9-(2,6-Difluoro­phenoxy­carbonyl)-10-methyl­acridinium trifluoro­methane­sulfonate and its precursor 2,6-difluoro­phenyl acridine-9-carboxyl­ate: C—H...O, C—F...π, S—O...π and π–π stacking inter­actions

The title compounds, C₂₁H₁₄F₂NO₂⁺·CF₃SO₃⁻, (I), and C₂₀H₁₁F₂NO₂, (II), form monoclinic and triclinic crystals, respectively. Adjacent cations of (I) are oriented in a `head-to-tail' manner and are linked to one another via networks of C—H...O, C—F...π, S—O...π and multidirectional π–π inter­actions. Adjacent mol­ecules of (II) are also arranged in a `head-to-tail' manner and are linked via networks of C—H...O and multidirectional π–π inter­actions. The mean planes of the acridine moieties lie parallel in the lattices of both compounds. The benzene rings are also parallel. However, the acridine and difluoro­phenyl rings are mutually oriented at an angle of 17.3 (2)° in (I) and 5.8 (2)° in (II). This mutual orientation in various phenyl acridine-9-carboxyl­ates and related compounds is strongly influenced by the nature of the substituents on the phenyl fragment.

S1. Comment

Most commercially available immunoassay tests utilizing chemiluminescence employ derivatives of acridine-9-carboxylic acid (Weeks et al., 1986; Rongen et al., 1994; Razawi & McCapra, 2000a,b; Smith et al., 2000). Sensitivities at the attomole level are available with this method, which makes acridine-based labels more profitable than standard radioisotopic techniques (e.g. ¹²⁵I or ³H) (Zomer & Jacquemijns, 2001). Among the most frequently used of these derivatives are the phenyl esters of the 10-methylacridinium-9-carboxylic acid cation (Dodeigne et al., 2000), although other compounds, like hydroxamic or sulfohydroxamic esters, have been tested in order to develop new assay options (Renotte et al., 2000). These compounds react with H₂O₂ in alkaline media to produce molecules of electronically excited 10-methyl-9-acridinone (Rak et al., 1999), which emits light. The intensity of the light is related directly to the concentration of the entity assayed and this is the foundation for the analytical application of chemiluminescence. Nevertheless, the use of acridinium esters for labelling biomolecules entails certain disadvantages. Although their chemiluminescence efficiency in aqueous solutions is relatively high (up to 10%), they are not very stable (Rak et al., 1999; Razawi & McCapra, 2000a,b): they can react relatively fast with OH⁻, which attacks the C atom in position 9. Many attempts have been made to enhance their resistance to hydrolysis, since this reaction competes with the chemiluminescence pathway in alkaline media, yielding a non-luminescent product, the non-excited 10-methyl-9-acridinone (Hammond et al., 1991). Since the phenyl fragment is removed during oxidation of phenyl 10-methylacridinium 9-carboxylates, it is thought that the phenyl ring substituents exert the greatest influence on the ability to chemiluminesce and on the properties of this group of compounds (Sato, 1996; Rak et al., 1999). Wilson et al. (2001) noted that reduction of 9-(2,6-difluorophenoxycarbonyl)-10-methylacridinium (the title cation) yielded the corresponding ester of acridan, which is not susceptible to nucleophilic substitution (and thus hydrolysis). In this case, chemiluminescence was triggered by the cathodic oxidation of the acridan, which regenerates to the original acridinium salt and decomposes to the electronically excited 10-methyl-9-acridinone (a light emitter). It can thus be expected that the presence of F atoms in the phenyl ring will improve the resistance of such compounds to alkaline hydrolysis, and enhance their susceptibility to oxidation and their chemiluminescence ability. These were the premises for undertaking investigations on the title chemiluminogens, 9-(2,6-difluorophenoxycarbonyl)-10-methylacridinium trifluoromethanesulfonate, (I), and 2,6-difluorophenyl acridine-9-carboxylate, (II).

In this paper, we present the results of our crystal structure investigations, which were paralleled by laboratory studies on the relationship between the structural and chemiluminogenic properties of this group of compounds.

Parameters characterizing the geometry of the central ring of the acridine moiety and the carboxyl fragment in (I) are given in Table 1. The acridine moiety, with an average deviation from planarity for its constituent atoms of 0.015 Å, and the phenyl ring in (I) are mutually oriented at an angle of 17.3 (2)° (denoted by δ, this is the angle between the mean planes delineated by all the non-H atoms of the acridine and phenyl moieties) (Fig. 1). The carboxyl group is twisted at an angle of 67.6 (2)° relative to the acridine skeleton (denoted by ε, this is the angle between the mean planes delineated by all the non-H atoms of the acridine moiety and atoms C15, O16 and O17). The H atoms of the methyl group are disordered over two orientations, twisted through 60° with respect to one another, each with an occupancy of 0.5.

In the crystalline phase, two adjacent cations of (I), arranged in a `head-to-tail' manner and related by a centre of symmetry, are linked via two C—H···O interactions to yield dimers, which are, in turn, linked to anions via C—H···O interactions to form strips (Fig. 2 and Table 2). These strips are linked by networks of two types of C—H···O, C—F···π, S—O···π and π–π transverse interactions involving F atoms, O atoms from the anion, and the acridine or phenyl rings (Fig. 2, Tables 3 and 4). This variety of interactions, rare in other acridine derivatives, accounts for the stability of the crystalline phase of (I).

Parameters characterizing the geometry of the central ring of the acridine moiety and carboxyl fragment in (II) are given in Table 5. A ngle δ between the acridine (average deviation from planarity for its constituent atoms = 0.003 Å) and phenyl moieties in (II) is 5.8 (2)° (Fig. 3). The carboxyl group in (II) is twisted at an angle ε = 78.8 (2)° relative to the acridine skeleton. Comparison of the δ and ε angles for (I) and (II) yields an inverse relationship.

Arranged in a `head-to-tail' manner and related by a centre of symmetry, two adjacent molecules of (II) are linked via two C—H···O interactions [as in (I)] to produce dimers (Fig. 4 and Table 6). These are further linked by a network of multidirectional π–π interactions involving the central acridine ring, one of the lateral acridine rings and the phenyl ring (Fig. 4 and Table 7), all of which makes for a stable molecular crystal lattice.

The geometry of the molecules in the crystalline phase is the product of intramolecular forces and intermolecular interactions. If some fragments are rigid, as with the acridine, phenyl and carboxyl (O═C—O—) moieties in compounds (I) and (II), the molecules can exist in a variety of structures as a result of rotation around the single bonds, in the present case C9—C15 and O16—C18. This provides the opportunity to investigate the influence of the structure of the molecular fragments on their mutual arrangement and on the structure of the whole molecules. Table 8 lists the angles δ, reflecting the mutual arrangement of the acridine and phenyl rings, and the angles ε, representing the relative arrangement of the acridine ring and the carboxyl (or vinyl) group, for a series of phenyl acridine-9-carboxylates, their relevant 10-methylacridinium cations and related compounds. The angles δ are the largest in two known structures of styrylacridines. They are quite large if bulky groups (Et) or atoms (Br, I) are ortho-substituted in the phenyl ring of phenyl acridine-9-carboxylates. As far as the halogen-disubstituted compounds are concerned, the angle δ in the fluoro derivatives of phenyl acridine-9-carboxylates and their 10-methylacridinium cations is relatively small and increases with the size of the halogen atom. All of the angles ε listed in Table 8 are larger than 50° and are not correlated with either the angles δ or the size and number of the substituents in the phenyl fragment. The angles ε are most probably the outcome of the most efficient crystal packing. A property which does not arise directly from the δ values listed in Table 8, but which emerges from a meticulous analysis of crystal phase structures, is that there is a relatively large number and variety of intermolecular interactions in the difluoro derivatives, which may be a consequence of the nearly parallel mutual orientation of the acridine and phenyl rings.

S2. Experimental

Compound (II) was prepared by heating anhydrous acridine-9-carboxylic acid with a tenfold molar excess of thionyl chloride, followed by esterification of the resulting acid chloride with an equimolar quantity of 2,6-difluorophenol (Sato, 1996). The reaction was carried out in anhydrous dichloromethane in the presence of triethylamine (1.5 molar excess) and a catalytic quantity of 4-(N,N-dimethyl)aminopyridine. The crude product was subsequently washed with dilute HCl, NaHCO₃ and saturated saline, and then purified chromatographically with silica gel as the stationary phase and cyclohexane–ethyl acetate (1/1 v/v) as the mobile phase (yield 79%). Analysis, calculated for C₂₂H₁₄F₅NO₅S: C 71.6, H 3.3, N 4.2%; found: C 71.5, H 3.3, N 25.1%. Yellow crystals of (II) suitable for X-ray analysis were grown from cyclohexane (m.p. 454–455 K). Compound (I) was synthesized by treating compound (II) dissolved in anhydrous dichloromethane with a fivefold molar excess of methyl trifluoromethanesulfonate dissolved in the same solvent (in an Ar atmosphere at room temperature for 4 h). The crude salt was purified by repeated precipitation from an ethanol–diethyl ether solution (Ratio?) (yield 86%). Pale-yellow crystals of (I) suitable for X-ray investigations were grown from absolute ethanol (m.p. 504–506 K).

S3. Refinement

The methyl H atoms in (I) were located in difference Fourier syntheses and refined as a rigid rotating group, with C—H = 0.96 Å and U_iso(H) = 1.5U_eq(C). These H atoms were assumed to have two unique disordered orientations with an occupancy factor of 0.5. A l l other H atoms in (I) and (II) were placed geometrically and refined using a riding model, with C—H distances of 0.93 Å and with U_iso(H) = 1.2U_eq(C).

Computing details

For both compounds, data collection: KM-4 Software (Kuma Diffraction, 1989); cell refinement: KM-4 Software; data reduction: KM-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme and 25% probability displacement ellipsoids. H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The arrangement of the ions of (I) in the unit cell. The C—H···O interactions are represented by dashed lines, and the Y—X···π and π–π interactions by dotted lines. H atoms not involved in C—H···O interactions have been omitted. [Symmetry codes: (i) x − 1, y, 1 + z; (ii) 1 − x, 1 − y, 1 − z; (iii) 1 − x, −y, 1 − z; (iv) x, 1/2 − y, z − 1/2; (v) 1 + x, 1/2 − y, z − 1/2; (vi) x, 1/2 − y, z − 1/2].
	Fig. 3. The molecular structure of (II), showing the atom-labelling scheme and 25% probability displacement ellipsoids. H atoms are shown as small spheres of arbitrary radii.
	Fig. 4. The arrangement of the molecules of (II) in the unit cell. The C—-H···O interactions are represented by dashed lines and the π–π interactions by dotted lines. H atoms not involved in C—H···O interactions have been omitted. [Symmetry codes: (i) −1 − x, 1 − y,1 − z; (ii) −x, 1 − y, −z; (iii) −x, 1 − y, 1 − z].

(I) 9-(2,6-difluorophenoxycarbonyl)-10-methylacridinium trifluoromethanesulfonate

Crystal data

C21H14F2NO2^+·CF3O3S^−	F(000) = 1016
Mr = 499.40	Dx = 1.576 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 50 reflections
a = 11.382 (2) Å	θ = 2.1–25.0°
b = 14.048 (3) Å	µ = 0.23 mm^−1
c = 13.162 (3) Å	T = 290 K
β = 91.16 (3)°	Prism, yellow
V = 2104.1 (8) Å^3	0.5 × 0.3 × 0.2 mm
Z = 4

Data collection

Kuma KM-4 diffractometer	Rint = 0.029
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.1°
Graphite monochromator	h = −13→13
θ/2θ scans	k = 0→16
3874 measured reflections	l = 0→15
3700 independent reflections	3 standard reflections every 200 reflections
1760 reflections with I > 2σ(I)	intensity decay: 4.5%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.048	H-atom parameters constrained
wR(F^2) = 0.144	w = 1/[σ^2(Fo^2) + (0.0693P)^2 + 0.9523P] where P = (Fo^2 + 2Fc^2)/3
S = 0.97	(Δ/σ)max < 0.001
3700 reflections	Δρmax = 0.27 e Å^−3
309 parameters	Δρmin = −0.32 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0096 (9)
Secondary atom site location: difference Fourier map

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	Occ. (<1)
C1	0.2189 (3)	0.1066 (3)	0.7437 (3)	0.0627 (11)
H1	0.2645	0.0770	0.6951	0.075*
C2	0.1649 (4)	0.0526 (3)	0.8147 (4)	0.0801 (14)
H2	0.1731	−0.0132	0.8154	0.096*
C3	0.0957 (4)	0.0998 (4)	0.8878 (3)	0.0812 (15)
H3	0.0596	0.0636	0.9374	0.097*
C4	0.0803 (3)	0.1935 (4)	0.8879 (3)	0.0680 (12)
H4	0.0341	0.2215	0.9372	0.082*
C5	0.1544 (4)	0.5034 (3)	0.7376 (3)	0.0652 (11)
H5	0.1040	0.5323	0.7830	0.078*
C6	0.2102 (4)	0.5563 (3)	0.6693 (4)	0.0757 (13)
H6	0.1975	0.6217	0.6677	0.091*
C7	0.2870 (4)	0.5158 (3)	0.6008 (3)	0.0722 (12)
H7	0.3266	0.5542	0.5552	0.087*
C8	0.3039 (3)	0.4215 (3)	0.6004 (3)	0.0575 (10)
H8	0.3542	0.3951	0.5532	0.069*
C9	0.2634 (3)	0.2634 (2)	0.6712 (2)	0.0412 (8)
N10	0.1186 (3)	0.3475 (2)	0.8115 (2)	0.0545 (8)
C11	0.2072 (3)	0.2069 (2)	0.7423 (3)	0.0462 (9)
C12	0.1337 (3)	0.2509 (3)	0.8139 (3)	0.0521 (9)
C13	0.2473 (3)	0.3613 (2)	0.6697 (2)	0.0442 (8)
C14	0.1712 (3)	0.4037 (3)	0.7413 (3)	0.0481 (9)
C15	0.3510 (3)	0.2186 (2)	0.6045 (3)	0.0445 (8)
O16	0.3152 (2)	0.21948 (17)	0.50565 (17)	0.0538 (7)
O17	0.4403 (2)	0.1845 (2)	0.63328 (19)	0.0648 (8)
C18	0.3917 (3)	0.1757 (3)	0.4379 (3)	0.0506 (9)
C19	0.4711 (3)	0.2286 (3)	0.3850 (3)	0.0597 (10)
C20	0.5439 (4)	0.1868 (4)	0.3164 (3)	0.0712 (12)
H20	0.5976	0.2229	0.2805	0.085*
C21	0.5352 (4)	0.0905 (4)	0.3021 (3)	0.0767 (14)
H21	0.5839	0.0613	0.2556	0.092*
C22	0.4576 (4)	0.0363 (3)	0.3537 (3)	0.0766 (13)
H22	0.4526	−0.0290	0.3430	0.092*
C23	0.3872 (3)	0.0807 (3)	0.4220 (3)	0.0587 (10)
F24	0.4756 (2)	0.32225 (18)	0.4024 (2)	0.0864 (8)
F25	0.3091 (2)	0.02991 (18)	0.4759 (2)	0.0868 (8)
C26	0.0408 (4)	0.3927 (3)	0.8875 (3)	0.0813 (14)
H26A	−0.0079	0.3450	0.9175	0.122*	0.50
H26B	−0.0079	0.4396	0.8544	0.122*	0.50
H26C	0.0882	0.4227	0.9395	0.122*	0.50
H26D	0.0562	0.4599	0.8901	0.122*	0.50
H26E	0.0561	0.3652	0.9532	0.122*	0.50
H26F	−0.0399	0.3822	0.8680	0.122*	0.50
S27	0.88935 (9)	0.23332 (7)	0.13665 (7)	0.0559 (3)
O28	0.9571 (2)	0.3156 (2)	0.1202 (2)	0.0762 (8)
O29	0.9331 (3)	0.1496 (2)	0.0894 (2)	0.0884 (11)
O30	0.8512 (3)	0.2203 (3)	0.2387 (2)	0.0909 (10)
C31	0.7557 (4)	0.2562 (3)	0.0694 (3)	0.0627 (10)
F32	0.7735 (3)	0.2671 (3)	−0.02924 (19)	0.1216 (12)
F34	0.7029 (2)	0.3343 (2)	0.1027 (2)	0.1024 (9)
F33	0.6787 (2)	0.1873 (2)	0.0769 (2)	0.1012 (9)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.056 (2)	0.053 (3)	0.078 (3)	−0.004 (2)	0.000 (2)	0.014 (2)
C2	0.066 (3)	0.071 (3)	0.102 (4)	−0.009 (2)	−0.002 (3)	0.035 (3)
C3	0.060 (3)	0.112 (5)	0.071 (3)	−0.021 (3)	−0.003 (2)	0.041 (3)
C4	0.053 (2)	0.098 (4)	0.053 (3)	−0.011 (2)	0.0046 (19)	0.019 (2)
C5	0.066 (3)	0.064 (3)	0.065 (3)	0.015 (2)	−0.008 (2)	−0.019 (2)
C6	0.099 (4)	0.041 (2)	0.086 (3)	0.006 (2)	−0.016 (3)	−0.002 (2)
C7	0.100 (3)	0.051 (3)	0.066 (3)	−0.006 (2)	0.001 (2)	0.005 (2)
C8	0.072 (3)	0.047 (3)	0.054 (2)	0.001 (2)	0.0049 (19)	−0.0005 (19)
C9	0.0402 (18)	0.040 (2)	0.0431 (19)	−0.0002 (15)	−0.0066 (14)	0.0024 (16)
N10	0.0447 (17)	0.070 (2)	0.0484 (19)	0.0019 (16)	−0.0005 (14)	−0.0114 (17)
C11	0.0350 (18)	0.052 (2)	0.052 (2)	−0.0020 (16)	−0.0038 (16)	0.0077 (18)
C12	0.0397 (18)	0.071 (3)	0.046 (2)	−0.0098 (19)	−0.0064 (15)	0.005 (2)
C13	0.0444 (19)	0.046 (2)	0.042 (2)	0.0010 (16)	−0.0046 (16)	0.0028 (17)
C14	0.043 (2)	0.050 (2)	0.051 (2)	−0.0007 (17)	−0.0053 (17)	−0.0074 (18)
C15	0.044 (2)	0.040 (2)	0.049 (2)	−0.0009 (16)	−0.0031 (16)	0.0010 (17)
O16	0.0502 (14)	0.0664 (18)	0.0444 (14)	0.0152 (12)	−0.0050 (11)	−0.0038 (12)
O17	0.0524 (16)	0.086 (2)	0.0552 (16)	0.0209 (15)	−0.0054 (13)	−0.0059 (13)
C18	0.046 (2)	0.060 (3)	0.045 (2)	0.0107 (19)	−0.0038 (16)	−0.0060 (18)
C19	0.064 (2)	0.064 (3)	0.051 (2)	0.004 (2)	−0.004 (2)	−0.005 (2)
C20	0.062 (3)	0.101 (4)	0.050 (2)	0.010 (3)	0.006 (2)	0.006 (2)
C21	0.074 (3)	0.107 (4)	0.049 (2)	0.033 (3)	0.003 (2)	−0.003 (3)
C22	0.090 (3)	0.072 (3)	0.067 (3)	0.034 (3)	−0.015 (3)	−0.016 (3)
C23	0.057 (2)	0.062 (3)	0.057 (2)	0.011 (2)	−0.005 (2)	−0.003 (2)
F24	0.105 (2)	0.0733 (19)	0.0813 (17)	−0.0105 (15)	0.0128 (14)	−0.0015 (14)
F25	0.0962 (19)	0.0684 (17)	0.0961 (19)	−0.0082 (14)	0.0110 (15)	−0.0033 (14)
C26	0.074 (3)	0.100 (4)	0.071 (3)	0.002 (3)	0.024 (2)	−0.028 (3)
S27	0.0549 (6)	0.0667 (7)	0.0463 (5)	0.0080 (5)	0.0058 (4)	0.0063 (5)
O28	0.0634 (18)	0.086 (2)	0.079 (2)	−0.0215 (16)	−0.0007 (15)	0.0021 (16)
O29	0.099 (2)	0.063 (2)	0.104 (2)	0.0305 (17)	0.042 (2)	0.0125 (17)
O30	0.096 (2)	0.136 (3)	0.0410 (15)	0.005 (2)	0.0115 (15)	0.0156 (17)
C31	0.061 (2)	0.075 (3)	0.052 (2)	−0.007 (2)	0.0061 (18)	−0.009 (2)
F32	0.100 (2)	0.208 (4)	0.0568 (16)	0.004 (2)	−0.0165 (14)	0.0227 (19)
F34	0.0767 (18)	0.0843 (19)	0.146 (3)	0.0292 (15)	−0.0048 (17)	−0.0114 (18)
F33	0.0772 (17)	0.114 (2)	0.113 (2)	−0.0329 (17)	0.0097 (16)	−0.0345 (17)

Geometric parameters (Å, º)

C1—C2	1.360 (5)	C15—O17	1.179 (4)
C1—C11	1.415 (5)	O16—C18	1.401 (4)
C1—H1	0.9300	C18—C23	1.352 (5)
C2—C3	1.419 (7)	C18—C19	1.370 (5)
C2—H2	0.9300	C19—F24	1.336 (5)
C3—C4	1.329 (6)	C19—C20	1.370 (6)
C3—H3	0.9300	C20—C21	1.369 (6)
C4—C12	1.412 (5)	C20—H20	0.9300
C4—H4	0.9300	C21—C22	1.358 (6)
C5—C6	1.337 (6)	C21—H21	0.9300
C5—C14	1.415 (5)	C22—C23	1.367 (6)
C5—H5	0.9300	C22—H22	0.9300
C6—C7	1.390 (6)	C23—F25	1.352 (4)
C6—H6	0.9300	C26—H26A	0.9600
C7—C8	1.339 (5)	C26—H26B	0.9600
C7—H7	0.9300	C26—H26C	0.9600
C8—C13	1.409 (5)	C26—H26D	0.9600
C8—H8	0.9300	C26—H26E	0.9600
C9—C13	1.389 (5)	C26—H26F	0.9600
C9—C11	1.393 (5)	S27—O28	1.409 (3)
C9—C15	1.482 (5)	S27—O29	1.425 (3)
N10—C12	1.367 (5)	S27—O30	1.432 (3)
N10—C14	1.363 (5)	S27—C31	1.774 (4)
N10—C26	1.491 (5)	C31—F33	1.311 (5)
C11—C12	1.415 (5)	C31—F32	1.328 (4)
C13—C14	1.423 (5)	C31—F34	1.329 (5)
C15—O16	1.355 (4)
C2—C1—C11	121.3 (4)	F24—C19—C20	120.9 (4)
C2—C1—H1	119.3	F24—C19—C18	118.0 (4)
C11—C1—H1	119.3	C20—C19—C18	121.1 (4)
C1—C2—C3	118.1 (4)	C21—C20—C19	118.1 (4)
C1—C2—H2	121.0	C21—C20—H20	121.0
C3—C2—H2	121.0	C19—C20—H20	121.0
C4—C3—C2	122.6 (4)	C22—C21—C20	122.1 (4)
C4—C3—H3	118.7	C22—C21—H21	119.0
C2—C3—H3	118.7	C20—C21—H21	119.0
C3—C4—C12	120.4 (4)	C21—C22—C23	118.0 (5)
C3—C4—H4	119.8	C21—C22—H22	121.0
C12—C4—H4	119.8	C23—C22—H22	121.0
C6—C5—C14	120.6 (4)	C18—C23—F25	117.6 (3)
C6—C5—H5	119.7	C18—C23—C22	122.1 (4)
C14—C5—H5	119.7	F25—C23—C22	120.3 (4)
C5—C6—C7	121.4 (4)	N10—C26—H26A	109.5
C5—C6—H6	119.3	N10—C26—H26B	109.5
C7—C6—H6	119.3	H26A—C26—H26B	109.5
C8—C7—C6	120.0 (4)	N10—C26—H26C	109.5
C8—C7—H7	120.0	H26A—C26—H26C	109.5
C6—C7—H7	120.0	H26B—C26—H26C	109.5
C7—C8—C13	121.5 (4)	N10—C26—H26D	109.5
C7—C8—H8	119.2	H26A—C26—H26D	141.1
C13—C8—H8	119.2	H26B—C26—H26D	56.3
C13—C9—C11	120.8 (3)	H26C—C26—H26D	56.3
C13—C9—C15	120.2 (3)	N10—C26—H26E	109.5
C11—C9—C15	118.7 (3)	H26A—C26—H26E	56.3
C14—N10—C12	122.2 (3)	H26B—C26—H26E	141.1
C14—N10—C26	118.9 (3)	H26C—C26—H26E	56.3
C12—N10—C26	119.0 (3)	H26D—C26—H26E	109.5
C9—C11—C1	122.1 (3)	N10—C26—H26F	109.5
C9—C11—C12	118.9 (3)	H26A—C26—H26F	56.3
C1—C11—C12	118.9 (3)	H26B—C26—H26F	56.3
N10—C12—C4	121.8 (4)	H26C—C26—H26F	141.1
N10—C12—C11	119.7 (3)	H26D—C26—H26F	109.5
C4—C12—C11	118.6 (4)	H26E—C26—H26F	109.5
C9—C13—C8	122.8 (3)	O28—S27—O29	114.45 (18)
C9—C13—C14	119.1 (3)	O28—S27—O30	115.2 (2)
C8—C13—C14	118.1 (3)	O29—S27—O30	114.76 (19)
N10—C14—C5	122.4 (4)	O28—S27—C31	104.0 (2)
N10—C14—C13	119.3 (3)	O29—S27—C31	103.6 (2)
C5—C14—C13	118.3 (4)	O30—S27—C31	102.55 (18)
C9—C15—O16	111.9 (3)	F33—C31—F32	105.9 (4)
C9—C15—O17	124.6 (3)	F33—C31—F34	106.1 (3)
C15—O16—C18	115.4 (3)	F32—C31—F34	107.8 (4)
O16—C15—O17	123.6 (3)	F33—C31—S27	113.4 (3)
C23—C18—C19	118.7 (4)	F32—C31—S27	111.2 (3)
C23—C18—O16	120.6 (3)	F34—C31—S27	112.0 (3)
C19—C18—O16	120.7 (4)
C11—C1—C2—C3	0.2 (6)	C8—C13—C14—N10	−177.7 (3)
C1—C2—C3—C4	1.2 (7)	C9—C13—C14—C5	−179.0 (3)
C2—C3—C4—C12	−0.1 (7)	C8—C13—C14—C5	1.5 (5)
C14—C5—C6—C7	−0.6 (7)	C13—C9—C15—O17	109.2 (4)
C5—C6—C7—C8	1.8 (7)	C13—C9—C15—O16	−72.1 (4)
C6—C7—C8—C13	−1.3 (6)	C11—C9—C15—O16	114.6 (3)
C13—C9—C11—C1	178.0 (3)	O17—C15—O16—C18	0.6 (5)
C15—C9—C11—C1	−8.7 (5)	C9—C15—O16—C18	−178.1 (3)
C13—C9—C11—C12	−0.4 (5)	C11—C9—C15—O17	−64.2 (5)
C15—C9—C11—C12	172.9 (3)	C15—O16—C18—C23	84.9 (4)
C2—C1—C11—C9	178.9 (4)	C15—O16—C18—C19	−96.3 (4)
C2—C1—C11—C12	−2.7 (5)	C23—C18—C19—F24	−179.2 (3)
C14—N10—C12—C4	178.9 (3)	O16—C18—C19—F24	2.0 (5)
C26—N10—C12—C4	−1.8 (5)	C23—C18—C19—C20	0.8 (6)
C14—N10—C12—C11	0.7 (5)	O16—C18—C19—C20	−178.0 (3)
C26—N10—C12—C11	−180.0 (3)	F24—C19—C20—C21	179.8 (4)
C3—C4—C12—N10	179.4 (4)	C18—C19—C20—C21	−0.1 (6)
C3—C4—C12—C11	−2.4 (6)	C19—C20—C21—C22	−0.2 (7)
C9—C11—C12—N10	0.4 (5)	C20—C21—C22—C23	−0.3 (6)
C1—C11—C12—N10	−178.0 (3)	C19—C18—C23—F25	179.3 (3)
C9—C11—C12—C4	−177.8 (3)	O16—C18—C23—F25	−1.9 (5)
C1—C11—C12—C4	3.7 (5)	C19—C18—C23—C22	−1.3 (6)
C11—C9—C13—C8	178.8 (3)	O16—C18—C23—C22	177.6 (3)
C15—C9—C13—C8	5.6 (5)	C21—C22—C23—C18	1.0 (6)
C11—C9—C13—C14	−0.7 (5)	C21—C22—C23—F25	−179.6 (4)
C15—C9—C13—C14	−173.9 (3)	O28—S27—C31—F33	−178.9 (3)
C7—C8—C13—C9	−179.8 (4)	O29—S27—C31—F33	61.1 (3)
C7—C8—C13—C14	−0.3 (6)	O30—S27—C31—F33	−58.6 (3)
C12—N10—C14—C5	179.0 (3)	O28—S27—C31—F32	61.8 (4)
C26—N10—C14—C5	−0.3 (5)	O29—S27—C31—F32	−58.1 (4)
C12—N10—C14—C13	−1.8 (5)	O30—S27—C31—F32	−177.8 (3)
C26—N10—C14—C13	178.9 (3)	O28—S27—C31—F34	−58.9 (3)
C6—C5—C14—N10	178.1 (4)	O29—S27—C31—F34	−178.8 (3)
C6—C5—C14—C13	−1.1 (6)	O30—S27—C31—F34	61.5 (3)
C9—C13—C14—N10	1.8 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O29^i	0.93	2.54	3.225 (5)	131
C5—H5···O28^ii	0.93	2.59	3.417 (5)	148
C22—H22···O17^iii	0.93	2.52	3.316 (5)	144

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

(II) 2,6-difluorophenyl acridine-9-carboxylate

Crystal data

C20H11F2NO2	Z = 2
Mr = 335.30	F(000) = 344
Triclinic, P1	Dx = 1.460 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.306 (2) Å	Cell parameters from 50 reflections
b = 9.057 (2) Å	θ = 2.5–25.0°
c = 11.423 (2) Å	µ = 0.11 mm^−1
α = 69.94 (3)°	T = 290 K
β = 77.80 (3)°	Prism, yellow
γ = 72.16 (3)°	0.4 × 0.3 × 0.2 mm
V = 762.9 (3) Å^3

Data collection

Kuma KM-4 diffractometer	Rint = 0.023
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.5°
Graphite monochromator	h = −9→9
θ/2θ scans	k = −10→10
2875 measured reflections	l = 0→13
2681 independent reflections	3 standard reflections every 200 reflections
1314 reflections with I > 2σ(I)	intensity decay: 1.0%

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)] = 0.042	H-atom parameters constrained
wR(F^2) = 0.129	w = 1/[σ^2(Fo^2) + (0.0607P)^2 + 0.1152P] where P = (Fo^2 + 2Fc^2)/3
S = 1.01	(Δ/σ)max < 0.001
2681 reflections	Δρmax = 0.18 e Å^−3
227 parameters	Δρmin = −0.16 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0025 (4)

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	−0.0776 (3)	0.6168 (3)	0.1656 (2)	0.0559 (6)
H1	−0.1679	0.6153	0.2296	0.067*
C2	−0.0846 (4)	0.7473 (3)	0.0628 (3)	0.0659 (7)
H2	−0.1798	0.8353	0.0569	0.079*
C3	0.0491 (4)	0.7527 (3)	−0.0357 (2)	0.0678 (8)
H3	0.0410	0.8436	−0.1062	0.081*
C4	0.1891 (4)	0.6276 (3)	−0.0290 (2)	0.0602 (7)
H4	0.2769	0.6334	−0.0948	0.072*
C5	0.5148 (3)	0.1091 (3)	0.1858 (3)	0.0632 (7)
H5	0.6000	0.1182	0.1183	0.076*
C6	0.5382 (3)	−0.0231 (3)	0.2866 (3)	0.0684 (8)
H6	0.6399	−0.1036	0.2883	0.082*
C7	0.4114 (3)	−0.0412 (3)	0.3893 (3)	0.0624 (7)
H7	0.4300	−0.1335	0.4584	0.075*
C8	0.2629 (3)	0.0734 (3)	0.3892 (2)	0.0514 (6)
H8	0.1790	0.0584	0.4573	0.062*
C9	0.0851 (3)	0.3411 (3)	0.27999 (19)	0.0400 (5)
N10	0.3465 (2)	0.3660 (2)	0.07906 (17)	0.0534 (5)
C11	0.0667 (3)	0.4819 (3)	0.17662 (19)	0.0431 (6)
C12	0.2044 (3)	0.4867 (3)	0.0773 (2)	0.0487 (6)
C13	0.2333 (3)	0.2167 (3)	0.2860 (2)	0.0422 (5)
C14	0.3613 (3)	0.2357 (3)	0.1807 (2)	0.0472 (6)
C15	−0.0594 (3)	0.3239 (3)	0.3817 (2)	0.0414 (5)
O16	−0.03122 (18)	0.35588 (19)	0.48181 (14)	0.0501 (5)
O17	−0.1824 (2)	0.2872 (2)	0.37816 (15)	0.0681 (6)
C18	−0.1595 (3)	0.3494 (3)	0.5831 (2)	0.0442 (6)
C19	−0.1398 (3)	0.2205 (3)	0.6894 (2)	0.0549 (7)
C20	−0.2582 (4)	0.2158 (4)	0.7937 (2)	0.0676 (8)
H20	−0.2427	0.1273	0.8657	0.081*
C21	−0.3992 (3)	0.3434 (4)	0.7898 (2)	0.0680 (8)
H21	−0.4805	0.3410	0.8598	0.082*
C22	−0.4226 (3)	0.4748 (4)	0.6845 (2)	0.0615 (7)
H22	−0.5185	0.5617	0.6821	0.074*
C23	−0.3012 (3)	0.4746 (3)	0.5829 (2)	0.0519 (6)
F24	−0.0005 (2)	0.09652 (19)	0.69054 (14)	0.0841 (6)
F25	−0.31815 (19)	0.60132 (19)	0.47740 (14)	0.0791 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0566 (15)	0.0487 (15)	0.0511 (15)	−0.0047 (12)	−0.0026 (12)	−0.0108 (12)
C2	0.0758 (18)	0.0470 (15)	0.0584 (17)	−0.0025 (13)	−0.0142 (15)	−0.0033 (13)
C3	0.091 (2)	0.0542 (17)	0.0450 (16)	−0.0177 (17)	−0.0096 (15)	0.0023 (13)
C4	0.0785 (19)	0.0564 (16)	0.0394 (14)	−0.0230 (16)	0.0048 (13)	−0.0083 (12)
C5	0.0500 (15)	0.0576 (17)	0.0721 (18)	−0.0102 (13)	0.0214 (13)	−0.0272 (15)
C6	0.0476 (15)	0.0536 (17)	0.086 (2)	0.0014 (13)	0.0024 (15)	−0.0180 (16)
C7	0.0558 (16)	0.0512 (15)	0.0641 (17)	−0.0046 (13)	−0.0005 (14)	−0.0094 (13)
C8	0.0475 (14)	0.0470 (14)	0.0486 (14)	−0.0070 (12)	0.0039 (11)	−0.0104 (12)
C9	0.0412 (12)	0.0410 (13)	0.0352 (12)	−0.0107 (10)	0.0020 (10)	−0.0119 (10)
N10	0.0593 (13)	0.0502 (13)	0.0446 (12)	−0.0169 (11)	0.0132 (9)	−0.0155 (10)
C11	0.0463 (13)	0.0428 (13)	0.0371 (12)	−0.0102 (11)	−0.0002 (10)	−0.0120 (11)
C12	0.0590 (15)	0.0498 (14)	0.0358 (13)	−0.0183 (13)	0.0039 (11)	−0.0126 (11)
C13	0.0399 (13)	0.0428 (13)	0.0403 (13)	−0.0086 (11)	0.0026 (10)	−0.0141 (10)
C14	0.0464 (14)	0.0456 (14)	0.0476 (14)	−0.0139 (11)	0.0104 (11)	−0.0191 (12)
C15	0.0378 (13)	0.0406 (13)	0.0385 (13)	−0.0047 (10)	−0.0004 (10)	−0.0100 (10)
O16	0.0450 (9)	0.0677 (11)	0.0391 (9)	−0.0176 (8)	0.0086 (7)	−0.0231 (8)
O17	0.0535 (11)	0.1069 (16)	0.0573 (11)	−0.0363 (11)	0.0112 (8)	−0.0376 (10)
C18	0.0397 (12)	0.0541 (14)	0.0369 (13)	−0.0106 (11)	0.0029 (10)	−0.0168 (11)
C19	0.0498 (14)	0.0574 (16)	0.0488 (15)	−0.0027 (12)	−0.0009 (13)	−0.0181 (13)
C20	0.0757 (19)	0.0725 (19)	0.0425 (15)	−0.0195 (16)	0.0100 (14)	−0.0119 (13)
C21	0.0628 (17)	0.096 (2)	0.0484 (17)	−0.0280 (17)	0.0197 (13)	−0.0342 (16)
C22	0.0426 (14)	0.0808 (19)	0.0578 (17)	−0.0030 (13)	0.0043 (13)	−0.0339 (16)
C23	0.0484 (15)	0.0559 (15)	0.0449 (15)	−0.0034 (13)	−0.0075 (12)	−0.0144 (12)
F24	0.0820 (11)	0.0667 (10)	0.0689 (10)	0.0119 (9)	0.0010 (8)	−0.0106 (8)
F25	0.0767 (10)	0.0689 (10)	0.0628 (10)	0.0062 (8)	−0.0087 (8)	−0.0054 (8)

Geometric parameters (Å, º)

C1—C2	1.347 (3)	C9—C15	1.488 (3)
C1—C11	1.416 (3)	N10—C12	1.339 (3)
C1—H1	0.9300	N10—C14	1.337 (3)
C2—C3	1.403 (4)	C11—C12	1.430 (3)
C2—H2	0.9300	C13—C14	1.427 (3)
C3—C4	1.346 (4)	C15—O16	1.352 (3)
C3—H3	0.9300	C15—O17	1.180 (3)
C4—C12	1.422 (3)	O16—C18	1.395 (2)
C4—H4	0.9300	C18—C23	1.361 (3)
C5—C6	1.343 (4)	C18—C19	1.364 (3)
C5—C14	1.426 (3)	C19—F24	1.342 (3)
C5—H5	0.9300	C19—C20	1.372 (3)
C6—C7	1.402 (4)	C20—C21	1.366 (4)
C6—H6	0.9300	C20—H20	0.9300
C7—C8	1.347 (3)	C21—C22	1.370 (4)
C7—H7	0.9300	C21—H21	0.9300
C8—C13	1.418 (3)	C22—C23	1.367 (3)
C8—H8	0.9300	C22—H22	0.9300
C9—C13	1.387 (3)	C23—F25	1.347 (3)
C9—C11	1.403 (3)
C2—C1—C11	120.3 (2)	N10—C12—C4	118.4 (2)
C2—C1—H1	119.8	N10—C12—C11	123.6 (2)
C11—C1—H1	119.8	C4—C12—C11	118.0 (2)
C1—C2—C3	121.2 (3)	C9—C13—C8	123.9 (2)
C1—C2—H2	119.4	C9—C13—C14	117.1 (2)
C3—C2—H2	119.4	C8—C13—C14	119.0 (2)
C4—C3—C2	120.6 (2)	N10—C14—C5	118.4 (2)
C4—C3—H3	119.7	N10—C14—C13	123.8 (2)
C2—C3—H3	119.7	C5—C14—C13	117.7 (2)
C3—C4—C12	120.9 (2)	C9—C15—O16	110.6 (2)
C3—C4—H4	119.6	C9—C15—O17	125.9 (2)
C12—C4—H4	119.6	C15—O16—C18	116.8 (2)
C6—C5—C14	121.1 (2)	O16—C15—O17	123.5 (2)
C6—C5—H5	119.5	C23—C18—C19	117.9 (2)
C14—C5—H5	119.5	C23—C18—O16	121.7 (2)
C5—C6—C7	120.8 (2)	C19—C18—O16	120.2 (2)
C5—C6—H6	119.6	F24—C19—C18	118.4 (2)
C7—C6—H6	119.6	F24—C19—C20	120.1 (2)
C8—C7—C6	120.8 (2)	C18—C19—C20	121.6 (2)
C8—C7—H7	119.6	C21—C20—C19	118.8 (2)
C6—C7—H7	119.6	C21—C20—H20	120.6
C7—C8—C13	120.5 (2)	C19—C20—H20	120.6
C7—C8—H8	119.7	C20—C21—C22	121.0 (2)
C13—C8—H8	119.7	C20—C21—H21	119.5
C13—C9—C11	120.8 (2)	C22—C21—H21	119.5
C13—C9—C15	120.05 (19)	C23—C22—C21	118.1 (2)
C11—C9—C15	119.11 (19)	C23—C22—H22	120.9
C14—N10—C12	117.89 (19)	C21—C22—H22	120.9
C9—C11—C1	124.3 (2)	F25—C23—C18	117.1 (2)
C9—C11—C12	116.7 (2)	F25—C23—C22	120.4 (2)
C1—C11—C12	119.0 (2)	C18—C23—C22	122.5 (2)
C11—C1—C2—C3	0.4 (4)	C6—C5—C14—N10	178.6 (3)
C1—C2—C3—C4	−0.7 (4)	C6—C5—C14—C13	−0.3 (4)
C2—C3—C4—C12	0.4 (4)	C9—C13—C14—N10	0.8 (3)
C14—C5—C6—C7	0.7 (4)	C8—C13—C14—N10	−179.8 (2)
C5—C6—C7—C8	0.2 (4)	C9—C13—C14—C5	179.7 (2)
C6—C7—C8—C13	−1.4 (4)	C8—C13—C14—C5	−0.9 (3)
C13—C9—C11—C1	−177.5 (2)	C13—C9—C15—O17	−99.8 (3)
C15—C9—C11—C1	4.7 (3)	C13—C9—C15—O16	80.0 (2)
C13—C9—C11—C12	2.4 (3)	C11—C9—C15—O16	−102.2 (2)
C15—C9—C11—C12	−175.4 (2)	O17—C15—O16—C18	−2.2 (3)
C2—C1—C11—C9	−180.0 (3)	C9—C15—O16—C18	178.01 (17)
C2—C1—C11—C12	0.1 (4)	C11—C9—C15—O17	78.1 (3)
C14—N10—C12—C4	178.5 (2)	C15—O16—C18—C23	−79.8 (3)
C14—N10—C12—C11	−1.5 (3)	C15—O16—C18—C19	104.9 (3)
C3—C4—C12—N10	−179.9 (2)	C23—C18—C19—F24	−180.0 (2)
C3—C4—C12—C11	0.1 (4)	O16—C18—C19—F24	−4.5 (3)
C9—C11—C12—N10	−0.3 (3)	C23—C18—C19—C20	0.0 (4)
C1—C11—C12—N10	179.6 (2)	O16—C18—C19—C20	175.5 (2)
C9—C11—C12—C4	179.7 (2)	F24—C19—C20—C21	−179.7 (2)
C1—C11—C12—C4	−0.4 (3)	C18—C19—C20—C21	0.3 (4)
C11—C9—C13—C8	178.0 (2)	C19—C20—C21—C22	−0.4 (4)
C15—C9—C13—C8	−4.2 (3)	C20—C21—C22—C23	0.2 (4)
C11—C9—C13—C14	−2.7 (3)	C19—C18—C23—F25	179.6 (2)
C15—C9—C13—C14	175.2 (2)	O16—C18—C23—F25	4.2 (3)
C7—C8—C13—C9	−178.9 (2)	C19—C18—C23—C22	−0.2 (4)
C7—C8—C13—C14	1.8 (4)	O16—C18—C23—C22	−175.6 (2)
C12—N10—C14—C5	−177.6 (2)	C21—C22—C23—F25	−179.7 (2)
C12—N10—C14—C13	1.3 (3)	C21—C22—C23—C18	0.1 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C22—H22···O17^i	0.93	2.55	3.395 (4)	151

Symmetry code: (i) −x−1, −y+1, −z+1.