of drug products.

S1. Introduction

Cancer is a disease of striking significance in the world today. It is the second leading cause of death in the world after cardiovascular diseases and is projected to become the primary cause of death in the coming years (Gibbs, 2000). Breast cancer (BC) is the most common malignancy and the second most common cause of cancer-related death. It is generally found in females, affecting around 1.3 million women worldwide each year and causing significant deaths annually (Parkin et al., 2005). BC is a complex disease caused by a number of factors. One has to do with the way genes mutate and inter­act with hormones in the body. Tyrosine kinases are a type of gene – part of the human genome – contributing to the formation and progression of different types of cancers, including breast cancer, when pathogenic. The ErbB receptor tyrosine kinase family, promotes growth and differentiation of both normal breast and malignant human breast cancer cells (Olayioye et al., 2000). One member of the family, epidermal growth factor (EGF) receptor (EGFR/ErbB1), is overexpressed in 20 to 80% of breast cancers (Cerra et al., 1995; Seshadri et al., 1996), and another member, HER2 (Humal ErbB2/neu), is amplified and/or overexpressed in 20 to 30% of breast cancers (Slamon et al., 1987, 1989). EGFR and HER2 are known to drive tumor growth and progression and have emerged as promising targets for cancer therapy.

Lapatinib (GW572016) is a dual tyrosine kinase (EGFR and HER2) inhibitor that inter­rupts cancer-causing cellular signals (Carter et al., 1999). It inhibits receptor-signal processes by binding to the ATP-binding pocket of the EFGR/HER2 protein kinase domain, preventing self-phospho­rlation and subsequent activation of the signal mechanism (Denny et al., 1996; Shewchuk et al., 2000). Lapatinib is a large 4-anilinoquinazoline derivative, distinguishing it from the small head group quinazoline tyrosine kinase inhibitors such as erlotinib and gefitinib. On March 13, 2007, the US Food and Drug Administration (FDA) approved lapatinib in combination therapy for breast cancer patients already using capecitabine (Xeloda, Roche). In humans, lapatinib is administered as a monohydrate di­tosyl­ate salt (Medina & Goodin, 2008). Each 250 mg tablet of TYKERB (trade name of GlaxoSmithKline) contains 405 mg of lapatinib di­tosyl­ate monohydrate, equivalent to 398 mg of lapatinib di­tosyl­ate or 250 mg lapatinib free base. As part of ongoing structural studies on pharmaceutical compounds in our laboratory (Ravikumar & Sridhar, 2010; Ravikumar et al., 2011, 2013), the crystal structures of lapatinb mono­tosyl­ate, (I), lapatinib di­tosyl­ate, (II), have been determined and reported here.

S2. Experimental

S2.1. Synthesis and crystallization

Crystals of (I) suitable for X-ray diffraction analysis were obtained by dissolving lapatinib tosyl­ate (100 mg; Natco Research Centre, Hyderabad) in di­methyl­formamide (15 ml) and allowing the solution to evaporate slowly. Suitable single crystals had grown after 15 d. Crystals of (II) were obtained by dissolving lapatinib di­tosyl­ate (100 mg; Natco Research Centre, Hyderabad) in aceto­nitrile–hexane (80:20 v/v, 25 ml). Suitable single crystals had grown after 4 d. As a precautionary measure, all the crystals were mounted on glass fibers and coated with ep­oxy resin.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. The site-occupancy factors of disordered atoms C4 and C5 of the fluoro­phenyl ring of (II) refined to 0.74 (2) and 0.26 (2). The anisotropic displacement parameters of these atoms were restrained to be similar and the direction of motion along the axis between these atoms was also restrained. The C—C bond lengths about the disordered atoms were restrained to be 1.39 (1) Å. All N-bound H atoms of the lapatinib cations in (I) and (II) were located in difference Fourier maps, and their positions and isotropic displacement parameter were refined. In (I), the N—H bond lengths were restrained with set values of 0.89 (1) Å. All other H atoms were positioned geometrically and were treated as riding on their parent C atoms, with C—H = 0.93–0.98 Å and U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) otherwise. The methyl groups were allowed to rotate but not to tip. In (I), the 011 reflection was partially obscured by the beam stop and was omitted.

S3. Results and discussion

The lapatinib molecule consists of a central quinazoline ring containing a chloro­aniline ring with fluoro­benzyl ether moiety substituted at the pyrimidine ring and a furan ring with methyl­sulfonyl­ethyl­methyl­amine substituted at the phenyl ring of the quinazoline ring system. The orientation of these two substitutents plays a significant role in the solid-state conformation and provides the overall shape of the lapatinib molecule. The shape of the lapatinib molecule can be best described as a distorted U-like conformation in both structures, with the quinazoline and furan ring systems forming the base of the `U' and the substitutents fluoro­benzyl­oxyaniline and methyl­sulfonyl­ethyl­methyl­amine representing the two arms on either side of the base portion. The two arms are unsymmetrical in length with the former arm longer than the latter, which makes the lapatinib molecule to look like a distorted `U' rather than a perfect one. Views of the components of (I) and (II) with the atom labeling are presented in Figs. 1 and 2, respectively.

The crystal structures of (I) and (II) are novel and different from that of the commercially marketed lapatinib di­tosyl­ate salt, which exists as a monohydrate, and crystallized in the orthorhombic space group Pbca with unit-cell dimensions a = 9.6850 Å, b = 29.364 Å and c = 30.733 Å. The atomic coordinates of this structure were not available in the latest version of the Cambridge Structural Database (CSD, Version 5.32 with May 2013 updates; Allen, 2002) or in the literature (Varlashkin, 2009).

Compound (I) crystallizes in the acentric orthorhombic space group P2₁2₁2₁ with one lapatinib cation and one toluene­sulfonate anion in the asymmetric unit, while (II) crystallizes in the centrosymmetric triclinic space group P1 with one lapatinib dication and two toluene­sulfonate anions in the asymmetric unit. Proton transfer from the sulfonic acid to methyl­amine atom N4 forms an aminium group in (I), and proton transfer from two sulfonic acids groups to methyl­amine atom N4 and pyrimidine atom N3 results in aminium and pyrimidinium groups, respectively, in (II), and confirms the presence of the salt forms of lapatinib in the studied crystals of (I) and (II). The salt formation in (I) and (II) is in line with the widely used ΔpK_a rule [ΔpK_a = pK_a(base H⁺) - pK_a(acid)] (Stahl & Wermuth, 2002). An organic salt is formed when ΔpK_a > 3 and a cocrystal is obtained when it is < 0. For a system with 0 < ΔpK_a < 3, there is a salt–cocrystal continuum (Childs & Hardcastle, 2007; Childs et al., 2007), and it is difficult to predict which form crystallizes. The pK_a values are 7.20 (N4), 3.80 (N3) for lapatinib (ChemAxon, 2012) and -1.34 for sulfonic acid (Stahl & Wermuth, 2002). The ΔpK_a values are greater than 3 for lapatinib [8.54 (N4) and 5.14 (N3)], indicating an effective salt formation in (I) and (II). The order of protonation is also consistent with the predicted values, with protonation of N4 taking precedence over protonation of N3.

There are three aspects of the two structures (I) and (II) that merit comparison: (a) the orientation between the aniline and quinazoline rings, and between the methyl­amine fragment and the furan rings; (b) the manner in which the tosyl­ate ion is held by the lapatinib molecule; (c) the crystal-packing environments.

The orientation of the aniline ring with respect to the pyrimidine ring defined by the torsion angle C14—N1—C11—C12 (τ₁) is nearly planar [13.6 (7)°] in (I), while it is inclined close to perpendicular [-76.8 (5)°] in (II). This near-planar orientation of the two rings favours an intra­molecular C12—H12···N2 inter­action in (I), creating a pseudo-six-membered ring (atoms N2/C14/N1/C11/C12/H12). This results in a widening of the three inter­ior bond angles (C11—N1—C14, N2—C14—N1 and N1—C11—C12) of the above-described ring by about 6° and a narrowing of the exterior angle (C10—C11—N1) by 4°, when compared with the corresponding values of (II) (Table 2). These features are also observed and found to be similar in geftinib (Tanaka et al., 2004) and erlotinib salt structures (Selvanayagam et al., 2008; Sridhar et al., 2010) (see Scheme).

Computational calculations were performed using the crystallographic structure parameters of (I) and (II) separately as a starting point. The density functional theory (DFT) method was applied at the B3LYP hybrid exchange correlation function level (Becke, 1993; Lee et al., 1988) using the 6–31G(d,p) basis set (Bauschlicher & Partridge, 1995) as implemented in GAUSSIAN03 (Frisch et al., 2004). Geometry optimization of (I) and (II) also results in a planar conformation, with τ₁ = 2.1° and the above-mentioned bond angles as 131.6, 119.8, 124.4 and 116.8°, successively.

In order to understand the inter­relationship between the torsion angle τ₁ and the previously noted bond angles, a search of the CSD was undertaken for all molecules containing similar a pyrimidine–aniline fragment (three-dimensional structures, no errors, no polymeric, R factor < 0.07, no powder structures and only organics were used as search criteria), which resulted in 54 hits. Inter­estingly, a significant correlation is seen between τ₁ and all the four bond angles (Fig. 3). The concentration of the points is mostly between ±15°, representing near planar orientation of the aniline ring to the pyrimidine ring. An inverse relationship can be noticed between τ₁ and the three inter­ior bond angles, while there is a direct relationship to the fourth exterior angle. This widening and narrowing of bond angles is consistent with those observed in (I) and (II).

The O2—C25—C26—N4 torsion angle defining the twist of the methyl­amine fragment to the furan ring is 87.7 (3)° in (I), perhaps due to the participation of atom C26 in an inter­action with atom O4ⁱⁱ, whereas this torsion angle is 50.3 (4)° in (II) [symmetry code: (ii) x-1/2, -y+1/2, -z+2.]

As a consequence of the protonation at atom N3 of the pyrimidine ring in (II), the intra-ring angle at N3 is about 6.2° larger than in (I), while the intra-ring angles at C20 and C21 decrease by about 4.9 and 4.7°, respectively. A similar trend is seen in the crystal structures of erlotinib and its salts (Sridhar et al., 2010; Selvanayagam et al., 2008), ErbB2 inhibitor and its salts (Li et al., 2006), and is also comparable with geftinib (Tanaka et al., 2004).

In both (I) and (II), the tosyl­ate anion is clamped between the two arms of the lapatinate cation through N—H···O hydrogen bonds. However, in (I), two C—H···O inter­actions augment the binding of the tosyl­ate anion, resulting in R₂¹(6) and R₂²(7) motifs (Etter, 1990; Etter et al., 1990; Bernstein et al., 1995). The N1—H1N···O5 hydrogen-bond distance is noted to be longer in (I) (Table 3) than in (II) (Table 4), indicating that the tosyl­ate anion is weakly bound in (I). This has been confirmed by the approximate energies calculated from the tosyl­ate anion and lapatinib cation inter­actions and other van der Waals forces, using UNI force field (Filippini & Gavezotti, 1993; Gavezotti & Filippini, 1994) implemented in the program Mercury (Macrae et al., 2008), which indicate that the inter­molecular potential is -66.6 kJ mol^-1 for (I) and -84.1 kJ mol^-1 in (II).

The tosyl­ate anion in both structures is oriented differently between the two arms of the cation. This can be seen from the dihedral angle between the least-squares planes of this tosyl­ate anion (atoms C30–C35) and (a) the ethyl­methyl­amine atoms (atoms C26/N4/C27/C28) [87.9 (3)° in (I) and 48.3 (3)° in (II)] and (b) the chloro­phenyl ring (atoms C8–C13) [53.4 (2)° in (I) and 67.4 (2)° in (II)]. Further, with reference to the quinazoline–furan ring system, the tosyl­ate anion is significantly inclined [43.02 (19)°] in (I), while it is almost parallel [5.14 (5)°] in (II). In the lapatinib cation, the distance between benzyl­oxy atom O1 and sulfonyl atom O3 is 11.063 (4) Å in (I) and 10.078 (4) Å in (II), indicating that the two arms are slightly apart in (I). Consequently, the tosyl­ate anion fits nicely between the arms in (I), while it is displaced slightly away in (II).

The additional tosyl­ate anion in (II) forms a pair of N4—H4N···O10 and C27—H27B···O8 inter­actions between the methyl­sulfonyl­ethyl­methyl­amine side chain and the tosyl­ate ion.

Fig. 4 shows the overlay of the lapatinib cations of (I) and (II), along with the lapatinib ligand extracted from the crystal structure of the complex of lapatinib bound to the Epidermal Growth Factor (EPGR) [Wood et al., 2004, Protein Data Bank (PDB: Berman et al., 2000) entry 1xkk]. The conformational flexibility provided by the amine groups and ether linkages in the lapatinib cation allows the substituents in the free and enzyme-bound molecules to adopt different orientations. It is inter­esting to note that, within the fluoro­benzyl­oxyaniline side chain in the enzyme-bound lapatinib molecule, the binding mode required the aniline ring to adopt a similar orientation as in (II), but the orientation of the lipophilic fluoro­phenyl ring is different. As observed by Wood et al., (2004), the conformation in the enzyme-bound molecule may be necessary to provide favorable hydro­phobic inter­actions at the active site. On the other hand, the orientation of the fluoro­benzyl­oxyaniline side chain in the optimized structure is similar to that found in (I). The orientations of the methyl­sulfonyl­ethyl­methyl­amine side chain are dissimilar, which suggests that different hydrogen-bonding inter­actions in the bound and unbound state may be influencing the conformation of the hydro­philic end of the molecule.

The crystal packing in (I) and (II) is influenced by a combination of N—H···O hydrogen bonds and C—H···O inter­actions (Tables 2 and 3). In (I), aminium atom N4 of the lapatinib cation acts as a donor and forms a hydrogen bond to acceptor atom O6 of the tosyl­ate anion, related by translation into an infinite chain running parallel to the [100] direction (Fig. 5). A C26—H26A···O4ⁱⁱ inter­action [symmetry code: (ii) x-1/2, -y+1/2, -z+2] between the methyl­sulfonyl­ethyl­methyl­amine side chains links the screw-related lapatinib cations into an infinite helical chain also running parallel to the [100] direction. An inter­molecular offset π-stacking between the C15–C20 phenyl ring of the quinazoline system and the C8–C13 chloro­phenyl ring [the centroid of the chloro­phenyl ring stacks above atoms C15^vii and C16^vii; symmetry code: (vii) x-1, y, z] with and atom-to-centroid distances of 3.636 (11) and 3.602 (14) Å, respectively] assists the close packing of the translationally related lapatinib cations along the a axis. A similar observation was noted earlier (Komiya et al., 2013; Krause et al., 2013) and also suggested by Janiak (2000) that such an arrangement is indicative of a possible π–σ attraction.

The presence of an additional tosyl­ate anion in (II) adds complexity to the crystal packing (Fig. 6). It forms an R₂²(7) graph-set motif involving N4—H5N···O10 and C27—H27B···O8 inter­actions with the methyl­ethyl­amine fragment. The molecules form two types of centrosymmetric cation–cation dimers which are linked by (i) C—H···O and (ii) a combination of N—H···O and C—H···O inter­actions. In the first case, a dimer is formed between the furanyl­ethyl­amine­sulfonyl side chains [C24—H24···O4^v; -x+1, -y+1, -z], generating an R₂²(18) graph-set motif. In the second case, a dimer is formed via the tosyl­ate ion, using pyrimidine atom N3 and atom C21 as donors and tosyl­ate sulfonyl atoms O9 and O10 as acceptors, resulting in a tetra­meric R₄⁴(14) graph-set motif. These dimers form tapes running parallel to the (213) plane. Subsequently, parallel tapes are joined by (tosyl­ate)C34—H34···Cl1ⁱⁱ and flouro­phenyl–tosyl­ate C5—H5···O5ⁱⁱ inter­actions to form a two-dimensional crystal network [symmetry code: (ii) -x+2, -y, -z+1]. Atoms C18 and C23 of the quinazoline–furan ring system link the inversion-related tosyl­ate anion (O6 and O5) to generate an R₂²(7) graph-set motif. Further, the ethyl­amine–tosyl­ate C28—H28A···O10^vi and tosyl­ate–tosyl­ate C38—H38···O7^vi inter­actions build the three-dimensional hydrogen-bonding network [symmetry code: (vi) -x+2, -y+1, -z]. The C—H···O inter­actions mentioned above exist within the accepted range for C—H···O hydrogen bonds (Desiraju, 1996). It is reported that such weak inter­actions can play an important role in drug action and polymorphism (Umezawa & Nishio, 2005; Desiraju, 1997, 2005; Braga et al., 2009). Inter­layer networks are further stabilized by π–π stacking inter­actions related by inversion [Cg1···Cg3^viii = 3.601 (2) Å and Cg2···Cg3^viii = 3.635 (2) Å; Cg1 is centroid of the O2/C22—C25 ring, Cg2 is the centroid of the N2/N3/C14/C15/C20/C21 ring and Cg3 is the centroid of the C15–C20 ring; symmetry code: (viii) -x+1, -y, -z].

In both (I) and (II), ether atom O1 and furan atom O2 are not involved in any hydrogen-bonding inter­actions.

As mentioned earlier, the lapatinib mono­tosyl­ate salt, (I), crystallizes in the acentric chiral space group P2₁2₁2₁, while, the lapatinib di­tosyl­ate salt, (II), crystallizes in the centrosymmetric space group P1. Such examples of achiral molecules crystallizing in acentric space groups, although not rare (they account for 15.2% of the CSD total statistics; Dey & Pidcock, 2008), may be distinguished by certain structural features leading to the choice of space group. In our opinion, the following observations help to consolidate the acentric crystal packing in (I) and the centrosymmetry in (II).

(i) The formation of an infinite helical chain viaa C26—H26A···O4 inter­action along the ethyl­amine­sulfonyl­methyl side chain appears to be an important factor for the structure favouring an acentric space group [rewording OK]. This inter­action is formed by the screw-related molecules in (I), whereas in (II), these side chains slightly reorganize to facilitate a centrosymmetric C24—H24···O24 motif.

(ii) π–π stacking occurs between translation-related lapatinib cations in (I), whereas, they are observed between inversion-related cations in (II).

(iii) The quinazoline ring does not participate in any conventional hydrogen bonding in (I), whereas it forms a centrosymmetric R₄⁴(14) ring motif with the second tosyl­ate anion in (II). Moreover, in (II), the di­tosyl­ate salt forms several centrosymmetric ring motifs favoring centrosymmetry, while the mono­tosyl­ate in (I) lacks these motifs and shows infinite helical chains favoring the acentric.

In conclusion, the crystal structures aid our understanding of the inter­actions between cations and anions which might provide a clue for the stability of lapatinib tosyl­ate salts. Further, for a given crystalline drug substance, such structural studies enhance our knowledge through understanding the types of inter- and intra­molecular inter­actions in solid state manifested by the molecular packing arrangement, which can then be useful for correlation to physiochemical properties of drug products.

Related literature

For related literature, see: Allen (2002); Bauschlicher & Partridge (1995); Becke (1993); Berman et al. (2000); Bernstein et al. (1995); Braga et al. (2009); Carter et al. (1999); Cerra et al. (1995); Chemaxon (2012); Childs & Hardcastle (2007); Childs, Stahly & Park (2007); Denny et al. (1996); Desiraju (1996, 1997, 2005); Dey & Pidcock (2008); Etter (1990); Etter, MacDonald & Bernstein (1990); Filippini & Gavezotti (1993); Frisch (2004); Gavezotti & Filippini (1994); Gibbs (2000); Janiak (2000); Komiya et al. (2013); Krause et al. (2013); Lee et al. (1988); Li et al. (2006); Macrae et al. (2008); Medina & Goodin (2008); Olayioye et al. (2000); Parkin et al. (2005); Ravikumar & Sridhar (2010); Ravikumar et al. (2011, 2013); Selvanayagam et al. (2008); Seshadri et al. (1996); Shewchuk et al. (2000); Slamon et al. (1987, 1989); Sridhar et al. (2010); Stahl & Wermuth (2002); Tanaka et al. (2004); Umezawa & Nishio (2005); Varlashkin (2009); Wood et al. (2004).

Computing details

For both compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. A asymmetric unit of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. The dashed lines indicate N—H···O and C—H···O interactions.
	Fig. 2. A asymmetric unit of (II), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. The dashed lines indicate N—H···O and C—H···O interactions. The minor disordered atoms C4'/C5' of the fluorophenyl ring have been omitted for clartiy.
	Fig. 3. Scatterplot illustrating the distribution of the four bond angles (°), C11—N1—C14 (denoted 1), N2—C14—N1 (2), N1—C11—C12 (3) and C10—C11—N1 (4) with respect to the C14—N1—C11—C12 torsion angle (τ1, °) that relates the orientation of the aniline ring to the pyrimidine ring. The τ1 values have been restricted to the range from -90 to +90°.
	Fig. 4. The superposition of the conformations of the cations in (I), (II), optimized structure (labelled as 3) and lapatinib–EGFR complex (4), showing the orientation difference of the substituents at atoms C14 and C25. The overlay was made by making a least-squares fit through the quinazoline ring system of (I).
	Fig. 5. Molecular interactions (dashed lines) between the laptinib cations and tosylate anions in (I), in a perspective view of the partial packing in the unit cell. H atoms not involved in the interactions have been omitted for clarity. Selected atoms of the molecules are labelled, primarily to provide a key for the coding of the atoms. [Symmetry codes (i) x+1, y, z; (ii) x-1/2, -y+1/2, -z+2.]
	Fig. 6. Molecular interactions (dashed lines) between the laptinib cations and tosylate anions in (II), in a perspective view of the partial packing in the unit cell. H atoms not involved in the interactions have been omitted for clarity. Selected atoms of the molecules are labelled, primarily to provide a key for the coding of the atoms. [Symmetry codes (i)x, y-1, z; (ii) -x+2, -y, -z+1; (iii) -x+1, -y, -z; (iv) -x+1, -y+1, -z; (v) -x+2, -y, -z; (vi) -x+2, -y+1, -z.]

(I) ({5-[4-({3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)quinazolin-6-yl]furan-2-yl}methyl)[2-(methylsulfonyl)ethyl]azanium 4-methylbenzenesulfonate

Crystal data

C29H27ClFN4O4S^+·C7H7O3S^−	F(000) = 1568
Mr = 753.24	Dx = 1.415 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 7472 reflections
a = 5.7828 (4) Å	θ = 2.3–20.7°
b = 20.7395 (14) Å	µ = 0.29 mm^−1
c = 29.4867 (19) Å	T = 294 K
V = 3536.4 (4) Å^3	Block, colorless
Z = 4	0.18 × 0.16 × 0.07 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer	6217 independent reflections
Radiation source: fine-focus sealed tube	5614 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.043
ω scan	θmax = 25.0°, θmin = 1.7°
Absorption correction: multi-scan (SABABS; Bruker, 2001)	h = −6→6
Tmin = 0.93, Tmax = 0.97	k = −24→24
34209 measured reflections	l = −35→35

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.057	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.137	w = 1/[σ^2(Fo^2) + (0.0832P)^2 + 0.154P] where P = (Fo^2 + 2Fc^2)/3
S = 1.12	(Δ/σ)max = 0.002
6217 reflections	Δρmax = 0.39 e Å^−3
472 parameters	Δρmin = −0.22 e Å^−3
3 restraints	Absolute structure: Flack & Bernardinelli (2000), 2627 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.04 (8)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	−1.0966 (11)	−0.2518 (3)	0.90832 (19)	0.0939 (16)
C2	−0.9231 (9)	−0.2075 (3)	0.89817 (18)	0.0876 (14)
H2	−0.8064	−0.1987	0.9190	0.105*
C3	−0.9284 (7)	−0.17695 (19)	0.85619 (14)	0.0598 (10)
C4	−1.0988 (7)	−0.1930 (2)	0.82603 (15)	0.0633 (10)
H4	−1.1001	−0.1737	0.7975	0.076*
C5	−1.2687 (8)	−0.2370 (2)	0.83693 (18)	0.0808 (13)
H5	−1.3850	−0.2464	0.8162	0.097*
C6	−1.2663 (10)	−0.2671 (3)	0.87843 (19)	0.0864 (15)
H6	−1.3788	−0.2973	0.8859	0.104*
C7	−0.7533 (8)	−0.1254 (2)	0.84659 (14)	0.0688 (11)
H7A	−0.8199	−0.0833	0.8525	0.083*
H7B	−0.6202	−0.1309	0.8662	0.083*
C8	−0.5077 (6)	−0.08963 (17)	0.78753 (12)	0.0504 (8)
C9	−0.4205 (7)	−0.03953 (17)	0.81345 (12)	0.0531 (9)
H9	−0.4882	−0.0298	0.8412	0.064*
C10	−0.2333 (7)	−0.00386 (17)	0.79834 (11)	0.0507 (8)
H10	−0.1781	0.0297	0.8162	0.061*
C11	−0.1262 (6)	−0.01680 (16)	0.75751 (11)	0.0451 (8)
C12	−0.2171 (7)	−0.06552 (17)	0.73047 (12)	0.0528 (9)
H12	−0.1505	−0.0750	0.7026	0.063*
C13	−0.4069 (7)	−0.09954 (17)	0.74545 (12)	0.0536 (9)
C14	0.1867 (6)	0.02662 (16)	0.70771 (12)	0.0474 (8)
C15	0.3854 (6)	0.06920 (16)	0.70498 (11)	0.0453 (8)
C16	0.4752 (6)	0.10539 (15)	0.74121 (11)	0.0430 (8)
H16	0.4025	0.1038	0.7693	0.052*
C17	0.6687 (6)	0.14297 (16)	0.73578 (11)	0.0455 (8)
C18	0.7789 (7)	0.14502 (17)	0.69300 (11)	0.0514 (8)
H18	0.9093	0.1707	0.6891	0.062*
C19	0.6963 (7)	0.10983 (19)	0.65744 (12)	0.0579 (10)
H19	0.7726	0.1111	0.6297	0.069*
C20	0.4972 (7)	0.07170 (18)	0.66228 (11)	0.0525 (9)
C21	0.2386 (9)	0.0027 (2)	0.63321 (13)	0.0740 (13)
H21	0.1849	−0.0202	0.6082	0.089*
C22	0.7739 (6)	0.17932 (16)	0.77281 (10)	0.0436 (8)
C23	0.9778 (6)	0.21085 (18)	0.77690 (12)	0.0535 (9)
H25	1.0920	0.2147	0.7549	0.064*
C24	0.9832 (7)	0.23701 (19)	0.82147 (12)	0.0540 (9)
H24	1.1022	0.2609	0.8344	0.065*
C25	0.7839 (6)	0.22055 (15)	0.84114 (11)	0.0435 (8)
C26	0.6890 (6)	0.23139 (17)	0.88745 (11)	0.0470 (8)
H26A	0.7457	0.2722	0.8991	0.056*
H26B	0.5217	0.2337	0.8860	0.056*
C27	0.6896 (6)	0.19041 (17)	0.96624 (10)	0.0442 (8)
H27A	0.5223	0.1919	0.9684	0.053*
H27B	0.7504	0.2317	0.9762	0.053*
C28	0.7824 (7)	0.13714 (18)	0.99647 (11)	0.0509 (8)
H28A	0.9493	0.1405	0.9987	0.061*
H28B	0.7448	0.0954	0.9836	0.061*
C29	0.8112 (10)	0.0891 (3)	1.08416 (16)	0.0919 (16)
H29A	0.7593	0.0910	1.1150	0.138*
H29B	0.9729	0.0994	1.0829	0.138*
H29C	0.7870	0.0464	1.0725	0.138*
Cl1	−0.5193 (3)	−0.16048 (6)	0.71101 (4)	0.0914 (4)
F1	−1.0903 (9)	−0.2811 (2)	0.94872 (14)	0.1661 (19)
N1	0.0706 (5)	0.02027 (15)	0.74711 (10)	0.0499 (7)
H1N	0.122 (6)	0.0420 (13)	0.7699 (8)	0.035 (8)*
N2	0.1165 (6)	−0.00595 (16)	0.67114 (10)	0.0620 (9)
N3	0.4207 (7)	0.03795 (19)	0.62545 (11)	0.0701 (10)
N4	0.7584 (5)	0.17841 (14)	0.91859 (9)	0.0407 (6)
H2N	0.906 (3)	0.1690 (17)	0.9171 (12)	0.052 (11)*
H3N	0.687 (5)	0.1424 (10)	0.9098 (9)	0.027 (8)*
O1	−0.6837 (5)	−0.12955 (13)	0.80053 (9)	0.0622 (7)
O2	0.6519 (4)	0.18415 (11)	0.81247 (7)	0.0447 (5)
O3	0.4188 (5)	0.12592 (16)	1.04900 (9)	0.0724 (8)
O4	0.6994 (6)	0.20850 (14)	1.06728 (9)	0.0729 (8)
S1	0.65535 (16)	0.14452 (5)	1.05150 (3)	0.0498 (2)
C30	0.1508 (7)	0.01584 (18)	0.93247 (12)	0.0517 (9)
C31	0.2522 (12)	0.0006 (3)	0.97364 (16)	0.0996 (19)
H31	0.3876	0.0212	0.9826	0.120*
C32	0.1531 (13)	−0.0448 (3)	1.00105 (18)	0.113 (2)
H32	0.2217	−0.0541	1.0288	0.135*
C33	−0.0432 (11)	−0.0770 (3)	0.98899 (16)	0.0861 (15)
C34	−0.1433 (9)	−0.0604 (2)	0.94913 (16)	0.0793 (13)
H34	−0.2801	−0.0806	0.9406	0.095*
C35	−0.0499 (7)	−0.0147 (2)	0.92077 (14)	0.0622 (10)
H35	−0.1232	−0.0045	0.8936	0.075*
C36	−0.1492 (17)	−0.1276 (4)	1.0192 (2)	0.144 (3)
H36A	−0.3093	−0.1330	1.0115	0.216*
H36B	−0.1365	−0.1143	1.0503	0.216*
H36C	−0.0692	−0.1677	1.0151	0.216*
O5	0.1652 (5)	0.07126 (14)	0.85390 (9)	0.0684 (8)
O6	0.2122 (4)	0.13866 (12)	0.92030 (9)	0.0602 (7)
O7	0.5173 (4)	0.06791 (12)	0.89815 (9)	0.0594 (7)
S2	0.26889 (15)	0.07797 (4)	0.89787 (3)	0.0484 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.102 (4)	0.094 (4)	0.085 (4)	−0.008 (3)	0.011 (3)	0.023 (3)
C2	0.083 (3)	0.099 (4)	0.080 (3)	−0.013 (3)	−0.003 (3)	0.002 (3)
C3	0.060 (2)	0.057 (2)	0.062 (2)	0.0085 (19)	0.016 (2)	−0.0101 (19)
C4	0.053 (2)	0.068 (3)	0.069 (3)	0.003 (2)	0.004 (2)	−0.006 (2)
C5	0.060 (3)	0.089 (3)	0.093 (3)	−0.003 (3)	0.009 (3)	−0.018 (3)
C6	0.080 (3)	0.079 (3)	0.100 (4)	−0.020 (3)	0.028 (3)	−0.009 (3)
C7	0.072 (3)	0.072 (3)	0.062 (2)	−0.010 (2)	0.010 (2)	−0.022 (2)
C8	0.049 (2)	0.049 (2)	0.053 (2)	0.0023 (17)	−0.0017 (17)	−0.0080 (16)
C9	0.059 (2)	0.053 (2)	0.047 (2)	0.0014 (18)	0.0043 (17)	−0.0130 (16)
C10	0.057 (2)	0.0505 (19)	0.0450 (18)	−0.0029 (18)	−0.0100 (17)	−0.0111 (15)
C11	0.049 (2)	0.0433 (18)	0.0435 (18)	0.0031 (16)	−0.0099 (16)	−0.0026 (14)
C12	0.060 (2)	0.054 (2)	0.0445 (18)	0.0001 (18)	0.0026 (17)	−0.0114 (16)
C13	0.060 (2)	0.052 (2)	0.048 (2)	−0.0055 (18)	−0.0069 (18)	−0.0160 (17)
C14	0.051 (2)	0.0470 (18)	0.0444 (18)	0.0088 (16)	−0.0029 (16)	−0.0025 (15)
C15	0.0502 (19)	0.0465 (19)	0.0393 (17)	0.0093 (16)	−0.0039 (15)	−0.0024 (14)
C16	0.048 (2)	0.0456 (18)	0.0354 (16)	0.0082 (15)	0.0008 (15)	0.0014 (14)
C17	0.051 (2)	0.0452 (18)	0.0406 (17)	0.0075 (16)	0.0015 (15)	0.0049 (14)
C18	0.052 (2)	0.058 (2)	0.0441 (18)	−0.0018 (18)	0.0030 (16)	0.0035 (16)
C19	0.066 (3)	0.074 (2)	0.0339 (17)	0.007 (2)	0.0112 (17)	−0.0004 (17)
C20	0.062 (2)	0.055 (2)	0.0404 (18)	0.0080 (19)	0.0021 (17)	−0.0032 (17)
C21	0.084 (3)	0.095 (3)	0.043 (2)	−0.008 (3)	−0.002 (2)	−0.025 (2)
C22	0.046 (2)	0.0515 (18)	0.0328 (16)	0.0060 (16)	0.0028 (14)	0.0076 (14)
C23	0.047 (2)	0.071 (2)	0.0417 (19)	−0.0062 (18)	0.0080 (16)	0.0050 (17)
C24	0.049 (2)	0.067 (2)	0.0458 (19)	−0.0071 (18)	−0.0042 (17)	0.0010 (17)
C25	0.0441 (19)	0.0468 (18)	0.0395 (17)	−0.0007 (15)	−0.0044 (15)	0.0013 (14)
C26	0.0457 (19)	0.0539 (19)	0.0412 (17)	0.0053 (16)	−0.0035 (15)	−0.0022 (15)
C27	0.0412 (18)	0.0545 (19)	0.0368 (16)	0.0009 (15)	0.0036 (14)	−0.0060 (14)
C28	0.051 (2)	0.062 (2)	0.0389 (17)	0.0045 (18)	0.0049 (15)	−0.0027 (16)
C29	0.104 (4)	0.112 (4)	0.060 (3)	0.020 (3)	0.000 (3)	0.032 (3)
Cl1	0.1061 (10)	0.0959 (9)	0.0722 (7)	−0.0483 (7)	0.0190 (7)	−0.0430 (6)
F1	0.167 (4)	0.192 (4)	0.139 (3)	−0.042 (3)	−0.011 (3)	0.083 (3)
N1	0.0525 (19)	0.0543 (18)	0.0429 (17)	−0.0032 (14)	−0.0044 (14)	−0.0075 (14)
N2	0.068 (2)	0.069 (2)	0.0483 (18)	−0.0041 (18)	−0.0041 (17)	−0.0184 (15)
N3	0.077 (3)	0.089 (3)	0.0442 (18)	−0.008 (2)	0.0044 (17)	−0.0183 (17)
N4	0.0330 (15)	0.0523 (17)	0.0367 (14)	0.0036 (14)	−0.0008 (12)	−0.0063 (12)
O1	0.0616 (17)	0.0678 (16)	0.0573 (15)	−0.0142 (14)	0.0075 (13)	−0.0152 (13)
O2	0.0438 (13)	0.0508 (13)	0.0394 (12)	−0.0017 (11)	0.0000 (10)	0.0024 (10)
O3	0.0665 (18)	0.093 (2)	0.0577 (16)	−0.0189 (16)	0.0089 (14)	−0.0050 (15)
O4	0.089 (2)	0.0787 (19)	0.0506 (15)	−0.0122 (17)	0.0059 (15)	−0.0204 (13)
S1	0.0551 (5)	0.0600 (5)	0.0341 (4)	−0.0041 (4)	0.0016 (4)	−0.0033 (4)
C30	0.056 (2)	0.053 (2)	0.0468 (19)	0.0036 (18)	−0.0044 (17)	−0.0113 (16)
C31	0.123 (5)	0.104 (4)	0.072 (3)	−0.046 (4)	−0.034 (3)	0.014 (3)
C32	0.151 (6)	0.127 (5)	0.060 (3)	−0.037 (4)	−0.045 (4)	0.025 (3)
C33	0.116 (4)	0.083 (3)	0.060 (3)	−0.015 (3)	0.004 (3)	0.009 (2)
C34	0.071 (3)	0.088 (3)	0.079 (3)	−0.017 (3)	−0.003 (3)	0.007 (3)
C35	0.054 (2)	0.070 (3)	0.063 (2)	−0.004 (2)	−0.0056 (19)	0.005 (2)
C36	0.193 (8)	0.147 (6)	0.092 (4)	−0.053 (6)	0.004 (5)	0.038 (4)
O5	0.0692 (18)	0.0766 (18)	0.0595 (16)	−0.0165 (16)	−0.0102 (14)	0.0054 (14)
O6	0.0403 (13)	0.0548 (15)	0.0854 (18)	0.0044 (12)	−0.0035 (13)	−0.0118 (13)
O7	0.0455 (14)	0.0577 (15)	0.0751 (17)	0.0070 (12)	−0.0006 (13)	−0.0146 (14)
S2	0.0403 (4)	0.0484 (5)	0.0564 (5)	0.0017 (4)	−0.0055 (4)	−0.0091 (4)

Geometric parameters (Å, º)

C1—F1	1.338 (6)	C22—O2	1.369 (4)
C1—C6	1.357 (7)	C23—C24	1.422 (5)
C1—C2	1.392 (7)	C23—H25	0.9300
C2—C3	1.391 (6)	C24—C25	1.335 (5)
C2—H2	0.9300	C24—H24	0.9300
C3—C4	1.369 (6)	C25—O2	1.366 (4)
C3—C7	1.499 (6)	C25—C26	1.489 (5)
C4—C5	1.380 (6)	C26—N4	1.487 (4)
C4—H4	0.9300	C26—H26A	0.9700
C5—C6	1.373 (7)	C26—H26B	0.9700
C5—H5	0.9300	C27—N4	1.481 (4)
C6—H6	0.9300	C27—C28	1.518 (5)
C7—O1	1.419 (5)	C27—H27A	0.9700
C7—H7A	0.9700	C27—H27B	0.9700
C7—H7B	0.9700	C28—S1	1.788 (3)
C8—O1	1.367 (4)	C28—H28A	0.9700
C8—C13	1.386 (5)	C28—H28B	0.9700
C8—C9	1.385 (5)	C29—S1	1.750 (5)
C9—C10	1.385 (5)	C29—H29A	0.9600
C9—H9	0.9300	C29—H29B	0.9600
C10—C11	1.380 (5)	C29—H29C	0.9600
C10—H10	0.9300	N1—H1N	0.862 (18)
C11—C12	1.390 (5)	N4—H2N	0.878 (19)
C11—N1	1.407 (4)	N4—H3N	0.892 (17)
C12—C13	1.377 (5)	O3—S1	1.423 (3)
C12—H12	0.9300	O4—S1	1.429 (3)
C13—Cl1	1.747 (3)	C30—C35	1.366 (5)
C14—N2	1.336 (5)	C30—C31	1.385 (6)
C14—N1	1.348 (5)	C30—S2	1.780 (4)
C14—C15	1.451 (5)	C31—C32	1.367 (8)
C15—C16	1.405 (5)	C31—H31	0.9300
C15—C20	1.416 (5)	C32—C33	1.364 (8)
C16—C17	1.373 (5)	C32—H32	0.9300
C16—H16	0.9300	C33—C34	1.355 (7)
C17—C18	1.414 (5)	C33—C36	1.507 (7)
C17—C22	1.460 (5)	C34—C35	1.374 (6)
C18—C19	1.364 (5)	C34—H34	0.9300
C18—H18	0.9300	C35—H35	0.9300
C19—C20	1.404 (6)	C36—H36A	0.9600
C19—H19	0.9300	C36—H36B	0.9600
C20—N3	1.366 (5)	C36—H36C	0.9600
C21—N3	1.302 (6)	O5—S2	1.435 (3)
C21—N2	1.335 (5)	O6—S2	1.459 (3)
C21—H21	0.9300	O7—S2	1.452 (3)
C22—C23	1.354 (5)
F1—C1—C6	119.5 (5)	C24—C25—C26	132.7 (3)
F1—C1—C2	118.1 (6)	O2—C25—C26	116.5 (3)
C6—C1—C2	122.4 (5)	N4—C26—C25	110.8 (3)
C3—C2—C1	118.4 (5)	N4—C26—H26A	109.5
C3—C2—H2	120.8	C25—C26—H26A	109.5
C1—C2—H2	120.8	N4—C26—H26B	109.5
C4—C3—C2	118.9 (4)	C25—C26—H26B	109.5
C4—C3—C7	122.5 (4)	H26A—C26—H26B	108.1
C2—C3—C7	118.6 (4)	N4—C27—C28	109.9 (3)
C3—C4—C5	121.5 (4)	N4—C27—H27A	109.7
C3—C4—H4	119.3	C28—C27—H27A	109.7
C5—C4—H4	119.3	N4—C27—H27B	109.7
C6—C5—C4	120.1 (5)	C28—C27—H27B	109.7
C6—C5—H5	120.0	H27A—C27—H27B	108.2
C4—C5—H5	120.0	C27—C28—S1	109.0 (2)
C1—C6—C5	118.7 (5)	C27—C28—H28A	109.9
C1—C6—H6	120.6	S1—C28—H28A	109.9
C5—C6—H6	120.6	C27—C28—H28B	109.9
O1—C7—C3	109.2 (3)	S1—C28—H28B	109.9
O1—C7—H7A	109.8	H28A—C28—H28B	108.3
C3—C7—H7A	109.8	S1—C29—H29A	109.5
O1—C7—H7B	109.8	S1—C29—H29B	109.5
C3—C7—H7B	109.8	H29A—C29—H29B	109.5
H7A—C7—H7B	108.3	S1—C29—H29C	109.5
O1—C8—C13	118.3 (3)	H29A—C29—H29C	109.5
O1—C8—C9	124.8 (3)	H29B—C29—H29C	109.5
C13—C8—C9	116.9 (4)	C14—N1—C11	130.1 (3)
C10—C9—C8	120.5 (3)	C14—N1—H1N	117 (2)
C10—C9—H9	119.7	C11—N1—H1N	113 (2)
C8—C9—H9	119.7	C14—N2—C21	116.6 (4)
C11—C10—C9	121.8 (3)	C21—N3—C20	114.2 (3)
C11—C10—H10	119.1	C27—N4—C26	112.9 (3)
C9—C10—H10	119.1	C27—N4—H2N	110 (2)
C10—C11—C12	118.1 (3)	C26—N4—H2N	113 (2)
C10—C11—N1	116.5 (3)	C27—N4—H3N	107.0 (19)
C12—C11—N1	125.3 (3)	C26—N4—H3N	108.4 (19)
C13—C12—C11	119.3 (3)	H2N—N4—H3N	104 (3)
C13—C12—H12	120.3	C8—O1—C7	116.3 (3)
C11—C12—H12	120.3	C25—O2—C22	106.3 (3)
C12—C13—C8	123.1 (3)	O3—S1—O4	116.1 (2)
C12—C13—Cl1	118.7 (3)	O3—S1—C29	110.2 (2)
C8—C13—Cl1	118.1 (3)	O4—S1—C29	109.8 (2)
N2—C14—N1	119.7 (3)	O3—S1—C28	108.96 (18)
N2—C14—C15	120.2 (3)	O4—S1—C28	107.56 (18)
N1—C14—C15	120.1 (3)	C29—S1—C28	103.4 (2)
C16—C15—C20	119.2 (3)	C35—C30—C31	118.4 (4)
C16—C15—C14	125.1 (3)	C35—C30—S2	121.1 (3)
C20—C15—C14	115.7 (3)	C31—C30—S2	120.4 (3)
C17—C16—C15	121.1 (3)	C32—C31—C30	119.9 (5)
C17—C16—H16	119.5	C32—C31—H31	120.1
C15—C16—H16	119.5	C30—C31—H31	120.1
C16—C17—C18	119.2 (3)	C33—C32—C31	122.1 (5)
C16—C17—C22	123.1 (3)	C33—C32—H32	118.9
C18—C17—C22	117.6 (3)	C31—C32—H32	118.9
C19—C18—C17	120.8 (3)	C34—C33—C32	117.2 (5)
C19—C18—H18	119.6	C34—C33—C36	121.1 (6)
C17—C18—H18	119.6	C32—C33—C36	121.6 (5)
C18—C19—C20	120.7 (3)	C33—C34—C35	122.4 (5)
C18—C19—H19	119.7	C33—C34—H34	118.8
C20—C19—H19	119.7	C35—C34—H34	118.8
N3—C20—C19	118.3 (3)	C30—C35—C34	120.0 (4)
N3—C20—C15	122.7 (4)	C30—C35—H35	120.0
C19—C20—C15	119.1 (3)	C34—C35—H35	120.0
N3—C21—N2	130.6 (4)	C33—C36—H36A	109.5
N3—C21—H21	114.7	C33—C36—H36B	109.5
N2—C21—H21	114.7	H36A—C36—H36B	109.5
C23—C22—O2	109.7 (3)	C33—C36—H36C	109.5
C23—C22—C17	132.8 (3)	H36A—C36—H36C	109.5
O2—C22—C17	117.5 (3)	H36B—C36—H36C	109.5
C22—C23—C24	106.6 (3)	O5—S2—O7	113.86 (17)
C22—C23—H25	126.7	O5—S2—O6	113.54 (17)
C24—C23—H25	126.7	O7—S2—O6	110.10 (15)
C25—C24—C23	106.6 (3)	O5—S2—C30	106.70 (17)
C25—C24—H24	126.7	O7—S2—C30	105.82 (18)
C23—C24—H24	126.7	O6—S2—C30	106.17 (17)
C24—C25—O2	110.8 (3)
F1—C1—C2—C3	179.9 (5)	O2—C22—C23—C24	−0.2 (4)
C6—C1—C2—C3	1.6 (8)	C17—C22—C23—C24	−179.8 (4)
C1—C2—C3—C4	−2.1 (7)	C22—C23—C24—C25	−0.7 (4)
C1—C2—C3—C7	175.1 (4)	C23—C24—C25—O2	1.3 (4)
C2—C3—C4—C5	2.1 (6)	C23—C24—C25—C26	177.8 (4)
C7—C3—C4—C5	−175.0 (4)	C24—C25—C26—N4	−88.6 (5)
C3—C4—C5—C6	−1.5 (7)	O2—C25—C26—N4	87.7 (3)
F1—C1—C6—C5	−179.3 (5)	N4—C27—C28—S1	−169.7 (2)
C2—C1—C6—C5	−1.0 (8)	N2—C14—N1—C11	−0.4 (6)
C4—C5—C6—C1	1.0 (7)	C15—C14—N1—C11	178.9 (3)
C4—C3—C7—O1	−40.2 (5)	C10—C11—N1—C14	−167.5 (4)
C2—C3—C7—O1	142.8 (4)	C12—C11—N1—C14	13.6 (6)
O1—C8—C9—C10	176.5 (4)	N1—C14—N2—C21	179.8 (4)
C13—C8—C9—C10	−3.3 (5)	C15—C14—N2—C21	0.5 (5)
C8—C9—C10—C11	−0.4 (6)	N3—C21—N2—C14	0.6 (8)
C9—C10—C11—C12	2.6 (5)	N2—C21—N3—C20	−0.4 (8)
C9—C10—C11—N1	−176.4 (3)	C19—C20—N3—C21	178.4 (4)
C10—C11—C12—C13	−1.0 (5)	C15—C20—N3—C21	−1.0 (6)
N1—C11—C12—C13	177.9 (3)	C28—C27—N4—C26	−175.5 (3)
C11—C12—C13—C8	−2.9 (6)	C25—C26—N4—C27	173.8 (3)
C11—C12—C13—Cl1	179.9 (3)	C13—C8—O1—C7	169.0 (4)
O1—C8—C13—C12	−174.8 (3)	C9—C8—O1—C7	−10.8 (5)
C9—C8—C13—C12	5.0 (6)	C3—C7—O1—C8	−173.9 (3)
O1—C8—C13—Cl1	2.4 (5)	C24—C25—O2—C22	−1.5 (4)
C9—C8—C13—Cl1	−177.8 (3)	C26—C25—O2—C22	−178.6 (3)
N2—C14—C15—C16	−179.6 (3)	C23—C22—O2—C25	1.0 (4)
N1—C14—C15—C16	1.1 (5)	C17—C22—O2—C25	−179.3 (3)
N2—C14—C15—C20	−1.6 (5)	C27—C28—S1—O3	71.8 (3)
N1—C14—C15—C20	179.1 (3)	C27—C28—S1—O4	−54.8 (3)
C20—C15—C16—C17	0.1 (5)	C27—C28—S1—C29	−170.9 (3)
C14—C15—C16—C17	178.0 (3)	C35—C30—C31—C32	1.0 (8)
C15—C16—C17—C18	−0.1 (5)	S2—C30—C31—C32	176.5 (5)
C15—C16—C17—C22	−177.4 (3)	C30—C31—C32—C33	1.0 (11)
C16—C17—C18—C19	−0.5 (5)	C31—C32—C33—C34	−2.6 (10)
C22—C17—C18—C19	176.9 (3)	C31—C32—C33—C36	179.2 (7)
C17—C18—C19—C20	1.2 (6)	C32—C33—C34—C35	2.1 (8)
C18—C19—C20—N3	179.3 (4)	C36—C33—C34—C35	−179.6 (5)
C18—C19—C20—C15	−1.3 (6)	C31—C30—C35—C34	−1.5 (6)
C16—C15—C20—N3	180.0 (3)	S2—C30—C35—C34	−176.9 (3)
C14—C15—C20—N3	1.9 (5)	C33—C34—C35—C30	−0.1 (8)
C16—C15—C20—C19	0.6 (5)	C35—C30—S2—O5	−18.8 (4)
C14—C15—C20—C19	−177.5 (3)	C31—C30—S2—O5	165.8 (4)
C16—C17—C22—C23	168.7 (4)	C35—C30—S2—O7	−140.4 (3)
C18—C17—C22—C23	−8.7 (6)	C31—C30—S2—O7	44.2 (4)
C16—C17—C22—O2	−10.9 (5)	C35—C30—S2—O6	102.6 (3)
C18—C17—C22—O2	171.8 (3)	C31—C30—S2—O6	−72.8 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O5	0.86 (2)	2.56 (2)	3.367 (4)	156 (3)
N4—H3N···O7	0.89 (2)	1.86 (2)	2.749 (4)	173 (3)
N4—H2N···O6^i	0.88 (2)	1.88 (2)	2.751 (4)	171 (4)
C10—H10···O5	0.93	2.43	3.228 (5)	144
C12—H12···N2	0.93	2.30	2.883 (5)	120
C26—H26B···O4^ii	0.97	2.61	3.369 (5)	135
C27—H27A···O6	0.97	2.54	3.257 (4)	131

Symmetry codes: (i) x+1, y, z; (ii) x−1/2, −y+1/2, −z+2.

(II) 4-({3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)-6-]5-({[2-(methylsulfonyl)ethyl]azaniumyl}methyl)furan-2-yl[quinazolin-1-ium bis(4-methylbenzenesulfonate)

Crystal data

C29H28ClFN4O4S^2+·2C7H7O3S^−	Z = 2
Mr = 925.44	F(000) = 964
Triclinic, P1	Dx = 1.403 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 9.2122 (6) Å	Cell parameters from 5462 reflections
b = 13.2387 (9) Å	θ = 2.3–24.0°
c = 18.3758 (12) Å	µ = 0.30 mm^−1
α = 95.387 (1)°	T = 294 K
β = 92.463 (1)°	Needle, colorless
γ = 100.359 (1)°	0.15 × 0.07 × 0.05 mm
V = 2190.7 (3) Å^3

Data collection

Bruker SMART APEX CCD area-detector diffractometer	7684 independent reflections
Radiation source: fine-focus sealed tube	5892 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.028
ω scan	θmax = 25.0°, θmin = 1.6°
Absorption correction: multi-scan (SABABS; Bruker, 2001)	h = −10→10
Tmin = 0.95, Tmax = 0.99	k = −15→15
21274 measured reflections	l = −21→21

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.062	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.174	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0898P)^2 + 1.6704P] where P = (Fo^2 + 2Fc^2)/3
7684 reflections	(Δ/σ)max < 0.001
633 parameters	Δρmax = 0.61 e Å^−3
244 restraints	Δρmin = −0.58 e Å^−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C3	1.4382 (5)	0.1251 (4)	0.5449 (3)	0.0932 (11)
C1	1.6136 (10)	0.1935 (8)	0.6432 (4)	0.0994 (11)	0.579 (10)
C2	1.5598 (9)	0.1953 (7)	0.5730 (4)	0.0973 (11)	0.579 (10)
H2	1.6059	0.2444	0.5443	0.117*	0.579 (10)
C4	1.3848 (10)	0.0436 (7)	0.5847 (4)	0.0954 (12)	0.579 (10)
H4	1.3079	−0.0082	0.5647	0.115*	0.579 (10)
C5	1.4465 (11)	0.0397 (7)	0.6547 (4)	0.0966 (12)	0.579 (10)
H5	1.4121	−0.0156	0.6810	0.116*	0.579 (10)
C6	1.5587 (13)	0.1177 (10)	0.6850 (5)	0.0977 (11)	0.579 (10)
H6	1.5959	0.1185	0.7329	0.117*	0.579 (10)
F1	1.7237 (8)	0.2691 (6)	0.6723 (3)	0.1044 (12)	0.579 (10)
C1'	1.6268 (11)	0.1817 (13)	0.6397 (5)	0.0993 (11)	0.421 (10)
C2'	1.5748 (11)	0.1804 (12)	0.5687 (5)	0.0973 (12)	0.421 (10)
H2'	1.6327	0.2173	0.5364	0.117*	0.421 (10)
C4'	1.3526 (10)	0.0722 (11)	0.5949 (5)	0.0956 (12)	0.421 (10)
H4'	1.2594	0.0343	0.5799	0.115*	0.421 (10)
C5'	1.4063 (11)	0.0760 (12)	0.6672 (5)	0.0968 (12)	0.421 (10)
H5'	1.3473	0.0429	0.7010	0.116*	0.421 (10)
C6'	1.5468 (14)	0.1286 (16)	0.6890 (6)	0.0979 (12)	0.421 (10)
H6'	1.5861	0.1277	0.7363	0.117*	0.421 (10)
F1'	1.7688 (8)	0.2235 (9)	0.6585 (5)	0.1031 (12)	0.421 (10)
C7	1.3831 (6)	0.1320 (5)	0.4684 (3)	0.0974 (17)
H7A	1.3524	0.1978	0.4650	0.117*
H7B	1.4615	0.1272	0.4354	0.117*
C8	1.1938 (5)	0.0461 (3)	0.3811 (2)	0.0641 (10)
C9	1.2369 (5)	0.1107 (4)	0.3282 (2)	0.0742 (12)
H9	1.3193	0.1631	0.3377	0.089*
C10	1.1584 (5)	0.0981 (3)	0.2613 (2)	0.0690 (11)
H10	1.1885	0.1419	0.2260	0.083*
C11	1.0371 (4)	0.0219 (3)	0.24671 (18)	0.0519 (9)
C12	0.9934 (5)	−0.0435 (3)	0.2986 (2)	0.0622 (10)
H12	0.9112	−0.0961	0.2887	0.075*
C13	1.0712 (5)	−0.0313 (3)	0.3650 (2)	0.0656 (11)
C14	0.9585 (3)	−0.0609 (2)	0.12440 (16)	0.0383 (7)
C15	0.8712 (3)	−0.0654 (2)	0.05690 (16)	0.0347 (6)
C16	0.7902 (3)	0.0095 (2)	0.03956 (16)	0.0360 (7)
H16	0.7911	0.0671	0.0728	0.043*
C17	0.7090 (3)	−0.0009 (2)	−0.02607 (16)	0.0356 (7)
C18	0.7050 (3)	−0.0896 (2)	−0.07516 (17)	0.0425 (7)
H18	0.6466	−0.0987	−0.1187	0.051*
C19	0.7859 (4)	−0.1627 (2)	−0.05968 (18)	0.0444 (8)
H19	0.7839	−0.2206	−0.0929	0.053*
C20	0.8710 (3)	−0.1504 (2)	0.00575 (16)	0.0372 (7)
C21	1.0440 (4)	−0.2043 (2)	0.08338 (19)	0.0460 (8)
H21	1.1052	−0.2516	0.0907	0.055*
C22	0.6292 (3)	0.0791 (2)	−0.04530 (16)	0.0366 (7)
C23	0.5463 (4)	0.0934 (3)	−0.10440 (17)	0.0455 (8)
H23	0.5205	0.0477	−0.1464	0.055*
C24	0.5061 (4)	0.1910 (3)	−0.09031 (19)	0.0488 (8)
H24	0.4496	0.2221	−0.1215	0.059*
C25	0.5647 (3)	0.2304 (2)	−0.02366 (18)	0.0426 (7)
C26	0.5518 (4)	0.3228 (3)	0.0249 (2)	0.0499 (8)
H26A	0.4847	0.3027	0.0625	0.060*
H26B	0.5092	0.3698	−0.0033	0.060*
C27	0.6770 (4)	0.4676 (3)	0.1117 (2)	0.0506 (8)
H27A	0.6082	0.4448	0.1479	0.061*
H27B	0.6366	0.5169	0.0848	0.061*
C28	0.8237 (4)	0.5180 (3)	0.1492 (2)	0.0553 (9)
H28A	0.8904	0.5436	0.1128	0.066*
H28B	0.8662	0.4672	0.1734	0.066*
C29	0.9865 (5)	0.6616 (3)	0.2530 (3)	0.0745 (12)
H29A	1.0187	0.6051	0.2741	0.112*
H29B	0.9890	0.7177	0.2905	0.112*
H29C	1.0510	0.6840	0.2157	0.112*
Cl1	1.0162 (2)	−0.11460 (11)	0.42947 (7)	0.1196 (6)
N1	0.9534 (4)	0.0115 (2)	0.17828 (16)	0.0534 (8)
H1N	0.883 (5)	0.039 (3)	0.179 (2)	0.065 (13)*
N2	1.0496 (3)	−0.1280 (2)	0.13479 (15)	0.0449 (6)
N3	0.9598 (3)	−0.2201 (2)	0.02225 (17)	0.0450 (7)
H3N	0.960 (4)	−0.269 (3)	−0.0050 (19)	0.042 (10)*
N4	0.6962 (3)	0.3779 (2)	0.06073 (18)	0.0423 (6)
H4N	0.740 (4)	0.342 (3)	0.084 (2)	0.053 (11)*
H5N	0.751 (4)	0.393 (3)	0.025 (2)	0.045 (10)*
O1	1.2627 (4)	0.0509 (2)	0.44838 (15)	0.0827 (9)
O2	0.6410 (2)	0.16301 (16)	0.00589 (11)	0.0400 (5)
O3	0.7153 (4)	0.5828 (3)	0.26913 (19)	0.0945 (11)
O4	0.7649 (4)	0.7023 (2)	0.1764 (2)	0.0884 (10)
S1	0.80573 (10)	0.62160 (7)	0.21453 (6)	0.0576 (3)
C30	0.7483 (4)	0.2540 (3)	0.30262 (18)	0.0486 (8)
C31	0.7192 (6)	0.3459 (3)	0.3335 (2)	0.0774 (13)
H31	0.6628	0.3833	0.3073	0.093*
C32	0.7749 (6)	0.3825 (4)	0.4043 (3)	0.0902 (16)
H32	0.7556	0.4455	0.4246	0.108*
C33	0.8564 (5)	0.3302 (3)	0.4452 (2)	0.0688 (11)
C34	0.8843 (6)	0.2390 (4)	0.4134 (2)	0.0795 (13)
H34	0.9409	0.2017	0.4397	0.095*
C35	0.8307 (5)	0.2009 (3)	0.3433 (2)	0.0714 (12)
H35	0.8508	0.1381	0.3232	0.086*
C36	0.9165 (7)	0.3705 (4)	0.5223 (2)	0.1003 (18)
H36A	1.0221	0.3772	0.5251	0.151*
H36B	0.8750	0.3232	0.5557	0.151*
H36C	0.8906	0.4367	0.5350	0.151*
O5	0.6890 (4)	0.0996 (2)	0.20398 (15)	0.0761 (8)
O6	0.5451 (4)	0.2338 (3)	0.19762 (18)	0.0947 (11)
O7	0.7944 (3)	0.2610 (2)	0.16591 (15)	0.0820 (9)
S2	0.68687 (10)	0.20802 (6)	0.21086 (5)	0.0480 (2)
C37	0.7794 (4)	0.5348 (3)	−0.1792 (2)	0.0502 (8)
C38	0.8595 (5)	0.6084 (3)	−0.2176 (2)	0.0654 (10)
H38	0.9395	0.6550	−0.1945	0.078*
C39	0.8207 (6)	0.6125 (4)	−0.2899 (3)	0.0898 (15)
H39	0.8778	0.6608	−0.3155	0.108*
C40	0.7027 (6)	0.5492 (6)	−0.3254 (3)	0.0962 (17)
C41	0.6245 (5)	0.4751 (5)	−0.2878 (3)	0.1011 (19)
H41	0.5450	0.4289	−0.3118	0.121*
C42	0.6612 (4)	0.4673 (4)	−0.2143 (2)	0.0773 (13)
H42	0.6062	0.4169	−0.1895	0.093*
C43	0.6548 (8)	0.5570 (7)	−0.4050 (3)	0.153 (3)
H43A	0.5880	0.6048	−0.4065	0.229*
H43B	0.6061	0.4903	−0.4272	0.229*
H43C	0.7401	0.5808	−0.4312	0.229*
O8	0.7021 (3)	0.5569 (2)	−0.04567 (15)	0.0664 (7)
O9	0.9604 (3)	0.60424 (17)	−0.06784 (13)	0.0503 (6)
O10	0.8426 (3)	0.42505 (17)	−0.07730 (14)	0.0563 (6)
S3	0.82358 (9)	0.52955 (6)	−0.08538 (5)	0.0431 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C3	0.0821 (18)	0.120 (2)	0.0677 (16)	−0.0028 (17)	−0.0257 (14)	0.0162 (16)
C1	0.0852 (17)	0.126 (2)	0.0755 (16)	−0.0037 (16)	−0.0277 (14)	0.0093 (16)
C2	0.0845 (18)	0.124 (2)	0.0726 (17)	−0.0045 (17)	−0.0260 (15)	0.0127 (17)
C4	0.0844 (19)	0.122 (2)	0.0699 (18)	−0.0027 (18)	−0.0249 (16)	0.0164 (17)
C5	0.0854 (19)	0.124 (2)	0.0709 (17)	−0.0022 (18)	−0.0243 (15)	0.0153 (17)
C6	0.0855 (18)	0.125 (2)	0.0720 (17)	−0.0020 (17)	−0.0259 (15)	0.0125 (16)
F1	0.0883 (19)	0.129 (2)	0.0830 (17)	−0.0040 (18)	−0.0293 (16)	0.0037 (18)
C1'	0.0853 (17)	0.126 (2)	0.0755 (16)	−0.0036 (16)	−0.0275 (14)	0.0095 (16)
C2'	0.0845 (18)	0.124 (2)	0.0727 (17)	−0.0043 (18)	−0.0261 (15)	0.0126 (17)
C4'	0.0843 (19)	0.123 (2)	0.0700 (18)	−0.0027 (18)	−0.0247 (16)	0.0162 (18)
C5'	0.0854 (19)	0.124 (2)	0.0711 (17)	−0.0024 (18)	−0.0246 (16)	0.0149 (17)
C6'	0.0857 (18)	0.125 (2)	0.0723 (17)	−0.0024 (17)	−0.0260 (15)	0.0125 (16)
F1'	0.087 (2)	0.129 (3)	0.0816 (18)	−0.0029 (18)	−0.0278 (16)	0.0053 (18)
C7	0.095 (4)	0.123 (4)	0.062 (3)	−0.011 (3)	−0.030 (3)	0.026 (3)
C8	0.073 (3)	0.076 (3)	0.042 (2)	0.016 (2)	−0.0180 (19)	0.0068 (19)
C9	0.076 (3)	0.088 (3)	0.052 (2)	−0.001 (2)	−0.014 (2)	0.010 (2)
C10	0.080 (3)	0.081 (3)	0.044 (2)	0.011 (2)	−0.009 (2)	0.013 (2)
C11	0.069 (2)	0.053 (2)	0.0366 (18)	0.0266 (18)	−0.0100 (16)	−0.0023 (16)
C12	0.079 (3)	0.052 (2)	0.053 (2)	0.0109 (19)	−0.0178 (19)	0.0035 (18)
C13	0.091 (3)	0.059 (2)	0.046 (2)	0.011 (2)	−0.017 (2)	0.0096 (18)
C14	0.0420 (17)	0.0336 (16)	0.0391 (17)	0.0056 (13)	0.0020 (13)	0.0060 (13)
C15	0.0347 (15)	0.0328 (15)	0.0364 (16)	0.0041 (12)	0.0048 (12)	0.0056 (12)
C16	0.0402 (16)	0.0330 (15)	0.0339 (16)	0.0066 (13)	0.0007 (13)	0.0002 (12)
C17	0.0341 (15)	0.0362 (16)	0.0354 (16)	0.0031 (12)	0.0031 (12)	0.0042 (12)
C18	0.0439 (17)	0.0435 (18)	0.0350 (16)	−0.0020 (14)	−0.0017 (13)	−0.0012 (14)
C19	0.0528 (19)	0.0339 (17)	0.0427 (18)	0.0030 (14)	0.0016 (15)	−0.0050 (13)
C20	0.0392 (16)	0.0302 (15)	0.0410 (17)	0.0020 (13)	0.0069 (13)	0.0044 (13)
C21	0.0491 (19)	0.0398 (18)	0.052 (2)	0.0138 (15)	0.0055 (16)	0.0094 (15)
C22	0.0359 (16)	0.0379 (16)	0.0329 (16)	0.0002 (13)	−0.0009 (12)	0.0020 (13)
C23	0.0459 (18)	0.0497 (19)	0.0375 (17)	0.0020 (15)	−0.0071 (14)	0.0049 (14)
C24	0.0433 (18)	0.054 (2)	0.050 (2)	0.0089 (15)	−0.0105 (15)	0.0146 (16)
C25	0.0352 (16)	0.0418 (17)	0.052 (2)	0.0097 (13)	−0.0023 (14)	0.0110 (15)
C26	0.0383 (18)	0.048 (2)	0.065 (2)	0.0150 (15)	−0.0052 (16)	0.0051 (17)
C27	0.0459 (19)	0.0469 (19)	0.060 (2)	0.0148 (15)	0.0016 (16)	−0.0020 (16)
C28	0.0459 (19)	0.048 (2)	0.071 (2)	0.0106 (16)	0.0058 (17)	−0.0033 (18)
C29	0.063 (3)	0.072 (3)	0.082 (3)	0.008 (2)	−0.019 (2)	−0.007 (2)
Cl1	0.1692 (15)	0.0991 (10)	0.0735 (8)	−0.0261 (9)	−0.0422 (9)	0.0427 (7)
N1	0.067 (2)	0.0552 (19)	0.0418 (16)	0.0308 (16)	−0.0141 (14)	−0.0030 (13)
N2	0.0485 (16)	0.0417 (15)	0.0471 (16)	0.0151 (12)	−0.0010 (12)	0.0072 (12)
N3	0.0523 (17)	0.0313 (15)	0.0522 (18)	0.0108 (13)	0.0073 (14)	0.0007 (13)
N4	0.0413 (16)	0.0399 (16)	0.0480 (17)	0.0118 (13)	0.0031 (14)	0.0076 (13)
O1	0.093 (2)	0.095 (2)	0.0513 (16)	−0.0023 (18)	−0.0295 (15)	0.0160 (15)
O2	0.0392 (11)	0.0414 (12)	0.0395 (12)	0.0111 (9)	−0.0078 (9)	0.0018 (9)
O3	0.082 (2)	0.093 (2)	0.102 (3)	0.0019 (18)	0.0345 (19)	−0.0135 (19)
O4	0.088 (2)	0.0536 (17)	0.124 (3)	0.0278 (15)	−0.0257 (19)	−0.0053 (17)
S1	0.0489 (5)	0.0459 (5)	0.0750 (7)	0.0099 (4)	−0.0017 (5)	−0.0092 (4)
C30	0.058 (2)	0.0436 (19)	0.0425 (19)	0.0048 (16)	0.0002 (15)	0.0050 (15)
C31	0.113 (4)	0.061 (3)	0.060 (3)	0.031 (2)	−0.017 (2)	−0.006 (2)
C32	0.141 (5)	0.061 (3)	0.066 (3)	0.028 (3)	−0.015 (3)	−0.017 (2)
C33	0.093 (3)	0.061 (3)	0.045 (2)	−0.003 (2)	−0.005 (2)	0.0061 (19)
C34	0.109 (4)	0.082 (3)	0.053 (2)	0.031 (3)	−0.010 (2)	0.015 (2)
C35	0.102 (3)	0.067 (3)	0.051 (2)	0.034 (2)	−0.007 (2)	0.0000 (19)
C36	0.145 (5)	0.087 (3)	0.055 (3)	−0.007 (3)	−0.023 (3)	−0.001 (2)
O5	0.120 (2)	0.0518 (16)	0.0538 (16)	0.0121 (16)	−0.0035 (16)	0.0000 (12)
O6	0.079 (2)	0.121 (3)	0.082 (2)	0.042 (2)	−0.0255 (17)	−0.0286 (19)
O7	0.083 (2)	0.096 (2)	0.0549 (17)	−0.0171 (17)	−0.0118 (14)	0.0182 (15)
S2	0.0552 (5)	0.0434 (5)	0.0433 (5)	0.0066 (4)	−0.0052 (4)	0.0020 (4)
C37	0.0402 (18)	0.055 (2)	0.058 (2)	0.0177 (16)	0.0017 (16)	0.0029 (17)
C38	0.067 (2)	0.066 (3)	0.066 (3)	0.014 (2)	−0.001 (2)	0.019 (2)
C39	0.095 (4)	0.113 (4)	0.069 (3)	0.028 (3)	0.005 (3)	0.033 (3)
C40	0.076 (3)	0.156 (5)	0.064 (3)	0.044 (4)	0.000 (3)	0.011 (3)
C41	0.056 (3)	0.159 (6)	0.077 (3)	0.011 (3)	−0.012 (2)	−0.026 (4)
C42	0.052 (2)	0.101 (3)	0.070 (3)	−0.003 (2)	0.006 (2)	−0.007 (2)
C43	0.145 (6)	0.253 (10)	0.073 (4)	0.079 (6)	−0.020 (4)	0.012 (5)
O8	0.0580 (16)	0.0799 (18)	0.0708 (18)	0.0319 (14)	0.0207 (13)	0.0126 (14)
O9	0.0550 (14)	0.0410 (12)	0.0534 (14)	0.0097 (10)	0.0005 (11)	−0.0030 (10)
O10	0.0565 (14)	0.0410 (13)	0.0737 (17)	0.0141 (11)	0.0025 (12)	0.0084 (12)
S3	0.0424 (4)	0.0393 (4)	0.0511 (5)	0.0155 (3)	0.0071 (4)	0.0048 (3)

Geometric parameters (Å, º)

C3—C2	1.368 (6)	C24—H24	0.9300
C3—C2'	1.368 (7)	C25—O2	1.366 (4)
C3—C4	1.389 (7)	C25—C26	1.472 (5)
C3—C4'	1.393 (8)	C26—N4	1.490 (4)
C3—C7	1.491 (6)	C26—H26A	0.9700
C1—F1	1.343 (5)	C26—H26B	0.9700
C1—C6	1.359 (6)	C27—N4	1.484 (4)
C1—C2	1.366 (5)	C27—C28	1.502 (5)
C2—H2	0.9300	C27—H27A	0.9700
C4—C5	1.392 (5)	C27—H27B	0.9700
C4—H4	0.9300	C28—S1	1.772 (4)
C5—C6	1.380 (6)	C28—H28A	0.9700
C5—H5	0.9300	C28—H28B	0.9700
C6—H6	0.9300	C29—S1	1.751 (4)
C1'—F1'	1.342 (5)	C29—H29A	0.9600
C1'—C6'	1.360 (6)	C29—H29B	0.9600
C1'—C2'	1.367 (5)	C29—H29C	0.9600
C2'—H2'	0.9300	N1—H1N	0.79 (4)
C4'—C5'	1.391 (6)	N3—H3N	0.78 (3)
C4'—H4'	0.9300	N4—H4N	0.82 (4)
C5'—C6'	1.378 (6)	N4—H5N	0.86 (4)
C5'—H5'	0.9300	O3—S1	1.407 (3)
C6'—H6'	0.9300	O4—S1	1.427 (3)
C7—O1	1.407 (6)	C30—C35	1.368 (5)
C7—H7A	0.9700	C30—C31	1.368 (5)
C7—H7B	0.9700	C30—S2	1.771 (3)
C8—O1	1.356 (4)	C31—C32	1.388 (6)
C8—C9	1.379 (6)	C31—H31	0.9300
C8—C13	1.382 (6)	C32—C33	1.359 (6)
C9—C10	1.379 (5)	C32—H32	0.9300
C9—H9	0.9300	C33—C34	1.362 (6)
C10—C11	1.362 (6)	C33—C36	1.510 (6)
C10—H10	0.9300	C34—C35	1.376 (6)
C11—C12	1.373 (5)	C34—H34	0.9300
C11—N1	1.428 (4)	C35—H35	0.9300
C12—C13	1.369 (5)	C36—H36A	0.9600
C12—H12	0.9300	C36—H36B	0.9600
C13—Cl1	1.725 (4)	C36—H36C	0.9600
C14—N1	1.320 (4)	O5—S2	1.432 (3)
C14—N2	1.347 (4)	O6—S2	1.425 (3)
C14—C15	1.440 (4)	O7—S2	1.444 (3)
C15—C16	1.396 (4)	C37—C42	1.372 (5)
C15—C20	1.396 (4)	C37—C38	1.381 (5)
C16—C17	1.374 (4)	C37—S3	1.765 (4)
C16—H16	0.9300	C38—C39	1.369 (6)
C17—C18	1.407 (4)	C38—H38	0.9300
C17—C22	1.454 (4)	C39—C40	1.348 (7)
C18—C19	1.366 (4)	C39—H39	0.9300
C18—H18	0.9300	C40—C41	1.369 (8)
C19—C20	1.387 (4)	C40—C43	1.527 (7)
C19—H19	0.9300	C41—C42	1.396 (7)
C20—N3	1.384 (4)	C41—H41	0.9300
C21—N2	1.309 (4)	C42—H42	0.9300
C21—N3	1.315 (4)	C43—H43A	0.9600
C21—H21	0.9300	C43—H43B	0.9600
C22—C23	1.349 (4)	C43—H43C	0.9600
C22—O2	1.372 (3)	O8—S3	1.443 (2)
C23—C24	1.411 (5)	O9—S3	1.458 (2)
C23—H23	0.9300	O10—S3	1.446 (2)
C24—C25	1.336 (5)
C2—C3—C4	118.7 (5)	N4—C26—H26B	109.0
C2'—C3—C4	115.4 (6)	H26A—C26—H26B	107.8
C2—C3—C4'	116.9 (6)	N4—C27—C28	109.5 (3)
C2'—C3—C4'	118.5 (6)	N4—C27—H27A	109.8
C2—C3—C7	117.6 (5)	C28—C27—H27A	109.8
C2'—C3—C7	118.1 (5)	N4—C27—H27B	109.8
C4—C3—C7	123.1 (5)	C28—C27—H27B	109.8
C4'—C3—C7	123.2 (5)	H27A—C27—H27B	108.2
F1—C1—C6	118.7 (5)	C27—C28—S1	111.5 (2)
F1—C1—C2	119.2 (5)	C27—C28—H28A	109.3
C6—C1—C2	122.1 (5)	S1—C28—H28A	109.3
C1—C2—C3	120.0 (5)	C27—C28—H28B	109.3
C1—C2—H2	120.0	S1—C28—H28B	109.3
C3—C2—H2	120.0	H28A—C28—H28B	108.0
C3—C4—C5	120.0 (5)	S1—C29—H29A	109.5
C3—C4—H4	120.0	S1—C29—H29B	109.5
C5—C4—H4	120.0	H29A—C29—H29B	109.5
C6—C5—C4	120.0 (6)	S1—C29—H29C	109.5
C6—C5—H5	120.0	H29A—C29—H29C	109.5
C4—C5—H5	120.0	H29B—C29—H29C	109.5
C1—C6—C5	118.5 (5)	C14—N1—C11	124.0 (3)
C1—C6—H6	120.7	C14—N1—H1N	118 (3)
C5—C6—H6	120.7	C11—N1—H1N	115 (3)
F1'—C1'—C6'	118.3 (5)	C21—N2—C14	116.7 (3)
F1'—C1'—C2'	118.9 (5)	C21—N3—C20	120.4 (3)
C6'—C1'—C2'	122.0 (5)	C21—N3—H3N	120 (3)
C1'—C2'—C3	120.5 (6)	C20—N3—H3N	119 (3)
C1'—C2'—H2'	119.8	C27—N4—C26	111.2 (3)
C3—C2'—H2'	119.8	C27—N4—H4N	107 (3)
C5'—C4'—C3	120.2 (6)	C26—N4—H4N	114 (3)
C5'—C4'—H4'	119.9	C27—N4—H5N	115 (2)
C3—C4'—H4'	119.9	C26—N4—H5N	105 (2)
C6'—C5'—C4'	120.1 (6)	H4N—N4—H5N	105 (3)
C6'—C5'—H5'	120.0	C8—O1—C7	118.0 (3)
C4'—C5'—H5'	120.0	C25—O2—C22	106.6 (2)
C1'—C6'—C5'	118.6 (5)	O3—S1—O4	118.4 (2)
C1'—C6'—H6'	120.7	O3—S1—C29	108.4 (2)
C5'—C6'—H6'	120.7	O4—S1—C29	109.0 (2)
O1—C7—C3	109.1 (4)	O3—S1—C28	108.91 (19)
O1—C7—H7A	109.9	O4—S1—C28	108.3 (2)
C3—C7—H7A	109.9	C29—S1—C28	102.56 (19)
O1—C7—H7B	109.9	C35—C30—C31	118.5 (3)
C3—C7—H7B	109.9	C35—C30—S2	120.9 (3)
H7A—C7—H7B	108.3	C31—C30—S2	120.5 (3)
O1—C8—C9	125.5 (4)	C30—C31—C32	119.3 (4)
O1—C8—C13	116.3 (4)	C30—C31—H31	120.3
C9—C8—C13	118.2 (3)	C32—C31—H31	120.3
C8—C9—C10	120.4 (4)	C33—C32—C31	122.6 (4)
C8—C9—H9	119.8	C33—C32—H32	118.7
C10—C9—H9	119.8	C31—C32—H32	118.7
C11—C10—C9	120.5 (4)	C32—C33—C34	117.1 (4)
C11—C10—H10	119.7	C32—C33—C36	122.4 (4)
C9—C10—H10	119.7	C34—C33—C36	120.6 (4)
C10—C11—C12	119.8 (3)	C33—C34—C35	121.5 (4)
C10—C11—N1	120.2 (3)	C33—C34—H34	119.2
C12—C11—N1	120.0 (4)	C35—C34—H34	119.2
C13—C12—C11	119.8 (4)	C30—C35—C34	120.9 (4)
C13—C12—H12	120.1	C30—C35—H35	119.5
C11—C12—H12	120.1	C34—C35—H35	119.5
C12—C13—C8	121.3 (4)	C33—C36—H36A	109.5
C12—C13—Cl1	119.4 (3)	C33—C36—H36B	109.5
C8—C13—Cl1	119.3 (3)	H36A—C36—H36B	109.5
N1—C14—N2	117.6 (3)	C33—C36—H36C	109.5
N1—C14—C15	120.4 (3)	H36A—C36—H36C	109.5
N2—C14—C15	122.0 (3)	H36B—C36—H36C	109.5
C16—C15—C20	118.9 (3)	O6—S2—O5	114.9 (2)
C16—C15—C14	124.4 (3)	O6—S2—O7	111.2 (2)
C20—C15—C14	116.7 (3)	O5—S2—O7	110.6 (2)
C17—C16—C15	120.8 (3)	O6—S2—C30	107.84 (18)
C17—C16—H16	119.6	O5—S2—C30	105.92 (16)
C15—C16—H16	119.6	O7—S2—C30	105.89 (16)
C16—C17—C18	119.2 (3)	C42—C37—C38	119.1 (4)
C16—C17—C22	120.7 (3)	C42—C37—S3	120.0 (3)
C18—C17—C22	120.1 (3)	C38—C37—S3	120.9 (3)
C19—C18—C17	120.8 (3)	C39—C38—C37	119.8 (4)
C19—C18—H18	119.6	C39—C38—H38	120.1
C17—C18—H18	119.6	C37—C38—H38	120.1
C18—C19—C20	119.7 (3)	C40—C39—C38	122.5 (5)
C18—C19—H19	120.1	C40—C39—H39	118.7
C20—C19—H19	120.1	C38—C39—H39	118.7
N3—C20—C19	121.7 (3)	C39—C40—C41	117.8 (5)
N3—C20—C15	117.8 (3)	C39—C40—C43	122.7 (6)
C19—C20—C15	120.5 (3)	C41—C40—C43	119.5 (6)
N2—C21—N3	126.0 (3)	C40—C41—C42	121.5 (5)
N2—C21—H21	117.0	C40—C41—H41	119.2
N3—C21—H21	117.0	C42—C41—H41	119.2
C23—C22—O2	109.3 (3)	C37—C42—C41	119.2 (5)
C23—C22—C17	134.9 (3)	C37—C42—H42	120.4
O2—C22—C17	115.7 (2)	C41—C42—H42	120.4
C22—C23—C24	107.0 (3)	C40—C43—H43A	109.5
C22—C23—H23	126.5	C40—C43—H43B	109.5
C24—C23—H23	126.5	H43A—C43—H43B	109.5
C25—C24—C23	107.0 (3)	C40—C43—H43C	109.5
C25—C24—H24	126.5	H43A—C43—H43C	109.5
C23—C24—H24	126.5	H43B—C43—H43C	109.5
C24—C25—O2	110.1 (3)	O8—S3—O10	112.16 (16)
C24—C25—C26	133.8 (3)	O8—S3—O9	112.42 (16)
O2—C25—C26	115.8 (3)	O10—S3—O9	112.28 (14)
C25—C26—N4	113.0 (3)	O8—S3—C37	107.22 (16)
C25—C26—H26A	109.0	O10—S3—C37	106.76 (16)
N4—C26—H26A	109.0	O9—S3—C37	105.46 (16)
C25—C26—H26B	109.0
F1—C1—C2—C3	−173.4 (11)	C16—C17—C22—O2	−0.2 (4)
C6—C1—C2—C3	6.2 (15)	C18—C17—C22—O2	−179.5 (2)
C2'—C3—C2—C1	−85 (2)	O2—C22—C23—C24	0.9 (3)
C4—C3—C2—C1	−9.4 (10)	C17—C22—C23—C24	−176.8 (3)
C4'—C3—C2—C1	16.1 (11)	C22—C23—C24—C25	−0.7 (4)
C7—C3—C2—C1	179.1 (7)	C23—C24—C25—O2	0.1 (4)
C2—C3—C4—C5	5.8 (13)	C23—C24—C25—C26	−172.9 (4)
C2'—C3—C4—C5	17.9 (15)	C24—C25—C26—N4	−137.0 (4)
C4'—C3—C4—C5	−85.6 (14)	O2—C25—C26—N4	50.3 (4)
C7—C3—C4—C5	176.8 (8)	N4—C27—C28—S1	−176.8 (3)
C3—C4—C5—C6	1.2 (17)	N2—C14—N1—C11	−0.7 (5)
F1—C1—C6—C5	−179.5 (11)	C15—C14—N1—C11	−179.6 (3)
C2—C1—C6—C5	1 (2)	C10—C11—N1—C14	104.6 (4)
C4—C5—C6—C1	−5 (2)	C12—C11—N1—C14	−76.8 (5)
F1'—C1'—C2'—C3	170.1 (16)	N3—C21—N2—C14	1.3 (5)
C6'—C1'—C2'—C3	0 (3)	N1—C14—N2—C21	174.4 (3)
C2—C3—C2'—C1'	86 (3)	C15—C14—N2—C21	−6.7 (4)
C4—C3—C2'—C1'	−23.9 (19)	N2—C21—N3—C20	3.1 (5)
C4'—C3—C2'—C1'	1 (2)	C19—C20—N3—C21	177.2 (3)
C7—C3—C2'—C1'	176.1 (12)	C15—C20—N3—C21	−1.8 (4)
C2—C3—C4'—C5'	−12.7 (17)	C28—C27—N4—C26	177.4 (3)
C2'—C3—C4'—C5'	−0.1 (19)	C25—C26—N4—C27	−177.4 (3)
C4—C3—C4'—C5'	88.0 (16)	C9—C8—O1—C7	4.1 (7)
C7—C3—C4'—C5'	−174.6 (10)	C13—C8—O1—C7	−176.7 (4)
C3—C4'—C5'—C6'	−3 (2)	C3—C7—O1—C8	177.8 (4)
F1'—C1'—C6'—C5'	−173.0 (16)	C24—C25—O2—C22	0.5 (3)
C2'—C1'—C6'—C5'	−3 (3)	C26—C25—O2—C22	174.9 (3)
C4'—C5'—C6'—C1'	4 (3)	C23—C22—O2—C25	−0.9 (3)
C2—C3—C7—O1	177.2 (7)	C17—C22—O2—C25	177.3 (2)
C2'—C3—C7—O1	164.5 (10)	C27—C28—S1—O3	62.2 (3)
C4—C3—C7—O1	6.1 (10)	C27—C28—S1—O4	−67.9 (3)
C4'—C3—C7—O1	−21.0 (11)	C27—C28—S1—C29	176.9 (3)
O1—C8—C9—C10	179.6 (4)	C35—C30—C31—C32	0.6 (7)
C13—C8—C9—C10	0.4 (7)	S2—C30—C31—C32	−176.9 (4)
C8—C9—C10—C11	0.2 (7)	C30—C31—C32—C33	−0.8 (8)
C9—C10—C11—C12	−0.7 (6)	C31—C32—C33—C34	1.0 (8)
C9—C10—C11—N1	177.9 (4)	C31—C32—C33—C36	−180.0 (5)
C10—C11—C12—C13	0.6 (6)	C32—C33—C34—C35	−0.9 (7)
N1—C11—C12—C13	−178.0 (4)	C36—C33—C34—C35	−180.0 (5)
C11—C12—C13—C8	0.0 (6)	C31—C30—C35—C34	−0.5 (7)
C11—C12—C13—Cl1	−179.5 (3)	S2—C30—C35—C34	176.9 (4)
O1—C8—C13—C12	−179.8 (4)	C33—C34—C35—C30	0.7 (8)
C9—C8—C13—C12	−0.5 (7)	C35—C30—S2—O6	145.3 (4)
O1—C8—C13—Cl1	−0.3 (6)	C31—C30—S2—O6	−37.3 (4)
C9—C8—C13—Cl1	179.0 (4)	C35—C30—S2—O5	21.9 (4)
N1—C14—C15—C16	7.5 (5)	C31—C30—S2—O5	−160.8 (4)
N2—C14—C15—C16	−171.3 (3)	C35—C30—S2—O7	−95.6 (4)
N1—C14—C15—C20	−173.5 (3)	C31—C30—S2—O7	81.8 (4)
N2—C14—C15—C20	7.7 (4)	C42—C37—C38—C39	−0.4 (6)
C20—C15—C16—C17	1.3 (4)	S3—C37—C38—C39	−178.3 (3)
C14—C15—C16—C17	−179.7 (3)	C37—C38—C39—C40	2.3 (7)
C15—C16—C17—C18	1.7 (4)	C38—C39—C40—C41	−3.3 (8)
C15—C16—C17—C22	−177.6 (3)	C38—C39—C40—C43	177.0 (5)
C16—C17—C18—C19	−3.0 (4)	C39—C40—C41—C42	2.4 (8)
C22—C17—C18—C19	176.3 (3)	C43—C40—C41—C42	−177.8 (5)
C17—C18—C19—C20	1.1 (5)	C38—C37—C42—C41	−0.4 (6)
C18—C19—C20—N3	−177.1 (3)	S3—C37—C42—C41	177.6 (4)
C18—C19—C20—C15	1.9 (5)	C40—C41—C42—C37	−0.6 (8)
C16—C15—C20—N3	175.9 (3)	C42—C37—S3—O8	−64.9 (4)
C14—C15—C20—N3	−3.2 (4)	C38—C37—S3—O8	113.0 (3)
C16—C15—C20—C19	−3.1 (4)	C42—C37—S3—O10	55.4 (3)
C14—C15—C20—C19	177.8 (3)	C38—C37—S3—O10	−126.7 (3)
C16—C17—C22—C23	177.5 (3)	C42—C37—S3—O9	175.0 (3)
C18—C17—C22—C23	−1.8 (5)	C38—C37—S3—O9	−7.0 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O5	0.79 (4)	2.14 (4)	2.922 (5)	168 (4)
N3—H3N···O9^i	0.78 (3)	1.95 (4)	2.726 (4)	176 (4)
N4—H4N···O7	0.82 (4)	2.02 (4)	2.804 (4)	161 (4)
N4—H5N···O10	0.86 (4)	2.14 (4)	2.988 (4)	167 (3)
C5—H5···O5^ii	0.93	2.61	3.472 (8)	154
C18—H18···O6^iii	0.93	2.57	3.344 (4)	142
C21—H21···O10^iv	0.93	2.42	3.270 (4)	152
C23—H23···O5^iii	0.93	2.59	3.371 (4)	142
C24—H24···O4^v	0.93	2.58	3.475 (4)	162
C27—H27B···O8	0.97	2.58	3.228 (5)	125
C28—H28A···O10^vi	0.97	2.54	3.387 (4)	145
C34—H34···Cl1^ii	0.93	2.81	3.619 (4)	147
C38—H38···O7^vi	0.93	2.51	3.392 (5)	158

Symmetry codes: (i) x, y−1, z; (ii) −x+2, −y, −z+1; (iii) −x+1, −y, −z; (iv) −x+2, −y, −z; (v) −x+1, −y+1, −z; (vi) −x+2, −y+1, −z.