Two new N-oxide compounds, namely glycinium 2-carboxy-1-(λ1-oxidaneyl)-1λ4-pyridine-6-carboxylate–glycine–water (1/1/1), C2H6NO2+·C7H4NO5−·C2H5NO2·H2O or [(2,6-HpydcO)(HGLY)(GLY)(H2O)], 1, and methyl 6-carboxy-1-(λ1-oxidaneyl)-1λ4-pyridine-2-carboxylate, C8H7NO5 or 2,6-HMepydcO, 2, were prepared and identified by elemental analysis, FT–IR, Raman spectroscopy and single-crystal X-ray diffraction. The X-ray analysis of 1 revealed an ionic compound containing a 2,6-HpydcO− anion, a glycinium cation, a neutral glycine molecule and a water molecule. Compound 2 is a neutral compound with two independent units in its crystal structure. In addition to the hydrogen bonds, the crystal network is stabilized by π–π stacking interactions of the types pyridine–carboxylate and carboxylate–carboxylate. The thermodynamic stability and charge-distribution patterns for isolated molecules of 2,6-H2pydcO and 2,6-HMepydcO, and their two similar derivatives, pyridine-2,6-dicarboxylic acid (2,6-H2pydc) and dimethyl 1-(λ1-oxidaneyl)-1λ4-pyridine-2,6-dicarboxylate (2,6-Me2pydcO), were studied by density functional theory (DFT) and natural bond orbital (NBO) analysis, respectively. The ability of these compounds and their analogues to interact with nine selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) was investigated using docking calculations.
Supporting information
CCDC references: 1878768; 1878767
For both structures, data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007); program(s) used to refine structure: JANA2006 (Petříček et al., 2014); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: JANA2006 (Petříček et al., 2014).
Glycinium
2-carboxy-1-(
λ1-oxidaneyl)-1
λ4-pyridine-6-carboxylate–glycine–water
(1/1/1) (1)
top
Crystal data top
C2H6NO2+·C7H4NO5−·C2H5NO2·H2O | F(000) = 736 |
Mr = 351.2 | Dx = 1.594 Mg m−3 |
Orthorhombic, Pca21 | Cu Kα radiation, λ = 1.54184 Å |
Hall symbol: P 2c -2ac | Cell parameters from 6609 reflections |
a = 10.9307 (3) Å | θ = 4.2–74.2° |
b = 10.4069 (4) Å | µ = 1.25 mm−1 |
c = 12.8686 (4) Å | T = 95 K |
V = 1463.86 (8) Å3 | Polygonal shape, colourless |
Z = 4 | 0.49 × 0.06 × 0.03 × 0.06 (radius) mm |
Data collection top
Rigaku OD SuperNova Dual source diffractometer with an AtlasS2 detector | 2482 independent reflections |
Radiation source: X-ray tube | 2432 reflections with I > 3σ(I) |
Mirror monochromator | Rint = 0.020 |
Detector resolution: 5.2027 pixels mm-1 | θmax = 74.5°, θmin = 4.3° |
ω scans | h = −13→12 |
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2018) | k = −12→12 |
Tmin = 0.736, Tmax = 1 | l = −15→12 |
8004 measured reflections | |
Refinement top
Refinement on F2 | H atoms treated by a mixture of independent and constrained refinement |
R[F > 3σ(F)] = 0.025 | Weighting scheme based on measured s.u.'s w = 1/(σ2(I) + 0.0016I2) |
wR(F) = 0.080 | (Δ/σ)max = 0.004 |
S = 1.65 | Δρmax = 0.19 e Å−3 |
2482 reflections | Δρmin = −0.16 e Å−3 |
230 parameters | Extinction correction: B-C type 1 Gaussian isotropic (Becker & Coppens, 1974) |
3 restraints | Extinction coefficient: 1200 (200) |
57 constraints | Absolute structure: 925 of Friedel pairs used in the refinement |
Special details top
Refinement. The refinement was carried out against all reflections. The conventional
R-factor is always based on F. The goodness of fit as well as the weighted
R-factor are based on F and F2 for refinement carried out on F and F2,
respectively. The threshold expression is used only for calculating
R-factors etc. and it is not relevant to the choice of reflections for
refinement. The program used for refinement, Jana2006, uses the weighting scheme
based on the experimental expectations, see _refine_ls_weighting_details,
that does not force S to be one. Therefore the values of S are usually larger
than the ones from the SHELX program. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.20407 (12) | 0.10762 (10) | 0.01347 (11) | 0.0197 (3) | |
O2 | 0.77050 (10) | 0.37972 (10) | 0.13865 (10) | 0.0137 (3) | |
O3 | 0.40294 (10) | −0.12662 (10) | −0.07686 (10) | 0.0148 (3) | |
O4 | 0.02520 (9) | 0.21107 (10) | 0.17074 (10) | 0.0152 (3) | |
O5 | 0.35303 (11) | −0.50934 (11) | −0.07973 (11) | 0.0187 (3) | |
O6 | −0.17205 (9) | 0.15411 (10) | 0.16340 (10) | 0.0154 (3) | |
O7 | 0.33622 (11) | 0.32755 (13) | 0.24976 (11) | 0.0233 (4) | |
O8 | 0.59044 (10) | 0.30478 (10) | 0.19672 (10) | 0.0158 (3) | |
O9 | 0.48123 (10) | −0.34364 (11) | −0.06606 (10) | 0.0165 (3) | |
O10 | 0.26647 (11) | 0.10554 (10) | −0.15284 (10) | 0.0163 (3) | |
N1 | 0.28764 (10) | −0.17250 (12) | −0.08201 (11) | 0.0108 (3) | |
N2 | 0.10677 (11) | −0.02976 (12) | 0.18420 (11) | 0.0127 (3) | |
N3 | 0.68827 (11) | 0.61109 (11) | 0.08930 (11) | 0.0131 (4) | |
C1 | 0.37227 (15) | −0.39423 (15) | −0.07919 (13) | 0.0136 (4) | |
C2 | 0.22655 (12) | 0.05559 (14) | −0.07094 (14) | 0.0123 (4) | |
C3 | 0.19476 (13) | −0.08761 (14) | −0.07802 (13) | 0.0110 (4) | |
C4 | −0.05550 (13) | 0.13130 (14) | 0.16902 (13) | 0.0113 (4) | |
C5 | 0.65682 (14) | 0.39050 (13) | 0.15903 (12) | 0.0113 (4) | |
C6 | 0.26737 (13) | −0.30155 (14) | −0.08985 (12) | 0.0109 (4) | |
C7 | 0.07547 (14) | −0.13133 (14) | −0.08257 (13) | 0.0132 (4) | |
C8 | 0.05009 (14) | −0.26118 (15) | −0.09625 (12) | 0.0143 (4) | |
C9 | 0.59873 (13) | 0.51869 (14) | 0.13372 (13) | 0.0138 (4) | |
C10 | −0.02688 (12) | −0.01116 (13) | 0.17693 (13) | 0.0113 (4) | |
C11 | 0.14828 (16) | −0.34626 (14) | −0.09984 (12) | 0.0146 (4) | |
H1 | 0.304 (2) | 0.2570 (18) | 0.286 (2) | 0.0279* | |
H2 | 0.4208 (12) | 0.316 (2) | 0.245 (2) | 0.0279* | |
H1o9 | 0.463 (2) | −0.2560 (13) | −0.069 (2) | 0.0198* | |
H1n3 | 0.650488 | 0.681111 | 0.07101 | 0.0158* | |
H2n3 | 0.743505 | 0.629239 | 0.13571 | 0.0158* | |
H3n3 | 0.723226 | 0.577016 | 0.035172 | 0.0158* | |
H1n2 | 0.123128 | −0.111542 | 0.186117 | 0.0152* | |
H2n2 | 0.141987 | 0.004565 | 0.130303 | 0.0152* | |
H3n2 | 0.133944 | 0.006733 | 0.240478 | 0.0152* | |
H1c7 | 0.009245 | −0.071258 | −0.076184 | 0.0159* | |
H1c8 | −0.032565 | −0.291212 | −0.103019 | 0.0172* | |
H1c9 | 0.53288 | 0.506055 | 0.085428 | 0.0165* | |
H2c9 | 0.563273 | 0.55449 | 0.195522 | 0.0165* | |
H1c10 | −0.065464 | −0.046048 | 0.237715 | 0.0135* | |
H2c10 | −0.057381 | −0.054555 | 0.116404 | 0.0135* | |
H1c11 | 0.133539 | −0.436444 | −0.109288 | 0.0175* | |
H1o6 | −0.1919 (19) | 0.2412 (13) | 0.1577 (19) | 0.0185* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0297 (6) | 0.0130 (5) | 0.0163 (6) | −0.0019 (4) | 0.0065 (5) | −0.0021 (5) |
O2 | 0.0095 (5) | 0.0124 (5) | 0.0192 (6) | 0.0018 (4) | 0.0016 (4) | 0.0023 (4) |
O3 | 0.0098 (5) | 0.0135 (5) | 0.0212 (6) | −0.0029 (4) | −0.0011 (5) | 0.0010 (5) |
O4 | 0.0129 (5) | 0.0106 (5) | 0.0221 (6) | −0.0019 (4) | 0.0025 (4) | 0.0004 (5) |
O5 | 0.0212 (5) | 0.0129 (5) | 0.0219 (6) | 0.0033 (4) | 0.0030 (5) | 0.0008 (5) |
O6 | 0.0105 (5) | 0.0113 (5) | 0.0244 (6) | 0.0019 (4) | −0.0007 (4) | 0.0016 (4) |
O7 | 0.0176 (5) | 0.0245 (6) | 0.0276 (7) | 0.0009 (5) | −0.0028 (5) | 0.0086 (5) |
O8 | 0.0152 (5) | 0.0116 (4) | 0.0208 (6) | 0.0008 (4) | 0.0023 (4) | 0.0019 (4) |
O9 | 0.0142 (5) | 0.0151 (5) | 0.0200 (6) | 0.0036 (4) | −0.0014 (4) | 0.0014 (4) |
O10 | 0.0213 (5) | 0.0112 (5) | 0.0164 (6) | −0.0003 (4) | 0.0043 (5) | 0.0019 (4) |
N1 | 0.0101 (6) | 0.0115 (6) | 0.0107 (6) | −0.0010 (4) | 0.0005 (5) | 0.0004 (5) |
N2 | 0.0153 (6) | 0.0093 (5) | 0.0134 (6) | 0.0021 (4) | 0.0003 (5) | 0.0004 (5) |
N3 | 0.0126 (6) | 0.0103 (6) | 0.0165 (7) | 0.0021 (5) | −0.0002 (5) | 0.0010 (5) |
C1 | 0.0159 (6) | 0.0147 (7) | 0.0103 (7) | 0.0035 (5) | 0.0023 (6) | 0.0025 (6) |
C2 | 0.0134 (6) | 0.0093 (6) | 0.0143 (7) | 0.0014 (5) | 0.0008 (6) | 0.0004 (6) |
C3 | 0.0116 (6) | 0.0108 (6) | 0.0105 (7) | −0.0012 (5) | 0.0012 (5) | 0.0019 (6) |
C4 | 0.0119 (6) | 0.0113 (6) | 0.0108 (7) | 0.0013 (5) | 0.0010 (6) | 0.0013 (5) |
C5 | 0.0128 (6) | 0.0113 (7) | 0.0099 (7) | 0.0012 (5) | −0.0014 (5) | −0.0011 (6) |
C6 | 0.0105 (6) | 0.0105 (7) | 0.0117 (8) | 0.0000 (5) | 0.0008 (5) | 0.0004 (6) |
C7 | 0.0149 (7) | 0.0130 (7) | 0.0118 (7) | 0.0010 (5) | −0.0002 (6) | −0.0004 (6) |
C8 | 0.0131 (6) | 0.0152 (7) | 0.0147 (8) | −0.0024 (6) | −0.0004 (5) | 0.0023 (6) |
C9 | 0.0107 (6) | 0.0111 (7) | 0.0195 (8) | 0.0009 (5) | 0.0020 (6) | 0.0029 (6) |
C10 | 0.0086 (7) | 0.0099 (6) | 0.0153 (7) | −0.0001 (5) | 0.0017 (6) | 0.0001 (6) |
C11 | 0.0215 (8) | 0.0101 (7) | 0.0121 (8) | −0.0016 (6) | −0.0009 (6) | 0.0019 (5) |
Geometric parameters (Å, º) top
O1—C2 | 1.238 (2) | N3—H1n3 | 0.87 |
O2—C5 | 1.2749 (18) | N3—H2n3 | 0.87 |
O4—C4 | 1.2116 (18) | N3—H3n3 | 0.87 |
O5—C1 | 1.2164 (19) | C1—C6 | 1.505 (2) |
O6—C4 | 1.2979 (18) | C2—C3 | 1.533 (2) |
O6—H1o6 | 0.935 (14) | C3—C7 | 1.382 (2) |
O7—H1 | 0.93 (2) | C4—C10 | 1.519 (2) |
O7—H2 | 0.934 (13) | C5—C9 | 1.513 (2) |
O8—C5 | 1.2481 (18) | C6—C11 | 1.388 (2) |
O9—C1 | 1.3131 (19) | C7—C8 | 1.391 (2) |
O9—H1o9 | 0.935 (14) | C7—H1c7 | 0.96 |
O10—C2 | 1.254 (2) | C8—C11 | 1.392 (2) |
N1—C3 | 1.3467 (19) | C8—H1c8 | 0.96 |
N1—C6 | 1.3649 (19) | C9—H1c9 | 0.96 |
N2—C10 | 1.4767 (18) | C9—H2c9 | 0.96 |
N2—H1n2 | 0.87 | C10—H1c10 | 0.96 |
N2—H2n2 | 0.87 | C10—H2c10 | 0.96 |
N2—H3n2 | 0.87 | C11—H1c11 | 0.96 |
N3—C9 | 1.4864 (19) | | |
| | | |
C4—O6—H1o6 | 114.2 (12) | O2—C5—O8 | 125.71 (13) |
H1—O7—H2 | 108 (2) | O2—C5—C9 | 116.25 (12) |
C1—O9—H1o9 | 101.0 (13) | O8—C5—C9 | 118.03 (13) |
C3—N1—C6 | 121.73 (12) | N1—C6—C1 | 120.02 (13) |
C10—N2—H1n2 | 109.47 | N1—C6—C11 | 119.26 (13) |
C10—N2—H2n2 | 109.47 | C1—C6—C11 | 120.54 (13) |
C10—N2—H3n2 | 109.47 | C3—C7—C8 | 120.89 (14) |
H1n2—N2—H2n2 | 109.47 | C3—C7—H1c7 | 119.56 |
H1n2—N2—H3n2 | 109.47 | C8—C7—H1c7 | 119.56 |
H2n2—N2—H3n2 | 109.47 | C7—C8—C11 | 117.94 (14) |
C9—N3—H1n3 | 109.47 | C7—C8—H1c8 | 121.03 |
C9—N3—H2n3 | 109.47 | C11—C8—H1c8 | 121.03 |
C9—N3—H3n3 | 109.47 | N3—C9—C5 | 112.14 (12) |
H1n3—N3—H2n3 | 109.47 | N3—C9—H1c9 | 109.47 |
H1n3—N3—H3n3 | 109.47 | N3—C9—H2c9 | 109.47 |
H2n3—N3—H3n3 | 109.47 | C5—C9—H1c9 | 109.47 |
O5—C1—O9 | 123.53 (15) | C5—C9—H2c9 | 109.47 |
O5—C1—C6 | 119.94 (14) | H1c9—C9—H2c9 | 106.66 |
O9—C1—C6 | 116.49 (13) | N2—C10—C4 | 109.63 (11) |
O1—C2—O10 | 128.70 (14) | N2—C10—H1c10 | 109.47 |
O1—C2—C3 | 115.61 (14) | N2—C10—H2c10 | 109.47 |
O10—C2—C3 | 115.59 (14) | C4—C10—H1c10 | 109.47 |
N1—C3—C2 | 117.98 (12) | C4—C10—H2c10 | 109.47 |
N1—C3—C7 | 119.58 (13) | H1c10—C10—H2c10 | 109.31 |
C2—C3—C7 | 122.44 (13) | C6—C11—C8 | 120.44 (14) |
O4—C4—O6 | 126.18 (14) | C6—C11—H1c11 | 119.78 |
O4—C4—C10 | 121.18 (13) | C8—C11—H1c11 | 119.78 |
O6—C4—C10 | 112.61 (12) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O7—H1···O10i | 0.93 (2) | 1.93 (2) | 2.8582 (17) | 175 (2) |
O7—H2···O8 | 0.934 (13) | 1.958 (15) | 2.8712 (16) | 165 (3) |
O9—H1o9···O3 | 0.935 (14) | 1.500 (15) | 2.4192 (15) | 167 (2) |
O9—H1o9···N1 | 0.935 (14) | 2.11 (2) | 2.7735 (16) | 127.0 (16) |
N3—H1n3···O1ii | 0.87 | 2.39 | 3.0905 (16) | 137.48 |
N3—H1n3···O4ii | 0.87 | 2.19 | 2.7750 (16) | 124.63 |
N3—H2n3···O7ii | 0.87 | 1.84 | 2.6994 (19) | 169.48 |
N3—H3n3···O5iii | 0.87 | 2.17 | 3.0160 (18) | 165.09 |
N2—H1n2···O6iii | 0.87 | 2.30 | 2.7553 (16) | 112.63 |
N2—H1n2···O8iv | 0.87 | 2.05 | 2.8721 (16) | 157.98 |
N2—H2n2···O1 | 0.87 | 1.97 | 2.8289 (19) | 170.28 |
N2—H3n2···O10i | 0.87 | 2.03 | 2.8810 (18) | 165.11 |
C7—H1c7···O3iv | 0.96 | 2.36 | 3.2815 (19) | 159.62 |
C8—H1c8···O5v | 0.96 | 2.44 | 3.2231 (19) | 138.39 |
O6—H1o6···O2vi | 0.935 (14) | 1.519 (14) | 2.4512 (15) | 175 (2) |
O6—H1o6···C5vi | 0.935 (14) | 2.269 (18) | 3.0910 (17) | 146.3 (17) |
Symmetry codes: (i) −x+1/2, y, z+1/2; (ii) x+1/2, −y+1, z; (iii) x+1/2, −y, z; (iv) x−1/2, −y, z; (v) x−1/2, −y−1, z; (vi) x−1, y, z. |
Methyl 6-carboxy-1-(
λ1-oxidaneyl)-1
λ4-pyridine-2-carboxylate (1_1)
top
Crystal data top
C8H7NO5 | F(000) = 816 |
Mr = 197.15 | Dx = 1.619 Mg m−3 |
Monoclinic, P21/n | Cu Kα radiation, λ = 1.54184 Å |
Hall symbol: -P 2yn | Cell parameters from 901 reflections |
a = 7.3758 (8) Å | θ = 7.2–71.7° |
b = 11.7446 (10) Å | µ = 1.20 mm−1 |
c = 18.9211 (17) Å | T = 95 K |
β = 99.328 (8)° | Polygon shape, white |
V = 1617.4 (3) Å3 | 0.08 × 0.03 × 0.02 mm |
Z = 8 | |
Data collection top
Rigaku OD SuperNova Dual source diffractometer with an AtlasS2 detector | 4549 independent reflections |
Radiation source: X-ray tube | 1931 reflections with I > 3σ(I) |
Mirror monochromator | Rint = 0 |
Detector resolution: 5.2027 pixels mm-1 | θmax = 74.4°, θmin = 6.1° |
ω scans | h = −9→8 |
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2018) | k = −14→14 |
Tmin = 0.974, Tmax = 1 | l = −23→23 |
4549 measured reflections | |
Refinement top
Refinement on F2 | 50 constraints |
R[F > 3σ(F)] = 0.040 | H atoms treated by a mixture of independent and constrained refinement |
wR(F) = 0.062 | Weighting scheme based on measured s.u.'s w = 1/(σ2(I) + 0.000016I2) |
S = 1.02 | (Δ/σ)max = 0.004 |
4549 reflections | Δρmax = 0.28 e Å−3 |
260 parameters | Δρmin = −0.25 e Å−3 |
1 restraint | |
Special details top
Refinement. The refinement was carried out against all reflections. The conventional
R-factor is always based on F. The goodness of fit as well as the weighted
R-factor are based on F and F2 for refinement carried out on F and F2,
respectively. The threshold expression is used only for calculating
R-factors etc. and it is not relevant to the choice of reflections for
refinement. The program used for refinement, Jana2006, uses the weighting scheme
based on the experimental expectations, see _refine_ls_weighting_details,
that does not force S to be one. Therefore the values of S are usually larger
than the ones from the SHELX program. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.3114 (3) | 0.27930 (16) | 0.00008 (11) | 0.0207 (8) | |
O2 | −0.1809 (3) | 0.3197 (2) | −0.21714 (13) | 0.0283 (9) | |
O3 | 0.6339 (3) | 0.88713 (18) | 0.20312 (12) | 0.0231 (8) | |
O4 | 0.7857 (3) | 0.75471 (19) | 0.27406 (11) | 0.0263 (8) | |
O5 | 0.4132 (3) | 0.82622 (16) | 0.10106 (12) | 0.0219 (8) | |
O6 | 0.3106 (3) | 0.10620 (17) | 0.05051 (12) | 0.0244 (8) | |
O7 | −0.2756 (3) | 0.1632 (2) | −0.27922 (13) | 0.0355 (9) | |
O8 | 0.1663 (3) | 0.57316 (18) | −0.02712 (11) | 0.0235 (8) | |
O9 | 0.2014 (3) | 0.76235 (18) | −0.01753 (12) | 0.0308 (9) | |
O10 | 0.0292 (3) | 0.30052 (15) | −0.10587 (13) | 0.0258 (9) | |
N1 | 0.4579 (4) | 0.71601 (18) | 0.11373 (14) | 0.0144 (9) | |
N2 | 0.0331 (4) | 0.18752 (19) | −0.11308 (15) | 0.0188 (9) | |
C1 | 0.6324 (4) | 0.5774 (3) | 0.18552 (16) | 0.0201 (11) | |
C2 | 0.5499 (4) | 0.4914 (3) | 0.14217 (17) | 0.0214 (11) | |
C3 | 0.1381 (4) | 0.0062 (2) | −0.06910 (17) | 0.0208 (12) | |
C4 | 0.5855 (4) | 0.6893 (2) | 0.17203 (17) | 0.0162 (10) | |
C5 | 0.2615 (5) | 0.1820 (3) | −0.00161 (17) | 0.0196 (11) | |
C6 | 0.6762 (5) | 0.7804 (3) | 0.22125 (19) | 0.0222 (12) | |
C7 | 0.1396 (4) | 0.1230 (2) | −0.06249 (17) | 0.0154 (11) | |
C8 | −0.0705 (4) | 0.1367 (3) | −0.17122 (17) | 0.0180 (11) | |
C9 | −0.1869 (5) | 0.2091 (3) | −0.2282 (2) | 0.0273 (13) | |
C10 | 0.2393 (5) | 0.6685 (3) | 0.00369 (17) | 0.0194 (11) | |
C11 | 0.3755 (4) | 0.6352 (2) | 0.06885 (17) | 0.0139 (10) | |
C12 | 0.0316 (4) | 0.5923 (2) | −0.09234 (16) | 0.0266 (11) | |
C13 | 0.4194 (4) | 0.5222 (2) | 0.08253 (17) | 0.0170 (11) | |
C14 | −0.0712 (5) | 0.0213 (2) | −0.17781 (17) | 0.0222 (11) | |
C15 | 0.0325 (4) | −0.0469 (2) | −0.12710 (16) | 0.0231 (12) | |
C16 | 0.4371 (5) | 0.1496 (2) | 0.11261 (18) | 0.0280 (12) | |
H1c1 | 0.724337 | 0.558646 | 0.225807 | 0.0241* | |
H1c2 | 0.580451 | 0.413055 | 0.15238 | 0.0257* | |
H1c3 | 0.211264 | −0.0391 | −0.033002 | 0.025* | |
H1c12 | −0.0154 | 0.520353 | −0.111294 | 0.0319* | |
H2c12 | −0.067626 | 0.637985 | −0.080982 | 0.0319* | |
H3c12 | 0.089978 | 0.63088 | −0.127326 | 0.0319* | |
H1c13 | 0.360522 | 0.464209 | 0.051132 | 0.0204* | |
H1c14 | −0.14532 | −0.013414 | −0.218513 | 0.0267* | |
H1c15 | 0.031586 | −0.128257 | −0.131876 | 0.0277* | |
H1c16 | 0.481036 | 0.087424 | 0.143648 | 0.0336* | |
H2c16 | 0.539129 | 0.186608 | 0.096573 | 0.0336* | |
H3c16 | 0.373758 | 0.20315 | 0.138208 | 0.0336* | |
H1o3 | 0.540 (3) | 0.884 (2) | 0.1651 (14) | 0.0277* | |
H1o2 | −0.093 (4) | 0.341 (3) | −0.1795 (15) | 0.034* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0254 (14) | 0.0121 (12) | 0.0242 (13) | −0.0018 (10) | 0.0027 (10) | −0.0017 (9) |
O2 | 0.0272 (16) | 0.0325 (15) | 0.0247 (14) | 0.0106 (13) | 0.0026 (11) | 0.0076 (11) |
O3 | 0.0187 (15) | 0.0212 (13) | 0.0268 (14) | −0.0056 (11) | −0.0037 (11) | −0.0040 (10) |
O4 | 0.0236 (13) | 0.0290 (14) | 0.0229 (13) | 0.0008 (12) | −0.0065 (10) | −0.0007 (11) |
O5 | 0.0272 (15) | 0.0098 (11) | 0.0262 (14) | −0.0009 (10) | −0.0026 (11) | −0.0035 (9) |
O6 | 0.0305 (15) | 0.0216 (13) | 0.0183 (12) | −0.0041 (11) | −0.0041 (10) | 0.0020 (9) |
O7 | 0.0264 (16) | 0.0546 (17) | 0.0219 (14) | −0.0045 (14) | −0.0066 (12) | 0.0055 (13) |
O8 | 0.0256 (14) | 0.0171 (11) | 0.0241 (13) | 0.0030 (11) | −0.0068 (10) | −0.0031 (10) |
O9 | 0.0422 (17) | 0.0163 (12) | 0.0286 (14) | −0.0042 (12) | −0.0100 (12) | 0.0088 (11) |
O10 | 0.0360 (17) | 0.0123 (12) | 0.0278 (15) | 0.0059 (11) | 0.0017 (12) | 0.0014 (9) |
N1 | 0.0174 (16) | 0.0104 (13) | 0.0156 (14) | −0.0006 (12) | 0.0031 (12) | 0.0002 (10) |
N2 | 0.0195 (17) | 0.0167 (14) | 0.0216 (15) | −0.0006 (13) | 0.0074 (12) | 0.0003 (11) |
C1 | 0.0171 (19) | 0.0266 (18) | 0.0157 (17) | 0.0024 (17) | 0.0003 (13) | 0.0039 (15) |
C2 | 0.020 (2) | 0.0226 (18) | 0.0231 (17) | 0.0043 (16) | 0.0063 (14) | 0.0057 (14) |
C3 | 0.022 (2) | 0.024 (2) | 0.0163 (18) | −0.0008 (16) | 0.0047 (14) | 0.0014 (14) |
C4 | 0.0165 (18) | 0.0184 (16) | 0.0155 (17) | −0.0043 (15) | 0.0074 (14) | 0.0011 (13) |
C5 | 0.021 (2) | 0.0224 (19) | 0.0172 (17) | 0.0023 (16) | 0.0071 (14) | 0.0027 (14) |
C6 | 0.021 (2) | 0.0226 (19) | 0.025 (2) | −0.0049 (16) | 0.0098 (16) | −0.0051 (15) |
C7 | 0.016 (2) | 0.0159 (17) | 0.0143 (17) | 0.0013 (15) | 0.0017 (14) | −0.0006 (13) |
C8 | 0.017 (2) | 0.0240 (18) | 0.0133 (17) | 0.0017 (15) | 0.0025 (14) | 0.0031 (14) |
C9 | 0.020 (2) | 0.038 (2) | 0.026 (2) | 0.0080 (18) | 0.0108 (16) | 0.0090 (16) |
C10 | 0.018 (2) | 0.0233 (19) | 0.0172 (18) | −0.0011 (15) | 0.0049 (14) | −0.0035 (14) |
C11 | 0.0104 (19) | 0.0146 (16) | 0.0175 (17) | −0.0006 (13) | 0.0049 (14) | −0.0004 (12) |
C12 | 0.026 (2) | 0.0299 (19) | 0.0196 (18) | 0.0028 (17) | −0.0092 (15) | −0.0077 (14) |
C13 | 0.018 (2) | 0.0153 (16) | 0.0172 (17) | −0.0019 (14) | 0.0007 (14) | −0.0019 (13) |
C14 | 0.023 (2) | 0.0296 (19) | 0.0151 (17) | −0.0078 (17) | 0.0075 (15) | −0.0036 (14) |
C15 | 0.032 (2) | 0.0138 (17) | 0.026 (2) | −0.0065 (16) | 0.0123 (16) | −0.0048 (13) |
C16 | 0.027 (2) | 0.037 (2) | 0.0168 (18) | −0.0055 (18) | −0.0061 (16) | −0.0012 (16) |
Geometric parameters (Å, º) top
O1—C5 | 1.200 (4) | C2—H1c2 | 0.96 |
O2—C9 | 1.316 (4) | C3—C7 | 1.377 (4) |
O2—H1o2 | 0.92 (3) | C3—C15 | 1.387 (4) |
O3—C6 | 1.324 (4) | C3—H1c3 | 0.96 |
O3—H1o3 | 0.92 (2) | C4—C6 | 1.503 (4) |
O4—C6 | 1.216 (4) | C5—C7 | 1.510 (4) |
O6—C5 | 1.334 (4) | C8—C9 | 1.524 (5) |
O6—C16 | 1.468 (4) | C8—C14 | 1.361 (4) |
O7—C9 | 1.203 (4) | C10—C11 | 1.511 (4) |
O8—C10 | 1.335 (4) | C11—C13 | 1.380 (4) |
O8—C12 | 1.470 (3) | C12—H1c12 | 0.96 |
O9—C10 | 1.190 (4) | C12—H2c12 | 0.96 |
N1—C4 | 1.365 (4) | C12—H3c12 | 0.96 |
N1—C11 | 1.351 (4) | C13—H1c13 | 0.96 |
N2—C7 | 1.365 (4) | C14—C15 | 1.382 (4) |
N2—C8 | 1.370 (4) | C14—H1c14 | 0.96 |
C1—C2 | 1.379 (4) | C15—H1c15 | 0.96 |
C1—C4 | 1.373 (4) | C16—H1c16 | 0.96 |
C1—H1c1 | 0.96 | C16—H2c16 | 0.96 |
C2—C13 | 1.406 (4) | C16—H3c16 | 0.96 |
| | | |
C9—O2—H1o2 | 113.4 (19) | O2—C9—O7 | 124.8 (3) |
C6—O3—H1o3 | 106.4 (18) | O2—C9—C8 | 116.0 (3) |
C5—O6—C16 | 114.9 (2) | O7—C9—C8 | 119.2 (3) |
C10—O8—C12 | 114.1 (2) | O8—C10—O9 | 125.0 (3) |
C4—N1—C11 | 121.8 (2) | O8—C10—C11 | 107.8 (2) |
C7—N2—C8 | 120.2 (2) | O9—C10—C11 | 127.2 (3) |
C2—C1—C4 | 121.1 (3) | N1—C11—C10 | 120.2 (3) |
C2—C1—H1c1 | 119.45 | N1—C11—C13 | 119.3 (3) |
C4—C1—H1c1 | 119.45 | C10—C11—C13 | 120.5 (3) |
C1—C2—C13 | 117.9 (3) | O8—C12—H1c12 | 109.47 |
C1—C2—H1c2 | 121.04 | O8—C12—H2c12 | 109.47 |
C13—C2—H1c2 | 121.04 | O8—C12—H3c12 | 109.47 |
C7—C3—C15 | 121.0 (3) | H1c12—C12—H2c12 | 109.47 |
C7—C3—H1c3 | 119.5 | H1c12—C12—H3c12 | 109.47 |
C15—C3—H1c3 | 119.5 | H2c12—C12—H3c12 | 109.47 |
N1—C4—C1 | 119.4 (3) | C2—C13—C11 | 120.4 (3) |
N1—C4—C6 | 121.1 (2) | C2—C13—H1c13 | 119.79 |
C1—C4—C6 | 119.5 (3) | C11—C13—H1c13 | 119.79 |
O1—C5—O6 | 124.8 (3) | C8—C14—C15 | 121.3 (3) |
O1—C5—C7 | 126.9 (3) | C8—C14—H1c14 | 119.34 |
O6—C5—C7 | 108.3 (3) | C15—C14—H1c14 | 119.34 |
O3—C6—O4 | 123.0 (3) | C3—C15—C14 | 117.8 (3) |
O3—C6—C4 | 116.8 (3) | C3—C15—H1c15 | 121.12 |
O4—C6—C4 | 120.1 (3) | C14—C15—H1c15 | 121.12 |
N2—C7—C3 | 119.6 (3) | O6—C16—H1c16 | 109.47 |
N2—C7—C5 | 118.9 (3) | O6—C16—H2c16 | 109.47 |
C3—C7—C5 | 121.4 (3) | O6—C16—H3c16 | 109.47 |
N2—C8—C9 | 120.1 (3) | H1c16—C16—H2c16 | 109.47 |
N2—C8—C14 | 120.1 (3) | H1c16—C16—H3c16 | 109.47 |
C9—C8—C14 | 119.8 (3) | H2c16—C16—H3c16 | 109.47 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C1—H1c1···O4 | 0.96 | 2.49 | 2.794 (4) | 98.17 |
C2—H1c2···O4i | 0.96 | 2.43 | 3.330 (4) | 155.24 |
C3—H1c3···O6 | 0.96 | 2.36 | 2.681 (4) | 98.80 |
C3—H1c3···O9ii | 0.96 | 2.35 | 3.037 (4) | 127.80 |
C13—H1c13···O1 | 0.96 | 2.38 | 3.287 (3) | 157.20 |
C13—H1c13···O8 | 0.96 | 2.28 | 2.626 (3) | 100.24 |
C14—H1c14···O7 | 0.96 | 2.49 | 2.792 (4) | 98.24 |
O3—H1o3···O5 | 0.92 (2) | 1.56 (2) | 2.423 (3) | 155 (3) |
O3—H1o3···N1 | 0.92 (2) | 2.24 (3) | 2.806 (3) | 120 (2) |
O2—H1o2···O10 | 0.92 (3) | 1.60 (3) | 2.414 (3) | 145 (3) |
O2—H1o2···N2 | 0.92 (3) | 2.31 (3) | 2.788 (3) | 112 (2) |
Symmetry codes: (i) −x+3/2, y−1/2, −z+1/2; (ii) x, y−1, z. |
Selected bond lengths (Å) and angles (°) for compounds 1
and 2 topBond lengths (Å) | | Bond angles (°) | |
1 | | | |
C1—O5 | 1.216 (2) | C1—C6—N1 | 120.0 (1) |
C1—O9 | 1.313 (2) | C3—C2—O10 | 115.6 (1) |
C2—O1 | 1.238 (2) | C4—C10—N2 | 109.6 (1) |
C2—O10 | 1.254 (2) | C6—N1—O3 | 120.2 (1) |
C4—O4 | 1.212 (2) | C10—C4—O4 | 121.2 (1) |
C4—O6 | 1.298 (2) | O1—C2—O10 | 128.7 (1) |
C5—O8 | 1.248 (2) | O2—C5—O8 | 125.7 (1) |
C5—O2 | 1.275 (2) | O2—C5—C9 | 116.3 (1) |
N1—O3 | 1.349 (2) | O4—C4—O6 | 126.2 (1) |
| | | |
2 | | | |
C5—O1 | 1.199 (4) | C7—N2—O10 | 120.0 (2) |
C5—O6 | 1.334 (4) | C12—O8—C10 | 114.1 (2) |
C6—O4 | 1.217 (4) | O1—C5—O6 | 124.8 (3) |
C10—O8 | 1.335 (4) | O2—C9—O7 | 124.8 (3) |
C10—O9 | 1.191 (4) | O3—C6—C4 | 116.8 (3) |
O2—C9 | 1.315 (4) | O4—C6—O3 | 123.0 (3) |
O3—C6 | 1.323 (4) | O5—N1—C4 | 118.8 (2) |
O5—N1 | 1.348 (3) | O5—N1—C11 | 119.4 (2) |
O7—C9 | 1.202 (4) | O9—C10—O8 | 125.0 (3) |
O10—N2 | 1.335 (3) | O9—C10—C11 | 127.1 (3) |
Selected hydrogen-bond dimensions (Å, °) in compounds 1
and 2 topD—H···A | D—H | H···A | D—H···A | D···A |
1 | | | | |
O9—H1o9···O3 | 0.935 | 1.500 | 167 | 2.419 (2) |
C8—H1c8···O5i | 0.96 | 2.44 | 138.4 | 3.223 (2) |
C7—H1c7···O3ii | 0.96 | 2.36 | 159.6 | 3.282 (2) |
O6—H1o6···O2iii | 0.935 | 1.519 | 175 | 2.451 (1) |
| | | | |
N2—H3n2···O10iv | 0.87 | 2.03 | 165.11 | 2.881 (2) |
N2—H1n2···O8ii | 0.870 | 2.05 | 157.98 | 2.872 (2) |
| | | | |
N2—H2n2···O1 | 0.87 | 1.97 | 170.28 | 2.829 (2) |
O7—H1···O10iv | 0.93 | 1.93 | 175 | 2.859 (2) |
O7—H2···O8 | 0.934 | 1.958 | 165 | 2.871 (2) |
| | | | |
2 | | | | |
C2—H1c2···O4v | 0.96 | 2.43 | 155.24 | 3.330 (4) |
C13—H1c13···O1 | 0.96 | 2.38 | 157.20 | 3.287 (3) |
O3—H1o3···O5 | 0.92 | 1.56 | 155 | 2.423 (3) |
| | | | |
O2—H1o2···O10 | 0.92 | 1.60 | 145 | 2.414 (3) |
Symmetry codes: (i) x-1/2, -y-1, z;
(ii) x-1/2, -y, z;
(iii) x-1, y, z;
(iv) -x+1/2, y, z+1/2;
(v) -x+3/2, y-1/2, -z+1/2. |
π–π stacking interactions dimensions (Å, °) in compounds 1
and 2 top | Centroid–centroid distance | Angle between the planes | Perpendicular distance | Slippage | Type |
1 | 3.485 | 6.39 | | | 2,6-H2pydcOpy···GLYCOO |
| 3.661 | 20.14 | | | 2,6-H2pydcOpy···GLYCOO |
| 3.384 | 20.37 | | | 2,6-H2pydcOCOO···GLYCOO |
2 | 3.550 | 2.91 | | | 2,6-HMepydcOpy···2,6-HMepydcOCOO |
The NBO analysis results for 2,6-H2pydcopt, 2,6-H2pydcOopt,
2,6-HMepydcOopt and 2,6-Me2pydcOopt. The values are the average of
charge on similar atoms top | Cpy | CCOO | CMe | Hpy | HCOOH | HMe | Npy | OC=O | OC═O(Me) | OO—H | OMe | ON—O |
2,6-H2pydcopt | -0.09 | 0.80 | | 0.27 | 0.51 | | -0.39 | -0.60 | | -0.68 | | |
2,6-H2pydcOopt | -0.12 | 0.80 | | 0.27 | 0.51 | | 0.13 | -0.61 | | -0.67 | | -0.41 |
2,6-HMepydcOopt | -0.12 | 0.80 | -0.34 | 0.27 | 0.51 | 0.23 | 0.13 | -0.61 | -0.60 | -0.67 | -0.51 | -0.43 |
2,6-Me2pydcOopt | -0.11 | 0.80 | -0.34 | 0.27 | , | 0.23 | 0.12 | | -0.60 | | -0.51 | -0.43 |
HOMO and LUMO orbitals for the optimized structures of 2,6-H2pydcopt,
2,6-H2pydcOopt, 2,6-HMepydcOopt and 2,6-Me2pydcOopt, along with the
calculated the total energy and HOMO/LUMO gap top | LUMO | HOMO | Total Energy (kcal mol-1) | HOMO/LUMO Gap (eV) |
2,6-H2pydcopt | (a) | (b) | -392462.17 | 5.38 |
2,6-H2pydcOopt | (c) | (d) | -439616.12 | 4.38 |
2,6-HMepydcOopt | (e) | (f) | -464280.44 | 4.36 |
2,6-Me2pydcOopt | (g) | (h) | -488944.73 | 4.39 |
The calculated fitness values for 2,6-H2pydcopt, 2,6-H2pydcOopt,
2,6-HMepydcOopt and 2,6-Me2pydcOopt structures top | BRAF-Kinase | CatB | DNA-Gyrase | HDAC7 | rHA | RNR | TrxR | TS | Top II |
2,6-H2pydcopt | 24.12 | 18.51 | 31.19 | 30.79 | 27.84 | 29.11 | 35.91 | 27.81 | 30.77 |
2,6-H2pydcOopt | 26.04 | 19.49 | 30.04 | 31.90 | 29.15 | 30.97 | 41.02 | 30.76 | 29.00 |
2,6-HMepydcOopt | 29.68 | 25.83 | 33.61 | 36.77 | 33.29 | 36.06 | 35.88 | 32.91 | 33.51 |
2,6-Me2pydcOopt | 32.45 | 23.87 | 36.18 | 40.05 | 36.03 | 38.15 | 37.77 | 37.73 | 34.89 |