Structural study of three heteroaryl oximes, heteroaryl-N=OH: Compounds forming strong C3 molecular chains European Journal of Chemistry 9 (3) (2018) 151-160 European Journal of Chemistry View Journal Online View Article Online Structural study of three heteroaryl oximes, heteroaryl-N=OH: Compounds forming strong C3 molecular chains John Nicolson Low 1, James Lewis Wardell 1,2, Cristiane Franca da Costa 2, Marcus Vicinius Nora Souza 2 and Ligia Rebelo Gomes 3,4,* 1 Department of Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen, AB24 3UE, Scotland jnlow111@gmail.com (J.N.L.), jms_wardell@yahoo.co.uk (J.L.W.) 2 Instituto de Tecnologia em Fármacos e Farmanguinhos, Fundação Oswaldo Cruz, 21041-250 Rio de Janeiro, Rio de Janeiro, Brazil crisfrancaufjf@gmail.com (C.F.C.), marcos_souza@far.fiocruz.br (M.N.S) 3 FP-ENAS-Faculdade de Ciências de Saúde, Escola Superior de Saúde da UFP, Universidade Fernando Pessoa, Rua Carlos da Maia, 296, P-4200-150 Porto, Portugal lrgomes@ufp.edu.pt (L.R.G.) 4 REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007, Porto, Portugal * Corresponding author at: FP-ENAS-Faculdade de Ciências de Saúde, Escola Superior de Saúde da UFP, Universidade Fernando Pessoa, Rua Carlos da Maia, 296, P-4200-150 Porto, Portugal. Tel: +351.22.5074630 Fax: +351.22.5074637 e-mail: lrgomes@ufp.edu.pt (L.R. Gomes). 10.5155/eurjchem.9.3.151-160.1734 Received: 14 May 2018 Received in revised form: 04 June 2018 Accepted: 05 June 2018 Published online: 30 September 2018 Printed: 30 September 2018 In order to further investigate the structural chemistry of oximes and to further establish the main structural arrangements adopted, we have determined the crystal structure of and carried out Hirshfeld surface calculations on three heteroaryl oximes, namely (Z)-thiophene- 2-carbaldehyde oxime (1), (Z)-1H-pyrrole-2 carbaldehyde oxime (2) and (Z)-5-nitrofuran-2- carbaldehyde oxime (3). As confirmed by both techniques, the major intermolecular interactions in each compound are classical N—H···O hydrogen bonds, which link the molecules into C3 chains. Such an arrangement has been previous reported as an important aggregation mode for oximes. Secondary interactions, C—H···π and C—H···O interactions, in compounds 1 and 2, and interactions involving the nitro group oxygen atoms in compound 3 link the chains into three dimensional arrays. Oximes Hydrogen bonds X-ray crystallography Molecular interactions Heteroaryl compounds Hirshfeld surface calculations Cite this: Eur. J. Chem. 2018, 9(3), 151-160 Journal website: www.eurjchem.com 1. Introduction The oxime group, R1R2C=NOH, is found in many biologically active compounds [1,2], with a wide range of uses including as antitumor agents [3-6], acaricidal and insec- ticidal agents [7], thymidine phosphorylase inhibitors [8], anti- microbial agents [9], bactericides [10], anti-inflammatory agents [11] and in the treatment of nerve-gas poisoning [12- 15]. In the plant kingdom, oximes play a vital role in metabolisms [16]. As an important group of organic compounds, it is not surprising that crystal structures of various oximes have attracted attention [16-19]. Oximes with their =N-OH func- tional group are ideally arranged for classical hydrogen bonding. The last survey of the classical hydrogen bonding patterns in oximes reported in 2010 by Low et al. [19] confirmed that the most frequently found arrangements in oximes are R22(6) dimers and C3 chains, see Figure 1. Hydrogen bonds are considered as the strongest and most directional of intermolecular interactions available in molecules [20] and thus play the major roles in determining the overall supramolecular structures. However the involvement of weaker intermolecular interactions, such C— H···O hydrogen bonds and C—H···π interactions can have further significant influences [21]. We have continued our studies of oximes by determining the crystal structures of three five-membered heteroaryl oximes, namely (Z)-thiophene-2-carbaldehyde oxime (1), (Z)- 1H-pyrrole-2-carbaldehyde oxime (2) and (Z)-5-nitrofuran-2- carbaldehyde oxime (3) Scheme 1. In each case, classical O— H···N hydrogen bonds form the C3 chains. Also present generally in compounds 1-3 are C—H···O and C—H···π interactions. The structural features have been also analysed by computing the Hirshfeld surfaces mapped over dnorm. ABSTRACT RESEARCH ARTICLE KEYWORDS European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2018 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.9.3.151-160.1734 http://dx.doi.org/10.5155/eurjchem.9.3.151-160.1734 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.9.3.151-160.1734&domain=pdf&date_stamp=2018-09-30 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.9.3.151-160.1734 mailto:jnlow111@gmail.com mailto:jms_wardell@yahoo.co.uk mailto:crisfrancaufjf@gmail.com mailto:marcos_souza@far.fiocruz.br mailto:lrgomes@ufp.edu.pt mailto:lrgomes@ufp.edu.pt http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.9.3.151-160.1734&domain=pdf&date_stamp=2018-09-30� 152 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 S NN HO H N HO O2N HO N O 1 2 3 Ar O H NH2 OH K2CO3 , H2O Cl Ar N H OH Ar = S H N O NO2 Scheme 1. Synthetic route and schematic representation of compounds 1-3. C N O H R2 N C O H R1 R2 R1 NC OR1 R2 H N C R1 R2 O H C N OR1 R2 H H O N C R2 R1 (a) (b) Figure 1. The most common hydrogen bonding motifs in oximes: (a) representative R22(6) ring (b) representative C3 chain. 2. Experimental 2.1. Synthesis The compounds, 1-3, were generally prepared on refluxing the corresponding aldehyde with hydroxylamine in an aqueous solution containing potassium carbonate, following a general procedure [22]: a mixture of an aldehyde (2 mmol), hydoxyamine.hydrochloride (2.2 mmol) and potassium carbonate (4 mmol) in water (20 mL) was refluxed for 1 hour. The reaction mixture was extracted into ether, dried over magnesium sulphate and rotary evaporated. The solid residue was recrystallised twice from ethanol. (Scheme 1). The samples used in the structure determinations were further recrystallized from methanol. Compound 1: M.p.: 131-143 °C: Lit. [23] M.p.: 132-136 °C; Compound 2: M.p.: 161-163 °C: Lit. [24] M.p.: 163-166 °C; Compound 3: M.p.: 121-122 °C: Lit. [25] M.p.: 121-122 °C. 2.2. Experimental crystallography Data collection, data reduction and cell refinement utilized CrysAlis PRO 1.171.39.9g [26] for compounds 1 and 3, and CrysAlis PRO 1.171.39.30d [27] for compound 2. For all compounds, programs used to solve structures were OSCAIL [28], SHELXT [29] and programs used to refine structure were OSCAIL [28], ShelXle [30] and SHELXL2017/1 [31]. The molecular graphics program was Mercury [32] and PLATON [33]. Software used to prepare material for publication were OSCAIL [28] SHELXL2017/1 [31], Absorption corrections were carried out using Multi-scan CrysAlis PRO 1.171.39.9g [26] with empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. The positions of the hydroxyl hydrogens were located in the difference map, and refined as riding atoms and rotating group about the N-O bonds. Other H atoms were treated as riding atoms with C-H (aryl) and C-H(alkyl) = 0.95 and 0.99 Å. 2.3. Hirshfeld surfaces analysis The Hirshfeld surfaces and two-dimensional fingerprint (FP) plots [34] were generated using Crystal Explorer 3.1 [35]. The Hirshfeld surface mapped over dnorm is scaled between - 0.750 to 1.560. 3. Results and discussion Crystal data and structure refinement details are listed in Table 1. As the bond angles and lengths fall in the normal regions found for these compounds, they are not further discussed here. There are two similar but independent molecules in both the asymmetric units of compounds 1 and 2, (Mol A and Mol B in both cases), while only one molecule is found in the asymmetric unit of compound 3. All three compounds crystallize in orthorhombic phases: compound 1 in the Pca21 space group, with Z = 8, compound 3 in the space group P212121 with Z = 8 and compound 2 in the Pna21 space group with Z = 4. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 153 Table 1. Crystal data and details of the structure refinement for compound 1-3. Parameters Compound 1 Compound 2 Compound 3 Empirical formula C5H5NOS C5H6N2O C5H4N2O4 Formula weight 127.16 110.12 156.10 Temperature (K) 100 100 100 Crystal system Orthorhombic Orthorhombic Orthorhombic Space group Pca21 Pna21 P212121 a, (Å) 11.4684(3) 6.9338(1) 5.2711(2) b, (Å) 13.6834(5) 11.2109(1) 5.5198(2) c, (Å) 7.3641(2) 13.7319(1) 21.2019(7) Volume (Å3) 1155.62(6) 1067.44(2) 616.88(4) Z 8 8 4 ρcalc (g/cm3) 1.462 1.370 1.681 μ (mm-1) 0.45 0.83 0.15 F(000) 528 464 320 Crystal size (mm) 0.20 × 0.03 × 0.02 0.20 × 0.15 × 0.05 0.08 × 0.07 × 0.03 Radiation MoKα (λ = 0.71073) MoKα (λ = 0.71073) MoKα (λ = 0.71073) Θ range for data collection (o) 1.488 to 27.482 5.093 to 68.199 1.921 to 27.478 Index range -14 ≤ h ≤ 12 -12 ≤ k ≤ 17 -8 ≤ l ≤ 9 -8 ≤ h ≤ 8 -13 ≤ k ≤ 13 -16 ≤ l ≤ 16 -6 ≤ h ≤ 6 -7 ≤ k ≤ 7 -27 ≤ l ≤ 27 Reflections collected 8080 18404 8390 Independent reflections) 2459 1945 1411 Observed reflections [I ≥ 2σ(I)] 2518 [Rint = 0.021] 2518 [Rint = 0.029] 2518 [Rint = 0.019] Data/restraint/ parameters 2518/154/1 1945/161/1 1411/104/0 Goodness-of-fit on F2 1.09 1.06 1.07 Final R indexes [I ≥ 2σ(I) R1 = 0.035; wR2 = 0.099 R1 = 0.024; wR2 =0.063 R1 = 0.021; wR2 =0.056 Final R indexes [all data] R1 = 0.035; wR2 = 0.099 R1 = 0.024; wR2 =0.063 R1 = 0.024; wR2 =0.063 Largst diff. peak/hole (e.Å-3) 0.49 0.13 0.19 Absolute structure Refined as an inversion twin Refined as a perfect inversion twin Refined as a perfect inversion twin Flack parameter 0.39(12) 0.5 0.5 CCDC number 1839089 1839091 1839090 Molecules of the thienyl derivative, 1, exhibit small percentages (5 %) of disorder (flip disorder) involving a 180 ° rotation about C12—C121 bond in Mol A and C22—C221 in Mol B. Such disorder is a fairly common finding for thienyl derivatives [36]. The atom arrangements and numbering schemes for all molecules, excluding the minor component of compound 1, are illustrated in Figure 2. Due to the very small extent of the disorder and the lack of any directional involvement of the sulfur atom in the intermolecular interactions, the minor component has been ignored in the structural discussion. As shown in Figure 2, there are different arrangements of the CH=NOH side chains, w.r.t the heteroaryl group, in compound 3, on one hand, and in compounds 1 and 2, on the other. The set-up in compound 2 allows the formation of classical intramolecular N—H···O hydrogen bonds. The intramolecular S···O separations in the two independent molecules of compound 1 are 2.691(3) and 2.703(2) Å, which are well within the sum of the contact radii of 3.32 Å, and do suggest a positive interaction. Intramolecular S···O interact- tions have been well reported [37,38]. The molecular confor- mation of compound 3 precludes any O—H···O classical intramolecular hydrogen bonds but instead allows a weak C— H···O interaction. 3.1. Intermolecular interactions A complete list of the intermolecular interactions is shown in Table 2. As well as the strong classical O—H···N hydrogen bonds, each compound exhibits weaker C—H···O hydrogen bonds and C—H···π interactions. In compound 3, there are additional interactions involving the two oxygen atoms of its nitro substituent. The only heteroatoms in the aryl units to be involved in interactions are those in compound 2. As indicated in the article by Low et al. [19], oximes commonly use the strong classical O—H···N intermolecular hydrogen bonds to form R22(6) dimers or C3 chains, see Figure 1. Each of the three compounds studied here use such bonds to form the C3 chains, as illustrated in Figures 3a, 4a and 5a, for compounds 1, 2 and 3, respectively. These hydrogen-bonding chains form the backbone of the structures. However the additional weaker intermolecular interactions are involved in augmenting the strength of the chain and linking the C3 chains into more elaborate arrangements. In the case of compound 1, the augmentation of the chains is provided by C121—H121···O123 hydrogen bonds and C13—H13···π interactions, see Figure 3b. With involvement of the weaker C121—H121···O123 hydrogen bonds, R33(8) rings are present within the C3 chains. The C3 chains are linked by C221—H221··· π interactions into a three dimensional array: Figure 3c illustrates the linkage of two partial C3 chains drawn in different colors. In the case of compound 2, the augmentation of the chains is provided by three different interactions within a C3 chain: C221—H221···O223 hydrogen bonds and C15—H15···π (Mol A) and C23—H23···π (Mol B) interactions, see Figure 4b. Similar to the situation in compound 1, R33(8) rings are derived within the C3 chains from the involvement of the weaker C221—H221···O223 hydrogen bonds. In the case of compound 2, more complex linkages of the C3 chains into a three-dimensional array occur from the involvement of various other weaker intermolecular interactions. Despite the differences in the intermolecular interaction in compounds 1 and 2, the two compounds possess similar packing arran- gements, see Figure 6. The situation in compound 3 is somewhat different from those in compounds 1 and 2. Unlike the situation in compounds 1 and 2, there are no additional interactions within a C3 chain and links between the C3 chains are solely generated from interactions involving the nitro group oxygen atoms, namely C3—H3···O53 and C4—H4···O52 hydrogen bonds and N52—H52···π interactions. In each of these three interactions, forms different connections: Figures 5b-d illustrate some interchain interactions. Figure 6c contrasts the packing of compound 3 with those of compounds 1 and 2. 3.2. Hirshfeld surfaces analysis The Hirshfeld surfaces and two-dimensional fingerprint (FP) plots [34,35] provide complementary information concerning the intermolecular interactions discussed upper. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 154 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 Table 2. Geometric parameters and symmetry operations for hydrogen bonds and intermolecular interactions (Å, °). Compound D—H···A D—H H···A D···A D—H···A Symmetry code Intramolecular hydrogen bonds 2 N11—H11···O123 0.89(2) 2.14(3) 2.657(2) 116.7(18) - 2 N21—H21···O223 0.91(2) 2.09(3) 2.658(2) 119.2(19) - 3 C3—H3···O23 0.95 2.40 2.8039(16) 105 - Intermolecular hydrogen bonds 1 O123—H123···N222 0.78(5) 1.96(5) 2.743(4)(17) 177(6) x, y, z 1 O223—H223···N122 0.85(5) 1.90(6) 2.749(4) 178(8) 1/2-x, y, -1/2+z 1 C121—H121···O123 0.95 2.52 3.316(4) 142 1/2-x, y, 1/2+z 2 O123—H123···N222 0.94(3) 1.80(3) 2.728(2) 170(3) -1/2+x, 1/2-y, z 2 O223—H223···N122 0.97(3) 1.78(3) 2.754(2) 177(2) x, y, z 2 C221—H221···O223 0.95 2.60 3.372(2) 139 1/2+x, 1/2-y, z 3 O23—H23···N22 0.87(2) 1.93(2) 2.7876(15) 170.3(19) 1/2+x, 5/2-y, 1-z 3 C3—H3···O53 0.95 2.48 3.3604(15) 155 1+x, 1+y, z 3 C4—H4···O52 0.95 2.38 3.2043(16) 144 2-x, 1/2+y, 3/2-z Y—X···π interactions Compound Y—X···Cg a X···Cg Xperp b γ c Y—X···Cg Y···Cg d Symmetry code 1 C13—H13···Cg1 (Mol A) e 2.96 2.93 7.49 157 3.854(3) 1/2-x, y, 1/2+z 1 C221—H221···Cg2 (Mol B) e 2.54 2.54 1.36 168 3.476(4) 1-x, 1-y, 1/2+z 2 C15—H15···Cg1 (Mol A) e 2.72 2.70 7.42 138 3.488(2) -1/2+x, 1/2-y, z 2 N21—H21···Cg1 (Mol A) e 2.73(3) 2.69 9.14 146(2) 3.5199(17) 1-x, 1-y, -1/2+z 2 C23—H23···Cg2 (Mol B) e 2.79 2.78 4.58 148 3.637(2) 1/2+x, 1/2-y, z 2 C121—H121···Cg2 (Mol B) e 2.48 2.48 1.90 163 3.406(2) 2-x, 1-y, 1/2+z 3 N51—O52···Cg1 e 3.4950(11) 3.152 25.59 91.63(7) 3.7379(12) x, -1+y, z a Center of gravity of ring J (Plane number above). b Perpendicular distance of H to ring plane J. c Angle between Cg-H vector and ring J normal. d Distance between C-atom and the nearest carbon atom in the aromatic ring. e Cg1 and Cg2 for compound 1 are the centroids of the ring containing S11 and S21, respectively. Cg1 and Cg2 for compound 2 are the centroids of the ring containing N11 and N21, respectively. Cg1 for compound 3 is the centroid of the ring containing O1. (a) Mol A of compound 1 (b) Mol B of compound 1 (c) Mol A of compound 2 (d) Mol B of compound 2 (e) Compound 3 Figure 2. Atom arrangements and numbering schemes for compounds 1-3. Probability ellipsoids have been drawn at the 50% level. Intermolecular hydrogen bonds have been drawn as dashed lines. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 155 (a) (b) (c) Figure 3. Compound 1, (a) A part of a C3 chain, generated from alternating Mol A and Mol B units, linked by classical O123—H123···N222 and O223— H223···N122 hydrogen bonds, (b) part of the arrangement generated from the involvement of additional C13—H13···π interactions and C121—H121···O123 hydrogen bonds within a C3 chain, (c) an illustration of the linkage of two C3 chains, drawn in different colors, by C221—H221···π interactions. Intermolecular interactions are drawn as thin dashed lines. Symmetry operations are listed in Table 2. (a) (b) Figure 4. Compound 2. (a) A part of a C3 chain, generated from alternating Mol A and Mol B units, linked by classical O123—H123···N222 and O223— H223···N122 hydrogen bonds, (b) part of the arrangement generated from the involvement of additional C15—H15···π (Mol A) and C23—H23···π (Mol B) interactions and C121—H121···O123 hydrogen bonds within a C3 chain. Intermolecular interactions are drawn as thin dashed lines. Symmetry operations are listed in Table 2. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 156 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 (a) (b) (c) (d) Figure 5. Compound 3, (a) A part of a C3 chain of molecules generated from classical O23—H23···N22 hydrogen bonds, (b) an illustration of the linkage of molecules from different C3 chains by C4—H4···O52 and C3—H3···O53 hydrogen bonds, (c) an illustration of the linkage of C3 chains by N51—H52···π interactions, (d) a view of Figure 5b using different colours for the C3 chains. Intermolecular interactions are drawn as thin dashed lines. Symmetry operations are listed in Table 2. (a) (b) (c) Figure 6. Packing arrangements of compounds 1 (a), 2 (b) and 3 (c). The structural features of compounds 1-3 will be analysed by computing the Hirshfeld surfaces mapped over dnorm (-0.680 to 1.16 range). As said, compound 1 presents two molecules in the asymmetric unit that are identified as Mol A and Mol B. The Hirshfeld surface of Mol A is depicted in Figure 7 in two views. The left frame shows two pair sets of red spots, one pair with a spreader area that is due to the contacts involving the nitrogen and the oxygen atoms of the oxime, those making a C(3) chain. The other pair of spots are due to O···H–C close contacts involving the acidic hydrogen atom H121 and the O123 oxygen atom. The right hand frame shows a pair of light red spots that are close S···C close contacts. Mol B presents the corresponding N···H–O contacts with Mol A, those give the two strong red are spots that are complementary to the spots near the atoms involved in the same interactions in Mol A. Mol B also presents S···C close contacts as detected by red spot areas shown in the right frame of Figure 8 and contacts involving the acidic H atom H221 but, in contrast with Mol A, the hydrogen atom establishes contacts with all atoms of the thiophene ring giving spots looking like “flower petals” in the Hirshfeld surface (left frame, Figure 8, those include the C-H···π interactions). 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 157 Figure 7. Views of both faces of the Hirshfeld surface mapped over dnorm for compound 1 (Mol A). The highlighted red spots on the left picture indicate contact points with the atoms participating in the O—H···N and C—H···O intermolecular interactions. The picture in the right side show the other face of the surface; the bright red areas that suggest for the existence of S···C contacts. The N···H close contacts are responsible for the pair of sharp spikes in the FP plot that end at de/di near 1.1 Å. Figure 8. Views of the Hirshfeld surface mapped over dnorm (up) and fingerprint plot (down) for compound 1 (Mol B). The large red areas in the HS correspond to the O—H···N contacts; The looking like “flower petals” in the Hirshfeld surface of the left picture are due to close contacts between the acidic H atom and the carbon and sulphur atoms of the thiophene ring. Those contacts are confirmed by the analysis of the FP plots for the molecule (see the bottom figure of the HS for details). FP plot in the left shows a pair of wings that are due to close H … C contacts while the FP plot on the right side shows wings that are due to H…S close contacts). Those short contacts are perfectly identified in the FP plot of the Mol B, that is depicted in Figure 8, down, together with the HS. In Table 3, the percentages of atom…atom close contacts are given. Apart from the H…H contacts, relevant contacts are of C···H/H···C and S···H/H···S type in both molecules, followed by the N···H/ H···N and O···H/ H···O ones. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 158 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 Figure 9. Views of the Hirshfeld surface mapped over dnorm for compounds 2 (Mol A) (up) and (Mol B) (down). The large red areas in the HS correspond to the O—H···N contacts; The looking like “flower petals” in the Hirshfeld surface are due to close contacts between the H121 atom and the nitrogen and carbon atoms of the pyrrolic ring. As in compound 1, those contacts were confirmed by the analysis of the FP plots for the molecule. Figure 10. The FP plots for compound 2 (Mol A) (right) and Mol B (left) show a couple of spikes corresponding to N···H contacts. The asymmetric shape of the wings in the FP plots, left side in FP plot of Mol A and right side in Mol B include to the N···H and C···H contacts with the pyrrol involving the H atom H15. Compound 2 presents two molecules (Mol A and Mol B) in the asymmetric unit as well. The HS reveal several red areas as can be viewed in Figure 9. The upper pictures show the HS for Mol A, where a pair of spread red areas parallel to the OH group and to the nitrogen atom of the oxime can be visualised, those are surfaces that show close contacts involving the oxime: those are the N···H/H···N contacts that make chains in a similar way as described for compound 1 connecting Mol A with Mol B. Apart from those red areas, a set of red regions that presents complementary intensity and shape has been also detected by the HS calculations, one near the hydrogen atom H15 of Mol A (see frame right and above) and another parallel to the heterocycle ring of the same molecule suggesting for the existence of close contacts involving the referred H atom and the ring. Finally there is a set of light red spots in the HS of Mol A near H atom H121 that has correspondence in intensity and shape in Mol B that account for H···π contacts. The FP plots (Figure 10) for Mol A and Mol B display a couple of spikes corresponding to N···H contacts. The asymmetric shape of the wings in the FP plots, left side in FP plot of Mol A and right side in Mol B include to the N···H and C···H contacts with the pyrrole involving the H atom H15. The contributions from various atom to atom contacts for both molecules of compound 2, are listed in Table 3. Apart from the H···H contacts the most significant are the H···O/O···H that are higher than 25%. The presence of the nitro substituent in compound 3 increases the possibility of the establishment of close O···H contacts. This is confirmed by the HS analysis for the compound but, in spite of that, the prevalent contacts are of C···H type, as can be confirmed by the % of atom to atom close contacts in Table 3. Several views of the HS surface are depicted in Figure 11. Apart from the N···H/H···N close contact due to the N22···H23–O23 hydrogen bond (identified in Figure 4), the surface presents a set of red areas near the oxygen atoms of the nitro group that are complementary in shape and size with those being near the hydrogen atoms of the pyran ring suggesting for O···H interactions, as can be visualised in Figure 11. In addition the surface shows several other red areas also near the nitro oxygen atoms and in the area parallel to the aromatic ring that are probably due to O···C close contacts. The nature of those contacts is confirmed by the partial analysis of the HS surface based on the element contacts given by the PF plot of the surface, as can be visualizes in the frames of Figure 12. The FP for 3 displays two pairs of spikes; the outer ones ending at (de, di) ≅ (1.1, 0.7) Å (and vice versa) corresponding to the N···H/H···N contacts and the inner ones ending at (de, di) ≅ (1.3, 1.0) Å corresponding to the H···O/O···H contacts. The C···O/O···C contacts contribute to high the percentage of atom···atom close contacts involving both elements as can be confirmed in Table 3. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 159 Table 3. Percentages of atom-atom contacts for compound 1-3 (%). Compound H···H H···O/O···H H···C/C···H O···C/C...O H···N/N···H H···S/S···H C···S/S···C 1 Mol A 33.0 7.9 18.9 2.8 16.4 11.4 7.9 1 Mol B 30.1 12.0 22.4 0.6 11.7 11.9 6.8 2 Mol A 42.5 5.2 28.5 0.9 21.2 - - 2 Mol B 42.2 11.0 26.5 0.7 19.3 - - 3 12.3 39.3 7.2 15.3 12.0 - - Figure 11. Views of both faces of the Hirshfeld surface mapped over dnorm for compound 3 (Mol A). The highlighted red spots on the left picture indicate contact points with the atoms participating in the O—H···N and C—H···O intermolecular interactions. The picture in the right side show the other face of the surface; the bright red areas that suggest for the existence of S … C contacts. The N···H close contacts are responsible for the pair of sharp spikes in the FP plot that end at de/di near 1.1 Å. Figure 12. Views of the Hirshfeld surface mapped over dnorm (up) and fingerprint plot (down) for compound 3. The highlighted red spots on the the face of the surfaces indicate contact points with the atoms participating in the C···O, H···O and N···H contacts. The FP displays two pairs of spikes; the outer ones ending at (de, di) ≅ (1.1, 0.7) Å (and vice versa) corresponding to the N···H/H···N contacts and the inner ones ending at (de ,di) ≅ (1.3, 1.0) Å corresponding to the H···O/O···H contacts. The C···O/O···C contacts contribute to high the percentage of atom···atom close contacts involving both elements as can be confirmed in Table 3. 4. Conclusion The studies confirm that a significant aggregation mode of oximes involves classical N—H---O hydrogen bonds, which provided C3 molecular chains. Further association of the C3 chains into 3-dimensional structures occurs in the case of compounds 1 and 2 from combinations of weaker C—H···O and C-H···π interactions and in the case of compound 3, by interactions involving the nitro group oxygen atoms. The majority of oximes form R22 (6) dimers as opposed to C3 chains which were classically claimed as the usual oxime H-bond pattern [19]. These C3 chains are, in fact, rarely observed being mostly found in aldoxime structures [19] as is the case here. Acknowledgements The authors thank the National Crystallographic Service, University of Southampton, UK, for the data collection, and for their help and advice. LRG thanks the Portuguese Foundation for Science and Technology (FCT) UID/Multi/04546/2013 for support. JLW thanks CNPq, Brazil for support. 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 160 Low et al. / European Journal of Chemistry 9 (3) (2018) 151-160 Supporting information CCDC-1839089, CCDC-1839090 and CCDC-1839091 contain the supplementary crystallographic data for compounds 1, 3, and 2, respectively. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/ structures/, or by e-mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223- 336033. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. ORCID John Nicolson Low http://orcid.org/0000-0003-4743-7448 James Lewis Wardell http://orcid.org/0000-0003-2195-8827 Cristiane Franca da Costa http://orcid.org/0000-0001-7385-9201 Marcus Vicinius Nora Souza http://orcid.org/0000-0003-1566-8110 Lígia Rebelo Gomes http://orcid.org/0000-0002-3496-6052 References [1]. Abele, E.; Abele, R.; Lukevics, E. Chem. Heterocycl. Cmpds. 2018, 44, 769-792. [2]. Nikitjuka, A.; Jirgensons, A. 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The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). 2018 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.9.3.151-160.1734 https://www.ccdc.cam.ac.uk/%20structures/ https://www.ccdc.cam.ac.uk/%20structures/ mailto:data_request@ccdc.cam.ac.uk http://orcid.org/0000-0003-4743-7448 http://orcid.org/0000-0003-2195-8827 http://orcid.org/0000-0001-7385-9201 http://orcid.org/0000-0003-1566-8110 http://orcid.org/0000-0002-3496-6052 http://www.chemspider.com/Chemical-Structure.5268628.html http://www.chemspider.com/Chemical-Structure.15526334.html http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Synthesis 2.2. Experimental crystallography 2.3. Hirshfeld surfaces analysis 3. Results and discussion 3.1. Intermolecular interactions 3.2. Hirshfeld surfaces analysis 4. Conclusion Acknowledgements Supporting information Disclosure statement ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField18: PrintField19: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: PrintField28: PrintField29: