New salt forms of the antioxidant drug emoxypine (EMX, 2-ethyl-6-methylpyridin-3-ol) with pharmaceutically acceptable maleic (Mlt), malonic (Mln) and adipic (Adp) acids were obtained {emoxypinium maleate, C8H12NO+·C4H3O4−, [EMX+Mlt], emoxypinium malonate, C8H12NO+·C3H3O4−, [EMX+Mln], and emoxypinium adipate, C8H12NO+·C6H9O4−, [EMX+Adp]} and their crystal structures determined. The molecular packing in the three EMX salts was studied by means of solid-state density functional theory (DFT), followed by QTAIMC (quantum theory of atoms in molecules and crystals) analysis. It was found that the major contribution to the packing energy comes from pyridine–carboxylate and hydroxy–carboxylate heterosynthons forming infinite one-dimensional ribbons, with [EMX+Adp] additionally stabilized by hydrogen-bonded C(9) chains of Adp− ions. The melting processes of the [EMX+Mlt] (1:1), [EMX+Mln] (1:1) and [EMX+Adp] (1:1) salts were studied and the fusion enthalpy was found to increase with the increase of the calculated lattice energy. The dissolution process of the EMX salts in buffer (pH 7.4) was also studied. It was found that the formation of binary crystals of EMX with dicarboxylic acids increases the EMX solubility by more than 30 times compared to its pure form.
Supporting information
CCDC references: 1836239; 1836241; 1836240
For all structures, data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).
2-Ethyl-3-hydroxy-6-methylpyridin-1-ium 3-carboxyprop-2-enoate (I)
top
Crystal data top
C8H12NO+·C4H3O4− | F(000) = 1072 |
Mr = 253.25 | Dx = 1.356 Mg m−3 |
Orthorhombic, Pccn | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ab 2ac | Cell parameters from 6269 reflections |
a = 26.571 (3) Å | θ = 3.0–30.1° |
b = 6.9074 (8) Å | µ = 0.11 mm−1 |
c = 13.5152 (16) Å | T = 150 K |
V = 2480.6 (5) Å3 | Parallelepiped, colourless |
Z = 8 | 0.35 × 0.20 × 0.20 mm |
Data collection top
Bruker SMART APEXII diffractometer | 2713 independent reflections |
Radiation source: fine-focus sealed tube | 2282 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.026 |
ω scans | θmax = 27.0°, θmin = 3.0° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −33→33 |
Tmin = 0.964, Tmax = 0.979 | k = −8→8 |
19445 measured reflections | l = −17→16 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.037 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.101 | All H-atom parameters refined |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0506P)2 + 0.7672P] where P = (Fo2 + 2Fc2)/3 |
2713 reflections | (Δ/σ)max < 0.001 |
223 parameters | Δρmax = 0.23 e Å−3 |
0 restraints | Δρmin = −0.19 e Å−3 |
Special details top
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. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and
goodness of fit S are based on F2, conventional R-factors R are based
on F, with F set to zero for negative F2. The threshold expression of
F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is
not relevant to the choice of reflections for refinement. R-factors based
on F2 are statistically about twice as large as those based on F, and R-
factors based on ALL data will be even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.23337 (3) | 0.51028 (14) | 0.25508 (7) | 0.0328 (2) | |
H2 | 0.2066 (8) | 0.492 (3) | 0.2909 (13) | 0.057 (5)* | |
N1 | 0.36097 (4) | 0.57375 (14) | 0.32811 (8) | 0.0253 (2) | |
H1 | 0.3918 (6) | 0.588 (2) | 0.2955 (11) | 0.037 (4)* | |
C1 | 0.31985 (4) | 0.56061 (17) | 0.27019 (9) | 0.0246 (3) | |
C2 | 0.27330 (4) | 0.52561 (17) | 0.31535 (9) | 0.0257 (3) | |
C3 | 0.27151 (5) | 0.51191 (18) | 0.41811 (9) | 0.0294 (3) | |
C4 | 0.31499 (5) | 0.53136 (18) | 0.47344 (9) | 0.0293 (3) | |
C5 | 0.36080 (5) | 0.56154 (17) | 0.42794 (9) | 0.0276 (3) | |
C6 | 0.41005 (6) | 0.5867 (3) | 0.48088 (11) | 0.0394 (3) | |
C7 | 0.32582 (5) | 0.5779 (2) | 0.16069 (9) | 0.0293 (3) | |
C8 | 0.32970 (6) | 0.3791 (2) | 0.11233 (10) | 0.0412 (4) | |
H3 | 0.2400 (6) | 0.488 (2) | 0.4490 (11) | 0.033 (4)* | |
H4 | 0.3130 (6) | 0.524 (2) | 0.5448 (12) | 0.039 (4)* | |
H61 | 0.4111 (8) | 0.505 (3) | 0.5358 (18) | 0.079 (7)* | |
H62 | 0.4123 (8) | 0.718 (3) | 0.5043 (16) | 0.085 (7)* | |
H63 | 0.4384 (7) | 0.563 (3) | 0.4393 (15) | 0.060 (5)* | |
H71 | 0.3554 (6) | 0.659 (2) | 0.1477 (11) | 0.037 (4)* | |
H72 | 0.2954 (6) | 0.648 (2) | 0.1362 (11) | 0.039 (4)* | |
H81 | 0.2974 (7) | 0.301 (3) | 0.1274 (12) | 0.059 (5)* | |
H82 | 0.3334 (6) | 0.391 (3) | 0.0408 (13) | 0.049 (5)* | |
H83 | 0.3600 (6) | 0.312 (2) | 0.1389 (12) | 0.049 (5)* | |
O11 | 0.51272 (4) | 0.55390 (18) | 0.29968 (7) | 0.0456 (3) | |
H11 | 0.5546 (9) | 0.540 (3) | 0.2876 (16) | 0.083 (7)* | |
O12 | 0.44379 (3) | 0.59189 (18) | 0.21062 (8) | 0.0479 (3) | |
O13 | 0.65378 (3) | 0.55089 (16) | 0.14008 (7) | 0.0394 (3) | |
O14 | 0.60222 (4) | 0.52160 (17) | 0.26715 (7) | 0.0422 (3) | |
C11 | 0.48987 (5) | 0.5836 (2) | 0.21751 (10) | 0.0329 (3) | |
C12 | 0.51939 (5) | 0.6098 (2) | 0.12445 (10) | 0.0371 (3) | |
C13 | 0.56863 (5) | 0.5967 (2) | 0.10733 (10) | 0.0338 (3) | |
C14 | 0.61100 (4) | 0.55363 (18) | 0.17691 (9) | 0.0265 (3) | |
H12 | 0.4980 (6) | 0.642 (2) | 0.0678 (12) | 0.046 (4)* | |
H13 | 0.5794 (6) | 0.614 (2) | 0.0406 (12) | 0.041 (4)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0171 (4) | 0.0484 (6) | 0.0329 (5) | −0.0021 (4) | 0.0017 (3) | 0.0017 (4) |
N1 | 0.0185 (5) | 0.0295 (5) | 0.0279 (5) | −0.0003 (4) | 0.0020 (4) | 0.0006 (4) |
C1 | 0.0201 (5) | 0.0265 (6) | 0.0271 (6) | 0.0005 (4) | 0.0016 (4) | 0.0014 (4) |
C2 | 0.0191 (5) | 0.0273 (6) | 0.0308 (6) | 0.0007 (4) | 0.0019 (4) | 0.0007 (5) |
C3 | 0.0254 (6) | 0.0306 (6) | 0.0320 (7) | −0.0009 (5) | 0.0092 (5) | 0.0004 (5) |
C4 | 0.0328 (6) | 0.0305 (6) | 0.0247 (6) | 0.0005 (5) | 0.0037 (5) | −0.0003 (5) |
C5 | 0.0281 (6) | 0.0280 (6) | 0.0268 (6) | 0.0005 (5) | −0.0013 (5) | −0.0028 (5) |
C6 | 0.0315 (7) | 0.0538 (9) | 0.0329 (7) | −0.0023 (6) | −0.0064 (6) | −0.0047 (7) |
C7 | 0.0201 (6) | 0.0413 (7) | 0.0264 (6) | −0.0001 (5) | 0.0021 (4) | 0.0078 (5) |
C8 | 0.0424 (8) | 0.0549 (9) | 0.0262 (7) | 0.0094 (7) | 0.0031 (6) | −0.0026 (6) |
O11 | 0.0258 (5) | 0.0780 (8) | 0.0329 (5) | 0.0000 (5) | 0.0072 (4) | 0.0056 (5) |
O12 | 0.0184 (5) | 0.0698 (8) | 0.0557 (7) | 0.0039 (4) | 0.0079 (4) | 0.0079 (6) |
O13 | 0.0173 (4) | 0.0647 (7) | 0.0363 (5) | 0.0045 (4) | 0.0007 (4) | 0.0083 (5) |
O14 | 0.0233 (5) | 0.0745 (8) | 0.0287 (5) | −0.0030 (5) | −0.0019 (3) | 0.0090 (5) |
C11 | 0.0213 (6) | 0.0386 (7) | 0.0388 (7) | 0.0008 (5) | 0.0057 (5) | 0.0011 (6) |
C12 | 0.0209 (6) | 0.0590 (9) | 0.0315 (7) | 0.0058 (6) | −0.0019 (5) | 0.0045 (6) |
C13 | 0.0231 (6) | 0.0527 (8) | 0.0256 (6) | 0.0042 (6) | 0.0007 (5) | 0.0053 (6) |
C14 | 0.0192 (5) | 0.0308 (6) | 0.0296 (6) | −0.0004 (4) | −0.0015 (4) | 0.0017 (5) |
Geometric parameters (Å, º) top
O1—C2 | 1.3419 (14) | C7—C8 | 1.524 (2) |
O1—H2 | 0.87 (2) | C7—H71 | 0.979 (15) |
N1—C1 | 1.3471 (15) | C7—H72 | 0.999 (16) |
N1—C5 | 1.3519 (16) | C8—H81 | 1.035 (18) |
N1—H1 | 0.936 (16) | C8—H82 | 0.976 (18) |
C1—C2 | 1.4004 (16) | C8—H83 | 0.995 (17) |
C1—C7 | 1.4932 (17) | O11—C11 | 1.2821 (16) |
C2—C3 | 1.3928 (18) | O11—H11 | 1.13 (2) |
C3—C4 | 1.3827 (18) | O12—C11 | 1.2294 (16) |
C3—H3 | 0.951 (15) | O13—C14 | 1.2412 (15) |
C4—C5 | 1.3795 (17) | O14—C14 | 1.2612 (16) |
C4—H4 | 0.968 (16) | C11—C12 | 1.4932 (18) |
C5—C6 | 1.5014 (18) | C12—C13 | 1.3318 (18) |
C6—H61 | 0.94 (2) | C12—H12 | 0.981 (16) |
C6—H62 | 0.96 (2) | C13—C14 | 1.4967 (17) |
C6—H63 | 0.95 (2) | C13—H13 | 0.954 (16) |
| | | |
C2—O1—H2 | 108.7 (12) | C1—C7—H71 | 107.9 (9) |
C1—N1—C5 | 124.96 (10) | C8—C7—H71 | 112.5 (9) |
C1—N1—H1 | 116.4 (9) | C1—C7—H72 | 106.3 (8) |
C5—N1—H1 | 118.6 (9) | C8—C7—H72 | 110.5 (9) |
N1—C1—C2 | 118.34 (11) | H71—C7—H72 | 108.2 (13) |
N1—C1—C7 | 118.97 (10) | C7—C8—H81 | 109.4 (10) |
C2—C1—C7 | 122.66 (11) | C7—C8—H82 | 110.7 (10) |
O1—C2—C3 | 124.96 (11) | H81—C8—H82 | 108.9 (13) |
O1—C2—C1 | 116.58 (11) | C7—C8—H83 | 108.6 (10) |
C3—C2—C1 | 118.45 (11) | H81—C8—H83 | 110.8 (14) |
C4—C3—C2 | 120.28 (11) | H82—C8—H83 | 108.4 (13) |
C4—C3—H3 | 121.1 (9) | C11—O11—H11 | 110.8 (11) |
C2—C3—H3 | 118.6 (9) | C14—O14—H11 | 111.6 (9) |
C5—C4—C3 | 120.72 (11) | O12—C11—O11 | 123.00 (12) |
C5—C4—H4 | 120.0 (9) | O12—C11—C12 | 116.98 (12) |
C3—C4—H4 | 119.3 (9) | O11—C11—C12 | 120.02 (11) |
N1—C5—C4 | 117.21 (11) | C13—C12—C11 | 130.85 (12) |
N1—C5—C6 | 117.73 (11) | C13—C12—H12 | 116.7 (9) |
C4—C5—C6 | 125.04 (12) | C11—C12—H12 | 112.4 (9) |
C5—C6—H61 | 109.6 (14) | C12—C13—C14 | 130.03 (12) |
C5—C6—H62 | 108.7 (13) | C12—C13—H13 | 116.9 (9) |
H61—C6—H62 | 107.9 (18) | C14—C13—H13 | 113.1 (9) |
C5—C6—H63 | 112.8 (12) | O13—C14—O14 | 123.67 (11) |
H61—C6—H63 | 109.9 (17) | O13—C14—C13 | 116.10 (11) |
H62—C6—H63 | 107.8 (16) | O14—C14—C13 | 120.23 (11) |
C1—C7—C8 | 111.12 (11) | | |
| | | |
C5—N1—C1—C2 | −2.13 (18) | C1—N1—C5—C6 | −177.81 (12) |
C5—N1—C1—C7 | 179.69 (12) | C3—C4—C5—N1 | 0.90 (18) |
N1—C1—C2—O1 | −178.93 (10) | C3—C4—C5—C6 | 179.29 (13) |
C7—C1—C2—O1 | −0.81 (18) | N1—C1—C7—C8 | 95.66 (14) |
N1—C1—C2—C3 | 1.91 (17) | C2—C1—C7—C8 | −82.44 (15) |
C7—C1—C2—C3 | −179.97 (12) | O12—C11—C12—C13 | −175.27 (16) |
O1—C2—C3—C4 | −179.51 (12) | O11—C11—C12—C13 | 4.6 (3) |
C1—C2—C3—C4 | −0.43 (19) | C11—C12—C13—C14 | −1.0 (3) |
C2—C3—C4—C5 | −1.00 (19) | C12—C13—C14—O13 | −179.87 (16) |
C1—N1—C5—C4 | 0.70 (18) | C12—C13—C14—O14 | 0.5 (2) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O11—H11···O14 | 1.13 (2) | 1.30 (2) | 2.4288 (14) | 176 (2) |
O1—H2···O13i | 0.87 (2) | 1.71 (2) | 2.5804 (13) | 178.5 (19) |
N1—H1···O12 | 0.936 (16) | 1.795 (17) | 2.7165 (14) | 167.5 (14) |
Symmetry code: (i) x−1/2, −y+1, −z+1/2. |
2-Ethyl-3-hydroxy-6-methylpyridin-1-ium 3-carboxypropanoate (II)
top
Crystal data top
C8H12NO+·C3H3O4− | Z = 4 |
Mr = 241.24 | F(000) = 512 |
Triclinic, P1 | Dx = 1.377 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 8.9211 (7) Å | Cell parameters from 5243 reflections |
b = 10.5301 (8) Å | θ = 2.5–30.6° |
c = 13.7175 (10) Å | µ = 0.11 mm−1 |
α = 80.0535 (11)° | T = 150 K |
β = 86.3313 (11)° | Prism, colourless |
γ = 66.5117 (10)° | 0.40 × 0.20 × 0.05 mm |
V = 1164.07 (15) Å3 | |
Data collection top
Bruker SMART APEXII diffractometer | 5599 independent reflections |
Radiation source: fine-focus sealed tube | 4307 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.020 |
ω scans | θmax = 28.0°, θmin = 2.4° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −11→11 |
Tmin = 0.958, Tmax = 0.995 | k = −13→13 |
12144 measured reflections | l = −18→18 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.039 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.108 | All H-atom parameters refined |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0632P)2 + 0.1019P] where P = (Fo2 + 2Fc2)/3 |
5599 reflections | (Δ/σ)max < 0.001 |
427 parameters | Δρmax = 0.33 e Å−3 |
0 restraints | Δρmin = −0.23 e Å−3 |
Special details top
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. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and
goodness of fit S are based on F2, conventional R-factors R are based
on F, with F set to zero for negative F2. The threshold expression of
F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is
not relevant to the choice of reflections for refinement. R-factors based
on F2 are statistically about twice as large as those based on F, and R-
factors based on ALL data will be even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.25059 (11) | 0.94822 (10) | 0.49431 (6) | 0.0303 (2) | |
H12 | 0.324 (2) | 0.866 (2) | 0.4794 (13) | 0.053 (5)* | |
N1 | 0.27799 (11) | 1.14462 (10) | 0.67428 (7) | 0.0191 (2) | |
H11 | 0.2147 (18) | 1.2292 (16) | 0.6934 (11) | 0.032 (4)* | |
C11 | 0.21972 (13) | 1.11105 (12) | 0.59834 (8) | 0.0194 (2) | |
C12 | 0.31050 (14) | 0.98134 (12) | 0.56914 (8) | 0.0210 (2) | |
C13 | 0.45557 (14) | 0.89267 (12) | 0.61915 (9) | 0.0225 (2) | |
C14 | 0.50934 (14) | 0.93460 (13) | 0.69542 (9) | 0.0228 (2) | |
C15 | 0.41919 (14) | 1.06403 (12) | 0.72318 (8) | 0.0210 (2) | |
C16 | 0.46939 (17) | 1.11937 (15) | 0.80301 (10) | 0.0278 (3) | |
C17 | 0.06539 (14) | 1.21647 (13) | 0.54769 (9) | 0.0253 (3) | |
C18 | 0.10265 (19) | 1.30767 (18) | 0.45902 (12) | 0.0439 (4) | |
H13 | 0.5167 (17) | 0.8008 (15) | 0.5993 (10) | 0.028 (4)* | |
H14 | 0.6073 (17) | 0.8775 (14) | 0.7317 (10) | 0.024 (3)* | |
H161 | 0.496 (2) | 1.055 (2) | 0.8627 (15) | 0.064 (6)* | |
H162 | 0.568 (3) | 1.137 (2) | 0.7861 (14) | 0.071 (6)* | |
H163 | 0.388 (2) | 1.202 (2) | 0.8186 (14) | 0.062 (6)* | |
H171 | 0.0018 (18) | 1.1681 (16) | 0.5262 (11) | 0.036 (4)* | |
H172 | −0.0015 (18) | 1.2712 (16) | 0.5950 (11) | 0.037 (4)* | |
H181 | 0.173 (2) | 1.245 (2) | 0.4109 (15) | 0.068 (6)* | |
H182 | 0.001 (2) | 1.3805 (19) | 0.4255 (13) | 0.057 (5)* | |
H183 | 0.156 (2) | 1.3620 (19) | 0.4801 (14) | 0.059 (5)* | |
N2 | 0.83343 (12) | 0.11657 (10) | 0.17789 (7) | 0.0205 (2) | |
H21 | 0.7931 (19) | 0.1931 (17) | 0.2111 (12) | 0.039 (4)* | |
O2 | 0.71557 (11) | −0.00878 (9) | −0.01610 (6) | 0.0281 (2) | |
H22 | 0.759 (2) | −0.092 (2) | −0.0455 (15) | 0.068 (6)* | |
C21 | 0.74586 (14) | 0.11303 (12) | 0.10278 (8) | 0.0206 (2) | |
C22 | 0.80482 (14) | −0.00756 (12) | 0.05829 (8) | 0.0205 (2) | |
C23 | 0.94858 (14) | −0.11854 (12) | 0.09343 (9) | 0.0222 (2) | |
C24 | 1.03252 (14) | −0.10822 (13) | 0.17156 (9) | 0.0224 (2) | |
C25 | 0.97484 (13) | 0.01199 (12) | 0.21409 (8) | 0.0208 (2) | |
C26 | 1.05829 (16) | 0.03354 (15) | 0.29668 (10) | 0.0282 (3) | |
C27 | 0.59039 (15) | 0.23649 (13) | 0.07126 (9) | 0.0269 (3) | |
C28 | 0.60503 (18) | 0.32019 (14) | −0.02888 (10) | 0.0326 (3) | |
H23 | 0.9861 (16) | −0.2020 (14) | 0.0647 (9) | 0.020 (3)* | |
H24 | 1.1283 (17) | −0.1833 (15) | 0.1985 (10) | 0.027 (4)* | |
H261 | 1.107 (2) | 0.1014 (19) | 0.2734 (13) | 0.056 (5)* | |
H262 | 0.985 (2) | 0.0716 (18) | 0.3475 (13) | 0.047 (5)* | |
H263 | 1.142 (2) | −0.058 (2) | 0.3272 (13) | 0.059 (5)* | |
H271 | 0.502 (2) | 0.2003 (17) | 0.0657 (12) | 0.043 (4)* | |
H272 | 0.5614 (17) | 0.2958 (15) | 0.1213 (11) | 0.031 (4)* | |
H281 | 0.498 (2) | 0.3990 (17) | −0.0499 (12) | 0.046 (4)* | |
H282 | 0.6397 (18) | 0.2554 (16) | −0.0781 (11) | 0.037 (4)* | |
H283 | 0.688 (2) | 0.3614 (18) | −0.0290 (13) | 0.052 (5)* | |
O31 | 0.47446 (13) | 0.44831 (11) | 0.27092 (8) | 0.0418 (3) | |
H31 | 0.393 (3) | 0.539 (2) | 0.3028 (16) | 0.087 (7)* | |
O32 | 0.74168 (13) | 0.32588 (10) | 0.28866 (8) | 0.0410 (3) | |
O33 | 0.47330 (12) | 0.71824 (10) | 0.44915 (7) | 0.0385 (2) | |
O34 | 0.33650 (12) | 0.65525 (11) | 0.35028 (8) | 0.0406 (3) | |
C31 | 0.61609 (17) | 0.42311 (13) | 0.30669 (9) | 0.0283 (3) | |
C32 | 0.62348 (16) | 0.51936 (13) | 0.37450 (10) | 0.0254 (3) | |
C33 | 0.46522 (16) | 0.64055 (13) | 0.39291 (9) | 0.0267 (3) | |
H321 | 0.6670 (19) | 0.4621 (16) | 0.4395 (12) | 0.038 (4)* | |
H322 | 0.6975 (19) | 0.5572 (16) | 0.3481 (11) | 0.036 (4)* | |
O41 | 1.18702 (11) | −0.57232 (10) | −0.14240 (8) | 0.0366 (2) | |
H41 | 1.147 (3) | −0.493 (2) | −0.0999 (16) | 0.084 (7)* | |
O42 | 1.06394 (11) | −0.61278 (9) | −0.26157 (7) | 0.0320 (2) | |
O43 | 0.79442 (11) | −0.21875 (9) | −0.10746 (7) | 0.0324 (2) | |
O44 | 1.04830 (11) | −0.36617 (10) | −0.06211 (7) | 0.0340 (2) | |
C41 | 1.06034 (15) | −0.54701 (12) | −0.19505 (9) | 0.0241 (3) | |
C42 | 0.90252 (16) | −0.43260 (14) | −0.17060 (11) | 0.0294 (3) | |
C43 | 0.91565 (15) | −0.33013 (12) | −0.10873 (8) | 0.0239 (3) | |
H421 | 0.842 (2) | −0.3832 (19) | −0.2290 (14) | 0.059 (5)* | |
H422 | 0.838 (2) | −0.4797 (19) | −0.1307 (13) | 0.056 (5)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0282 (5) | 0.0316 (5) | 0.0297 (5) | −0.0040 (4) | −0.0066 (4) | −0.0182 (4) |
N1 | 0.0195 (5) | 0.0172 (5) | 0.0195 (5) | −0.0047 (4) | −0.0006 (4) | −0.0065 (4) |
C11 | 0.0184 (5) | 0.0208 (6) | 0.0184 (5) | −0.0064 (4) | −0.0001 (4) | −0.0048 (4) |
C12 | 0.0208 (5) | 0.0228 (6) | 0.0199 (5) | −0.0074 (5) | 0.0005 (4) | −0.0080 (4) |
C13 | 0.0217 (6) | 0.0191 (6) | 0.0249 (6) | −0.0048 (5) | 0.0016 (4) | −0.0078 (5) |
C14 | 0.0199 (6) | 0.0221 (6) | 0.0239 (6) | −0.0051 (5) | −0.0032 (4) | −0.0035 (5) |
C15 | 0.0213 (5) | 0.0227 (6) | 0.0197 (5) | −0.0090 (5) | −0.0022 (4) | −0.0035 (4) |
C16 | 0.0290 (7) | 0.0287 (7) | 0.0260 (6) | −0.0090 (5) | −0.0077 (5) | −0.0086 (5) |
C17 | 0.0197 (6) | 0.0265 (6) | 0.0254 (6) | −0.0015 (5) | −0.0048 (5) | −0.0097 (5) |
C18 | 0.0335 (8) | 0.0404 (9) | 0.0431 (9) | −0.0044 (7) | −0.0106 (7) | 0.0096 (7) |
N2 | 0.0216 (5) | 0.0201 (5) | 0.0209 (5) | −0.0073 (4) | 0.0003 (4) | −0.0082 (4) |
O2 | 0.0281 (5) | 0.0272 (5) | 0.0280 (4) | −0.0051 (4) | −0.0080 (4) | −0.0133 (4) |
C21 | 0.0199 (5) | 0.0218 (6) | 0.0202 (5) | −0.0069 (4) | 0.0000 (4) | −0.0068 (4) |
C22 | 0.0214 (5) | 0.0214 (6) | 0.0194 (5) | −0.0076 (5) | −0.0005 (4) | −0.0071 (4) |
C23 | 0.0243 (6) | 0.0187 (6) | 0.0230 (6) | −0.0064 (5) | 0.0013 (4) | −0.0070 (4) |
C24 | 0.0204 (6) | 0.0223 (6) | 0.0216 (5) | −0.0049 (5) | −0.0016 (4) | −0.0036 (4) |
C25 | 0.0199 (5) | 0.0240 (6) | 0.0194 (5) | −0.0090 (5) | −0.0002 (4) | −0.0046 (4) |
C26 | 0.0274 (6) | 0.0337 (7) | 0.0255 (6) | −0.0120 (6) | −0.0055 (5) | −0.0083 (5) |
C27 | 0.0218 (6) | 0.0239 (6) | 0.0306 (6) | −0.0008 (5) | −0.0031 (5) | −0.0124 (5) |
C28 | 0.0317 (7) | 0.0248 (7) | 0.0349 (7) | −0.0030 (6) | −0.0072 (6) | −0.0058 (6) |
O31 | 0.0443 (6) | 0.0359 (6) | 0.0473 (6) | −0.0107 (5) | −0.0108 (5) | −0.0211 (5) |
O32 | 0.0459 (6) | 0.0291 (5) | 0.0450 (6) | −0.0050 (4) | 0.0010 (5) | −0.0229 (4) |
O33 | 0.0390 (5) | 0.0326 (5) | 0.0442 (6) | −0.0073 (4) | 0.0044 (4) | −0.0253 (4) |
O34 | 0.0287 (5) | 0.0366 (6) | 0.0541 (6) | −0.0048 (4) | −0.0041 (4) | −0.0193 (5) |
C31 | 0.0392 (7) | 0.0212 (6) | 0.0251 (6) | −0.0110 (5) | 0.0018 (5) | −0.0084 (5) |
C32 | 0.0272 (6) | 0.0232 (6) | 0.0275 (6) | −0.0094 (5) | 0.0046 (5) | −0.0115 (5) |
C33 | 0.0300 (6) | 0.0227 (6) | 0.0274 (6) | −0.0093 (5) | 0.0060 (5) | −0.0088 (5) |
O41 | 0.0276 (5) | 0.0338 (5) | 0.0433 (5) | −0.0010 (4) | −0.0053 (4) | −0.0185 (4) |
O42 | 0.0382 (5) | 0.0233 (5) | 0.0330 (5) | −0.0068 (4) | 0.0004 (4) | −0.0140 (4) |
O43 | 0.0335 (5) | 0.0265 (5) | 0.0354 (5) | −0.0044 (4) | −0.0047 (4) | −0.0164 (4) |
O44 | 0.0295 (5) | 0.0362 (5) | 0.0374 (5) | −0.0084 (4) | −0.0067 (4) | −0.0175 (4) |
C41 | 0.0292 (6) | 0.0177 (5) | 0.0246 (6) | −0.0083 (5) | 0.0018 (5) | −0.0048 (5) |
C42 | 0.0276 (7) | 0.0257 (6) | 0.0333 (7) | −0.0041 (5) | −0.0049 (5) | −0.0147 (5) |
C43 | 0.0286 (6) | 0.0234 (6) | 0.0212 (6) | −0.0106 (5) | 0.0014 (5) | −0.0069 (5) |
Geometric parameters (Å, º) top
O1—C12 | 1.3430 (13) | C23—H23 | 0.953 (14) |
O1—H12 | 0.901 (19) | C24—C25 | 1.3802 (16) |
N1—C15 | 1.3477 (15) | C24—H24 | 0.945 (14) |
N1—C11 | 1.3504 (14) | C25—C26 | 1.4902 (16) |
N1—H11 | 0.918 (15) | C26—H261 | 0.979 (18) |
C11—C12 | 1.3956 (16) | C26—H262 | 0.950 (17) |
C11—C17 | 1.4994 (16) | C26—H263 | 0.991 (18) |
C12—C13 | 1.3951 (16) | C27—C28 | 1.527 (2) |
C13—C14 | 1.3829 (16) | C27—H271 | 1.012 (16) |
C13—H13 | 0.979 (14) | C27—H272 | 0.962 (15) |
C14—C15 | 1.3841 (16) | C28—H281 | 1.005 (17) |
C14—H14 | 0.953 (14) | C28—H282 | 0.991 (16) |
C15—C16 | 1.4934 (16) | C28—H283 | 0.995 (18) |
C16—H161 | 0.94 (2) | O31—C31 | 1.2940 (17) |
C16—H162 | 0.97 (2) | O31—H31 | 1.09 (2) |
C16—H163 | 0.93 (2) | O32—C31 | 1.2257 (15) |
C17—C18 | 1.520 (2) | O33—C33 | 1.2417 (15) |
C17—H171 | 0.986 (15) | O34—C33 | 1.2639 (16) |
C17—H172 | 0.957 (16) | C31—C32 | 1.5113 (16) |
C18—H181 | 1.02 (2) | C32—C33 | 1.5215 (17) |
C18—H182 | 0.999 (18) | C32—H321 | 0.991 (16) |
C18—H183 | 0.966 (19) | C32—H322 | 0.924 (16) |
N2—C21 | 1.3465 (14) | O41—C41 | 1.2914 (16) |
N2—C25 | 1.3545 (15) | O41—H41 | 1.04 (2) |
N2—H21 | 0.927 (17) | O42—C41 | 1.2288 (14) |
O2—C22 | 1.3388 (14) | O43—C43 | 1.2406 (15) |
O2—H22 | 0.96 (2) | O44—C43 | 1.2683 (15) |
C21—C22 | 1.3984 (16) | C41—C42 | 1.5078 (17) |
C21—C27 | 1.4986 (16) | C42—C43 | 1.5257 (16) |
C22—C23 | 1.3902 (16) | C42—H421 | 0.944 (19) |
C23—C24 | 1.3888 (16) | C42—H422 | 0.985 (18) |
| | | |
C12—O1—H12 | 108.6 (11) | C25—C24—H24 | 117.9 (8) |
C15—N1—C11 | 125.23 (10) | C23—C24—H24 | 121.6 (8) |
C15—N1—H11 | 118.6 (9) | N2—C25—C24 | 117.49 (10) |
C11—N1—H11 | 116.2 (9) | N2—C25—C26 | 118.34 (10) |
N1—C11—C12 | 117.75 (10) | C24—C25—C26 | 124.18 (11) |
N1—C11—C17 | 118.57 (10) | C25—C26—H261 | 111.0 (10) |
C12—C11—C17 | 123.63 (10) | C25—C26—H262 | 112.7 (10) |
O1—C12—C13 | 123.55 (10) | H261—C26—H262 | 105.0 (14) |
O1—C12—C11 | 117.31 (10) | C25—C26—H263 | 109.7 (11) |
C13—C12—C11 | 119.13 (10) | H261—C26—H263 | 110.9 (14) |
C14—C13—C12 | 120.07 (11) | H262—C26—H263 | 107.4 (14) |
C14—C13—H13 | 121.5 (8) | C21—C27—C28 | 112.70 (10) |
C12—C13—H13 | 118.5 (8) | C21—C27—H271 | 108.0 (9) |
C13—C14—C15 | 120.33 (11) | C28—C27—H271 | 108.2 (9) |
C13—C14—H14 | 123.0 (8) | C21—C27—H272 | 108.1 (9) |
C15—C14—H14 | 116.7 (8) | C28—C27—H272 | 109.9 (8) |
N1—C15—C14 | 117.45 (10) | H271—C27—H272 | 109.9 (12) |
N1—C15—C16 | 118.48 (10) | C27—C28—H281 | 111.0 (9) |
C14—C15—C16 | 124.08 (11) | C27—C28—H282 | 108.0 (9) |
C15—C16—H161 | 112.3 (12) | H281—C28—H282 | 109.5 (12) |
C15—C16—H162 | 112.2 (12) | C27—C28—H283 | 113.1 (10) |
H161—C16—H162 | 104.6 (16) | H281—C28—H283 | 107.8 (13) |
C15—C16—H163 | 113.1 (12) | H282—C28—H283 | 107.5 (13) |
H161—C16—H163 | 106.1 (16) | C31—O31—H31 | 103.1 (12) |
H162—C16—H163 | 107.9 (16) | C33—O34—H31 | 101.0 (9) |
C11—C17—C18 | 111.01 (11) | O32—C31—O31 | 123.34 (12) |
C11—C17—H171 | 110.0 (9) | O32—C31—C32 | 119.43 (12) |
C18—C17—H171 | 109.8 (9) | O31—C31—C32 | 117.23 (11) |
C11—C17—H172 | 108.5 (9) | C31—C32—C33 | 117.58 (11) |
C18—C17—H172 | 111.8 (9) | C31—C32—H321 | 108.4 (9) |
H171—C17—H172 | 105.6 (12) | C33—C32—H321 | 107.7 (9) |
C17—C18—H181 | 108.5 (11) | C31—C32—H322 | 107.7 (9) |
C17—C18—H182 | 112.2 (10) | C33—C32—H322 | 107.5 (9) |
H181—C18—H182 | 110.5 (15) | H321—C32—H322 | 107.5 (13) |
C17—C18—H183 | 110.4 (11) | O33—C33—O34 | 124.93 (12) |
H181—C18—H183 | 111.7 (16) | O33—C33—C32 | 116.76 (12) |
H182—C18—H183 | 103.5 (15) | O34—C33—C32 | 118.31 (11) |
C21—N2—C25 | 125.04 (10) | C41—O41—H41 | 103.5 (12) |
C21—N2—H21 | 119.2 (10) | C43—O44—H41 | 100.7 (9) |
C25—N2—H21 | 115.7 (10) | O42—C41—O41 | 122.92 (11) |
C22—O2—H22 | 115.1 (12) | O42—C41—C42 | 120.08 (11) |
N2—C21—C22 | 117.81 (10) | O41—C41—C42 | 116.99 (10) |
N2—C21—C27 | 119.08 (10) | C41—C42—C43 | 116.76 (11) |
C22—C21—C27 | 123.11 (10) | C41—C42—H421 | 110.1 (11) |
O2—C22—C23 | 123.86 (10) | C43—C42—H421 | 110.2 (11) |
O2—C22—C21 | 116.74 (10) | C41—C42—H422 | 106.5 (11) |
C23—C22—C21 | 119.39 (10) | C43—C42—H422 | 105.7 (10) |
C24—C23—C22 | 119.83 (10) | H421—C42—H422 | 107.0 (15) |
C24—C23—H23 | 121.0 (8) | O43—C43—O44 | 125.41 (11) |
C22—C23—H23 | 119.2 (8) | O43—C43—C42 | 117.02 (11) |
C25—C24—C23 | 120.43 (11) | O44—C43—C42 | 117.57 (11) |
| | | |
C15—N1—C11—C12 | 1.50 (18) | N2—C21—C22—C23 | 0.76 (17) |
C15—N1—C11—C17 | −176.24 (11) | C27—C21—C22—C23 | −178.72 (11) |
N1—C11—C12—O1 | 179.24 (10) | O2—C22—C23—C24 | −179.54 (11) |
C17—C11—C12—O1 | −3.13 (18) | C21—C22—C23—C24 | −0.47 (18) |
N1—C11—C12—C13 | 0.19 (17) | C22—C23—C24—C25 | −0.51 (18) |
C17—C11—C12—C13 | 177.81 (11) | C21—N2—C25—C24 | −0.89 (17) |
O1—C12—C13—C14 | 179.87 (11) | C21—N2—C25—C26 | 179.01 (11) |
C11—C12—C13—C14 | −1.14 (18) | C23—C24—C25—N2 | 1.16 (17) |
C12—C13—C14—C15 | 0.53 (18) | C23—C24—C25—C26 | −178.74 (12) |
C11—N1—C15—C14 | −2.11 (18) | N2—C21—C27—C28 | 108.67 (13) |
C11—N1—C15—C16 | 177.54 (11) | C22—C21—C27—C28 | −71.86 (16) |
C13—C14—C15—N1 | 1.02 (18) | O32—C31—C32—C33 | 178.67 (12) |
C13—C14—C15—C16 | −178.60 (12) | O31—C31—C32—C33 | −1.77 (18) |
N1—C11—C17—C18 | 92.62 (14) | C31—C32—C33—O33 | 179.68 (11) |
C12—C11—C17—C18 | −84.99 (16) | C31—C32—C33—O34 | −0.52 (18) |
C25—N2—C21—C22 | −0.07 (17) | O42—C41—C42—C43 | −163.63 (12) |
C25—N2—C21—C27 | 179.43 (11) | O41—C41—C42—C43 | 17.38 (18) |
N2—C21—C22—O2 | 179.89 (10) | C41—C42—C43—O43 | 163.73 (12) |
C27—C21—C22—O2 | 0.42 (17) | C41—C42—C43—O44 | −17.02 (18) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O31—H31···O34 | 1.09 (2) | 1.38 (2) | 2.4410 (13) | 162 (2) |
O41—H41···O44 | 1.04 (2) | 1.44 (2) | 2.4428 (12) | 162 (2) |
O1—H12···O33 | 0.901 (19) | 1.69 (2) | 2.5925 (13) | 175.0 (17) |
O2—H22···O43 | 0.96 (2) | 1.62 (2) | 2.5610 (12) | 167.6 (19) |
N2—H21···O32 | 0.927 (17) | 1.800 (17) | 2.7196 (13) | 170.9 (15) |
N1—H11···O42i | 0.918 (15) | 1.850 (16) | 2.7604 (13) | 171.1 (13) |
Symmetry code: (i) x−1, y+2, z+1. |
2-Ethyl-3-hydroxy-6-methylpyridin-1-ium 6-carboxyhexanoate (III)
top
Crystal data top
C8H12NO+·C6H9O4− | Z = 2 |
Mr = 283.32 | F(000) = 304 |
Triclinic, P1 | Dx = 1.316 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 8.7831 (17) Å | Cell parameters from 2982 reflections |
b = 8.9442 (17) Å | θ = 2.4–30.3° |
c = 9.6114 (18) Å | µ = 0.10 mm−1 |
α = 77.301 (3)° | T = 150 K |
β = 76.142 (3)° | Prism, colourless |
γ = 85.677 (3)° | 0.45 × 0.40 × 0.30 mm |
V = 714.9 (2) Å3 | |
Data collection top
Bruker SMART APEXII diffractometer | 3122 independent reflections |
Radiation source: fine-focus sealed tube | 2569 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.021 |
ω scans | θmax = 27.0°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −11→11 |
Tmin = 0.957, Tmax = 0.971 | k = −11→11 |
6841 measured reflections | l = −12→12 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.041 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.114 | All H-atom parameters refined |
S = 1.05 | w = 1/[σ2(Fo2) + (0.0678P)2 + 0.0968P] where P = (Fo2 + 2Fc2)/3 |
3122 reflections | (Δ/σ)max < 0.001 |
265 parameters | Δρmax = 0.26 e Å−3 |
0 restraints | Δρmin = −0.22 e Å−3 |
Special details top
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. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and
goodness of fit S are based on F2, conventional R-factors R are based
on F, with F set to zero for negative F2. The threshold expression of
F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is
not relevant to the choice of reflections for refinement. R-factors based
on F2 are statistically about twice as large as those based on F, and R-
factors based on ALL data will be even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | −0.20593 (11) | 0.62338 (11) | 0.11713 (10) | 0.0292 (2) | |
H2 | −0.228 (2) | 0.700 (2) | 0.047 (2) | 0.064 (6)* | |
N1 | 0.13170 (12) | 0.45634 (12) | 0.23947 (11) | 0.0211 (2) | |
H1 | 0.153 (2) | 0.375 (2) | 0.306 (2) | 0.041 (5)* | |
C1 | −0.01767 (14) | 0.47705 (14) | 0.22500 (13) | 0.0208 (3) | |
C2 | −0.05585 (15) | 0.60828 (14) | 0.12762 (13) | 0.0221 (3) | |
C3 | 0.06186 (16) | 0.71071 (15) | 0.05091 (14) | 0.0245 (3) | |
C4 | 0.21377 (16) | 0.68091 (15) | 0.06912 (14) | 0.0249 (3) | |
C5 | 0.25044 (14) | 0.55150 (14) | 0.16525 (13) | 0.0227 (3) | |
C6 | 0.41058 (16) | 0.50777 (18) | 0.19083 (16) | 0.0296 (3) | |
C7 | −0.13652 (15) | 0.36075 (14) | 0.31264 (14) | 0.0243 (3) | |
C8 | −0.24304 (19) | 0.41427 (18) | 0.44312 (17) | 0.0348 (3) | |
H3 | 0.0377 (18) | 0.8016 (19) | −0.0186 (18) | 0.034 (4)* | |
H4 | 0.2981 (18) | 0.7486 (18) | 0.0168 (17) | 0.027 (4)* | |
H61 | 0.410 (3) | 0.493 (2) | 0.285 (3) | 0.067 (6)* | |
H62 | 0.447 (2) | 0.420 (2) | 0.154 (2) | 0.047 (5)* | |
H63 | 0.487 (2) | 0.585 (2) | 0.143 (2) | 0.049 (5)* | |
H71 | −0.0840 (18) | 0.2653 (18) | 0.3421 (17) | 0.031 (4)* | |
H72 | −0.1990 (19) | 0.3413 (18) | 0.2460 (19) | 0.036 (4)* | |
H81 | −0.180 (2) | 0.430 (2) | 0.510 (2) | 0.053 (5)* | |
H82 | −0.296 (2) | 0.512 (2) | 0.413 (2) | 0.052 (5)* | |
H83 | −0.321 (2) | 0.339 (2) | 0.4962 (19) | 0.040 (4)* | |
O11 | −0.00039 (12) | 0.15146 (13) | 0.59754 (12) | 0.0434 (3) | |
H11 | −0.051 (3) | 0.068 (3) | 0.692 (3) | 0.088 (8)* | |
O12 | 0.22294 (11) | 0.23943 (11) | 0.45206 (10) | 0.0300 (2) | |
O13 | 0.89348 (11) | −0.04695 (12) | 0.81496 (12) | 0.0393 (3) | |
O14 | 0.68104 (11) | −0.17891 (11) | 0.93355 (10) | 0.0315 (2) | |
C11 | 0.15037 (15) | 0.15899 (14) | 0.56614 (14) | 0.0248 (3) | |
C12 | 0.23604 (15) | 0.06199 (16) | 0.67565 (16) | 0.0278 (3) | |
C13 | 0.40362 (14) | 0.10703 (14) | 0.65759 (14) | 0.0223 (3) | |
C14 | 0.48701 (14) | −0.00703 (14) | 0.76002 (14) | 0.0232 (3) | |
C15 | 0.65418 (15) | 0.03752 (15) | 0.74244 (15) | 0.0244 (3) | |
C16 | 0.74819 (14) | −0.07165 (14) | 0.83756 (14) | 0.0237 (3) | |
H121 | 0.239 (2) | −0.044 (2) | 0.658 (2) | 0.047 (5)* | |
H122 | 0.175 (2) | 0.0607 (19) | 0.770 (2) | 0.039 (4)* | |
H131 | 0.4583 (18) | 0.1133 (17) | 0.5562 (18) | 0.028 (4)* | |
H132 | 0.4040 (18) | 0.2086 (18) | 0.6765 (17) | 0.031 (4)* | |
H141 | 0.4301 (19) | −0.0117 (18) | 0.8594 (19) | 0.034 (4)* | |
H142 | 0.4890 (16) | −0.1073 (17) | 0.7352 (16) | 0.023 (4)* | |
H151 | 0.7129 (18) | 0.0471 (18) | 0.6417 (19) | 0.032 (4)* | |
H152 | 0.6544 (19) | 0.138 (2) | 0.7678 (19) | 0.039 (4)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0238 (5) | 0.0301 (5) | 0.0287 (5) | 0.0001 (4) | −0.0120 (4) | 0.0106 (4) |
N1 | 0.0235 (6) | 0.0200 (5) | 0.0181 (5) | −0.0001 (4) | −0.0079 (4) | 0.0032 (4) |
C1 | 0.0231 (6) | 0.0208 (6) | 0.0174 (6) | 0.0003 (5) | −0.0070 (5) | 0.0003 (5) |
C2 | 0.0239 (6) | 0.0228 (6) | 0.0184 (6) | 0.0021 (5) | −0.0078 (5) | 0.0005 (5) |
C3 | 0.0303 (7) | 0.0217 (6) | 0.0186 (6) | −0.0003 (5) | −0.0075 (5) | 0.0040 (5) |
C4 | 0.0272 (7) | 0.0245 (6) | 0.0201 (6) | −0.0049 (5) | −0.0050 (5) | 0.0023 (5) |
C5 | 0.0235 (6) | 0.0250 (6) | 0.0185 (6) | −0.0015 (5) | −0.0055 (5) | −0.0011 (5) |
C6 | 0.0230 (7) | 0.0375 (8) | 0.0244 (7) | −0.0015 (6) | −0.0056 (5) | 0.0022 (6) |
C7 | 0.0253 (6) | 0.0210 (6) | 0.0248 (6) | −0.0021 (5) | −0.0100 (5) | 0.0040 (5) |
C8 | 0.0350 (8) | 0.0315 (8) | 0.0292 (7) | −0.0033 (6) | −0.0004 (6) | 0.0050 (6) |
O11 | 0.0224 (5) | 0.0530 (7) | 0.0418 (6) | −0.0050 (5) | −0.0145 (4) | 0.0269 (5) |
O12 | 0.0259 (5) | 0.0304 (5) | 0.0279 (5) | −0.0019 (4) | −0.0110 (4) | 0.0119 (4) |
O13 | 0.0226 (5) | 0.0459 (6) | 0.0404 (6) | −0.0045 (4) | −0.0153 (4) | 0.0205 (5) |
O14 | 0.0254 (5) | 0.0316 (5) | 0.0313 (5) | −0.0018 (4) | −0.0124 (4) | 0.0134 (4) |
C11 | 0.0220 (6) | 0.0229 (6) | 0.0273 (7) | −0.0020 (5) | −0.0113 (5) | 0.0064 (5) |
C12 | 0.0216 (7) | 0.0282 (7) | 0.0285 (7) | −0.0028 (5) | −0.0111 (6) | 0.0118 (6) |
C13 | 0.0204 (6) | 0.0203 (6) | 0.0238 (7) | −0.0004 (5) | −0.0088 (5) | 0.0049 (5) |
C14 | 0.0197 (6) | 0.0229 (6) | 0.0234 (7) | −0.0004 (5) | −0.0079 (5) | 0.0059 (5) |
C15 | 0.0214 (6) | 0.0229 (6) | 0.0260 (7) | −0.0007 (5) | −0.0103 (5) | 0.0059 (5) |
C16 | 0.0219 (6) | 0.0241 (6) | 0.0228 (6) | 0.0005 (5) | −0.0087 (5) | 0.0033 (5) |
Geometric parameters (Å, º) top
O1—C2 | 1.3405 (15) | C8—H82 | 0.97 (2) |
O1—H2 | 0.90 (2) | C8—H83 | 0.970 (18) |
N1—C1 | 1.3470 (16) | O11—C11 | 1.2892 (16) |
N1—C5 | 1.3533 (16) | O11—H11 | 1.07 (3) |
N1—H1 | 0.90 (2) | O12—C11 | 1.2303 (15) |
C1—C2 | 1.4050 (16) | O13—C16 | 1.2701 (16) |
C1—C7 | 1.4962 (17) | O14—C16 | 1.2470 (16) |
C2—C3 | 1.3901 (18) | C11—C12 | 1.5187 (16) |
C3—C4 | 1.3856 (19) | C12—C13 | 1.5149 (18) |
C3—H3 | 0.977 (17) | C12—H121 | 0.994 (19) |
C4—C5 | 1.3832 (17) | C12—H122 | 0.933 (18) |
C4—H4 | 0.961 (16) | C13—C14 | 1.5290 (16) |
C5—C6 | 1.4940 (18) | C13—H131 | 0.970 (16) |
C6—H61 | 0.89 (2) | C13—H132 | 0.965 (16) |
C6—H62 | 0.931 (19) | C14—C15 | 1.5109 (18) |
C6—H63 | 0.96 (2) | C14—H141 | 0.959 (17) |
C7—C8 | 1.520 (2) | C14—H142 | 0.975 (15) |
C7—H71 | 0.958 (16) | C15—C16 | 1.5227 (16) |
C7—H72 | 0.986 (17) | C15—H151 | 0.971 (16) |
C8—H81 | 0.98 (2) | C15—H152 | 0.984 (17) |
| | | |
C2—O1—H2 | 115.9 (13) | C7—C8—H83 | 110.9 (10) |
C1—N1—C5 | 125.04 (11) | H81—C8—H83 | 108.5 (15) |
C1—N1—H1 | 117.5 (11) | H82—C8—H83 | 109.0 (15) |
C5—N1—H1 | 117.4 (11) | C11—O11—H11 | 115.9 (13) |
N1—C1—C2 | 118.33 (11) | O12—C11—O11 | 122.00 (11) |
N1—C1—C7 | 119.23 (10) | O12—C11—C12 | 120.95 (11) |
C2—C1—C7 | 122.44 (11) | O11—C11—C12 | 117.04 (11) |
O1—C2—C3 | 125.40 (11) | C13—C12—C11 | 114.88 (11) |
O1—C2—C1 | 115.97 (11) | C13—C12—H121 | 107.7 (10) |
C3—C2—C1 | 118.63 (11) | C11—C12—H121 | 105.2 (11) |
C4—C3—C2 | 120.02 (11) | C13—C12—H122 | 112.8 (10) |
C4—C3—H3 | 120.3 (9) | C11—C12—H122 | 108.3 (11) |
C2—C3—H3 | 119.6 (9) | H121—C12—H122 | 107.4 (15) |
C5—C4—C3 | 121.00 (12) | C12—C13—C14 | 111.48 (10) |
C5—C4—H4 | 116.9 (9) | C12—C13—H131 | 108.6 (9) |
C3—C4—H4 | 122.1 (9) | C14—C13—H131 | 110.8 (9) |
N1—C5—C4 | 116.95 (11) | C12—C13—H132 | 109.4 (9) |
N1—C5—C6 | 117.92 (11) | C14—C13—H132 | 110.1 (9) |
C4—C5—C6 | 125.12 (12) | H131—C13—H132 | 106.4 (13) |
C5—C6—H61 | 110.7 (14) | C15—C14—C13 | 111.65 (10) |
C5—C6—H62 | 109.7 (11) | C15—C14—H141 | 109.8 (10) |
H61—C6—H62 | 111.1 (18) | C13—C14—H141 | 109.1 (10) |
C5—C6—H63 | 113.4 (11) | C15—C14—H142 | 108.3 (8) |
H61—C6—H63 | 105.5 (17) | C13—C14—H142 | 108.1 (9) |
H62—C6—H63 | 106.3 (15) | H141—C14—H142 | 109.9 (13) |
C1—C7—C8 | 112.50 (11) | C14—C15—C16 | 115.48 (10) |
C1—C7—H71 | 109.4 (9) | C14—C15—H151 | 111.2 (9) |
C8—C7—H71 | 111.7 (9) | C16—C15—H151 | 106.9 (9) |
C1—C7—H72 | 107.1 (10) | C14—C15—H152 | 109.4 (10) |
C8—C7—H72 | 110.2 (9) | C16—C15—H152 | 106.4 (10) |
H71—C7—H72 | 105.6 (13) | H151—C15—H152 | 107.1 (14) |
C7—C8—H81 | 109.1 (11) | O14—C16—O13 | 123.05 (11) |
C7—C8—H82 | 111.7 (11) | O14—C16—C15 | 119.66 (11) |
H81—C8—H82 | 107.5 (15) | O13—C16—C15 | 117.29 (11) |
| | | |
C5—N1—C1—C2 | −1.12 (18) | C3—C4—C5—N1 | 0.17 (19) |
C5—N1—C1—C7 | 179.02 (11) | C3—C4—C5—C6 | 178.91 (13) |
N1—C1—C2—O1 | 179.93 (10) | N1—C1—C7—C8 | 103.03 (14) |
C7—C1—C2—O1 | −0.21 (18) | C2—C1—C7—C8 | −76.83 (16) |
N1—C1—C2—C3 | −0.09 (18) | O12—C11—C12—C13 | 17.5 (2) |
C7—C1—C2—C3 | 179.77 (12) | O11—C11—C12—C13 | −163.33 (13) |
O1—C2—C3—C4 | −178.77 (12) | C11—C12—C13—C14 | −173.44 (12) |
C1—C2—C3—C4 | 1.25 (19) | C12—C13—C14—C15 | −179.96 (12) |
C2—C3—C4—C5 | −1.3 (2) | C13—C14—C15—C16 | −178.57 (12) |
C1—N1—C5—C4 | 1.07 (18) | C14—C15—C16—O14 | −7.79 (19) |
C1—N1—C5—C6 | −177.76 (12) | C14—C15—C16—O13 | 172.81 (12) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O11—H11···O13i | 1.07 (3) | 1.40 (3) | 2.4639 (15) | 176 (2) |
O1—H2···O14ii | 0.90 (2) | 1.66 (2) | 2.5355 (12) | 163 (2) |
N1—H1···O12 | 0.90 (2) | 1.83 (2) | 2.7181 (14) | 167.6 (16) |
Symmetry codes: (i) x−1, y, z; (ii) x−1, y+1, z−1. |
Geometric parameters (Å, °), graph-set notations and QTAIMC energies
(EHB)* of hydrogen bonds in the studied salt forms of EMX topInteraction | D—H | H···A | D···A | D—H···A | EHB (kJ mol-1) | Graph-set notation |
[EMX+Mlt] (1:1) | | | | | | |
O11—H11···O14* | 1.13 (2) | 1.30 (2) | 2.4288 (14) | 176 (2) | 88.2 | E(7) |
O1—H12···O-13i | 0.87 (2) | 1.71 (2) | 2.5804 (13) | 178.5 (19) | 54.1 | D |
N+1—H1···O12 | 0.936 (16) | 1.795 (17) | 2.7165 (14) | 167.5 (14) | 36.8 | D |
| | | | | | |
[EMX+Mln] (1:1) | | | | | | |
O31—H31···O34* | 1.09 (2) | 1.38 (2) | 2.4410 (13) | 162 (2) | 68.9 | E(6) |
O41—H41···O44* | 1.04 (2) | 1.44 (2) | 2.4428 (12) | 162 (2) | 65.1 | E(6) |
O1—H12···O-33 | 0.901 (19) | 1.69 (2) | 2.5925 (13) | 175.0 (17) | 53.6 | D |
O2—H22···O-43 | 0.96 (2) | 1.62 (2) | 2.5610 (12) | 167.6 (19) | 51.5 | D |
N+2—H21···O32 | 0.927 (17) | 1.800 (17) | 2.7196 (13) | 170.9 (15) | 34.8 | D |
N+1—H11···O42ii | 0.918 (15) | 1.850 (16) | 2.7604 (13) | 171.1 (13) | 30.9 | D |
| | | | | | |
[EMX+Adp] (1:1) | | | | | | |
O11—H11···O-13iii | 1.07 (3) | 1.40 (3) | 2.4639 (15) | 176 (2) | 72.5 | C(9) |
O1—H2···O14iv | 0.90 (2) | 1.66 (2) | 2.5355 (12) | 163 (2) | 59.9 | D |
N+1—H1···O12 | 0.90 (2) | 1.83 (2) | 2.7181 (14) | 167.6 (16) | 36.3 | D |
Note: (*) intramolecular hydrogen bond.
Symmetry codes:
(i) x-1/2, -y+1, -z+1/2;
(ii) x-1, y+2, z+1;
(iii) x-1, y, z;
(iv) x-1, y+1, z-1. |
Contributions of different types of stabilizing noncovalent interactions into
the lattice energy* of studied EMX salts topCrystal | [EMX+Mlt] | [EMX+Mln] | [EMX+Adp] |
Elatt | 226.3 | 213.7 | 315.8 |
ΣE(Hydrogen bonds) | 90.8 (40.1%) | 85.4 (39.9%) | 168.8 (53.4%) |
ΣE(C—H···O) | 70.1 (31.0%) | 80.1 (37.5%) | 88.6 (28.1%) |
ΣE(C—H···π) | 9.0 (4.0%) | 10.2 (4.8%) | 16.3 (5.2%) |
ΣE(H···H) | 29.7 (13.1%) | 15.4 (7.2%) | 26.3 (8.3%) |
ΣE(π–π) | 26.6 (11.8%) | 22.7 (10.6%) | 15.9 (5.0%) |
E(EMX–EMX) | 49.0 (21.7%) | 41.8 (19.5%) | 25.6 (8.1%) |
E(EMX–acid) | 167.7 (74.1%) | 153.0 (71.6%) | 192.1 (60.8%) |
E(acid–acid) | 9.5 (4.2%) | 18.9 (8.9%) | 98.1 (31.1%) |
Note: (*) all the energies are given in kJ mol-1 and % of Elatt
value |
Thermophysical data for emoxypine salts top | Tfus (salt) (°C) (onset) | ΔHfusTa (kJ mol-1) | Tfus (acid) (°C) |
[EMX+Mln] (1:1) | 124.8±0.2 | 27.4±0.6 | 135.60 |
[EMX+Mlt] (1:1) | 133.2±0.3 | 34.8±0.6 | 142.70 |
[EMX+Adp] (1:1) | 115.8±0.5 | 53.5±1.1 | 151.92 |
EMX | 168.81 | 16.6 | - |
Note: (a) for the salts, the values correspond to a mole of molecules
in the asymmetric unit. |
Solubilities at 25°C for EMX salts and pure EMX in pH 7.4 media top | Solubility (mol l-1) | Solid phase recovered after solubility experimenta |
[EMX+Mln] (1:1) | 1.8±0.1 | amorphous |
[EMX+Mlt] (1:1) | 1.7±0.1 | [EMX+Mlt] |
[EMX+Adp] (1:1) | 0.38±0.05 | [EMX+Adp] |
EMX | 0.047±0.01 | EMX |
Note: (a) the residual materials were identified by DSC and PXRD
analyses (Fig. S2–S5 in the supporting information). |