Intra- and intermolecular interactions in small bioactive molecules: cooperative features from experimental and theoretical charge-density analysis

Munshi, P.; Guru Row, T.N.

doi:10.1107/S0108768106017393

Intra- and intermolecular interactions in small bioactive molecules: cooperative features from experimental and theoretical charge-density analysis

The topological features of the charge densities, ρ(r), of three bioactive molecules, 2-thiouracil [2,3-dihydro-2-thioxopyrimidin-4(1H)-one], cytosine [4-aminopyrimidin-2(1H)-one] monohydrate and salicylic acid (2-hydroxybenzoic acid), have been determined from high-resolution X-ray diffraction data at 90 K. The corresponding results are compared with the periodic theoretical calculations, based on theoretical structure factors, performed using DFT (density-functional theory) at the B3LYP/6-31G** level. The molecules pack in the crystal lattices via weak intermolecular interactions as well as strong hydrogen bonds. All the chemical bonds, including the intra- and intermolecular interactions in all three compounds, have been quantitatively described by topological analysis based on Bader's quantum theory of `Atoms In Molecules'. The roles of interactions such as C—H

O, C—H

S, C—H

π and π

π have been investigated quantitatively in the presence of strong hydrogen bonds such as O—H

O, N—H

O and N—H

S, based on the criteria proposed by Koch and Popelier to characterize hydrogen bonds and van der Waals interactions. The features of weak intermolecular interactions, such as S

S in 2-thiouracil, the hydrogen bonds generated from the water molecule in cytosine monohydrate and the formation of the dimer via strong hydrogen bonds in salicylic acid, are highlighted on a quantum basis. Three-dimensional electrostatic potentials over the molecular surfaces emphasize the preferable binding sites in the structure and the interaction features of the atoms in the molecules, which are crucial for drug–receptor recognition.

Keywords: charge-density distributions; density-functional calculations; electrostatic potentials; topological analyses; X-ray diffraction.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S0108768106017393/lc5044sup1.cif Contains datablocks global, 2-thiouracil, cytosine, salicylicacid
	Structure factor file (CIF format) https://doi.org/10.1107/S0108768106017393/lc50442-thiouracilsup2.hkl Contains datablock 2THURCL
	Structure factor file (CIF format) https://doi.org/10.1107/S0108768106017393/lc5044cytosinesup3.hkl Contains datablock CYTO
	Structure factor file (CIF format) https://doi.org/10.1107/S0108768106017393/lc5044salicylicacidsup4.hkl Contains datablock SALI
	Portable Document Format (PDF) file https://doi.org/10.1107/S0108768106017393/lc5044sup5.pdf Electron density maps, Laplacian distributions, ORTEP diagrams and tables of population coefficients and radial parameters

CCDC references: 276206; 276207; 276208

Computing details top

For all compounds, data collection: SMART (Bruker, 2004); cell refinement: SMART; data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: Koritsanszky et al., (2003); molecular graphics: Koritsanszky et al., (2003); software used to prepare material for publication: Koritsanszky et al., (2003).

Figures top

(2-thiouracil) 2-thioxo-2,3-dihydropyrimidin-4(1H)-one top

Crystal data top

C₄H₄N₂OS	Z = 2
M_r = 128.16	F(000) = 132
Triclinic, P1	D_x = 1.661 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 4.2427 (4) Å	Cell parameters from 4983 reflections
b = 5.9648 (5) Å	θ = 3.6–51.6°
c = 10.5801 (10) Å	µ = 0.51 mm⁻¹
α = 105.736 (5)°	T = 90 K
β = 94.912 (5)°	Block, colorless
γ = 91.927 (4)°	0.39 × 0.19 × 0.12 mm
V = 256.32 (4) Å³

Data collection top

Bruker SMART APEX CCD area detector diffractometer	4983 independent reflections
Radiation source: fine-focus sealed tube	4697 reflections with > 3σ(I)
Graphite monochromator	R_int = 0.031
ϕ & ω scans	θ_max = 51.6°, θ_min = 3.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = 0→9
T_min = 0.831, T_max = 0.943	k = −13→13
4983 measured reflections	l = −23→22

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.014	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.017	H-atom parameters not refined
S = 1.93	w2 = 1/[s²(F_o²)]
4697 reflections	(Δ/σ)_max < 0.001
229 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₄H₄N₂OS	γ = 91.927 (4)°
M_r = 128.16	V = 256.32 (4) Å³
Triclinic, P1	Z = 2
a = 4.2427 (4) Å	Mo Kα radiation
b = 5.9648 (5) Å	µ = 0.51 mm⁻¹
c = 10.5801 (10) Å	T = 90 K
α = 105.736 (5)°	0.39 × 0.19 × 0.12 mm
β = 94.912 (5)°

Data collection top

Bruker SMART APEX CCD area detector diffractometer	4983 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	4697 reflections with > 3σ(I)
T_min = 0.831, T_max = 0.943	R_int = 0.031
4983 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.014	0 restraints
wR(F²) = 0.017	H-atom parameters not refined
S = 1.93	Δρ_max = 0.32 e Å⁻³
4697 reflections	Δρ_min = −0.20 e Å⁻³
229 parameters

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
S(2)	0.45628 (1)	0.64884 (1)	0.37117 (1)	0.012
O(4)	−0.24292 (6)	0.72104 (4)	−0.01050 (2)	0.016
N(1)	0.14216 (4)	1.02089 (3)	0.35761 (2)	0.011
N(3)	0.08327 (4)	0.71272 (3)	0.16998 (2)	0.011
C(2)	0.21656 (4)	0.80251 (3)	0.29574 (2)	0.010
C(4)	−0.13325 (4)	0.82225 (3)	0.10352 (2)	0.012
C(6)	−0.06598 (4)	1.14382 (3)	0.30023 (2)	0.012
C(5)	−0.21041 (5)	1.05168 (3)	0.17684 (2)	0.013
H(6)	−0.08610	1.31703	0.36384	0.025 (2)
H(5)	−0.37972	1.15188	0.13684	0.030 (3)
H(1)	0.25733	1.10703	0.44842	0.016 (2)
H(3)	0.13712	0.54835	0.11787	0.019 (2)
DUM0	0.00000	0.00000	0.00000	0.000	0.0000

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S(2)	0.01332 (2)	0.01045 (2)	0.01132 (2)	0.00233 (1)	−0.00329 (1)	0.00216 (1)
O(4)	0.01966 (9)	0.01683 (8)	0.00980 (7)	0.00640 (6)	−0.00425 (6)	0.00035 (6)
N(1)	0.01189 (6)	0.00996 (5)	0.00984 (5)	0.00190 (4)	−0.00153 (4)	0.00093 (4)
N(3)	0.01240 (6)	0.01115 (5)	0.00867 (5)	0.00316 (4)	−0.00155 (4)	0.00109 (4)
C(2)	0.01018 (6)	0.01001 (5)	0.00891 (5)	0.00149 (4)	−0.00099 (4)	0.00187 (4)
C(4)	0.01273 (6)	0.01243 (6)	0.00877 (5)	0.00309 (4)	−0.00129 (4)	0.00196 (5)
C(6)	0.01278 (6)	0.01019 (5)	0.01167 (6)	0.00238 (4)	−0.00070 (4)	0.00180 (5)
C(5)	0.01354 (7)	0.01200 (6)	0.01143 (6)	0.00349 (4)	−0.00124 (4)	0.00297 (5)

Geometric parameters (Å, º) top

S(2)—C(2)	1.6828 (2)	N(3)—C(4)	1.3942 (2)
O(4)—C(4)	1.2354 (3)	N(3)—H(3)	1.0300 (2)
N(1)—C(2)	1.3511 (2)	C(4)—C(5)	1.4420 (3)
N(1)—C(6)	1.3709 (2)	C(6)—C(5)	1.3538 (3)
N(1)—H(1)	1.0300 (2)	C(6)—H(6)	1.0800 (2)
N(3)—C(2)	1.3570 (2)	C(5)—H(5)	1.0800 (2)

C(2)—N(1)—C(6)	122.692 (16)	O(4)—C(4)—N(3)	119.512 (19)
C(2)—N(1)—H(1)	120.009 (16)	O(4)—C(4)—C(5)	125.049 (18)
C(6)—N(1)—H(1)	117.100 (15)	N(3)—C(4)—C(5)	115.439 (16)
C(2)—N(3)—C(4)	125.400 (16)	N(1)—C(6)—C(5)	121.437 (16)
C(2)—N(3)—H(3)	119.129 (15)	N(1)—C(6)—H(6)	111.386 (16)
C(4)—N(3)—H(3)	115.445 (15)	C(5)—C(6)—H(6)	127.130 (17)
S(2)—C(2)—N(1)	121.904 (13)	C(4)—C(5)—C(6)	118.709 (16)
S(2)—C(2)—N(3)	121.868 (13)	C(4)—C(5)—H(5)	122.272 (17)
N(1)—C(2)—N(3)	116.222 (15)	C(6)—C(5)—H(5)	119.018 (17)

C(6)—N(1)—C(2)—S(2)	−176.4 (1)	H(3)—N(3)—C(2)—S(2)	−2.5 (1)
C(6)—N(1)—C(2)—N(3)	2.7 (1)	H(3)—N(3)—C(2)—N(1)	178.5 (1)
C(2)—N(1)—C(6)—C(5)	0.1 (1)	H(3)—N(3)—C(4)—O(4)	−0.6 (1)
C(2)—N(1)—C(6)—H(6)	−177.6 (1)	H(3)—N(3)—C(4)—C(5)	179.6 (1)
H(1)—N(1)—C(2)—S(2)	8.9 (1)	O(4)—C(4)—C(5)—C(6)	−178.4 (1)
H(1)—N(1)—C(2)—N(3)	−172.1 (1)	O(4)—C(4)—C(5)—H(5)	1.8 (1)
H(1)—N(1)—C(6)—C(5)	174.9 (1)	N(3)—C(4)—C(5)—C(6)	1.4 (1)
H(1)—N(1)—C(6)—H(6)	−2.7 (1)	N(3)—C(4)—C(5)—H(5)	−178.3 (1)
C(4)—N(3)—C(2)—S(2)	175.6 (1)	N(1)—C(6)—C(5)—C(4)	−2.2 (1)
C(2)—N(3)—C(4)—O(4)	−178.7 (1)	N(1)—C(6)—C(5)—H(5)	177.6 (1)
C(4)—N(3)—C(2)—N(1)	−3.4 (1)	H(6)—C(6)—C(5)—C(4)	175.1 (1)
C(2)—N(3)—C(4)—C(5)	1.4 (1)	H(6)—C(6)—C(5)—H(5)	−5.1 (1)

(cytosine) top

Crystal data top

C₄H₅N₃O·H₂O	F(000) = 272
M_r = 129.13	D_x = 1.530 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5948 reflections
a = 7.7161 (8) Å	θ = 2.7–50.3°
b = 9.8337 (10) Å	µ = 0.12 mm⁻¹
c = 7.5131 (8) Å	T = 90 K
β = 100.523 (5)°	Block, colorless
V = 560.49 (10) Å³	0.32 × 0.22 × 0.03 mm
Z = 4

Data collection top

Bruker SMART APEX CCD area detector diffractometer	5948 independent reflections
Radiation source: fine-focus sealed tube	4792 reflections with > 3σ(I)
Graphite monochromator	R_int = 0.040
ϕ & ω scans	θ_max = 50.3°, θ_min = 2.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −16→16
T_min = 0.961, T_max = 0.996	k = 0→21
5948 measured reflections	l = 0→16

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.017	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.015	H-atom parameters not refined
S = 1.96	w2 = 1/[s²(F_o²)]
4792 reflections	(Δ/σ)_max < 0.001
337 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.17 e Å⁻³

Crystal data top

C₄H₅N₃O·H₂O	V = 560.49 (10) Å³
M_r = 129.13	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.7161 (8) Å	µ = 0.12 mm⁻¹
b = 9.8337 (10) Å	T = 90 K
c = 7.5131 (8) Å	0.32 × 0.22 × 0.03 mm
β = 100.523 (5)°

Data collection top

Bruker SMART APEX CCD area detector diffractometer	5948 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	4792 reflections with > 3σ(I)
T_min = 0.961, T_max = 0.996	R_int = 0.040
5948 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.017	0 restraints
wR(F²) = 0.015	H-atom parameters not refined
S = 1.96	Δρ_max = 0.27 e Å⁻³
4792 reflections	Δρ_min = −0.17 e Å⁻³
337 parameters

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
O(1)	0.35423 (3)	0.20877 (2)	0.47471 (3)	0.014
O(2)	0.14835 (3)	0.12075 (2)	0.71691 (3)	0.012
N(1)	−0.08534 (2)	0.00432 (2)	0.78140 (2)	0.010
N(3)	−0.07914 (2)	0.24444 (2)	0.78909 (3)	0.010
N(4)	−0.31101 (3)	0.36205 (2)	0.86904 (3)	0.013
C(2)	−0.00196 (2)	0.12502 (2)	0.76001 (2)	0.009
C(4)	−0.23597 (2)	0.24325 (2)	0.84319 (2)	0.009
C(5)	−0.32210 (2)	0.11871 (2)	0.87386 (3)	0.011
C(6)	−0.24197 (2)	0.00145 (2)	0.83951 (2)	0.011
H(1)	−0.01911	−0.08184	0.75113	0.012 (2)
H(1A)	0.27966	0.25771	0.37788	0.019 (2)
H(1B)	0.27054	0.17438	0.54462	0.022 (2)
H(4A)	−0.25000	0.44671	0.83268	0.018 (2)
H(4B)	−0.43057	0.35719	0.90660	0.016 (2)
H(5)	−0.44472	0.12010	0.92387	0.025 (2)
H(6)	−0.29795	−0.09781	0.85832	0.024 (2)
DUM0	0.00000	0.00000	0.00000	0.000	0.0000

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O(1)	0.01137 (6)	0.01433 (7)	0.01657 (8)	0.00056 (5)	0.00552 (6)	0.00132 (5)
O(2)	0.01007 (6)	0.01026 (7)	0.01724 (8)	−0.00009 (5)	0.00674 (6)	−0.00016 (5)
N(1)	0.01008 (6)	0.00669 (6)	0.01390 (7)	−0.00033 (4)	0.00441 (5)	−0.00016 (4)
N(3)	0.00906 (6)	0.00691 (6)	0.01323 (7)	−0.00036 (4)	0.00434 (5)	−0.00018 (4)
N(4)	0.01145 (6)	0.00802 (6)	0.01874 (8)	0.00080 (5)	0.00641 (5)	−0.00044 (5)
C(2)	0.00850 (6)	0.00734 (6)	0.01150 (7)	−0.00026 (4)	0.00377 (4)	0.00002 (4)
C(4)	0.00899 (6)	0.00715 (6)	0.01200 (7)	−0.00006 (4)	0.00374 (5)	−0.00009 (4)
C(5)	0.01042 (6)	0.00832 (6)	0.01573 (7)	−0.00063 (5)	0.00599 (5)	0.00022 (5)
C(6)	0.01081 (7)	0.00741 (6)	0.01419 (8)	−0.00109 (5)	0.00476 (5)	0.00035 (4)

Geometric parameters (Å, º) top

O(1)—H(1A)	0.9690 (2)	N(4)—C(4)	1.3337 (2)
O(1)—H(1B)	0.9650 (2)	N(4)—H(4A)	1.0180 (2)
O(2)—C(2)	1.2605 (2)	N(4)—H(4B)	1.0140 (2)
N(1)—C(2)	1.3734 (2)	C(4)—C(5)	1.4320 (2)
N(1)—C(6)	1.3583 (2)	C(5)—C(6)	1.3553 (2)
N(1)—H(1)	1.0360 (2)	C(5)—H(5)	1.0800 (2)
N(3)—C(2)	1.3524 (2)	C(6)—H(6)	1.0870 (2)
N(3)—C(4)	1.3451 (2)

H(1A)—O(1)—H(1B)	102.595 (19)	N(1)—C(2)—N(3)	120.129 (16)
C(2)—N(1)—C(6)	121.263 (16)	N(3)—C(4)—N(4)	118.349 (17)
C(2)—N(1)—H(1)	114.880 (16)	N(3)—C(4)—C(5)	121.711 (16)
C(6)—N(1)—H(1)	123.854 (16)	N(4)—C(4)—C(5)	119.939 (17)
C(2)—N(3)—C(4)	119.229 (16)	C(4)—C(5)—C(6)	117.113 (16)
C(4)—N(4)—H(4A)	116.292 (17)	C(4)—C(5)—H(5)	120.463 (16)
C(4)—N(4)—H(4B)	116.138 (17)	C(6)—C(5)—H(5)	122.420 (17)
H(4A)—N(4)—H(4B)	127.015 (18)	N(1)—C(6)—C(5)	120.473 (17)
O(2)—C(2)—N(1)	118.290 (17)	N(1)—C(6)—H(6)	117.292 (16)
O(2)—C(2)—N(3)	121.563 (17)	C(5)—C(6)—H(6)	122.231 (17)

C(6)—N(1)—C(2)—O(2)	175.5 (1)	H(4A)—N(4)—C(4)—N(3)	6.4 (1)
C(6)—N(1)—C(2)—N(3)	−3.0 (1)	H(4A)—N(4)—C(4)—C(5)	−173.9 (1)
C(2)—N(1)—C(6)—C(5)	1.6 (1)	H(4B)—N(4)—C(4)—N(3)	178.5 (1)
C(2)—N(1)—C(6)—H(6)	−177.7 (1)	H(4B)—N(4)—C(4)—C(5)	−1.8 (1)
H(1)—N(1)—C(2)—O(2)	−4.0 (1)	N(3)—C(4)—C(5)—C(6)	−2.4 (1)
H(1)—N(1)—C(2)—N(3)	177.6 (1)	N(3)—C(4)—C(5)—H(5)	176.8 (1)
H(1)—N(1)—C(6)—C(5)	−179.0 (1)	N(4)—C(4)—C(5)—C(6)	177.9 (1)
H(1)—N(1)—C(6)—H(6)	1.7 (1)	N(4)—C(4)—C(5)—H(5)	−2.9 (1)
C(4)—N(3)—C(2)—O(2)	−176.9 (1)	C(4)—C(5)—C(6)—N(1)	1.0 (1)
C(4)—N(3)—C(2)—N(1)	1.6 (1)	C(4)—C(5)—C(6)—H(6)	−179.7 (1)
C(2)—N(3)—C(4)—N(4)	−179.2 (1)	H(5)—C(5)—C(6)—N(1)	−178.2 (1)
C(2)—N(3)—C(4)—C(5)	1.1 (1)	H(5)—C(5)—C(6)—H(6)	1.0 (1)

(salicylicacid) 2-hydroxybenzoic acid top

Crystal data top

C₇H₆O₃	F(000) = 288
M_r = 138.12	D_x = 1.495 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 31354 reflections
a = 4.8818 (2) Å	θ = 2.6–50.3°
b = 11.2009 (5) Å	µ = 0.12 mm⁻¹
c = 11.2335 (5) Å	T = 90 K
β = 92.621 (2)°	Prism, colorless
V = 613.61 (5) Å³	0.25 × 0.22 × 0.2 mm
Z = 4

Data collection top

Bruker SMART APEX CCD area detector diffractometer	6440 independent reflections
Radiation source: fine-focus sealed tube	5439 reflections with > 3σ(I)
Graphite monochromator	R_int = 0.029
ϕ & ω scans	θ_max = 50.3°, θ_min = 2.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −10→10
T_min = 0.886, T_max = 0.977	k = −23→24
31354 measured reflections	l = −24→24

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.020	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.020	H-atom parameters not refined
S = 1.96	w2 = q/[s²(F_o²) + (0.00 P)² + 0.00 P + 0.00 + 0.00 sin(th)] where P = (0.3333 F_o² + 0.6667 F_c²) q = 1.0
5439 reflections	(Δ/σ)_max < 0.001
276 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₇H₆O₃	V = 613.61 (5) Å³
M_r = 138.12	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 4.8818 (2) Å	µ = 0.12 mm⁻¹
b = 11.2009 (5) Å	T = 90 K
c = 11.2335 (5) Å	0.25 × 0.22 × 0.2 mm
β = 92.621 (2)°

Data collection top

Bruker SMART APEX CCD area detector diffractometer	6440 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	5439 reflections with > 3σ(I)
T_min = 0.886, T_max = 0.977	R_int = 0.029
31354 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.020	0 restraints
wR(F²) = 0.020	H-atom parameters not refined
S = 1.96	Δρ_max = 0.27 e Å⁻³
5439 reflections	Δρ_min = −0.26 e Å⁻³
276 parameters

Special details top

Experimental. Crystal to Detector distance was 6.03 cm, ω range is 0.3 ° and exposure time was 20 s, 40 s and 80 s in three batches respectively.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
O(1)	0.83999 (4)	0.13928 (2)	−0.05215 (2)	0.014
O(3)	0.39275 (5)	0.06756 (2)	0.24999 (2)	0.016
O(2)	0.76762 (4)	0.01483 (2)	0.09897 (2)	0.013
C(1)	0.50516 (3)	0.19284 (2)	0.08238 (2)	0.010
C(3)	0.15873 (4)	0.24924 (2)	0.22021 (2)	0.014
C(6)	0.45370 (4)	0.29928 (2)	0.01908 (2)	0.013
C(2)	0.35609 (4)	0.16777 (2)	0.18410 (2)	0.012
C(5)	0.25886 (4)	0.37961 (2)	0.05541 (2)	0.015
C(4)	0.11104 (4)	0.35399 (2)	0.15648 (2)	0.015
C(7)	0.71398 (3)	0.10908 (2)	0.04397 (2)	0.010
H(6)	0.57311	0.31697	−0.05713	0.027 (2)
H(3)	0.04064	0.22880	0.29617	0.030 (2)
H(5)	0.21541	0.45737	0.00156	0.036 (2)
H(4)	−0.04312	0.41534	0.18430	0.036 (2)
H(2)	0.54071	0.02176	0.21898	0.017 (2)
H(1)	0.98372	0.07598	−0.07049	0.013 (2)
DUM0	0.00000	0.00000	0.00000	0.000	0.0000

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O(1)	0.01430 (7)	0.01378 (6)	0.01421 (6)	0.00347 (6)	0.00571 (5)	0.00264 (6)
O(3)	0.01832 (8)	0.01545 (7)	0.01425 (7)	0.00385 (6)	0.00600 (6)	0.00245 (6)
O(2)	0.01341 (6)	0.01152 (5)	0.01396 (6)	0.00309 (5)	0.00397 (5)	0.00218 (5)
C(1)	0.00986 (5)	0.01006 (5)	0.01145 (6)	0.00119 (5)	0.00128 (4)	−0.00038 (5)
C(3)	0.01351 (7)	0.01583 (7)	0.01403 (6)	0.00326 (6)	0.00273 (5)	−0.00293 (6)
C(6)	0.01237 (6)	0.01147 (6)	0.01546 (6)	0.00205 (5)	0.00152 (5)	0.00136 (5)
C(2)	0.01145 (6)	0.01200 (6)	0.01141 (6)	0.00152 (5)	0.00202 (5)	−0.00112 (5)
C(5)	0.01407 (7)	0.01204 (6)	0.01979 (8)	0.00347 (5)	0.00050 (6)	−0.00003 (6)
C(4)	0.01348 (7)	0.01417 (7)	0.01786 (7)	0.00388 (6)	0.00044 (6)	−0.00383 (6)
C(7)	0.01001 (5)	0.01005 (5)	0.01117 (5)	0.00092 (5)	0.00191 (4)	0.00023 (5)

Geometric parameters (Å, º) top

O(1)—C(7)	1.3113 (2)	C(3)—C(2)	1.4005 (3)
O(1)—H(1)	1.0250 (2)	C(3)—C(4)	1.3886 (3)
O(3)—C(2)	1.3519 (3)	C(3)—H(3)	1.0760 (2)
O(3)—H(2)	0.9640 (2)	C(6)—C(5)	1.3843 (3)
O(2)—C(7)	1.2450 (2)	C(6)—H(6)	1.0760 (2)
C(1)—C(6)	1.4049 (3)	C(5)—C(4)	1.4025 (3)
C(1)—C(2)	1.4107 (2)	C(5)—H(5)	1.0760 (2)
C(1)—C(7)	1.4648 (2)	C(4)—H(4)	1.0760 (2)

C(7)—O(1)—H(1)	109.777 (18)	O(3)—C(2)—C(3)	117.254 (18)
C(2)—O(3)—H(2)	109.061 (18)	C(1)—C(2)—C(3)	119.484 (18)
C(6)—C(1)—C(2)	119.465 (16)	C(6)—C(5)—C(4)	119.444 (19)
C(6)—C(1)—C(7)	120.344 (16)	C(6)—C(5)—H(5)	118.74 (2)
C(2)—C(1)—C(7)	120.187 (16)	C(4)—C(5)—H(5)	121.682 (19)
C(2)—C(3)—C(4)	120.166 (18)	C(3)—C(4)—C(5)	120.659 (18)
C(2)—C(3)—H(3)	119.45 (2)	C(3)—C(4)—H(4)	119.52 (2)
C(4)—C(3)—H(3)	120.356 (18)	C(5)—C(4)—H(4)	119.81 (2)
C(1)—C(6)—C(5)	120.781 (18)	O(1)—C(7)—O(2)	122.100 (17)
C(1)—C(6)—H(6)	117.917 (17)	O(1)—C(7)—C(1)	115.871 (17)
C(5)—C(6)—H(6)	121.291 (18)	O(2)—C(7)—C(1)	122.028 (16)
O(3)—C(2)—C(1)	123.262 (17)

H(1)—O(1)—C(7)—O(2)	−1.3 (1)	C(4)—C(3)—C(2)—O(3)	180.0 (1)
H(1)—O(1)—C(7)—C(1)	178.9 (1)	C(4)—C(3)—C(2)—C(1)	−0.2 (1)
H(2)—O(3)—C(2)—C(1)	3.7 (1)	C(2)—C(3)—C(4)—C(5)	0.1 (1)
H(2)—O(3)—C(2)—C(3)	−176.5 (1)	C(2)—C(3)—C(4)—H(4)	179.1 (1)
C(6)—C(1)—C(2)—O(3)	180.0 (1)	H(3)—C(3)—C(2)—O(3)	−1.8 (1)
C(6)—C(1)—C(2)—C(3)	0.1 (1)	H(3)—C(3)—C(2)—C(1)	178.1 (1)
C(2)—C(1)—C(6)—C(5)	0.0 (1)	H(3)—C(3)—C(4)—C(5)	−178.2 (1)
C(2)—C(1)—C(6)—H(6)	178.8 (1)	H(3)—C(3)—C(4)—H(4)	0.9 (1)
C(6)—C(1)—C(7)—O(1)	−1.3 (1)	C(1)—C(6)—C(5)—C(4)	−0.2 (1)
C(6)—C(1)—C(7)—O(2)	178.9 (1)	C(1)—C(6)—C(5)—H(5)	−176.0 (1)
C(7)—C(1)—C(6)—C(5)	−179.3 (1)	H(6)—C(6)—C(5)—C(4)	−178.9 (1)
C(7)—C(1)—C(6)—H(6)	−0.5 (1)	H(6)—C(6)—C(5)—H(5)	5.2 (1)
C(2)—C(1)—C(7)—O(1)	179.3 (1)	C(6)—C(5)—C(4)—C(3)	0.1 (1)
C(7)—C(1)—C(2)—O(3)	−0.7 (1)	C(6)—C(5)—C(4)—H(4)	−178.9 (1)
C(2)—C(1)—C(7)—O(2)	−0.4 (1)	H(5)—C(5)—C(4)—C(3)	175.8 (1)
C(7)—C(1)—C(2)—C(3)	179.5 (1)	H(5)—C(5)—C(4)—H(4)	−3.2 (1)

Experimental details

	(2-thiouracil)	(cytosine)	(salicylicacid)
Crystal data
Chemical formula	C₄H₄N₂OS	C₄H₅N₃O·H₂O	C₇H₆O₃
M_r	128.16	129.13	138.12
Crystal system, space group	Triclinic, P1	Monoclinic, P2₁/c	Monoclinic, P2₁/c
Temperature (K)	90	90	90
a, b, c (Å)	4.2427 (4), 5.9648 (5), 10.5801 (10)	7.7161 (8), 9.8337 (10), 7.5131 (8)	4.8818 (2), 11.2009 (5), 11.2335 (5)
α, β, γ (°)	105.736 (5), 94.912 (5), 91.927 (4)	90, 100.523 (5), 90	90, 92.621 (2), 90
V (Å³)	256.32 (4)	560.49 (10)	613.61 (5)
Z	2	4	4
Radiation type	Mo Kα	Mo Kα	Mo Kα
µ (mm⁻¹)	0.51	0.12	0.12
Crystal size (mm)	0.39 × 0.19 × 0.12	0.32 × 0.22 × 0.03	0.25 × 0.22 × 0.2

Data collection
Diffractometer	Bruker SMART APEX CCD area detector diffractometer	Bruker SMART APEX CCD area detector diffractometer	Bruker SMART APEX CCD area detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)	Multi-scan (SADABS; Sheldrick, 1996)	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.831, 0.943	0.961, 0.996	0.886, 0.977
No. of measured, independent and observed [ > 3σ(I)] reflections	4983, 4983, 4697	5948, 5948, 4792	31354, 6440, 5439
R_int	0.031	0.040	0.029
(sin θ/λ)_max (Å⁻¹)	1.103	1.082	1.083

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.014, 0.017, 1.93	0.017, 0.015, 1.96	0.020, 0.020, 1.96
No. of reflections	4697	4792	5439
No. of parameters	229	337	276
H-atom treatment	H-atom parameters not refined	H-atom parameters not refined	H-atom parameters not refined
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.20	0.27, −0.17	0.27, −0.26

Computer programs: SMART (Bruker, 2004), SMART, SAINT (Bruker, 2004), SHELXS97 (Sheldrick, 1997), Koritsanszky et al., (2003).

Selected geometric parameters (Å, º) for (2-thiouracil) top

S(2)—C(2)	1.6828 (2)	N(3)—C(4)	1.3942 (2)
O(4)—C(4)	1.2354 (3)	N(3)—H(3)	1.0300 (2)
N(1)—C(2)	1.3511 (2)	C(4)—C(5)	1.4420 (3)
N(1)—C(6)	1.3709 (2)	C(6)—C(5)	1.3538 (3)
N(1)—H(1)	1.0300 (2)	C(6)—H(6)	1.0800 (2)
N(3)—C(2)	1.3570 (2)	C(5)—H(5)	1.0800 (2)

C(2)—N(1)—C(6)	122.692 (16)	O(4)—C(4)—N(3)	119.512 (19)
C(2)—N(1)—H(1)	120.009 (16)	O(4)—C(4)—C(5)	125.049 (18)
C(6)—N(1)—H(1)	117.100 (15)	N(3)—C(4)—C(5)	115.439 (16)
C(2)—N(3)—C(4)	125.400 (16)	N(1)—C(6)—C(5)	121.437 (16)
C(2)—N(3)—H(3)	119.129 (15)	N(1)—C(6)—H(6)	111.386 (16)
C(4)—N(3)—H(3)	115.445 (15)	C(5)—C(6)—H(6)	127.130 (17)
S(2)—C(2)—N(1)	121.904 (13)	C(4)—C(5)—C(6)	118.709 (16)
S(2)—C(2)—N(3)	121.868 (13)	C(4)—C(5)—H(5)	122.272 (17)
N(1)—C(2)—N(3)	116.222 (15)	C(6)—C(5)—H(5)	119.018 (17)

C(6)—N(1)—C(2)—S(2)	−176.4 (1)	H(3)—N(3)—C(2)—S(2)	−2.5 (1)
C(6)—N(1)—C(2)—N(3)	2.7 (1)	H(3)—N(3)—C(2)—N(1)	178.5 (1)
C(2)—N(1)—C(6)—C(5)	0.1 (1)	H(3)—N(3)—C(4)—O(4)	−0.6 (1)
C(2)—N(1)—C(6)—H(6)	−177.6 (1)	H(3)—N(3)—C(4)—C(5)	179.6 (1)
H(1)—N(1)—C(2)—S(2)	8.9 (1)	O(4)—C(4)—C(5)—C(6)	−178.4 (1)
H(1)—N(1)—C(2)—N(3)	−172.1 (1)	O(4)—C(4)—C(5)—H(5)	1.8 (1)
H(1)—N(1)—C(6)—C(5)	174.9 (1)	N(3)—C(4)—C(5)—C(6)	1.4 (1)
H(1)—N(1)—C(6)—H(6)	−2.7 (1)	N(3)—C(4)—C(5)—H(5)	−178.3 (1)
C(4)—N(3)—C(2)—S(2)	175.6 (1)	N(1)—C(6)—C(5)—C(4)	−2.2 (1)
C(2)—N(3)—C(4)—O(4)	−178.7 (1)	N(1)—C(6)—C(5)—H(5)	177.6 (1)
C(4)—N(3)—C(2)—N(1)	−3.4 (1)	H(6)—C(6)—C(5)—C(4)	175.1 (1)
C(2)—N(3)—C(4)—C(5)	1.4 (1)	H(6)—C(6)—C(5)—H(5)	−5.1 (1)

Selected geometric parameters (Å, º) for (cytosine) top

O(1)—H(1A)	0.9690 (2)	N(4)—C(4)	1.3337 (2)
O(1)—H(1B)	0.9650 (2)	N(4)—H(4A)	1.0180 (2)
O(2)—C(2)	1.2605 (2)	N(4)—H(4B)	1.0140 (2)
N(1)—C(2)	1.3734 (2)	C(4)—C(5)	1.4320 (2)
N(1)—C(6)	1.3583 (2)	C(5)—C(6)	1.3553 (2)
N(1)—H(1)	1.0360 (2)	C(5)—H(5)	1.0800 (2)
N(3)—C(2)	1.3524 (2)	C(6)—H(6)	1.0870 (2)
N(3)—C(4)	1.3451 (2)

H(1A)—O(1)—H(1B)	102.595 (19)	N(1)—C(2)—N(3)	120.129 (16)
C(2)—N(1)—C(6)	121.263 (16)	N(3)—C(4)—N(4)	118.349 (17)
C(2)—N(1)—H(1)	114.880 (16)	N(3)—C(4)—C(5)	121.711 (16)
C(6)—N(1)—H(1)	123.854 (16)	N(4)—C(4)—C(5)	119.939 (17)
C(2)—N(3)—C(4)	119.229 (16)	C(4)—C(5)—C(6)	117.113 (16)
C(4)—N(4)—H(4A)	116.292 (17)	C(4)—C(5)—H(5)	120.463 (16)
C(4)—N(4)—H(4B)	116.138 (17)	C(6)—C(5)—H(5)	122.420 (17)
H(4A)—N(4)—H(4B)	127.015 (18)	N(1)—C(6)—C(5)	120.473 (17)
O(2)—C(2)—N(1)	118.290 (17)	N(1)—C(6)—H(6)	117.292 (16)
O(2)—C(2)—N(3)	121.563 (17)	C(5)—C(6)—H(6)	122.231 (17)

C(6)—N(1)—C(2)—O(2)	175.5 (1)	H(4A)—N(4)—C(4)—N(3)	6.4 (1)
C(6)—N(1)—C(2)—N(3)	−3.0 (1)	H(4A)—N(4)—C(4)—C(5)	−173.9 (1)
C(2)—N(1)—C(6)—C(5)	1.6 (1)	H(4B)—N(4)—C(4)—N(3)	178.5 (1)
C(2)—N(1)—C(6)—H(6)	−177.7 (1)	H(4B)—N(4)—C(4)—C(5)	−1.8 (1)
H(1)—N(1)—C(2)—O(2)	−4.0 (1)	N(3)—C(4)—C(5)—C(6)	−2.4 (1)
H(1)—N(1)—C(2)—N(3)	177.6 (1)	N(3)—C(4)—C(5)—H(5)	176.8 (1)
H(1)—N(1)—C(6)—C(5)	−179.0 (1)	N(4)—C(4)—C(5)—C(6)	177.9 (1)
H(1)—N(1)—C(6)—H(6)	1.7 (1)	N(4)—C(4)—C(5)—H(5)	−2.9 (1)
C(4)—N(3)—C(2)—O(2)	−176.9 (1)	C(4)—C(5)—C(6)—N(1)	1.0 (1)
C(4)—N(3)—C(2)—N(1)	1.6 (1)	C(4)—C(5)—C(6)—H(6)	−179.7 (1)
C(2)—N(3)—C(4)—N(4)	−179.2 (1)	H(5)—C(5)—C(6)—N(1)	−178.2 (1)
C(2)—N(3)—C(4)—C(5)	1.1 (1)	H(5)—C(5)—C(6)—H(6)	1.0 (1)

Selected geometric parameters (Å, º) for (salicylicacid) top

O(1)—C(7)	1.3113 (2)	C(3)—C(2)	1.4005 (3)
O(1)—H(1)	1.0250 (2)	C(3)—C(4)	1.3886 (3)
O(3)—C(2)	1.3519 (3)	C(3)—H(3)	1.0760 (2)
O(3)—H(2)	0.9640 (2)	C(6)—C(5)	1.3843 (3)
O(2)—C(7)	1.2450 (2)	C(6)—H(6)	1.0760 (2)
C(1)—C(6)	1.4049 (3)	C(5)—C(4)	1.4025 (3)
C(1)—C(2)	1.4107 (2)	C(5)—H(5)	1.0760 (2)
C(1)—C(7)	1.4648 (2)	C(4)—H(4)	1.0760 (2)

C(7)—O(1)—H(1)	109.777 (18)	O(3)—C(2)—C(3)	117.254 (18)
C(2)—O(3)—H(2)	109.061 (18)	C(1)—C(2)—C(3)	119.484 (18)
C(6)—C(1)—C(2)	119.465 (16)	C(6)—C(5)—C(4)	119.444 (19)
C(6)—C(1)—C(7)	120.344 (16)	C(6)—C(5)—H(5)	118.74 (2)
C(2)—C(1)—C(7)	120.187 (16)	C(4)—C(5)—H(5)	121.682 (19)
C(2)—C(3)—C(4)	120.166 (18)	C(3)—C(4)—C(5)	120.659 (18)
C(2)—C(3)—H(3)	119.45 (2)	C(3)—C(4)—H(4)	119.52 (2)
C(4)—C(3)—H(3)	120.356 (18)	C(5)—C(4)—H(4)	119.81 (2)
C(1)—C(6)—C(5)	120.781 (18)	O(1)—C(7)—O(2)	122.100 (17)
C(1)—C(6)—H(6)	117.917 (17)	O(1)—C(7)—C(1)	115.871 (17)
C(5)—C(6)—H(6)	121.291 (18)	O(2)—C(7)—C(1)	122.028 (16)
O(3)—C(2)—C(1)	123.262 (17)

H(1)—O(1)—C(7)—O(2)	−1.3 (1)	C(4)—C(3)—C(2)—O(3)	180.0 (1)
H(1)—O(1)—C(7)—C(1)	178.9 (1)	C(4)—C(3)—C(2)—C(1)	−0.2 (1)
H(2)—O(3)—C(2)—C(1)	3.7 (1)	C(2)—C(3)—C(4)—C(5)	0.1 (1)
H(2)—O(3)—C(2)—C(3)	−176.5 (1)	C(2)—C(3)—C(4)—H(4)	179.1 (1)
C(6)—C(1)—C(2)—O(3)	180.0 (1)	H(3)—C(3)—C(2)—O(3)	−1.8 (1)
C(6)—C(1)—C(2)—C(3)	0.1 (1)	H(3)—C(3)—C(2)—C(1)	178.1 (1)
C(2)—C(1)—C(6)—C(5)	0.0 (1)	H(3)—C(3)—C(4)—C(5)	−178.2 (1)
C(2)—C(1)—C(6)—H(6)	178.8 (1)	H(3)—C(3)—C(4)—H(4)	0.9 (1)
C(6)—C(1)—C(7)—O(1)	−1.3 (1)	C(1)—C(6)—C(5)—C(4)	−0.2 (1)
C(6)—C(1)—C(7)—O(2)	178.9 (1)	C(1)—C(6)—C(5)—H(5)	−176.0 (1)
C(7)—C(1)—C(6)—C(5)	−179.3 (1)	H(6)—C(6)—C(5)—C(4)	−178.9 (1)
C(7)—C(1)—C(6)—H(6)	−0.5 (1)	H(6)—C(6)—C(5)—H(5)	5.2 (1)
C(2)—C(1)—C(7)—O(1)	179.3 (1)	C(6)—C(5)—C(4)—C(3)	0.1 (1)
C(7)—C(1)—C(2)—O(3)	−0.7 (1)	C(6)—C(5)—C(4)—H(4)	−178.9 (1)
C(2)—C(1)—C(7)—O(2)	−0.4 (1)	H(5)—C(5)—C(4)—C(3)	175.8 (1)
C(7)—C(1)—C(2)—C(3)	179.5 (1)	H(5)—C(5)—C(4)—H(4)	−3.2 (1)

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