4-(Di­methyl­amino)­benzohydrazide

Kelley, S.P.; Mossine, V.V.; Mawhinney, T.P.

doi:10.1107/S2414314620013103

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 5| Part 10| October 2020| x201310

https://doi.org/10.1107/S2414314620013103

Open

access

4-(Dimethylamino)benzohydrazide

Steven P. Kelley,^a Valeri V. Mossine ^b ^* and Thomas P. Mawhinney ^b

^aDepartment of Chemistry, University of Missouri, Columbia, MO 65211, USA, and ^bDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA
^*Correspondence e-mail: MossineV@missouri.edu

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 21 September 2020; accepted 28 September 2020; online 9 October 2020)

The title compound, C₉H₁₃N₃O, crystallizes in the monoclinic space group C2/c and all non-hydrogen atoms are within 0.1 Å of the molecular mean plane. In the crystal, the hydrogen-bonding pattern results in [001] chains built up from fused R₂²(6) and R₂²(10) rings; the former consists of N—H⋯N bonds and the latter N—H⋯O bonds. Electrostatic and dispersion forces are major contributors to the lattice energy, which was estimated by DFT calculations to be −215.7 kJ mol⁻¹.

Keywords: crystal structure; acyl hydrazide; hydrogen bonding; lattice energy; DFT calculations.

CCDC reference: 2032776

Structure description

For decades, there has been an interest in aroyl hydrazides because of their numerous applications, for instance, as synthetic precursors to a large number of potential antimicrobial (Popiołek, 2017 ) or anticancer (Kumar & Narasimhan, 2013 ) drugs, in addition to their own anti-tubercular activities (Sah & Peoples, 1954 ). In our search for inhibitors of bacterial virulence factors (Mossine et al., 2016 , 2020 ), we turned our attention to the title compound, which can be viewed as a structural analogue of isoniazid (Andrade et al., 2008 ) and a potential precursor for pharmacologically active, iron-binding hydrazide-hydrazones. We now report its crystal structure.

The title compound crystallizes in the monoclinic space group C2/c, with eight molecules per unit cell. The asymmetric unit contains one molecule of the hydrazide (I), as shown in Fig. 1. All bond lengths and angles are within their expected ranges. The molecule is essentially flat, with the greatest deviation from the average molecular plane, among the non-hydrogen atoms, found for atom N1 at 0.074 (1) Å. The aromatic ring plane is at 1.08 (4)° to the molecular plane. The spatial arrangement of the hydrazido group, as defined by the torsion angle H2—N2—N3—H3B = 119.3 (15)°, corresponds to the lowest energy conformation that has been calculated for acyl hydrazides (Centore et al., 2010 ).

Figure 1
Atomic numbering and displacement ellipsoids at the 50% probability level for (I).

The conventional hydrogen bonding in the extended structure of (I) is limited to two intermolecular heteroatom contacts (Table 1) involving the hydrazido groups only and is shown in Fig. 2. The hydrogen-bonding pattern includes infinite chains that propagate in the [001] direction and consist of fused R₂²(10) and R₂²(6) rings (Fig. 2a). The R₂²(10) motif is formed by pairs of molecules linked by the N3—H3B⋯O1 hydrogen bonds related by twofold rotation symmetry, while the R₂²(6) motif is formed by centrosymmetric dimers of (I) linked by the N2—H2⋯N3 hydrogen bonds. In addition, one short intermolecular contact, C6—H6⋯O1, which satisfies the distance and directionality conditions [C6⋯O1ⁱⁱⁱ = 3.4111 (13) Å, C6—H6⋯O1ⁱⁱⁱ = 172°; symmetry code: (iii) x, 1 − y, ½ + z], and which is shown in Fig. 3 as a dotted line, may also contribute to the stability of the molecular packing in the crystal. The intermolecular non-polar interactions are dominated by hydrogen–hydrogen contacts between the methyl groups; the shortest of these contacts, H8C⋯H9B, is about 0.1 Å less than the sum of the VdW radii. These interactions form a pattern of infinite chains, propagating in the [001] direction, in parallel to the hydrogen-bonded chains (Fig. 2b and 2c). The crystal structure lacks any strong π–π stacking interactions. However, a short N3—H3A⋯Cg1 [H3A⋯Cg1^iv = 2.614 (15) Å; symmetry code: (iv) x, y − 1, z] contact is present.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯N3ⁱ	0.89 (2)	2.11 (2)	2.9203 (13)	151 (1)
N3—H3B⋯O1ⁱⁱ	0.92 (2)	2.09 (1)	2.9516 (11)	157 (1)
Symmetry codes: (i) ; (ii) $[-x, y, -z+{\script{1\over 2}}]$ .

Figure 2
Molecular packing and hydrogen bonding in (I). (a) Hydrogen-bonding motifs; (b) and (c) molecular packing views down [001] and [100], respectively. Hydrogen bonds are shown as cyan dotted lines.

Figure 3
Interaction energies in crystal structure of (I). (a) A view of interactions between a central molecule, shown as its Hirshfeld surface, and 13 molecules that share the interaction surfaces with the central molecule. Red areas on the Hirshfeld surface encode the closest intermolecular contacts, which are hydrogen bonds involving the hydrazido groups, a short C—H⋯O type contact is shown as a dotted line; (b) Calculated energies (electrostatic, polarization, dispersion, repulsion, and total) of pairwise interactions between the central molecule and those indicated by respective colours.

To account for all interactions involved in the build-up of the crystal structure of (I) we have performed DFT calculations, at the B3LYP/6–31 G(d,p) theory level (Mackenzie et al., 2017 ; Thomas et al., 2018 ), of the electrostatic, dispersion, polarization, and repulsion energies. According to these calculations, the interactions between hydrogen-bonded pairs of molecules contribute about 50% to the lattice energy, with the dispersion energy providing most of the attractive forces between non-hydrogen-bonded molecules of (I) (i.e. E_ele = −9.2 kJ mol⁻¹, E_dis = −44.2 kJ mol⁻¹ for symmetry code = x, y, z). To estimate the lattice energy, all total energies of unique pairwise interactions between molecules were summed up, thus yielding E_l (l = lattice) = −216 kJ mol⁻¹ for the crystal of (I). The calculated contributions to the overall lattice energy (kJ mol⁻¹) are as follows: E_ele = −165.3; E_pol = −46.0; E_dis = −173.9; E_rep = 234.1. The spatial distribution of the energetically most significant interactions is illustrated in Fig. 4, showing the interactions energy frameworks as cylinders penetrating the molecular packing of (I). As expected, the most extensive intermolecular interactions occur in the hydrogen-bonded chain direction parallel to [001].

Figure 4
Energy frameworks for separate (a) electrostatic and (b) dispersion contributions to the (c) total pairwise interaction energies in (I). The cylinders link molecular centroids, and the cylinder thickness is proportional to the magnitude of the energies (see Fig. 3

). For clarity, the cylinders corresponding to energies <5 kJ mol⁻¹ are not shown. The directionality of the crystallographic axes is the same for all three diagrams.

Synthesis and crystallization

A sample of commercial 4-dimethylaminobenzhydrazide was recrystallized from hot 95% ethanol solution, affording colorless needles.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₉H₁₃N₃O
M_r	179.22
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	100
a, b, c (Å)	24.7018 (6), 6.3093 (1), 13.2103 (3)
β (°)	118.0496 (8)
V (Å³)	1817.01 (7)
Z	8
Radiation type	Cu Kα
μ (mm⁻¹)	0.72
Crystal size (mm)	0.25 × 0.24 × 0.23

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (AXScale; Bruker, 2016 )
T_min, T_max	0.684, 0.754
No. of measured, independent and observed [I > 2σ(I)] reflections	15813, 1786, 1770
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.618

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.098, 1.07
No. of reflections	1786
No. of parameters	130
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.22
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXS (Sheldrick, 2008 ), SHELXL (Sheldrick, 2015 ), OLEX2 (Dolomanov et al., 2009 ), CrystalExplorer17.5 (Mackenzie et al., 2017), Mercury (Macrae et al., 2020 ), and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 2032776

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314620013103/hb4366sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314620013103/hb4366Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314620013103/hb4366Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: APEX3 and SAINT (Bruker, 2016); data reduction: APEX3 and SAINT (Bruker, 2016); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009), CrystalExplorer17.5 (Mackenzie et al., 2017) and Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

4-(Dimethylamino)benzohydrazide top

Crystal data top

C₉H₁₃N₃O	F(000) = 768
M_r = 179.22	D_x = 1.310 Mg m⁻³
Monoclinic, C2/c	Cu Kα radiation, λ = 1.54178 Å
a = 24.7018 (6) Å	Cell parameters from 9928 reflections
b = 6.3093 (1) Å	θ = 4.1–72.3°
c = 13.2103 (3) Å	µ = 0.72 mm⁻¹
β = 118.0496 (8)°	T = 100 K
V = 1817.01 (7) Å³	Irregular, colourless
Z = 8	0.25 × 0.24 × 0.23 mm

Data collection top

Bruker APEXII CCD diffractometer	1786 independent reflections
Radiation source: Incoatec IMuS microfocus Cu tube	1770 reflections with I > 2σ(I)
Multi-layer optics monochromator	R_int = 0.019
φ and ω scans	θ_max = 72.4°, θ_min = 4.1°
Absorption correction: multi-scan (AXScale; Bruker, 2016)	h = −29→26
T_min = 0.684, T_max = 0.754	k = −7→7
15813 measured reflections	l = −16→16

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.098	w = 1/[σ²(F_o²) + (0.0541P)² + 1.3587P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
1786 reflections	Δρ_max = 0.22 e Å⁻³
130 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints	Extinction correction: SHELXL2017/1 (Sheldrick 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0036 (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. The hydrazide H2, H3A, and H3B atoms were located in difference-Fourier maps while all other hydrogen atoms were initially placed in calculated positions with their coordinates constrained to ride on their carrier atoms [C—H(aromatic) = 0.95?Å, C—H(methyl) = 0.98?Å]. The constraint Uiso(H) = 1.2Ueq(carrier) or 1.5Ueq(methyl carrier) was applied in all cases.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.07812 (3)	0.16597 (12)	0.32634 (6)	0.0191 (2)
N2	0.03227 (4)	0.11655 (14)	0.43722 (7)	0.0155 (2)
H2	0.0261 (6)	0.151 (2)	0.4964 (12)	0.023*
N3	0.00327 (4)	−0.07477 (14)	0.38183 (7)	0.0155 (2)
H3A	0.0319 (7)	−0.162 (2)	0.3826 (12)	0.023*
H3B	−0.0235 (6)	−0.037 (2)	0.3076 (13)	0.023*
N1	0.18614 (4)	0.97723 (15)	0.64989 (8)	0.0218 (3)
C5	0.08706 (4)	0.50333 (16)	0.56022 (8)	0.0147 (2)
H5	0.060886	0.428200	0.582134	0.018*
C6	0.11601 (4)	0.68522 (16)	0.61942 (8)	0.0155 (2)
H6	0.109206	0.733294	0.680648	0.019*
C1	0.15565 (4)	0.80037 (16)	0.58975 (8)	0.0156 (2)
C2	0.16280 (5)	0.72556 (17)	0.49598 (9)	0.0174 (3)
H2A	0.188258	0.801208	0.472528	0.021*
C4	0.09528 (4)	0.42708 (16)	0.46894 (8)	0.0144 (2)
C3	0.13326 (5)	0.54379 (17)	0.43786 (9)	0.0166 (2)
H3	0.138925	0.496951	0.375132	0.020*
C7	0.06791 (4)	0.22760 (16)	0.40464 (8)	0.0141 (2)
C8	0.17404 (5)	1.06515 (18)	0.73873 (9)	0.0210 (3)
H8A	0.131656	1.116555	0.704356	0.032*
H8B	0.202237	1.183084	0.776385	0.032*
H8C	0.180052	0.955197	0.795469	0.032*
C9	0.22406 (5)	1.09916 (18)	0.61407 (10)	0.0222 (3)
H9A	0.258398	1.011548	0.620994	0.033*
H9B	0.239960	1.224711	0.662961	0.033*
H9C	0.199403	1.143461	0.534079	0.033*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0220 (4)	0.0209 (4)	0.0193 (4)	−0.0049 (3)	0.0137 (3)	−0.0052 (3)
N2	0.0196 (4)	0.0142 (4)	0.0150 (4)	−0.0038 (3)	0.0101 (4)	−0.0026 (3)
N3	0.0172 (4)	0.0139 (4)	0.0148 (4)	−0.0023 (3)	0.0071 (4)	−0.0015 (3)
N1	0.0232 (5)	0.0217 (5)	0.0240 (5)	−0.0086 (4)	0.0140 (4)	−0.0071 (4)
C5	0.0137 (5)	0.0157 (5)	0.0156 (5)	0.0009 (4)	0.0077 (4)	0.0024 (4)
C6	0.0157 (5)	0.0171 (5)	0.0143 (5)	0.0016 (4)	0.0075 (4)	0.0006 (4)
C1	0.0130 (5)	0.0153 (5)	0.0160 (5)	0.0007 (4)	0.0049 (4)	0.0007 (4)
C2	0.0167 (5)	0.0182 (5)	0.0194 (5)	−0.0023 (4)	0.0103 (4)	0.0012 (4)
C4	0.0135 (5)	0.0143 (5)	0.0145 (5)	0.0010 (4)	0.0058 (4)	0.0012 (4)
C3	0.0176 (5)	0.0188 (5)	0.0165 (5)	0.0006 (4)	0.0105 (4)	−0.0001 (4)
C7	0.0125 (5)	0.0159 (5)	0.0133 (5)	0.0018 (4)	0.0055 (4)	0.0016 (4)
C8	0.0214 (5)	0.0185 (5)	0.0225 (5)	−0.0020 (4)	0.0098 (4)	−0.0054 (4)
C9	0.0197 (5)	0.0199 (6)	0.0270 (6)	−0.0059 (4)	0.0109 (5)	−0.0024 (4)

Geometric parameters (Å, º) top

O1—C7	1.2371 (12)	N2—H2	0.891 (15)
N2—N3	1.4187 (12)	N3—H3A	0.892 (17)
N2—C7	1.3444 (13)	N3—H3B	0.920 (15)
N1—C1	1.3715 (14)	C2—H2A	0.95
N1—C8	1.4506 (14)	C3—H3	0.95
N1—C9	1.4526 (14)	C5—H5	0.95
C5—C6	1.3835 (14)	C6—H6	0.95
C5—C4	1.3989 (14)	C8—H8A	0.98
C6—C1	1.4146 (14)	C8—H8B	0.98
C1—C2	1.4120 (14)	C8—H8C	0.98
C2—C3	1.3821 (15)	C9—H9A	0.98
C4—C3	1.3976 (14)	C9—H9B	0.98
C4—C7	1.4909 (14)	C9—H9C	0.98

C7—N2—N3	121.75 (8)	H3A—N3—H3B	109.9 (13)
C1—N1—C8	120.93 (9)	C1—C2—H2A	120
C1—N1—C9	120.31 (9)	C3—C2—H2A	120
C8—N1—C9	118.09 (9)	C2—C3—H3	119
C6—C5—C4	121.76 (9)	C4—C3—H3	119
C5—C6—C1	120.70 (9)	C4—C5—H5	119
N1—C1—C6	121.36 (9)	C6—C5—H5	119
N1—C1—C2	121.27 (9)	C1—C6—H6	120
C2—C1—C6	117.37 (9)	C5—C6—H6	120
C3—C2—C1	120.90 (9)	N1—C8—H8A	109
C5—C4—C7	124.79 (9)	N1—C8—H8B	109
C3—C4—C5	117.50 (9)	N1—C8—H8C	109
C3—C4—C7	117.69 (9)	H8A—C8—H8B	109
C2—C3—C4	121.73 (9)	H8A—C8—H8C	109
O1—C7—N2	121.71 (10)	H8B—C8—H8C	109
O1—C7—C4	121.71 (9)	N1—C9—H9A	109
N2—C7—C4	116.58 (9)	N1—C9—H9B	109
N3—N2—H2	114.0 (9)	N1—C9—H9C	109
C7—N2—H2	124.2 (9)	H9A—C9—H9B	109
N2—N3—H3A	108.3 (10)	H9A—C9—H9C	109
N2—N3—H3B	105.4 (8)	H9B—C9—H9C	109

C8—N1—C1—C2	173.90 (10)	C1—N1—C9—H9A	−64
C8—N1—C1—C6	−6.35 (15)	C1—N1—C9—H9B	176
C9—N1—C1—C2	3.50 (16)	C1—N1—C9—H9C	56
C9—N1—C1—C6	−176.75 (10)	C8—N1—C9—H9A	125
N3—N2—C7—O1	−1.50 (15)	C8—N1—C9—H9B	5
N3—N2—C7—C4	179.43 (9)	C8—N1—C9—H9C	−115
N1—C1—C2—C3	178.16 (11)	C7—N2—N3—H3A	54.0 (10)
C6—C1—C2—C3	−1.60 (16)	C7—N2—N3—H3B	−63.6 (11)
N1—C1—C6—C5	−177.96 (10)	H2—N2—N3—H3A	−123.2 (14)
C2—C1—C6—C5	1.79 (15)	H2—N2—N3—H3B	119.3 (15)
C1—C2—C3—C4	0.07 (18)	H2—N2—C7—O1	175.4 (11)
C2—C3—C4—C5	1.28 (16)	H2—N2—C7—C4	−3.7 (11)
C2—C3—C4—C7	−177.07 (10)	N1—C1—C2—H2A	−2
C3—C4—C5—C6	−1.08 (15)	C6—C1—C2—H2A	178
C7—C4—C5—C6	177.14 (10)	N1—C1—C6—H6	2
C3—C4—C7—O1	−0.02 (15)	C2—C1—C6—H6	−178
C3—C4—C7—N2	179.06 (10)	C1—C2—C3—H3	−180
C5—C4—C7—O1	−178.23 (10)	H2A—C2—C3—C4	−180
C5—C4—C7—N2	0.84 (15)	H2A—C2—C3—H3	0
C4—C5—C6—C1	−0.47 (16)	H3—C3—C4—C5	−179
C1—N1—C8—H8A	−65	H3—C3—C4—C7	3
C1—N1—C8—H8B	175	C3—C4—C5—H5	179
C1—N1—C8—H8C	55	C7—C4—C5—H5	−3
C9—N1—C8—H8A	106	C4—C5—C6—H6	180
C9—N1—C8—H8B	−14	H5—C5—C6—C1	180
C9—N1—C8—H8C	−134	H5—C5—C6—H6	0

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N3ⁱ	0.89 (2)	2.11 (2)	2.9203 (13)	151 (1)
N3—H3B···O1ⁱⁱ	0.92 (2)	2.09 (1)	2.9516 (11)	157 (1)

Symmetry codes: (i) −x, −y, −z+1; (ii) −x, y, −z+1/2.

Funding information

Funding for this research was provided by: National Institute of Food and Agriculture (award No. Hatch 1023929); University of Missouri, Agriculture Experiment Station Chemical Laboratories .

References

Andrade, C. H., Salum, L. de B., Castilho, M. S., Pasqualoto, K. F. M., Ferreira, E. I. & Andricopulo, A. D. (2008). Mol. Divers. 12, 47–59. Web of Science CrossRef PubMed CAS Google Scholar
Bruker (2016). APEX3, SAINT and AXScale. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Centore, R., Carella, A., Tuzi, A., Capobianco, A. & Peluso, A. (2010). CrystEngComm, 12, 1186–1193. Web of Science CSD CrossRef CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Kumar, P. & Narasimhan, B. (2013). Mini Rev. Med. Chem. 13, 971–987. Web of Science CrossRef CAS PubMed Google Scholar
Mackenzie, C. F., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). IUCrJ, 4, 575–587. Web of Science CrossRef CAS PubMed IUCr Journals Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
Mossine, V. V., Kelley, S. P. & Mawhinney, T. P. (2020). Acta Cryst. E76, 557–561. Web of Science CSD CrossRef IUCr Journals Google Scholar
Mossine, V. V., Waters, J. K., Chance, D. L. & Mawhinney, T. P. (2016). Toxicol. Sci. 154, 403–415. Web of Science CrossRef CAS PubMed Google Scholar
Popiołek, Ł. (2017). Med. Chem. Res. 26, 287–301. Web of Science PubMed Google Scholar
Sah, P. P. T. & Peoples, S. A. (1954). J. Am. Pharm. Assoc. 43, 513–524. CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Thomas, S. P., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2018). J. Chem. Theory Comput. 14, 1614–1623. Web of Science CrossRef CAS PubMed Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.