5-Methyl-2-thiouracil

The molecular structure of the title compound, also known as 2-thio­thymine [systematic name: 2,3-di­hydro-5-methyl-2-thioxopyrimidin-4(1H)-one], C₅H₆N₂OS, is similar to that of thymine, with only small changes in the ring structure, apart from a significant difference at the substitution site [S=C = 1.674 (1) Å]. The mol­ecules are connected by hydrogen bonds, with N-H...O = 2.755 (2) Å and N-H...S = 3.352 (1) Å. The hydrogen-bond network is different from that in thymine, since it involves all the donor and acceptor atoms.

S1. Comment

Thio-nucleobases have been used as intrinsic photolabels to probe the structure and organization of RNA molecules in solution (Favre et al., 1998; Favre, 1990), and to identify the contacts between nucleic acids and proteins in nucleoprotein complexes (Meisenheimer & Koch, 1997). The thio-analogues of nucleic acid bases absorb light at long wavelengths and can be selectively photoactivated into the electronic triplet state, which leads to their high affinity to cross-link to other nucleic acid bases and amino acid residues in contact. It has also been shown that the thio-analogues of nucleic acid bases behave as good traps for the excess energy emittted by ionizing radiation (Sanković et al., 1991; Herak & Hüttermann, 1991; Herak et al., 1999, 2000).

In the study of the trapping properties of thio-nucleobases, it was observed that 5-methyl-2-thiouracil, (I), behaves differently from the other thio-nucleobases and all naturally occurring bases. In irradiated nucleic acids and their constituents, as well as in the crystals of thiocytosine and thioguanine, only radicals of the π-type were observed. In contrast, in irradiated crystals of (I), the electron-loss radicals are of the σ-type (Bešić et al., 2001). In order to learn more about the radicals formed and the relation of the observed electron paramagnetic resonance parameters to the radical molecular skeleton, the molecular structure is required (Matković-Čalogović & Sanković, 1999). Therefore, the detailed analysis of the crystal structure of (I) is reported here. \sch

The crystal structures of thymine (Ozeki et al., 1969) and thymine monohydrate (Gerdil, 1961) have been known for years, yet no structural data have been available for 2-thiothymine, (I), until now. The structural differences between (I) (Fig. 1) and thymine were derived by comparison with the recently redetermined structure of thymine (Portalone et al., 1999), and the same numbering scheme is used here.

The replacement of O by the S atom on C2 results in a significant bond-length change only at the substitution site [S—C2 1.674 (1) Å, instead of O—C2 1.244 (4) Å], and only in a small change of the ring structure, namely an increase of the C4—C5—C6 angle by 1.5°. The other angle alterations are of only marginal significance, being a decrease of C4—C5—C6 and an increase of C2—N1—C6 by 0.9°. Therefore, the thioketo derivative, (I), has a similar electron distribution to thymine.

However, the impact of the 2-thio substitution on the hydrogen-bond network is great, resulting in a different packing of the molecules in the unit cell (Fig. 2). A strong N1—H···O═C4 hydrogen bond of 2.755 (2) Å is formed in (I), yet the same O atom in thymine only forms a contact with atom C6 of the neighbouring molecule at 3.387 (4) Å. In thymine, both N—H groups form hydrogen bonds with O═C2 of two adjacent molecules [2.827 (3) and 2.833 (3) Å], forming endless ribbons of planar molecules, whereas in (I), the less electronegative S atom is involved only in a weaker N3—H3···S═C2 bond of 3.352 Å. Therefore, in (I), all the donor and acceptor atoms are involved in the hydrogen-bond network, which connects molecules in planes parallel to (102).

As in thymine, the methyl group in (I) has a conformation such that one of its H atoms is eclipsed with the ring C═C bond.

S2. Experimental

Single crystals of (I) were grown from an aqeuous saturated solution of 2-thiothymine (Aldrich) by slow evaporation in a thermostate (Memmert) at 310 K. The beaker containing the solution was covered with aluminium foil to reduce evaporation. Crystals of good quality were obtained after two weeks. The crystals were stable for months when exposed to the atmosphere.

S3. Refinement

H atoms were found in the difference Fourier map and were refined isotropically.

Computing details

Data collection: STADI4 (Stoe & Cie, 1995); cell refinement: X-RED (Stoe & Cie, 1995); data reduction: X-RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON98 (Spek, 1990); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. A view of (I) with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The packing of the molecules in the unit cell of (I). Hydrogen bonds are indicated by dashed lines.

2,3-dihydro-5-methyl-2-thioxopyrimidin-4(1H)-one

Crystal data

C5H6N2OS	F(000) = 296
Mr = 142.19	Dx = 1.490 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 46 reflections
a = 4.2626 (6) Å	θ = 10.6–18.2°
b = 14.512 (2) Å	µ = 0.42 mm^−1
c = 10.255 (2) Å	T = 295 K
β = 92.272 (11)°	Block, colourless
V = 633.86 (18) Å^3	0.57 × 0.18 × 0.17 mm
Z = 4

Data collection

Philips PW1100 updated by Stoe diffractometer	1339 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.048
Planar Graphite monochromator	θmax = 30.0°, θmin = 3.4°
ω scans	h = −5→5
Absorption correction: ψ scan (X-RED; Stoe & Cie, 1995)	k = 0→20
Tmin = 0.801, Tmax = 0.931	l = 0→13
1888 measured reflections	4 standard reflections every 90 min
1801 independent reflections	intensity decay: 4.0%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.106	All H-atom parameters refined
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0724P)^2] where P = (Fo^2 + 2Fc^2)/3
1801 reflections	(Δ/σ)max < 0.001
106 parameters	Δρmax = 0.27 e Å^−3
0 restraints	Δρmin = −0.31 e Å^−3

Special details

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. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Intensities were corrected for Lorentz, polarization and absorption effects (Stoe & Cie, 1995b). The structure was solved by direct methods.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S	0.27062 (9)	0.53296 (2)	0.67893 (3)	0.04442 (15)
N1	0.1812 (3)	0.71397 (8)	0.69128 (11)	0.0379 (3)
C2	0.1121 (3)	0.63339 (8)	0.63051 (12)	0.0331 (3)
N3	−0.0951 (3)	0.64062 (7)	0.52696 (10)	0.0346 (2)
C4	−0.2337 (3)	0.72100 (8)	0.47925 (12)	0.0330 (2)
O	−0.4214 (3)	0.71650 (7)	0.38559 (11)	0.0463 (3)
C5	−0.1428 (3)	0.80496 (8)	0.54716 (12)	0.0344 (3)
C6	0.0589 (3)	0.79718 (9)	0.65122 (13)	0.0373 (3)
C7	−0.2751 (4)	0.89488 (10)	0.49864 (16)	0.0457 (3)
H1	0.332 (5)	0.7119 (16)	0.764 (2)	0.074 (7)*
H3	−0.156 (5)	0.5895 (16)	0.478 (2)	0.070 (6)*
H6	0.127 (5)	0.8459 (15)	0.705 (2)	0.057 (5)*
H71	−0.220 (5)	0.9086 (13)	0.413 (2)	0.057 (5)*
H72	−0.226 (6)	0.9477 (19)	0.557 (2)	0.087 (8)*
H73	−0.491 (6)	0.8915 (13)	0.493 (2)	0.059 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S	0.0551 (2)	0.0332 (2)	0.0436 (2)	0.00484 (13)	−0.01521 (15)	0.00209 (12)
N1	0.0444 (6)	0.0335 (5)	0.0349 (5)	−0.0021 (4)	−0.0104 (4)	−0.0031 (4)
C2	0.0366 (6)	0.0305 (5)	0.0317 (5)	−0.0022 (4)	−0.0042 (4)	0.0013 (4)
N3	0.0422 (5)	0.0250 (4)	0.0356 (5)	−0.0024 (4)	−0.0108 (4)	−0.0002 (4)
C4	0.0384 (6)	0.0267 (5)	0.0336 (5)	−0.0019 (4)	−0.0035 (4)	0.0029 (4)
O	0.0573 (6)	0.0344 (5)	0.0453 (5)	0.0007 (4)	−0.0212 (5)	0.0017 (4)
C5	0.0398 (6)	0.0271 (5)	0.0364 (6)	−0.0016 (4)	0.0000 (5)	0.0011 (4)
C6	0.0449 (7)	0.0293 (5)	0.0375 (6)	−0.0035 (5)	−0.0026 (5)	−0.0044 (5)
C7	0.0600 (9)	0.0263 (6)	0.0504 (8)	0.0016 (6)	−0.0041 (7)	0.0020 (5)

Geometric parameters (Å, º)

S—C2	1.6735 (13)	C4—C5	1.4486 (16)
N1—C2	1.3521 (16)	C5—C6	1.3483 (19)
N1—C6	1.3717 (16)	C5—C7	1.4987 (18)
N1—H1	0.97 (2)	C6—H6	0.93 (2)
C2—N3	1.3579 (16)	C7—H71	0.94 (2)
N3—C4	1.3879 (15)	C7—H72	0.99 (3)
N3—H3	0.93 (2)	C7—H73	0.92 (2)
C4—O	1.2269 (15)
C2—N1—C6	123.37 (10)	C6—C5—C4	117.40 (11)
C2—N1—H1	117.1 (14)	C6—C5—C7	123.74 (12)
C6—N1—H1	119.4 (14)	C4—C5—C7	118.86 (12)
N1—C2—N3	114.63 (10)	C5—C6—N1	122.25 (11)
N1—C2—S	122.57 (9)	C5—C6—H6	125.0 (13)
N3—C2—S	122.80 (9)	N1—C6—H6	112.7 (13)
C2—N3—C4	126.53 (10)	C5—C7—H71	113.0 (11)
C2—N3—H3	121.3 (14)	C5—C7—H72	113.8 (15)
C4—N3—H3	112.1 (14)	H71—C7—H72	110.3 (18)
O—C4—N3	119.11 (11)	C5—C7—H73	109.6 (13)
O—C4—C5	125.09 (11)	H71—C7—H73	104.1 (19)
N3—C4—C5	115.80 (11)	H72—C7—H73	105 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O^i	0.97 (2)	1.91 (2)	2.7551 (17)	145 (2)
N3—H3···S^ii	0.93 (3)	2.43 (3)	3.3523 (13)	170.7 (17)

Symmetry codes: (i) x+1, −y+3/2, z+1/2; (ii) −x, −y+1, −z+1.