7,9-Bis(hy­droxy­meth­yl)-7H-purine-2,6,8(1H,3H,9H)trione

M Daudon; D Bazin; K Adil; A Le Bail

doi:10.1107/S1600536811018186

. 2011 May 20;67(Pt 6):o1458. doi: 10.1107/S1600536811018186

7,9-Bis(hydroxymethyl)-7H-purine-2,6,8(1H,3H,9H)trione

M Daudon ^a, D Bazin ^b, K Adil ^c, A Le Bail ^c,^*

PMCID: PMC3120625 PMID: 21754831

Abstract

The structure of the title uric acid derivative, C₇H₈N₄O₅, from human kidney stones, is characterized by the C and O atoms of one of the two hydroxymethyl groups being disordered nearly equally over three different sites. In the crystal, molecules are connected by a three-dimensional hydrogen-bonding scheme though they look stacked in planes nearly parallel to ( Inline graphic 04).

Related literature

For related structures, see: Ringertz (1966 ▶) for uric acid and Parkin & Hope (1998 ▶) for the dihydrate. For urolithiasis, see: Tanagho & McAninch (2000 ▶); Jungers et al. (2005 ▶); Moe (2006 ▶); Knoll (2007 ▶). For recent characterization of new urinary stones, see: Le Bail et al. (2009 ▶); For purine biosynthesis, see: Ashihara et al. (2008 ▶). For hydroxymethylation of uric acid, see: Lubczak et al. (2002 ▶).

Experimental

Crystal data

C₇H₈N₄O₅
M _r = 228.17
Monoclinic,
a = 5.3226 (6) Å
b = 11.5541 (13) Å
c = 14.5931 (18) Å
β = 97.340 (7)°
V = 890.09 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 150 K
0.22 × 0.12 × 0.06 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.677, T _max = 0.746
33302 measured reflections
3075 independent reflections
2127 reflections with I > 2σ(I)
R _int = 0.064

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.166
S = 1.03
3075 reflections
169 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.78 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶) and McMaille (Le Bail, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶) and ESPOIR (Le Bail, 2001 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2001 ▶) and ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811018186/zl2370sup1.cif

e-67-o1458-sup1.cif^{(15.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811018186/zl2370Isup2.hkl

e-67-o1458-Isup2.hkl^{(150.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811018186/zl2370Isup3.mol

Supplementary material file. DOI: 10.1107/S1600536811018186/zl2370Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O9—H9⋯O2ⁱ	1.04	1.70	2.7270 (18)	169
N1—H1⋯O6ⁱⁱ	0.86	1.98	2.8388 (18)	179
N3—H3⋯O8ⁱⁱⁱ	0.84	1.88	2.7104 (19)	167
O71—H71⋯O2^iv	0.84	2.04	2.873 (4)	172
O72—H72⋯O9ⁱ	0.84	2.01	2.834 (5)	169
O73—H73⋯O8^v	0.84	2.17	2.892 (6)	144

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The authors thank the reviewer for strong improvements of the description of the disordered part of the structure.

supplementary crystallographic information

Comment

Urolithiasis, which is as old as mankind is now the third most common urinary disease (Jungers et al., 2005; Moe, 2006; Knoll, 2007). This disease constitutes a major health problem and there is evidence to show that its incidence has increased continually in past decades (Tanagho & McAninch, 2000). Among the different chemical phases found in kidney stones, let's quote calcium oxalate, calcium phosphate, uric acid, ammonium hydrogen urate and magnesium ammonium phosphate which are the main components of stones, with differences in their distribution being found in different population groups.

Recently, at the surface of uric acid kidney stones, a green deposit has been observed for different patients. Since classical FTIR measurements were not able to characterize such deposit, X-ray diffraction experiments have been performed.

Powder diffraction revealed a mixture of uric acid (Ringertz, 1966) together with traces of its dihydrate (Parkin & Hope, 1998) and an unknown phase which could be indexed by using the McMaille software (Le Bail, 2004). An hypothesis for an uric acid derivative was suggested by the direct space software ESPOIR (Le Bail, 2001), however the structure could not be completed till a tiny single-crystal was selected in the powder. From the structure solution, a hydroxymethyl group was found attached to N9. High thermal parameters at room temperature obscured the nature of some disorder occurring around of the C7 atom: three peaks on the Fourier difference map, all looking lighter than a C atom, but heavier than a H one, two of them at 0.9 Å from each other were observed. At 150 K, the thermal motions were considerably smaller, allowing to propose an interpretation: a second hydroxymethyl group, CH₂OH attached to N7, nearly equally disordered over three different O atom sites. The largest difference densities (0.78, 0.54) in the final structural model are close to C9 of the not disordered hydroxymethyl group (exactly between H9A and H9B) and O8. If O8 may be slightly splitted, given its large U₃₃, the most intense residue close to C9 is unclear, possibly due to some disorder also for this hydroxymethyl group. Positional disorder was observed in uric acid dihydrate with superimposition of the six- and five-membered rings (Parkin and Hope, 1998). Such a disorder is unlikely to occur in the title compound. Different parts of the samples examined by powder diffraction may show variations in cell parameters as well as strong peak asymetries suggesting inhomogeneities, possibly corresponding to more or less disorder.

The ORTEP diagram of the title compound is shown in Fig. 1. Atoms numbering adopts the purine system. Molecules are connected by a three-dimensional hydrogen bonding scheme (Fig. 2 and Table 2), though they are stacked in planes nearly parallel to (104) (Fig. 3), corresponding by far to the most intense reflection.

In humans, uric acid is the main urinary metabolite of purines, therefore, its alteration is a mark of disorders associated with purine metabolism. A review on the biosynthesis of caffeine and related purine alkaloids was published recently (Ashihara et al., 2008). But how the title compound is biosynthesized in humans is not yet fully understood. Hydroxymethylation of uric acid is known to occur with formaldehyde (Lubczak et al., 2002).

Experimental

Samples are coming from human kidney stones, always identified as a green part at the surface of uric acid calculi. Either they could originate from a natural cause or from the consequence of a chemical treatment of the patients (about ten cases). Since the patients took various medications for different unsimilar pathologies or had no treatment at all, the cause looks more probably natural.