Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229615021130/yp3101sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229615021130/yp3101Isup2.hkl | |
Chemdraw file https://doi.org/10.1107/S2053229615021130/yp3101Isup3.cdx | |
Portable Document Format (PDF) file https://doi.org/10.1107/S2053229615021130/yp3101sup4.pdf |
CCDC reference: 1429659
Nicotinamide derivatives have garnered attention due to their biochemical importance, as well as their versatility in regards to both functionality and structural modification. In the 1940s, extensive research was conducted to find a cure for tuberculosis; during this time, substituted nicotinamides were studied for their tuberculostatic activity. Unfortunately, results indicated that the highly active nicotinamide species correlated with increased patient toxicity (Kushner et al., 1948). Nevertheless, a new library of biologically active molecules was now available for further investigation. Characterization of nicotinamide derivatives, as well as exploration of antifungal and additional inhibitory properties, has recently become a focus in both medicinal and agricultural sciences.
Ye and collaborators have studied the structure-activity relationship of nicotinamide derivatives. Congeners of nicotinamides were developed to function as succinate dehydrogenase inhibitors against crop fungi (Rhizoctonia solaniandSclerotinia sclerotiorum). Through their studies, it was concluded that specific substituent modifications were beneficial to the biological activity exhibited by these molecules (Ye et al., 2014).
1,3,4-Thiadiazole derivatives have also recently gained attention due to antimicrobial, antioxidant, and anti-inflammatory abilities correlating to the overall structure of the compound. The high aromaticity of 1,3,4-thiadiazole is a direct result of weak basicity that occurs due to inductive effects of the S atom (Hu et al., 2014). Concomitantly, the N atoms each possess a strong electron-withdrawing ability. This results in the remaining C atoms being more susceptible to nucleophilic attack, which is important in the formation of thiadiazole derivatives (Hu et al., 2014). Specifically, Kadi and collaborators investigated the antimicrobial activity of a thiadiazole derivative against Staphylococcus aureus and Bacillus subtilis, as well as confirmed acute anti-inflammatory activity of some of the compounds of interest (Kadi et al., 2010). In addition, scientists have experimentally confirmed that 1,3,4-thiadiazole derivatives exhibit antioxidant behaviour and are capable of inhibiting urease, presumably by similar structural characteristics (Khan et al., 2010).
The versatility of the nicotinamide and thiadiazole functional groups has been combined in order to utilize their inherent properties and biological activity. Specifically, the aquaporin inhibitor, 2-nicotinamido-1,3,4-thiadiazole (TGN-020), (I), was synthesized, radiolabeled, and developed to functionalize and diagnostically analyse aquaporin 4 (AQP4) (Nakamura et al., 2011). Through inhibition of AQP4 with the radiolabeled form of TGN-020, positron emission tomography (PET) can be used to visualize AQP4 within the brain. AQP4, a water specific membrane transporter in the central nervous system, has been shown to be upregulated as a result of brain oedemas (Aoki-Yoshino et al., 2005). A preliminary study concluded that TGN-020 reduced the overall severity of brain oedema due to brain ischemia (Igarashi et al. 2011). Continued characterization and functionalization of TGN-020 as an inhibitor of AQP4 is important to the understanding and treatment of brain injuries (Liang et al., 2015). These studies focused on the biological activity of the product TGN-020 but did not contain information confirming the connectivity that was produced by the synthetic combination of nicotinamide and thiadiazole moieties. To complement these efforts, we carried out a complete synthesis of TGN-020 using a modified method reported by Nakamura et al. (2011) (Fig. 1). Herein and for the first time, we report the characterization of TGN-020 by X-ray diffraction crystallography and NMR. The combination of one- (1D) and two-dimensional (2D) (COSY, HMQC) NMR techniques were utilized to gain spectral assignments. In addition to the above techniques, TGN-020 was also characterized by IR, elemental analysis, and UV–Vis spectroscopy. Moreover, blood–brain barrier permeation coefficients were also calculated to evaluate the impact of hybridization upon the combination of nicotinamide with thiadiazole to produce TGN-020.
The synthesis of (I) (Fig. 1) was adapted from the method of Nakamura et al. (2011). N-Methylmorpholine (3.5 ml, 0.0317 mol) was added to a chilled (273 K) solution of 2-amino-1,3,4-thiadiazole (1.0050 g, 0.0099 mol) in dichloromethane (50 ml) under nitrogen. The mixture was stirred for 10 min before nicotinoyl chloride hydrochloride (1.9878 g, 0.0112 mol) was added in one portion. The resulting mixture was allowed to stir under nitrogen for an additional 12 h at room temperature. The solvent was then evaporated under reduced pressure leaving a distinctive yellow solid. The product was extensively washed with ether (4 × 50 ml) and deionized water (30 × 50 ml) using vacuum filtration. The resulting white solid, TGN-020, was then collected and dried overnight (yield 1.4035 g, 68.5%).
1H NMR (400 MHz, DMSO): δ 13.32 (1H, s, NH), 9.27 (1H, s, N═CH—S), 9.24—9.23 (1H, d, J = 1.7606 Hz, C═CH—N), 8.83–8.82 (1H, dd, J = 6.2420, J = 3.3211 Hz, C—CH═CH), 8.46–8.44 (1H, ddd, J = 4.0013, J = 8.0026, J = 5.6818, J = 1.6805 Hz, CH—CH═N), 7.62–7.60 (1H, dq, J = 5.6018H J = 12.8042, J = 3.1610, J = 4.0813 Hz, C—CH═ CH—CH—N). 13C NMR (100 MHz, DMSO): δ 164.55 (CH═ C—CO), 159.71 (C—CO—NH), 153.68 (CH—CH═C), 149.82 (N═CH—C), 149.71 (S—CH═N), 136.60 (N—CH═CH), 128.21 (NH—C—S), 124.11 (CH═ CH—CH). IR (KBr, cm-1): 3173.3 (amine), 1669.8 (carbonyl stretch). UV–Vis λmax/nm (ε/M-1 cm-1): 354 (1.3539), 358 (1.4801), 361 (2.051). Elemental analysis found (calculated) for C8H6N4OS·HCl: C 46.59 (46.40), H 2.93 (2.90), N 27.17% (27.37%). Decomposition point: 555 K.
Crystals of (I) were grown by the vapor-diffusion method. A saturated solution was made dissolving TGN-020 in dimethylformamide (DMF; approximately 10 ml). The saturated solution (approximately 2 ml) was placed inside a small vial (capacity 5 ml), which was then gently set inside a larger vial (capacity 10 ml). To the larger vial, diethyl ether (6 ml) was added and the entire sample was capped, sealed with parafilm, and allowed to sit at room temperature. Long thin needle-like crystals of (I) formed after one week. One of the shorter crystals was selected and used as previous attempts to shorten the crystals resulted in cracking along the long crystal axis, yielding unusably thin fragments.
Crystal data, data collection and structure refinement details are summarized in Table 1. The structure was treated as a two-component inversion twin with a refined enatiomeric ratio of 0.44 (15). H atoms were calculated from idealized geometry, with Uiso(H) = 1.2Ueq(N,C).
The multiple ring structure of TGN-020 (Fig. 2) consists of one π-conjugated nicotinamide ring and a thiadiazole ring with a distinctive C7—S1—C8 angle of 85.98 (18)°. The molecule is not perfectly planar; the independent planes of the nicotinamide ring and the thiadiazole ring are angled at 9.23 (7)° with respect to one another. The conjugated π-system within the nicotinamide ring creates π–π stacking (Fig. 3) between centroids, with a centroid–centroid distance of 3.7097 (3) Å.
Although the H-atom position could not be refined, the N4···N2 interatomic separation of 2.997 (4) Å is consistent with a hydrogen-bonding interaction that links the molecules into coplanar chains. These flat chains are themselves oriented in a herringbone pattern within the lattice (Fig. 4). The pattern is composed of one pair of hydrogen-bonded TGN-020 molecule planes intersecting at an angle of 47.93 (5)°. The parallel planes of the TGN-020 molecules provide a plane-to-plane twist angle of 14.74 (4)°. Finally, based on the change in the position of the nicotinamide ring, molecules found in adjacent intersecting planes are twisted by 44.27 (12)° with respect to one another.
For additional insight, TGN-020 was structurally compared to two modified compounds with connectivity similarities containing the functional groups of interest (Table 2). Specifically, the distinctive constrained C—S—C angle [85.98 (18) Å] of the five-membered thiadiazole moiety contained within TGN-020 is constrained compared to other 1,3,4-thiadiazole derivatives. For example, the anti-inflammatory thiadiazole derivative studied by Hafez et al. (2008) was reported to contain a C—S—C angle of 90.35°. Therefore, the functionalization of the thiadiazole with nicotinamide results in a more strained five-membered ring which could enhance reactivity. Structural changes to the nicotinamide moiety of TGN-020 are less pronounced. Surprisingly, the angle formed between the C6 atom of the pyridine ring of nicotinamide and the amide changes little upon addition of the thiadiazole moiety compared to other functionalized nicotinamide systems; the C5—C6—N2 angle of TGN-020 is 118.4 (3)°. This is consistent with other nicotinamide-based systems, such as N,N'-ethane-1,2-diyldinicotinamide 1,1,2,2,3,3,4,4-octafluoro-1,4-diiodobutane, whose C—C—Nam angle (am is amide) is 117.25° (Aakeröy et al., 2014). The other angles are consistent with nicotinamide derivatives as well. Structural comparison of TGN-020 was also made (Table 2) with spiro[thioxanthene-9',2-[1,3,4]thiadiazole] and N,N'-ethane-1,2-diyldinicotinamide 1,1,2,2,3,3,4,4-octafluoro-1,4-diiodobutane (Aakeröy et al., 2014).
The TGN-020 molecule has been shown to modulate AQP4 activity (Nakamura et al., 2011; Aoki-Yoshino et al., 2005). The AQP4 system has been proposed as to play a role in neurodegenerative disorders such as Alzheimer's disease (Zlokovic, 2011; Pérez et al., 2007). Therefore, the TGN-020 molecule could be a potential molecule to study in relation to neurodegeneration using in vivo models where blood–brain barrier permeability would be necessary. Based on this potential, we have calculated the parameters defined by Lipinski to evaluate the ability of a molecule to be pharmacologically active and permeable to membrane such as the blood–brain barrier (Lipinski et al., 2001). The ability for a molecule to permeate through the blood–brain barrier is often predicted by Lipinski's rule of five, which encompass molecular characteristics such as lipophilicity and hydrogen-bond donor–acceptor potential. With a molecular weight of 206.22 g mol-1, TGN-020 satisfies the first requirement in which molecular weight should be less than 500 g mol-1. The partition coefficient of TGN-020, represented by the logP and clogP (ChemDraw Ultra 12.0; Perkin–Elmer Informatics, Massachusets, USA), was determined to be 0.98 and -0.168, respectively. This value increases only slightly when compared to the starting materials (Table 3), but is well within the parameters for the rule of 5 (logP below 5) as well as the calculated polar surface area of 66.18 Å2 (Rule: less than 140 Å2). TGN-020 fulfills the final two criteria by having only one hydrogen-bond donor and only four hydrogen-bond acceptors. Finally, the potential of TGN-020 to cross the blood–brain barrier was further supported by theoretical calculations of logKow using the software EPI suite (Version 1.68; US Environmental Protection Agency, Washington DC, USA). Systems with logKow values > 5 are considered to have high bioaccumulation potential similar to Lipinsky's rule of five. Conversely, compounds with low logKow (<1) will correlate to poor permeation and biodistribution. The TGN-020 system was calculated to have a logKow value of -0.3388, which is roughly an average of the nicotinamide and 2-amino-1,3,4-thiadiazole starting materials and is slightly lower than the values optimal for blood–brain barrier permeation. Based on these results, it is clear that modification of the nicotinamide moiety and production of TGN-020 results in improvement of permeability parameters. However, modification may be necessary to optimize the overall permeability in the future.
The 1H and 13C NMR spectra of TGN-020 are shown in Figs. S1 and S2 respectively (see Supporting information). The 1D NMR are consistent with amide bond formation between the nicotinamide group and 2-amino-1,3,4-thiadizaole. For complete spectral assignments of TGN-020 (Fig. 5), multiple 2D NMR methods were utilized. A 1H–1H correlated spectroscopy (Fig. 6) was used to identify the initial proton assignments before performing a 1H–13C heteronuclear multiple-quantum correlation to assign carbon spectra (Fig. 7). Overall, the connectivity shown in Fig. 5 was confirmed using NMR methods.
For a complete analysis of TGN-020, IR and UV–Vis spectrometry techniques were utilized and the corresponding figures are outlined within the Supporting information. IR showed a definitive amide N2—H(N2) stretch (3173.3 cm-1), as well as a carbonyl stretch (1669.8 cm-1), for the TGN-020 molecule. The position of the carbonyl stretch is consistent with an amide derived C═O stretch and supports the connectivity defined by X-ray diffractometry and NMR methods. Finally, the UV–Vis spectrum in dimethylformamide was predominated by a strong absorbance at 354 nm and a shoulder at 358 nm. A weaker absorbance band was also observed at 361 nm. The large aromaticity of the TGN-020 structure is consistent with this absorbance spectrum.
Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: olex2.solve (Bourhis et al., 2015); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).
C8H6N4OS | Dx = 1.694 Mg m−3 |
Mr = 206.23 | Melting point: 555 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
a = 3.7097 (3) Å | Cell parameters from 3955 reflections |
b = 9.5406 (10) Å | θ = 3.6–26.0° |
c = 22.841 (2) Å | µ = 0.37 mm−1 |
V = 808.42 (13) Å3 | T = 100 K |
Z = 4 | Needle, colourless |
F(000) = 424 | 0.82 × 0.24 × 0.22 mm |
Bruker APEXII CCD diffractometer | 1396 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.086 |
Absorption correction: multi-scan (SADABS; Bruker, 2014) | θmax = 26.7°, θmin = 3.4° |
Tmin = 0.649, Tmax = 0.745 | h = −4→4 |
13928 measured reflections | k = −12→12 |
1693 independent reflections | l = −28→28 |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.044 | w = 1/[σ2(Fo2) + (0.0323P)2 + 0.3974P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.080 | (Δ/σ)max < 0.001 |
S = 1.05 | Δρmax = 0.30 e Å−3 |
1693 reflections | Δρmin = −0.37 e Å−3 |
128 parameters | Absolute structure: Refined as an inversion twin. |
0 restraints | Absolute structure parameter: 0.44 (15) |
C8H6N4OS | V = 808.42 (13) Å3 |
Mr = 206.23 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 3.7097 (3) Å | µ = 0.37 mm−1 |
b = 9.5406 (10) Å | T = 100 K |
c = 22.841 (2) Å | 0.82 × 0.24 × 0.22 mm |
Bruker APEXII CCD diffractometer | 1693 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2014) | 1396 reflections with I > 2σ(I) |
Tmin = 0.649, Tmax = 0.745 | Rint = 0.086 |
13928 measured reflections |
R[F2 > 2σ(F2)] = 0.044 | H-atom parameters constrained |
wR(F2) = 0.080 | Δρmax = 0.30 e Å−3 |
S = 1.05 | Δρmin = −0.37 e Å−3 |
1693 reflections | Absolute structure: Refined as an inversion twin. |
128 parameters | Absolute structure parameter: 0.44 (15) |
0 restraints |
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. |
Refinement. Refined as a 2-component inversion twin. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.8507 (3) | 0.56853 (10) | 0.14786 (4) | 0.0107 (2) | |
O1 | 1.0560 (7) | 0.3558 (2) | 0.08312 (10) | 0.0143 (7) | |
N1 | 1.0574 (9) | −0.1352 (3) | 0.11801 (13) | 0.0143 (8) | |
N2 | 0.7859 (8) | 0.2846 (3) | 0.16649 (12) | 0.0102 (8) | |
H2 | 0.7121 | 0.2135 | 0.1879 | 0.012* | |
N3 | 0.5688 (9) | 0.4430 (3) | 0.23599 (12) | 0.0125 (8) | |
N4 | 0.5409 (9) | 0.5855 (3) | 0.24700 (12) | 0.0125 (7) | |
C1 | 1.1945 (11) | −0.1529 (4) | 0.06461 (16) | 0.0130 (9) | |
H1 | 1.2571 | −0.2453 | 0.0529 | 0.016* | |
C2 | 1.2508 (10) | −0.0461 (4) | 0.02543 (16) | 0.0141 (9) | |
H2A | 1.3439 | −0.0647 | −0.0125 | 0.017* | |
C3 | 1.1696 (10) | 0.0884 (4) | 0.04241 (14) | 0.0110 (8) | |
H3 | 1.2075 | 0.1648 | 0.0165 | 0.013* | |
C4 | 0.9767 (10) | −0.0040 (4) | 0.13376 (16) | 0.0125 (9) | |
H4 | 0.8765 | 0.0112 | 0.1715 | 0.015* | |
C5 | 1.0317 (10) | 0.1108 (3) | 0.09784 (15) | 0.0102 (9) | |
C6 | 0.9599 (10) | 0.2590 (4) | 0.11461 (15) | 0.0098 (9) | |
C7 | 0.7235 (10) | 0.4201 (4) | 0.18599 (14) | 0.0112 (8) | |
C8 | 0.6743 (11) | 0.6606 (4) | 0.20526 (14) | 0.0119 (8) | |
H8 | 0.6743 | 0.7601 | 0.2064 | 0.014* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0131 (5) | 0.0077 (4) | 0.0114 (4) | −0.0002 (4) | 0.0025 (5) | 0.0002 (4) |
O1 | 0.0196 (17) | 0.0119 (13) | 0.0114 (13) | 0.0001 (12) | 0.0018 (12) | 0.0031 (11) |
N1 | 0.016 (2) | 0.0113 (16) | 0.0156 (18) | 0.0016 (15) | 0.0034 (15) | −0.0019 (13) |
N2 | 0.0114 (19) | 0.0084 (15) | 0.0109 (17) | −0.0007 (13) | 0.0036 (14) | 0.0001 (12) |
N3 | 0.016 (2) | 0.0103 (17) | 0.0118 (16) | 0.0008 (16) | 0.0016 (14) | −0.0021 (13) |
N4 | 0.0184 (19) | 0.0068 (15) | 0.0124 (15) | 0.0019 (14) | 0.0003 (14) | −0.0002 (13) |
C1 | 0.011 (2) | 0.0114 (18) | 0.017 (2) | 0.0028 (17) | 0.0010 (18) | −0.0040 (15) |
C2 | 0.014 (2) | 0.017 (2) | 0.0109 (18) | −0.0005 (16) | 0.0026 (16) | −0.0023 (16) |
C3 | 0.008 (2) | 0.0133 (19) | 0.0114 (18) | 0.0007 (18) | −0.0005 (17) | 0.0002 (15) |
C4 | 0.011 (2) | 0.0146 (19) | 0.012 (2) | −0.0010 (17) | 0.0036 (16) | −0.0034 (15) |
C5 | 0.008 (2) | 0.0106 (19) | 0.0124 (19) | 0.0010 (14) | −0.0027 (16) | 0.0014 (14) |
C6 | 0.008 (2) | 0.0112 (19) | 0.010 (2) | −0.0005 (16) | −0.0021 (16) | −0.0011 (15) |
C7 | 0.011 (2) | 0.0107 (18) | 0.0116 (19) | 0.0008 (17) | −0.0005 (15) | 0.0014 (16) |
C8 | 0.015 (2) | 0.0094 (18) | 0.0113 (19) | 0.0005 (18) | −0.0036 (19) | 0.0008 (15) |
S1—C7 | 1.728 (4) | C1—H1 | 0.9500 |
S1—C8 | 1.708 (4) | C1—C2 | 1.373 (5) |
O1—C6 | 1.224 (4) | C2—H2A | 0.9500 |
N1—C1 | 1.332 (5) | C2—C3 | 1.374 (5) |
N1—C4 | 1.336 (4) | C3—H3 | 0.9500 |
N2—H2 | 0.8800 | C3—C5 | 1.382 (5) |
N2—C6 | 1.371 (4) | C4—H4 | 0.9500 |
N2—C7 | 1.387 (4) | C4—C5 | 1.384 (5) |
N3—N4 | 1.386 (4) | C5—C6 | 1.489 (5) |
N3—C7 | 1.297 (4) | C8—H8 | 0.9500 |
N4—C8 | 1.291 (5) | ||
C8—S1—C7 | 85.98 (18) | N1—C4—H4 | 118.4 |
C1—N1—C4 | 116.8 (3) | N1—C4—C5 | 123.3 (3) |
C6—N2—H2 | 119.3 | C5—C4—H4 | 118.4 |
C6—N2—C7 | 121.5 (3) | C3—C5—C4 | 118.4 (3) |
C7—N2—H2 | 119.3 | C3—C5—C6 | 116.7 (3) |
C7—N3—N4 | 111.0 (3) | C4—C5—C6 | 125.0 (3) |
C8—N4—N3 | 112.4 (3) | O1—C6—N2 | 120.7 (3) |
N1—C1—H1 | 118.0 | O1—C6—C5 | 120.9 (3) |
N1—C1—C2 | 124.1 (3) | N2—C6—C5 | 118.4 (3) |
C2—C1—H1 | 118.0 | N2—C7—S1 | 123.8 (3) |
C1—C2—H2A | 120.8 | N3—C7—S1 | 115.3 (3) |
C1—C2—C3 | 118.4 (3) | N3—C7—N2 | 120.9 (3) |
C3—C2—H2A | 120.8 | S1—C8—H8 | 122.3 |
C2—C3—H3 | 120.5 | N4—C8—S1 | 115.4 (3) |
C2—C3—C5 | 119.0 (3) | N4—C8—H8 | 122.3 |
C5—C3—H3 | 120.5 | ||
N1—C1—C2—C3 | 1.6 (6) | C4—N1—C1—C2 | −1.0 (6) |
N1—C4—C5—C3 | 1.5 (6) | C4—C5—C6—O1 | 171.1 (4) |
N1—C4—C5—C6 | −177.3 (4) | C4—C5—C6—N2 | −8.4 (5) |
N3—N4—C8—S1 | −0.2 (4) | C6—N2—C7—S1 | 0.6 (5) |
N4—N3—C7—S1 | 0.2 (4) | C6—N2—C7—N3 | −177.8 (3) |
N4—N3—C7—N2 | 178.8 (3) | C7—S1—C8—N4 | 0.3 (3) |
C1—N1—C4—C5 | −0.6 (6) | C7—N2—C6—O1 | −2.2 (5) |
C1—C2—C3—C5 | −0.6 (5) | C7—N2—C6—C5 | 177.3 (3) |
C2—C3—C5—C4 | −0.9 (5) | C7—N3—N4—C8 | 0.0 (4) |
C2—C3—C5—C6 | 178.0 (3) | C8—S1—C7—N2 | −178.8 (3) |
C3—C5—C6—O1 | −7.8 (5) | C8—S1—C7—N3 | −0.3 (3) |
C3—C5—C6—N2 | 172.8 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···N4i | 0.88 | 2.14 | 2.997 (4) | 164 |
Symmetry code: (i) −x+1, y−1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C8H6N4OS |
Mr | 206.23 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 100 |
a, b, c (Å) | 3.7097 (3), 9.5406 (10), 22.841 (2) |
V (Å3) | 808.42 (13) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.37 |
Crystal size (mm) | 0.82 × 0.24 × 0.22 |
Data collection | |
Diffractometer | Bruker APEXII CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2014) |
Tmin, Tmax | 0.649, 0.745 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13928, 1693, 1396 |
Rint | 0.086 |
(sin θ/λ)max (Å−1) | 0.631 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.044, 0.080, 1.05 |
No. of reflections | 1693 |
No. of parameters | 128 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.30, −0.37 |
Absolute structure | Refined as an inversion twin. |
Absolute structure parameter | 0.44 (15) |
Computer programs: APEX2 (Bruker, 2013), SAINT (Bruker, 2013), olex2.solve (Bourhis et al., 2015), SHELXL2014 (Sheldrick, 2015), OLEX2 (Dolomanov et al., 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···N4i | 0.88 | 2.14 | 2.997 (4) | 164.1 |
Symmetry code: (i) −x+1, y−1/2, −z+1/2. |