1,3-Dimethyl­isoguanine

The structure of 1,3-dimethyl­isoguanine [or 6-amino-1,3-dimethyl-1H-purin-2(3H)-one], C₇H₉N₅O, has been redetermined and the correct assignment of H atoms on the heterocycle is now reported. Inter­molecular hydrogen-bonding inter­actions confirm that this form is the correct mol­ecular structure; this form is also in agreement with an earlier reported structure of the trihydrate form.

S1. Comment

Methylated purine bases are frequently isolated from marine sponges and ascidians, and their presence is often associated with pronounced biological activity. Rapid dereplication of these compounds in polar extracts of sponges is complicated by difficulties in their characterization. One such example is 1,3-dimethylisoguanine, (I), which has been described by three different groups, but with differences in the ¹³C NMR and MS data published in each report (Chehade et al., 1997; Mitchell et al., 1997; Jeong et al., 2003). In addition to the form shown as (I), other tautomers, (II) and (III), are also possible.

Consequently, compound (I) has been subjected to two X-ray crystallographic studies. The crystal structure of the trihydrate of (I) has been reported (Do Prado Gambardella et al., 1999) where the tautomeric form (I) was identified. Hydrogen-bonding (H—O—H···N) interactions between the water molecules and the ring N-atoms N7 and N9 were identified in addition to N—H···O H-bonds from the exocyclic –NH₂ group to the water O-atoms. In a more recent paper (Jeong et al., 2003) the crystal structure of the putative 1,3-dimethylisoguaninium cation (IV) was reported but without any counterion. Herein we have redetermined the structure of this compound and have found that it is actually (I) in an anhydrous form.

A view of (I) is shown in Fig. 1. We have adopted the same atom numbering scheme used in the reported structure of the trihydrate form of (I) (Do Prado Gambardella et al., 1999). The H-atom positions on all C atoms were first identified from difference maps and then subsequently constrained using a riding model during refinement. In contrast, the N-bound H atoms were located from difference maps, and their positional and displacement parameters were refined without constraints so as to avoid introducing any bias into our model. As shown in Fig. 1 both protons reside on N13 (the primary amino group) while the two N atoms in the five membered ring (N7 and N9) are not protonated. The bond lengths (Table 1) and angles in (I) do not differ significantly from those reported for the trihydrate form of (I) (Do Prado Gambardella et al., 1999).

This protonation scheme was confirmed by examination of intermolecular hydrogen bonding within the structure. A view of the unit cell is shown in Fig. 2. Both of the N-bound H atoms participate in hydrogen bonds; one with each of the five-membered-ring N atoms (atoms N7 and N9; Table 2). Thus atoms N7 and N9 cannot be protonated while accepting hydrogen bonds from an –NH₂ group.

Structure (IV) was proposed (Jeong et al., 2003) for an isomorphous compound (which is evidently the same as that reported here). The presence of an H atom on N7 demands an anion to balance the charge but none was reported (Jeong et al., 2003). The origin of this error became apparent to us during refinement. At convergence, there is a small peak (0.23 e Å⁻³) ca 1.07 Å from atom N7. However, this peak is not coplanar with the purine ring (H8—C8—N7-peak dihedral angle of 40.8°) as it should be for a typical NH group within a heterocyclic ring. Jeong et al. (2003) have evidently assigned this peak to an H atom, despite the fact that doing so introduces an unbalanced positive charge, a fact unfortunately overlooked. If atom N7 was indeed protonated then an H atom would have to be removed from atom N13 to give the neutral tautomer (III). In refinement, both H atoms appeared quite clearly on atom N13 and could be refined without constraints. The –NH₂ bond lengths, angles and displacment parameters are sensible and the group is close to coplanar with the purine ring. Deviations of the –NH₂ group from this plane may be attributed to slight twisting of the C6—N13 bond to accommodate intermolecular hydrogen bonding.

One way of enforcing the exocyclic C═NH tautomeric form shown in (III) is by alkylation of atom N7. The structure of (V) (Kozai et al., 2000) is an example of this. The exocyclic C═NH bond length in (V) is 1.275 Å while the adjacent C—C bond is 1.429 Å. These may be compared with the corresponding bonds C6—N13 [1.322 (4) Å and C5—C6 [1.384 (5) Å] in (I), which indicates that electron delocalization across the N13—C6—C5 group in (I) is significantly greater than that in seen in the alternative analogous tautomeric form (V).

Our NMR data for (I) differ from those provided by Chehade et al. (1997) but match very closely the spectroscopic data reported by Mitchell et al. (1997) and Jeong et al. (2003). However, Mitchell et al. (1997) did not provide a chemical shift for C8, possibly as a consequence of a deuterium exchange experiment conducted on the sample. Facile deuterium exchange has been reported at atom C8 of 7,9-dimethylguanium salts (Yagi et al., 1994). Despite the differences in spectroscopic data, the solid-state molecular structure of (I) is the same as that described for the trihydrate (Do Prado Gambardella et al., 1999). Hydrogen-bonding interactions in the present structure of (I), involving the –NH₂ group as donor, and atoms N7 and N9 as acceptors, are replaced by comparable hydrogen bonds with water molecules in the trihydrate form (Do Prado Gambardella et al., 1999).

S2. Experimental

Compound (I) was obtained from a butanol extract from the sponge Xestospongia exigua collected at Lizard Island on the Northern Great Barrier Reef. The compound was isolated by flash chromatography on silica using 5:1 CHCl₃–MeOH. ¹H NMR (d₄-MeOH + CDCl₃, p.p.m.): δ 3.54 (N1—Me), 3.59 (N3—Me) and 7.58 (H-8); ¹³C NMR (d₄-MeOH + CDCl₃, p.p.m.): δ 150.3 (C-2), 152.1 (C-4), 110.7 (C-5), 151.4 (C-6), 151.1 (C-8), 31.0 (N1—Me) and 31.4 (N3—Me). After NMR analysis, slow recrystallization of the sample from MeOH–CHCl₃ provided suitable crystals for X-ray crystallographic analysis (m.p. 593–595 K).

S3. Refinement

A decay correction was applied based on the intensities of three standard reflections measured every 2 h. The scaling factor range was 0.9123 to 1.1265.

Computing details

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS86 (Sheldrick, 1985); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Version 1.70; Farrugia, 1999).

Figures

	Fig. 1. An ORTEP-3 plot (Farrugia, 1997) of (I) (30% probability displacement ellipsoids).
	Fig. 2. A PLATON plot (Spek, 2003) of the hydrogen bonding (dashed lines) in (I). See Table 2 for symmetry codes and bond lengths for hydrogen bonds.

6-amino-1,3-dimethyl-1H-purin-2(3H)-one

Crystal data

C7H9N5O	F(000) = 376
Mr = 179.19	Dx = 1.496 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 8.9352 (9) Å	θ = 8.3–15.5°
b = 6.1050 (6) Å	µ = 0.11 mm^−1
c = 14.678 (2) Å	T = 293 K
β = 96.37 (1)°	Prism, colourless
V = 795.73 (16) Å^3	0.33 × 0.3 × 0.3 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.143
Radiation source: Enraf Nonius FR590	θmax = 25.0°, θmin = 2.3°
Graphite monochromator	h = 0→10
Non–profiled ω/2θ scans	k = 0→7
1473 measured reflections	l = −17→17
1380 independent reflections	3 standard reflections every 120 min
771 reflections with I > 2σ(I)	intensity decay: −3%

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)] = 0.054	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.166	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	w = 1/[σ^2(Fo^2) + (0.0895P)^2] where P = (Fo^2 + 2Fc^2)/3
1380 reflections	(Δ/σ)max < 0.001
128 parameters	Δρmax = 0.23 e Å^−3
0 restraints	Δρmin = −0.22 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. A decay correction was applied based on the intensities of three standard reflections measured every 2 h. The scaling factor range was 0.9123 to 1.1265.

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.

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

	x	y	z	Uiso*/Ueq
C2	0.1524 (4)	−0.0738 (6)	0.6013 (2)	0.0348 (9)
C4	0.2709 (4)	0.2391 (6)	0.6739 (2)	0.0309 (8)
C5	0.3393 (4)	0.2893 (6)	0.5963 (2)	0.0323 (9)
C6	0.3145 (4)	0.1618 (6)	0.5181 (2)	0.0316 (9)
C8	0.3947 (4)	0.5266 (6)	0.6985 (2)	0.0379 (9)
H8	0.4357	0.6506	0.7284	0.045*
C10	0.2011 (4)	−0.1688 (6)	0.4459 (2)	0.0443 (10)
H10A	0.1499	−0.0942	0.3939	0.066*
H10B	0.1415	−0.2909	0.4618	0.066*
H10C	0.2969	−0.2204	0.431	0.066*
C12	0.1197 (4)	−0.0092 (6)	0.7608 (2)	0.0438 (10)
H12A	0.0119	−0.0168	0.7497	0.066*
H12B	0.148	0.0959	0.8082	0.066*
H12C	0.159	−0.1504	0.7795	0.066*
N1	0.2239 (3)	−0.0183 (5)	0.52332 (17)	0.0330 (7)
N3	0.1807 (3)	0.0574 (5)	0.67685 (17)	0.0329 (7)
N7	0.4217 (3)	0.4795 (5)	0.61344 (18)	0.0380 (8)
N9	0.3047 (3)	0.3871 (5)	0.74031 (18)	0.0332 (7)
N13	0.3733 (4)	0.2020 (7)	0.4410 (2)	0.0411 (9)
O2	0.0693 (3)	−0.2322 (5)	0.60014 (17)	0.0480 (8)
H3A	0.345 (4)	0.141 (7)	0.390 (3)	0.055 (13)*
H3B	0.427 (4)	0.322 (7)	0.435 (2)	0.038 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C2	0.0344 (19)	0.038 (2)	0.0330 (19)	−0.0022 (18)	0.0084 (15)	0.0029 (17)
C4	0.0332 (19)	0.036 (2)	0.0250 (16)	0.0033 (17)	0.0090 (15)	0.0011 (16)
C5	0.0341 (19)	0.041 (2)	0.0237 (17)	−0.0006 (18)	0.0101 (15)	0.0012 (16)
C6	0.0328 (18)	0.038 (2)	0.0248 (17)	0.0029 (17)	0.0082 (14)	0.0041 (16)
C8	0.043 (2)	0.040 (2)	0.0315 (18)	−0.0030 (19)	0.0080 (16)	−0.0028 (18)
C10	0.060 (2)	0.046 (2)	0.0294 (18)	−0.008 (2)	0.0149 (17)	−0.0078 (18)
C12	0.060 (2)	0.045 (2)	0.0294 (18)	−0.006 (2)	0.0204 (17)	0.0064 (18)
N1	0.0401 (16)	0.0365 (18)	0.0236 (14)	−0.0052 (15)	0.0088 (12)	−0.0029 (13)
N3	0.0421 (16)	0.0359 (18)	0.0227 (14)	−0.0052 (14)	0.0126 (12)	0.0020 (13)
N7	0.0422 (17)	0.047 (2)	0.0264 (15)	−0.0070 (16)	0.0106 (12)	−0.0015 (14)
N9	0.0371 (15)	0.0388 (18)	0.0254 (15)	−0.0003 (14)	0.0109 (12)	0.0006 (13)
N13	0.053 (2)	0.050 (2)	0.0223 (16)	−0.0120 (18)	0.0137 (14)	−0.0036 (16)
O2	0.0587 (17)	0.0479 (17)	0.0407 (14)	−0.0146 (15)	0.0195 (13)	−0.0047 (13)

Geometric parameters (Å, º)

C2—O2	1.218 (4)	C8—H8	0.9300
C2—N3	1.368 (5)	C10—N1	1.458 (4)
C2—N1	1.413 (4)	C10—H10A	0.9600
C4—N9	1.339 (4)	C10—H10B	0.9600
C4—N3	1.375 (4)	C10—H10C	0.9600
C4—C5	1.386 (4)	C12—N3	1.459 (4)
C5—N7	1.383 (4)	C12—H12A	0.9600
C5—C6	1.384 (5)	C12—H12B	0.9600
C6—N13	1.322 (4)	C12—H12C	0.9600
C6—N1	1.372 (4)	N13—H3A	0.85 (5)
C8—N7	1.329 (4)	N13—H3B	0.88 (4)
C8—N9	1.363 (4)
O2—C2—N3	122.2 (3)	H10A—C10—H10C	109.5
O2—C2—N1	120.6 (3)	H10B—C10—H10C	109.5
N3—C2—N1	117.2 (3)	N3—C12—H12A	109.5
N9—C4—N3	127.5 (3)	N3—C12—H12B	109.5
N9—C4—C5	111.4 (3)	H12A—C12—H12B	109.5
N3—C4—C5	121.2 (3)	N3—C12—H12C	109.5
N7—C5—C6	131.0 (3)	H12A—C12—H12C	109.5
N7—C5—C4	108.1 (3)	H12B—C12—H12C	109.5
C6—C5—C4	120.8 (3)	C6—N1—C2	124.1 (3)
N13—C6—N1	119.3 (3)	C6—N1—C10	119.6 (3)
N13—C6—C5	124.2 (3)	C2—N1—C10	116.3 (3)
N1—C6—C5	116.5 (3)	C2—N3—C4	120.2 (3)
N7—C8—N9	117.7 (3)	C2—N3—C12	117.9 (3)
N7—C8—H8	121.1	C4—N3—C12	121.7 (3)
N9—C8—H8	121.1	C8—N7—C5	101.8 (3)
N1—C10—H10A	109.5	C4—N9—C8	101.0 (3)
N1—C10—H10B	109.5	C6—N13—H3A	124 (3)
H10A—C10—H10B	109.5	C6—N13—H3B	120 (2)
N1—C10—H10C	109.5	H3A—N13—H3B	113 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N13—H3A···N9^i	0.85 (5)	2.20 (5)	2.992 (4)	156 (4)
N13—H3B···N7^ii	0.88 (4)	2.01 (4)	2.846 (5)	158 (3)

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