Structural and computational analysis of inter­molecular inter­actions in a new 2-thio­uracil polymorph

Fabijanić, I.; Matković-Čalogović, D.; Pilepić, V.; Sanković, K.

doi:10.1107/S205322961701542X

Structural and computational analysis of intermolecular interactions in a new 2-thiouracil polymorph

I. Fabijanić, D. Matković-Čalogović, V. Pilepić and K. Sanković

The crystallization and characterization of a new polymorph of 2-thiouracil by single-crystal X-ray diffraction, Hirshfeld surface analysis and periodic density functional theory (DFT) calculations are described. The previously published polymorph (A) crystallizes in the triclinic space group P $\overline{1}$ , while that described herein (B) crystallizes in the monoclinic space group P2₁/c. Periodic DFT calculations showed that the energies of polymorphs A and B, compared to the gas-phase geometry, were −108.8 and −29.4 kJ mol⁻¹, respectively. The two polymorphs have different intermolecular contacts that were analyzed and are discussed in detail. Significant differences in the molecular structure were found only in the bond lengths and angles involving heteroatoms that are involved in hydrogen bonds. Decomposition of the Hirshfeld fingerprint plots revealed that O

H and S

H contacts cover over 50% of the noncovalent contacts in both of the polymorphs; however, they are quite different in strength. Hydrogen bonds of the N—H

O and N—H

S types were found in polymorph A, whereas in polymorph B, only those of the N—H

O type are present, resulting in a different packing in the unit cell. QTAIM (quantum theory of atoms in molecules) computational analysis showed that the interaction energies for these weak-to-medium strength hydrogen bonds with a noncovalent or mixed interaction character were estimated to fall within the ranges 5.4–10.2 and 4.9–9.2 kJ mol⁻¹ for polymorphs A and B, respectively. Also, the NCI (noncovalent interaction) plots revealed weak stacking interactions. The interaction energies for these interactions were in the ranges 3.5–4.1 and 3.1–5.5 kJ mol⁻¹ for polymorphs A and B, respectively, as shown by QTAIM analysis.

Keywords: 2-thiouracil polymorph; X-ray diffraction; DNA model system; computational chemistry; crystal structure; QTAIM and NCI plot analysis.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S205322961701542X/ku3205sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S205322961701542X/ku3205Isup2.hkl Contains datablock I
	Portable Document Format (PDF) file https://doi.org/10.1107/S205322961701542X/ku3205sup3.pdf Photographs of the crystals of the title compounds

CCDC reference: 1535305

Computing details top

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: Mercury (Macrae at al., 2008) and ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015).

2-Thiouracil top

Crystal data top

C₄H₄N₂OS	F(000) = 264
M_r = 128.15	D_x = 1.562 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 4.1043 (2) Å	Cell parameters from 1185 reflections
b = 11.0458 (4) Å	θ = 5.4–32.0°
c = 12.0465 (4) Å	µ = 0.48 mm⁻¹
β = 93.740 (3)°	T = 298 K
V = 544.97 (4) Å³	Prismatic, colourless
Z = 4	0.42 × 0.16 × 0.12 mm

Data collection top

Agilent Xcalibur Sapphire3 diffractometer	1367 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1169 reflections with I > 2σ(I)
Detector resolution: 16.3426 pixels mm^-1	R_int = 0.016
ω scans	θ_max = 28.5°, θ_min = 5.0°
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	h = −4→5
T_min = 0.985, T_max = 1.000	k = −14→13
2639 measured reflections	l = −16→12

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.030	H-atom parameters constrained
wR(F²) = 0.081	w = 1/[σ²(F_o²) + (0.0426P)² + 0.0147P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.001
1367 reflections	Δρ_max = 0.24 e Å⁻³
73 parameters	Δρ_min = −0.24 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	U_iso*/U_eq
C2	0.1455 (3)	0.15324 (11)	0.72131 (10)	0.0273 (3)
C4	0.2895 (3)	0.15650 (11)	0.52702 (10)	0.0305 (3)
C5	0.4587 (3)	0.26792 (12)	0.54972 (11)	0.0345 (3)
H5	0.5709	0.3058	0.4948	0.041*
C6	0.4529 (3)	0.31692 (12)	0.65168 (10)	0.0335 (3)
H6	0.5600	0.3899	0.6664	0.040*
N1	0.2937 (3)	0.26216 (9)	0.73413 (8)	0.0317 (3)
H1	0.2873	0.2986	0.7971	0.038*
N3	0.1503 (3)	0.10482 (9)	0.61723 (8)	0.0297 (2)
H3	0.0578	0.0355	0.6067	0.036*
O1	0.2582 (3)	0.10499 (9)	0.43524 (8)	0.0415 (3)
S1	−0.03220 (9)	0.08280 (3)	0.82379 (3)	0.03738 (14)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C2	0.0299 (6)	0.0275 (6)	0.0243 (6)	0.0053 (5)	0.0013 (4)	−0.0009 (4)
C4	0.0403 (7)	0.0276 (6)	0.0236 (6)	0.0035 (6)	0.0031 (5)	0.0016 (4)
C5	0.0416 (8)	0.0322 (7)	0.0301 (6)	−0.0035 (6)	0.0053 (5)	0.0031 (5)
C6	0.0381 (7)	0.0261 (6)	0.0361 (7)	−0.0027 (6)	0.0005 (5)	−0.0005 (5)
N1	0.0420 (6)	0.0279 (5)	0.0254 (5)	0.0018 (5)	0.0021 (4)	−0.0056 (4)
N3	0.0401 (6)	0.0251 (5)	0.0240 (5)	−0.0014 (5)	0.0035 (4)	−0.0017 (4)
O1	0.0680 (7)	0.0342 (5)	0.0226 (5)	−0.0058 (5)	0.0066 (4)	−0.0014 (3)
S1	0.0456 (2)	0.0394 (2)	0.0283 (2)	−0.00086 (15)	0.01149 (15)	0.00031 (12)

Geometric parameters (Å, º) top

C2—N1	1.3524 (16)	C5—C6	1.3439 (18)
C2—N3	1.3645 (15)	C5—H5	0.9300
C2—S1	1.6670 (12)	C6—N1	1.3654 (16)
C4—O1	1.2427 (15)	C6—H6	0.9300
C4—N3	1.3836 (16)	N1—H1	0.8600
C4—C5	1.4307 (18)	N3—H3	0.8600

N1—C2—N3	114.86 (11)	C5—C6—N1	121.62 (12)
N1—C2—S1	123.09 (9)	C5—C6—H6	119.2
N3—C2—S1	122.06 (10)	N1—C6—H6	119.2
O1—C4—N3	119.06 (12)	C2—N1—C6	122.96 (11)
O1—C4—C5	125.78 (12)	C2—N1—H1	118.5
N3—C4—C5	115.15 (11)	C6—N1—H1	118.5
C6—C5—C4	118.93 (12)	C2—N3—C4	126.26 (11)
C6—C5—H5	120.5	C2—N3—H3	116.9
C4—C5—H5	120.5	C4—N3—H3	116.9

O1—C4—C5—C6	175.47 (14)	C5—C6—N1—C2	3.3 (2)
N3—C4—C5—C6	−4.11 (18)	N1—C2—N3—C4	−0.03 (19)
C4—C5—C6—N1	0.9 (2)	S1—C2—N3—C4	179.64 (10)
N3—C2—N1—C6	−3.66 (18)	O1—C4—N3—C2	−175.79 (11)
S1—C2—N1—C6	176.68 (10)	C5—C4—N3—C2	3.8 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.86	1.99	2.8443 (14)	175
N3—H3···O1ⁱⁱ	0.86	2.06	2.9057 (15)	166
C5—H5···S1ⁱⁱⁱ	0.86	2.97	3.9031 (14)	176
C6—H6···S1^iv	0.86	2.88	3.7780 (14)	163

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

2 Bond lengths (Å) and angles (°) in the crystal structures of 2-thiouracil polymorphs A and B
A^LT are data at 100 K (Jarzembska et al., 2012) and were obtained after transferable aspherical atom model (TAAM) refinement, A^RT are room-temperature data (Tiekink, 1989) using standard independent atom model (IAM) refinement and B is IAM refinement. top

Bond lengths	Bond angles
	A^LT	A^RT	B		A^LT	A^RT	B
C2—N1	1.3521 (4)	1.338 (4)	1.3524 (16)	N1—C2—N3	116.29 (3)	116.0 (3)	114.85 (11)
C2—N3	1.3558 (4)	1.357 (4)	1.3644 (15)	N1—C2—S	121.93 (3)	122.2 (2)	123.09 (9)
C2—S	1.6839 (4)	1.683 (3)	1.6670 (13)	N3—C2—S	121.78 (2)	121.8 (2)	122.06 (9)
C4—O	1.2318 (4)	1.227 (4)	1.2426 (15)	O—C4—N3	119.44 (4)	119.2 (3)	119.06 (11)
C4—N3	1.3951 (4)	1.389 (4)	1.3837 (16)	O—C4—C5	125.05 (4)	125.4 (3)	125.79 (12)
C4—C5	1.4443 (5)	1.432 (5)	1.4305 (18)	N3—C4—C5	115.51 (3)	115.4 (3)	115.15 (11)
C5—C6	1.3523 (5)	1.338 (5)	1.3439 (18)	C6—C5—C4	118.58 (4)	119.2 (3)	118.94 (12)
C6—N1	1.3707 (4)	1.373 (4)	1.3653 (16)	C5—C6—N1	121.57 (3)	121.2 (3)	121.62 (12)
				C2—N1—C6	122.64 (3)	122.9 (3)	122.96 (10)
				C2—N3—C4	125.32 (3)	125.2 (3)	126.26 (11)

Hydrogen-bond geometry (Å, °) for N—H···O, N—H···S and C—H···O interactions for polymorphs A and B (first row, at 100 K; Jarzembska et al., 2012) (the data were obtained after TAAM refinement); second row (at room temperature) (Tiekink, 1989). Contact geometry is given for C—H···S interactions. top

	D—H	H···A	D···A	D–H···A
Polymorph A
N1—H1···S1ⁱ	1.029 (1) 0.90	2.292 (2) 2.44	3.2991 (3) 3.315 (3)	165.7 (2) 164
N3—H3···O1ⁱⁱ	1.029 (1) 0.90	1.795 (1) 1.94	2.8202 (4) 2.835 (4)	173.6 (2) 175
C5—H5···O1ⁱⁱⁱ	1.083 (1) 0.83	2.263 (2) 2.54	3.3377 (4) 3.362 (4)	171.4 (1) 164
C6—H6···S1^iv	1.082 (1) 0.94	2.771 (4) 2.91	3.6363 (3) 3.663 (3)	136.8 (3) 138

Polymorph B
N1—H1···O1^v	0.86	1.99	2.8443 (14)	175
N3—H3···O1^vi	0.86	2.06	2.9057 (15)	166
C5—H5···S1^vii	0.86	2.97^b	3.9031 (14)	176
C6—H6···S1^viii	0.86	2.88^a	3.7780 (14)	163

Symmetry codes: (i) -x, -y, -z; (ii) -x+1, -y+1, -z+1; (iii) -x+2, -y, -z+1; (iv) x+1, y-1, z; (v) x, -y+1/2, z+1/2; (vi) -x, -y+1, -z; (vii) x+1, -y+1/2, z-1/2; (viii) -x, y-1/2, -z+1/2.

Notes: (a) the value is shorter than the sum of the van der Waals radii by only 0.12 Å; (b) the value is shorter than the sum of the van der Waals radii by only 0.03 Å. Contact radii are those given in Bondi (1964).

4 QTAIM descriptors^a of the selected bond path (3, -1) critical points (BCP) for intermolecular interactions in the crystal structures of polymorphs A^b and B^c. All values are in atomic units (a.u.) top

BCP		ρ(r)	\nabla²ρ(r)	G(r)	V(r)	H(r)	\|V(r)\|/G(r)	Symmetry code
Polymorph A
A1	H1···S1	0.0256	0.0493	0.0064	-0.0005	0.0059	0.0781	-x, -y, -z
A2	H3···O1	0.0368	0.1109	0.0117	0.0043	0.0160	0.3675	-x+1, -y+1, -z+1
A3	H5···O1	0.0130	0.0476	0.0021	0.0078	0.0098	3.7143	-x+2, -y, -z+1
A4	H6···S1	0.0090	0.0254	0.0011	0.0041	0.0052	3.7273	x+1, y-1, z
A5	N1···S1	0.0055	0.0164	0.0005	0.0031	0.0036	6.2000	x+1, y, z
A6	N3···S1	0.0060	0.0159	0.0006	0.0028	0.0034	4.6667	x+1, y, z
A7[	C5···C2	0.0070	0.0168	0.0007	0.0027	0.0035	3.8571	x+1, y, z
Polymorph B
B1	H1···O1	0.0352	0.1055	0.0109	0.0047	0.0155	0.3133	x, -y+1/2, z+1/2
B2	H3···O1	0.0302	0.0952	0.0084	0.0070	0.0154	0.8333	-x, -y+1, -z
B3	H5···S1	0.0080	0.0222	0.0009	0.0037	0.0046	4.1111	x+1, -y+1/2, z-1/2
B4	H6···S1	0.0097	0.0266	0.0013	0.0041	0.0054	3.1538	-x, y-1/2, -z+1/2
B5	S1···C5	0.0055	0.0152	0.0005	0.0028	0.0033	5.6000	x-1, -y+1/2, z+1/2
B6	S1···C6	0.0074	0.0232	0.0008	0.0042	0.0050	5.2500	x-1, y, z
B7	N1···S1	0.0070	0.0172	0.0007	0.0028	0.0035	4.0000	x-1, y, z
B8	C6···N3	0.0054	0.0136	0.0005	0.0024	0.0029	4.8000	x-1, y, z

Notes: (a) ρ(r) is the electron density, \nabla²ρ(r) is the Laplacian of the electron density, G(r) is the kinetic energy density, V(r) is the potential energy density, H(r) is the energy density and |V(r)|/G(r) is the ratio of the potential energy to the kinetic energy density. (b) BCP A1–A4 in Fig. 7(a and BCP A5–A7 in Fig. 8(a). (c) BCP B1–B4 in Fig. 7(b) and BCP B5–B8 in Fig. 8(b). All values are in atomic units (a.u.).

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Structural and computational analysis of inter­molecular inter­actions in a new 2-thio­uracil polymorph

Supporting information

Structural and computational analysis of intermolecular interactions in a new 2-thiouracil polymorph