Crystal structure of tetra-aquabis(1,3-dimethyl-2,6-dioxo-3,7-di-hydro-1H-purin-9-ido)magnesium.

The title complex, [Mg(C7H7N4O2)2(H2O)4], lies across an inversion centre and the Mg(II) atom is coordinated in a slightly distorted octa-hedral environment by four aqua ligands in the equatorial sites and two 1,3-dimethyl-2,6-dioxo-3,7-di-hydro-1H-purin-9-ide ligands, through imidazole ring N atoms, in the axial sites. An intra-molecular O-H⋯O hydrogen bond forms an S(7) graph-set motif. In the crystal, O-H⋯O and O-H⋯N hydrogen bonds link complex mol-ecules forming a three-dimensional network incorporating R 4 (2)(8) and R 2 (2)(18) graph-set motifs.

Chemical context

Co-crystallization represents a crystal engineering approach for modifying properties of active pharmaceutical ingredients (APIs) (Sun, 2013 ▸). Metal coordination is an alternative strategy without changing chemical structures of APIs (Ma & Moulton, 2007 ▸). Theophylline is a methylxanthine drug in the treatment of asthma and chronic obstructive pulmonary disease (Barnes, 2003 ▸). In this study, we reacted theophylline with the MgII ion in a basic solution to give rise to a tetra­aqua mononuclear MgII complex, (I).

Structural commentary

The mol­ecular structure of (I) is shown in Fig. 1 ▸. The complex lies across an inversion centre and the MgII atom is coordin­ated in a slightly distorted octa­hedral environment (Table 1 ▸) by four aqua ligands in the equatorial sites and two 1,3-dimethyl-2,6-dioxo-3,7-di­hydro-1H-purin-9-ide ligands, through imidazole ring N atoms [N1 and N1(−x + 1, −y, −z + 1)], in the axial sites. The symmetry-unique purine ring system is essentially planar, with a maximum deviation of 0.030 (2) Å for N3 and the bonded methyl C atoms C4 and C5 deviate from this mean plane by −0.118 (3) and 0.136 (2) Å, respectively.

Figure 1

The mol­ecular structure of the title complex, shown with 30% probability displacement ellipsoids [symmetry code: (A) x, −y, −z + 1).

Table 1

Selected geometric parameters (, )

Mg1O3i	2.0672(17)	Mg1N1i	2.2255(19)
Mg1O4i	2.081(2)
O3iMg1O3	180.00(3)	O4Mg1N1i	91.31(6)
O3Mg1O4i	87.98(7)	O3Mg1N1	90.06(6)
O3Mg1O4	92.02(7)	O4Mg1N1	88.69(6)
O4iMg1O4	180.0	N1iMg1N1	180.0
O3Mg1N1i	89.94(6)

Symmetry code: (i) .

Supra­molecular features

In the crystal, the coordinating water mol­ecules are involved in various hydrogen-bonding inter­actions (Table 2 ▸). A (8) graph-set motif (Bernstein et al., 1995 ▸) is formed through [O4⋯O1iii = 2.829 (3) Å and O4⋯O1iv = 2.780 (2) Å; symmetry codes: (iii) −x, −y, −z; (iv) x, y, z + 1] between a coordinating water mol­ecule and a carbonyl group of a symmetry-related theophylline group. The mononuclear units are connected into a layer parallel to (010) (Fig. 2 ▸), which is further connected into a three-dimensional structure (Fig. 3 ▸) by hydrogen-bonding inter­actions between coordin­ating water mol­ecules and symmetry-related imidazole groups [O3⋯N2ii = 2.809 (3) Å; symmetry code: (ii) x, −y + , z + ].

Table 2

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
O3H3AN2ii	0.88(1)	1.97(1)	2.809(3)	160(3)
O3H3BO2i	0.87(1)	1.80(1)	2.668(2)	173(3)
O4H4EO1iii	0.87(1)	1.93(1)	2.780(2)	168(3)
O4H4DO1iv	0.87(1)	1.96(1)	2.829(3)	178(3)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Figure 2

Part of the crystal structure, showing hydrogen bonds in two dimensions (dashed lines).

Figure 3

Part of the crystal structure, showing the overall three-dimensional hydrogen-bonded structure (dashed lines).

Database survey

A search of the Cambridge Structural Database (Version 5.36, November 2014; Groom & Allen, 2014 ▸) revealed 16 metal complexes of theophylline, including ternary, polynuclear complexes and coordination polymers but only five are mononuclear complexes. The most closely related compound to the title complex, in terms of the ligand types is tri­aqua­bis­(theophylline)copper(II) dihydrate (WEZYIJ; Begum & Manohar, 1994 ▸). The title compound is the first crystal structure reported to date of a complex of theophylline with an alkaline-earth metal.

Synthesis and crystallization

Theophylline (180 mg, 1 mmol) was dissolved in water (20 ml). An aqueous solution (15 ml) of NaOH (40 mg, 1 mmol) was added slowly. MgCl2·6H2O (102 mg, 0.5 mmol) in water (15 ml) was then added. The resulting solution was kept in air and, after several days, colourless block-shaped crystals were obtained.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3 ▸. H atoms bonded to C atoms were positioned geometrically (C—H = 0.95–0.98 Å) with U iso(H) = 1.2U eq(C) or 1.5U eq(C). H atoms bonded to O atoms were located in difference Fourier maps and were refined with a distance restraint of O—H = 0.87 (1) Å. The isotropic displacement parameters were refined freely.

Table 3

Experimental details

Crystal data
Chemical formula	[Mg(C7H7N4O2)2(H2O)4]
M r	454.71
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	295
a, b, c ()	7.694(4), 13.399(7), 9.739(5)
()	105.169(9)
V (3)	969.0(9)
Z	2
Radiation type	Mo K
(mm1)	0.16
Crystal size (mm)	0.2 0.2 0.2
Data collection
Diffractometer	Rigaku CCD
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2000 ▸)
T min, T max	0.949, 1.000
No. of measured, independent and observed [I > 2(I)] reflections	7442, 2153, 1738
R int	0.032
(sin /)max (1)	0.650
Refinement
R[F 2 > 2(F 2)], wR(F 2), S	0.049, 0.123, 1.09
No. of reflections	2153
No. of parameters	160
No. of restraints	4
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
max, min (e 3)	0.29, 0.25

Computer programs: CrystalClear (Rigaku, 2000 ▸), SHELXS97 and SHELXL97 (Sheldrick, 2008 ▸) and X-SEED (Barbour, 2001 ▸).

Crystal structure: contains datablock(s) I, LOU. DOI: 10.1107/S2056989015003758/lh5752sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015003758/lh5752Isup2.hkl

CCDC reference: 1050901

Additional supporting information: crystallographic information; 3D view; checkCIF report

[Mg(C7H7N4O2)2(H2O)4]	F(000) = 476
Mr = 454.71	Dx = 1.558 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2170 reflections
a = 7.694 (4) Å	θ = 2.7–27.5°
b = 13.399 (7) Å	µ = 0.16 mm−1
c = 9.739 (5) Å	T = 295 K
β = 105.169 (9)°	Prism, colorless
V = 969.0 (9) Å3	0.2 × 0.2 × 0.2 mm
Z = 2

Rigaku CCD diffractometer	2153 independent reflections
Radiation source: fine-focus sealed tube	1738 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
Detector resolution: 14.6306 pixels mm-1	θmax = 27.5°, θmin = 2.7°
CCD_Profile_fitting scans	h = −8→9
Absorption correction: multi-scan (CrystalClear; Rigaku, 2000)	k = −17→17
Tmin = 0.949, Tmax = 1.000	l = −11→12
7442 measured reflections

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.123	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ2(Fo2) + (0.0542P)2 + 0.4099P] where P = (Fo2 + 2Fc2)/3
2153 reflections	(Δ/σ)max < 0.001
160 parameters	Δρmax = 0.29 e Å−3
4 restraints	Δρmin = −0.25 e Å−3

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.

	x	y	z	Uiso*/Ueq
Mg1	0.5000	0.0000	0.5000	0.0220 (2)
O1	0.0856 (2)	−0.02565 (12)	−0.27579 (14)	0.0366 (4)
O2	0.2118 (2)	−0.14692 (11)	0.17770 (15)	0.0396 (4)
O3	0.5654 (2)	0.14587 (11)	0.56135 (16)	0.0361 (4)
O4	0.2306 (2)	0.02272 (14)	0.49391 (16)	0.0419 (4)
N1	0.4375 (2)	0.04557 (11)	0.27257 (16)	0.0253 (4)
N2	0.4425 (2)	0.16133 (12)	0.09955 (17)	0.0295 (4)
N3	0.2518 (2)	0.07368 (12)	−0.10112 (17)	0.0277 (4)
N4	0.1533 (2)	−0.08355 (12)	−0.04781 (17)	0.0260 (4)
C1	0.4967 (3)	0.13335 (14)	0.2386 (2)	0.0285 (4)
H1	0.5733	0.1745	0.3083	0.034*
C2	0.3344 (2)	0.01127 (14)	0.14086 (19)	0.0231 (4)
C3	0.3417 (3)	0.08329 (14)	0.0411 (2)	0.0241 (4)
C4	0.2540 (4)	0.15494 (17)	−0.2003 (2)	0.0426 (6)
H4A	0.3623	0.1497	−0.2350	0.064*
H4B	0.2543	0.2190	−0.1517	0.064*
H4C	0.1468	0.1507	−0.2809	0.064*
C5	0.0602 (3)	−0.17694 (16)	−0.1029 (2)	0.0379 (5)
H5A	−0.0695	−0.1645	−0.1367	0.057*
H5B	0.0827	−0.2270	−0.0269	0.057*
H5C	0.1054	−0.2016	−0.1819	0.057*
C6	0.1602 (2)	−0.01192 (15)	−0.1483 (2)	0.0263 (4)
C7	0.2344 (3)	−0.07757 (14)	0.1001 (2)	0.0256 (4)
H3A	0.505 (3)	0.2015 (13)	0.557 (3)	0.058 (8)*
H3B	0.644 (3)	0.149 (2)	0.6439 (17)	0.059 (9)*
H4D	0.188 (4)	0.007 (2)	0.566 (2)	0.072 (10)*
H4E	0.142 (3)	0.023 (2)	0.4175 (19)	0.055 (8)*

	U11	U22	U33	U12	U13	U23
Mg1	0.0247 (5)	0.0223 (4)	0.0169 (5)	0.0003 (3)	0.0018 (3)	0.0002 (3)
O1	0.0312 (8)	0.0563 (10)	0.0181 (7)	−0.0009 (7)	−0.0013 (6)	−0.0023 (6)
O2	0.0501 (9)	0.0329 (8)	0.0287 (8)	−0.0141 (7)	−0.0021 (7)	0.0066 (6)
O3	0.0495 (10)	0.0243 (7)	0.0278 (8)	0.0015 (7)	−0.0020 (7)	−0.0018 (6)
O4	0.0278 (8)	0.0722 (12)	0.0239 (9)	0.0027 (8)	0.0034 (7)	0.0008 (8)
N1	0.0292 (9)	0.0234 (8)	0.0207 (8)	−0.0013 (6)	0.0022 (7)	−0.0005 (6)
N2	0.0375 (9)	0.0255 (8)	0.0238 (9)	−0.0042 (7)	0.0052 (7)	0.0021 (6)
N3	0.0311 (9)	0.0309 (9)	0.0189 (8)	0.0003 (7)	0.0026 (7)	0.0055 (6)
N4	0.0252 (8)	0.0274 (8)	0.0225 (8)	−0.0018 (6)	0.0010 (7)	−0.0027 (6)
C1	0.0323 (10)	0.0253 (10)	0.0257 (10)	−0.0041 (8)	0.0037 (8)	−0.0012 (8)
C2	0.0242 (9)	0.0244 (9)	0.0193 (9)	0.0017 (7)	0.0035 (7)	0.0005 (7)
C3	0.0248 (9)	0.0253 (9)	0.0211 (9)	0.0040 (7)	0.0042 (7)	0.0007 (7)
C4	0.0566 (15)	0.0412 (13)	0.0274 (12)	0.0027 (11)	0.0064 (10)	0.0114 (9)
C5	0.0399 (12)	0.0357 (11)	0.0332 (12)	−0.0078 (9)	0.0011 (10)	−0.0100 (9)
C6	0.0202 (9)	0.0367 (11)	0.0205 (10)	0.0047 (8)	0.0029 (7)	−0.0006 (8)
C7	0.0257 (10)	0.0274 (9)	0.0223 (10)	0.0003 (7)	0.0039 (8)	0.0000 (7)

Mg1—O3i	2.0672 (17)	N3—C6	1.361 (3)
Mg1—O3	2.0672 (17)	N3—C3	1.383 (2)
Mg1—O4i	2.081 (2)	N3—C4	1.459 (3)
Mg1—O4	2.081 (2)	N4—C6	1.382 (3)
Mg1—N1i	2.2255 (19)	N4—C7	1.414 (3)
Mg1—N1	2.2255 (19)	N4—C5	1.472 (3)
O1—C6	1.238 (2)	C1—H1	0.9500
O2—C7	1.238 (2)	C2—C3	1.381 (3)
O3—H3A	0.875 (10)	C2—C7	1.416 (3)
O3—H3B	0.872 (10)	C4—H4A	0.9800
O4—H4D	0.873 (10)	C4—H4B	0.9800
O4—H4E	0.867 (10)	C4—H4C	0.9800
N1—C1	1.334 (3)	C5—H5A	0.9800
N1—C2	1.398 (2)	C5—H5B	0.9800
N2—C3	1.337 (2)	C5—H5C	0.9800
N2—C1	1.361 (3)
O3i—Mg1—O3	180.00 (3)	C6—N4—C5	115.94 (16)
O3i—Mg1—O4i	92.02 (7)	C7—N4—C5	117.55 (16)
O3—Mg1—O4i	87.98 (7)	N1—C1—N2	116.97 (17)
O3i—Mg1—O4	87.98 (7)	N1—C1—H1	121.5
O3—Mg1—O4	92.02 (7)	N2—C1—H1	121.5
O4i—Mg1—O4	180.0	C3—C2—N1	107.34 (17)
O3i—Mg1—N1i	90.06 (6)	C3—C2—C7	120.60 (17)
O3—Mg1—N1i	89.94 (6)	N1—C2—C7	132.06 (17)
O4i—Mg1—N1i	88.69 (6)	N2—C3—C2	111.89 (17)
O4—Mg1—N1i	91.31 (6)	N2—C3—N3	125.57 (17)
O3i—Mg1—N1	89.94 (6)	C2—C3—N3	122.53 (17)
O3—Mg1—N1	90.06 (6)	N3—C4—H4A	109.5
O4i—Mg1—N1	91.31 (6)	N3—C4—H4B	109.5
O4—Mg1—N1	88.69 (6)	H4A—C4—H4B	109.5
N1i—Mg1—N1	180.0	N3—C4—H4C	109.5
Mg1—O3—H3A	135.0 (19)	H4A—C4—H4C	109.5
Mg1—O3—H3B	111.8 (19)	H4B—C4—H4C	109.5
H3A—O3—H3B	103 (3)	N4—C5—H5A	109.5
Mg1—O4—H4D	122 (2)	N4—C5—H5B	109.5
Mg1—O4—H4E	125.3 (19)	H5A—C5—H5B	109.5
H4D—O4—H4E	108 (3)	N4—C5—H5C	109.5
C1—N1—C2	102.20 (16)	H5A—C5—H5C	109.5
C1—N1—Mg1	119.32 (12)	H5B—C5—H5C	109.5
C2—N1—Mg1	138.26 (13)	O1—C6—N3	121.81 (19)
C3—N2—C1	101.59 (16)	O1—C6—N4	120.91 (19)
C6—N3—C3	119.72 (16)	N3—C6—N4	117.28 (17)
C6—N3—C4	120.00 (17)	O2—C7—N4	118.96 (17)
C3—N3—C4	120.28 (17)	O2—C7—C2	127.74 (18)
C6—N4—C7	126.42 (16)	N4—C7—C2	113.31 (17)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3A···N2ii	0.88 (1)	1.97 (1)	2.809 (3)	160 (3)
O3—H3B···O2i	0.87 (1)	1.80 (1)	2.668 (2)	173 (3)
O4—H4E···O1iii	0.87 (1)	1.93 (1)	2.780 (2)	168 (3)
O4—H4D···O1iv	0.87 (1)	1.96 (1)	2.829 (3)	178 (3)