Crystal structure of 2,4-di­amino-7-(hydroxy­meth­yl)pteridin-1-ium nitrate

Palaniyappan Sivajeyanthi; Kasthuri Balasubramani; Muthaiah Jeevaraj; Kaliyaperumal Thanigaimani; Nuridayanti Che Khalib; Ibrahim Abdul Razak

doi:10.1107/S2056989015008397

. 2015 May 7;71(Pt 6):o376–o377. doi: 10.1107/S2056989015008397

Crystal structure of 2,4-diamino-7-(hydroxymethyl)pteridin-1-ium nitrate

Palaniyappan Sivajeyanthi ^a, Kasthuri Balasubramani ^a,^*, Muthaiah Jeevaraj ^a, Kaliyaperumal Thanigaimani ^b, Nuridayanti Che Khalib ^b, Ibrahim Abdul Razak ^b,^‡

PMCID: PMC4459323 PMID: 26090174

Abstract

In the crystal of the title molecular salt, C₇H₉N₆O⁺·NO₃ ⁻, the cations and anions are linked via N—H⋯O and O—H⋯O hydrogen bonds, forming sheets parallel to (100). Within the sheets there are numerous hydrogen-bonding ring motifs.

Keywords: crystal structure; pteridine; 2,4-diaminopteridinium; pteridin-1-ium nitrate; hydrogen bonding; ring motifs

Related literature

For background to and the biological activity of pteridine derivatives, see: Benkovic Annu (1980 ▸); Blakeley (1969 ▸); Van Beelen et al. (1984 ▸); Dolphin (1980 ▸); Pfleiderer (1982 ▸); Blakely & Cocco (1985 ▸); Pfleiderer & Taylor (1964 ▸); Müller et al. (1991 ▸); Weinstock et al. (1968 ▸). For related structures, see: Kuyper (1990 ▸); Schwalbe & Williams (1986 ▸); Robertson et al. (1998 ▸). For hydrogen-bond motifs, see: Etter (1990 ▸); Bernstein et al. (1995 ▸); Allen et al. (1998 ▸). graphic file with name e-71-0o376-scheme1.jpg

Experimental

Crystal data

C₇H₉N₆O⁺·NO₃ ⁻
M _r = 255.21
Orthorhombic,
a = 6.4060 (17) Å
b = 14.960 (6) Å
c = 10.867 (3) Å
V = 1041.4 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 294 K
0.27 × 0.10 × 0.07 mm

Data collection

Bruker SMART APEXII Duo CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▸) T _min = 0.964, T _max = 0.991
2866 measured reflections
862 independent reflections
720 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.074
S = 1.03
862 reflections
127 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.09 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▸); cell refinement: SAINT (Bruker, 2009 ▸); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: SHELXTL (Sheldrick, 2008 ▸); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015008397/su5127sup1.cif

e-71-0o376-sup1.cif^{(21.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015008397/su5127Isup2.hkl

e-71-0o376-Isup2.hkl^{(42.9KB, hkl)}

Click here for additional data file.^{(4.7KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015008397/su5127Isup3.cml

Click here for additional data file.^{(1.1MB, tif)}

. DOI: 10.1107/S2056989015008397/su5127fig1.tif

The molecular structure of the title salt, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The N-H⋯O hydrogen bonds are shown as dashed lines (see Table 1 for details).

Click here for additional data file.^{(1.4MB, tif)}

a . DOI: 10.1107/S2056989015008397/su5127fig2.tif

A view along the a axis of the crystal packing of the title molecular salt. The N-H⋯O hydrogen bonds are shown as dashed lines (see Table 1 for details).

CCDC reference: 1062258

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

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
N3H1N3O2	1.03(5)	1.82(5)	2.831(5)	167(4)
N6H2N6O4	0.98(3)	2.06(3)	3.019(6)	167(3)
O1H1O1O2ⁱ	0.95(6)	1.93(6)	2.846(4)	163(6)
N5H1N5O3ⁱⁱ	0.92(4)	2.09(4)	2.983(6)	164(4)
N5H2N5O1ⁱ	0.91(5)	2.15(5)	2.913(5)	141(4)
N6H1N6O3ⁱⁱⁱ	0.78(5)	2.35(4)	3.015(5)	145(5)
N6H1N6O4ⁱⁱⁱ	0.78(5)	2.44(5)	3.190(6)	162(5)

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

Acknowledgments

PS and KB thank the Department of Science and Technology (DST-SERB), grant No. SB/FT/CS–058/2013, New Delhi, India, for financial support. KT thanks the Academy of Sciences for the Developing World and USM for the TWAS–USM fellowship. The authors also thank the Malaysian Government and Universiti Sains Malaysia (USM) for the research facilities and a USM Short Term Grant, No. 304/PFIZIK/6312078, to conduct this work.

supplementary crystallographic information

S1. Structural commentary

Pteridine derivatives are found as the core structure of folic acid flavin adenine dinucleotide (FAD) and function as cofactors for enzymes involved in hydroxylation (Benkovic & Annu,1980) and methyl transfer (Blakeley, 1969; Van Beelen et al., 1984), as redox mediators (Dolphin, 1980) and as pigments for eyes and wings in certain insects (Pfleiderer, 1982). Variation of the substituents on the pteridine core of folates has provided synthetic anticancer drugs (Blakely & Cocco, 1985; Pfleiderer & Taylor, 1964). Pterdines are metabolites formed by a bicyclic pyrimidine-pyrazine moiety that occurs in a wide range of living systems and contributes in relevant biological functions (Muller et al., 1991). Pteridine derivatives have good diuretic activity and are also used as simple models for therapeutically valuable antifolate drugs (Weinstock et al., 1968). In order to study potential hydrogen bonding interactions, the title compound was synthesized and we report herein on its crystal structure.

The title molecular salt, Fig. 1, consists of a 2,4-diamino-7-(hydroxymethyl)pteridinum cation and a nitrate anion. During the synthesis of the molecular salt a proton was transferred from the hydroxyl group of nitric acid to atom N3 of the pteridine ring. The pteridine ring system (C1—C7/N1—N6/O1) is planar with a maximum deviation of 0.001 (1) Å for all the non H atoms. The bond lengths and angles are close to those found for similar compounds, viz. 2,4-diamino-6,7-dimethylpteridine hydrochloride monohydrate (Schwalbe & Williams, 1986) and triamterenium tetraphenylborate acetonitrile solvate (Robertson et al., 1998).

In the crystal, Fig. 2, the protonated N3 atom and the protonated 2-amino group (N6) are hydrogen-bonded to the nitrate O atoms (O2 and O4) via a pair of N3—H1N3···O2 and N6—H2N6···O4 hydrogen bonds, forming an R₂²(8) ring motif (Bernstein et al., 1995). This type of interaction is similar to the carboxylate-trimethoprim interaction observed in the trimethoprim cation-dihydrofolate reductase complex (Kuyper, 1990) and to the cyclic hydrogen bonded motif observed in many organic crystal structures (Allen et al., 1998). An R₁²(4) ring motif indicates a bifurcated hydrogen bond formed by N6–H1N6 to the two acceptors (O3 and O4). The 4-amino group and the hydroxyl group form hydrogen bonds with the O atoms of the nitrate ion leading to an R₃³(8) ring. The three center and bifurcated hydrogen bonds and fork like interaction form an R₄⁴(12) ring. Two R₃³(8) motifs and an R₂²(8) ring motif generate a new R₃²(18) ring motif. The above interactions lead to the formation a two dimensional network parallel to the bc plane (Table 1 and Fig. 2).

S2. Synthesis and crystallization

A few drops of nitric acid were added to a hot methanol solution (20 ml) of 2,4-diamino-6-(hydroxymethyl)pteridine (43 mg, Aldrich) which had been warmed over a heating magnetic stirrer hotplate for a few minutes. The resulting solution was allowed to cool slowly at room temperature and crystals of the title molecular salt appeared after a few days.

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The O– and N-bound H atoms were located in a difference Fourier map and freely refined (O–H = 0.94 (6) Å and N–H = 0.78 (5)– 1.03 (5) Å). The C-bound H atoms were positioned geometrically (C–H = 0.93–0.97 Å) and refined using a riding model with U_iso(H) = 1.2 U_eq(C).