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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoIUCrDATA
ISSN: 2414-3146
Volume 8| Part 1| January 2023| x221223
https://doi.org/10.1107/S2414314622012238

1H-Benzo[g]pteridine-2,4-dione

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Rao M. Uppua* and Frank R. Fronczekb

aDepartment of Environmental Toxicology, Southern University and A&M College, Baton Rouge, LA 70813, USA, and bDepartment of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
*Correspondence e-mail: rao_uppu@subr.edu

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 28 December 2022; accepted 29 December 2022; online 6 January 2023)

The structure of the title compound, C10H6N4O2, reported by Smalley et al. [(2021). Cryst. Growth Des. 22, 524–534] from powder diffraction data and 15N NMR spectroscopy, is confirmed using low-temperature data from a twinned crystal. The tautomer in the solid state is alloxazine (1H-benzo[g]pteridine-2,4-dione) rather than isoalloxazine (10H-benzo[g]pteridine-2,4-dione). In the extended structure, the mol­ecules form hydrogen-bonded chains propagating in the [0[\overline{1}]1] direction through alternating centrosymmetric R22(8) rings with pairwise N—H⋯O inter­actions and centrosymmetric R22(8) rings with pairwise N—H⋯N inter­actions. The crystal chosen for data collection was found to be a non-merohedral twin (180° rotation about [001]) in a 0.446 (4):0.554 (6) domain ratio.

CCDC reference: 2233313

Similar articles
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[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

1H-Benzo[g]pteridine-2,4-dione, popularly known as alloxazine, is a tautomer of isoalloxazine (10H-benzo[g]pteridine-2,4-dione), the same ring system that is present in riboflavin, flavin nucleotides (FMN and FAD), and flavoproteins. Unlike nicotinamide coenzymes, NAD(P)+ and NAD(P)H, flavin nucleotides serve in both one-electron and two-electron transfer reactions because the isoalloxazine ring can exist in several different ionization and/or redox states (Massey & Hemmerich, 1980[Massey, V. & Hemmerich, P. (1980). Biochem. Soc. Trans. 8, 246-257.]). Further, the strong but mostly non-covalent inter­actions within the flavoprotein binding site allow the fine-tuning of the redox chemistry of the isoalloxazine ring system (Ghisla et al., 1974[Ghisla, S., Massey, V., Lhoste, J. M. & Mayhew, S. G. (1974). Biochemistry, 13, 589-597.]; Hu et al., 2015[Hu, J., Chuenchor, W. & Rokita, S. E. (2015). J. Biol. Chem. 290, 590-600.]; van den Heuvel et al., 2002[Heuvel, R. H. van den, Fraaije, M. W. & van Berkel, W. J. (2002). Methods Enzymol. 353, 177-186.]) which, among many things, helps in minimizing the 1-electron reduction of mol­ecular oxygen to the superoxide anion radical. It is believed that the spatial arrangement of the reacting oxygen mol­ecule may have a direct bearing on the outcome of a flavoprotein serving as an oxidase or de­hydrogenase function (Chaiyen et al., 2012[Chaiyen, P., Fraaije, M. W. & Mattevi, A. (2012). Trends Biochem. Sci. 37, 373-380.]), a process that can be mimicked in simple chemical model systems of phenazine reacting with NAD(P)H in micelle forming surfactant solutions (Nishikimi et al., 1972[Nishikimi, N., Rao, N. A. & Yagi, K. (1972). Biochem. Biophys. Res. Commun. 46, 849-854.]; Rao, 1989a[Rao, U. M. (1989a). Free Radic. Biol. Med. 7, 513-519.],b[Rao, U. M. (1989b). Free Radic. Biol. Med. 7, 491-497.]; Uppu, 1995[Uppu, R. M. (1995). Langmuir, 11, 1038-1040.]). While there have been several efforts to define flavin–protein inter­actions that have mainly capitalized on differences in the chemical reactivity of the protein-bound flavin, we were surprised to note that, except for one recent study by Smalley et al. (2022[Smalley, C. J. H., Logsdail, A. J., Hughes, C. E., Iuga, D., Young, M. T. & Harris, K. D. M. (2022). Cryst. Growth Des. 22, 524-534.]), there are hardly any studies of the crystal structure of alloxazine itself.

In view of the above and since two-thirds of flavoprotein allelic variants are linked to human diseases (Lienhart et al. 2013[Lienhart, W. F., Gudipati, V. & Macheroux, P. (2013). Arch. Biochem. Biophys. 535, 150-162.]), we determined the crystal structure of alloxazine using a Bruker Kappa APEXII DUO diffractometer. Using low-temperature (90 K) data from twinned crystals, our results confirm the observations of Smalley et al. (2022[Smalley, C. J. H., Logsdail, A. J., Hughes, C. E., Iuga, D., Young, M. T. & Harris, K. D. M. (2022). Cryst. Growth Des. 22, 524-534.]), who used powder diffraction data along with 15N NMR spectroscopy. The tautomer in the solid state is alloxazine rather than isoalloxazine. The N-bound hydrogen atoms were located and their positions were refined in order to confirm the tautomer. The mol­ecule, shown in Fig. 1[link] is nearly planar, with an r.m.s deviation for 16 non-hydrogen atoms of 0.015 Å and a maximum deviation of 0.025 (3) Å for C5.

[Figure 1]
Figure 1
The title mol­ecule with 50% ellipsoids.

The inter­molecular hydrogen bonding (Table 1[link]) is shown in Fig. 2[link]. Atom N4 donates a hydrogen bond to N1, forming an R22(8) ring (Etter et al., 1990[Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256-262.]) about the inversion center at 0,1,½. Similarly, N3 donates a hydrogen bond to O2, forming a centrosymmetric R22(8) ring about 0,½,1. Thus, these two pairs of inter­actions combine to form a hydrogen-bonded chain propagating in the [0[\overline{1}]1] direction. The planes of the N,N dimers related by the N—H⋯O hydrogen bonds are offset by 0.915 (2) Å, as illus­trated in Fig. 3[link].

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N3—H3N⋯O2i 0.92 (3) 2.00 (4) 2.883 (3) 162 (3)
N4—H4N⋯N1ii 0.90 (3) 2.22 (3) 3.114 (3) 176 (3)
C3—H3⋯N2iii 0.95 2.58 3.520 (4) 173
C6—H6⋯O2ii 0.95 2.21 3.158 (4) 173
Symmetry codes: (i) [-x, -y+1, -z+2]; (ii) [-x, -y+2, -z+1]; (iii) [-x+2, -y+1, -z+1].
[Figure 2]
Figure 2
The hydrogen-bonded chain.
[Figure 3]
Figure 3
The unit cell, showing the offsets of hydrogen-bonded dimers.

Synthesis and crystallization

The title compound, C10H6N4O2 (alloxazine) was obtained from Sigma-Aldrich, St. Louis, Missouri, USA and was used without further purification. Single crystals in the form of pale yellow plates were prepared by slow cooling of a nearly saturated solution of alloxazine in dimethyl formamide at 135 ± 2°C

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The crystal chosen for data collection was refined as a two-component non-merohedral twin, by 180° rotation about the reciprocal [001] direction. Both twin components were integrated. Refinement was against an HKLF 5 file prepared using TWINABS. The refined BASF parameter is 0.446 (4). Seven outlier reflections were omitted from the refinement.

Table 2
Experimental details

Crystal data
Chemical formula C10H6N4O2
Mr 214.19
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 90
a, b, c (Å) 5.8027 (2), 7.5404 (3), 10.1345 (4)
α, β, γ (°) 70.483 (2), 84.150 (2), 84.208 (3)
V (Å3) 414.72 (3)
Z 2
Radiation type Cu Kα
μ (mm−1) 1.06
Crystal size (mm) 0.11 × 0.06 × 0.02
 
Data collection
Diffractometer Bruker Kappa APEXII DUO CCD
Absorption correction Multi-scan (TWINABS; Bruker, 2001[Bruker (2001). TWINABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.774, 0.979
No. of measured, independent and observed [I > 2σ(I)] reflections 6802, 6802, 4832
Rint ?
(sin θ/λ)max (Å−1) 0.607
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.048, 0.144, 1.07
No. of reflections 6802
No. of parameters 152
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.26, −0.28
Computer programs: APEX2 (Bruker, 2016[Bruker (2016). APEX2 and SAINT, Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT (Bruker, 2016[Bruker (2016). APEX2 and SAINT, Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2014/5 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2017/1 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data

CCDC reference: 2233313

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314622012238/hb4421sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314622012238/hb4421Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314622012238/hb4421Isup3.cml

checkCIF report


Computing details top

Data collection: APEX2 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017/1 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

1H-Benzo[g]pteridine-2,4-dione top
Crystal data top
C10H6N4O2Z = 2
Mr = 214.19F(000) = 220
Triclinic, P1Dx = 1.715 Mg m−3
a = 5.8027 (2) ÅCu Kα radiation, λ = 1.54184 Å
b = 7.5404 (3) ÅCell parameters from 4433 reflections
c = 10.1345 (4) Åθ = 4.6–69.1°
α = 70.483 (2)°µ = 1.06 mm−1
β = 84.150 (2)°T = 90 K
γ = 84.208 (3)°Plate, pale yellow
V = 414.72 (3) Å30.11 × 0.06 × 0.02 mm
Data collection top
Bruker Kappa APEXII DUO CCD
diffractometer		6802 independent reflections
Radiation source: IµS microfocus4832 reflections with I > 2σ(I)
QUAZAR multilayer optics monochromatorθmax = 69.4°, θmin = 4.6°
φ and ω scansh = −7→7
Absorption correction: multi-scan
(TWINABS; Bruker, 2001)		k = −9→9
Tmin = 0.774, Tmax = 0.979l = −12→12
6802 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.048H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.144 w = 1/[σ2(Fo2) + (0.0713P)2 + 0.0047P]
where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max < 0.001
6802 reflectionsΔρmax = 0.26 e Å−3
152 parametersΔρmin = −0.28 e Å−3
0 restraints
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refined as a 2-component twin, by 180 deg. rotation about reciprocal 0 0 1. Refinement was vs. an HKLF 5 file prepared using TWINABS. The refined BASF parameter is 0.446 (4). Seven outlier reflections were omitted from the refinement.

All H atoms were located in difference maps and those on C were thereafter treated as riding in geometrically idealized positions with C—H distances 0.95 Å. Coordinates of the N—H hydrogen atom were refined. Uiso(H) values were assigned as 1.2Ueq of the attached atom.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.6141 (4)0.4107 (3)0.8404 (2)0.0215 (6)
O2−0.0946 (3)0.7091 (3)0.8834 (2)0.0213 (6)
N10.2942 (4)0.8937 (4)0.4485 (2)0.0150 (6)
N20.6687 (4)0.6283 (4)0.5564 (2)0.0160 (6)
N30.2614 (4)0.5646 (4)0.8587 (3)0.0166 (6)
H3N0.231 (5)0.487 (5)0.949 (4)0.020*
N40.1014 (4)0.7992 (4)0.6692 (2)0.0160 (6)
H4N−0.018 (6)0.884 (5)0.638 (3)0.019*
C10.4878 (5)0.8700 (4)0.3647 (3)0.0154 (7)
C20.6759 (5)0.7382 (4)0.4193 (3)0.0154 (7)
C30.8747 (5)0.7183 (4)0.3300 (3)0.0165 (7)
H31.0011810.6311130.3663870.020*
C40.8827 (5)0.8255 (5)0.1911 (3)0.0181 (7)
H41.0142000.8117370.1303920.022*
C50.6963 (5)0.9562 (5)0.1379 (3)0.0179 (7)
H50.7049941.0301080.0413460.022*
C60.5034 (5)0.9801 (5)0.2209 (3)0.0171 (7)
H60.3805531.0699810.1824840.020*
C70.2926 (5)0.7827 (4)0.5806 (3)0.0135 (6)
C80.4803 (5)0.6503 (4)0.6354 (3)0.0147 (7)
C90.4648 (5)0.5301 (5)0.7850 (3)0.0163 (7)
C100.0784 (5)0.6913 (5)0.8079 (3)0.0164 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0173 (11)0.0228 (13)0.0192 (11)0.0062 (9)−0.0022 (9)−0.0018 (9)
O20.0187 (11)0.0237 (13)0.0164 (10)0.0027 (9)0.0043 (9)−0.0024 (9)
N10.0137 (12)0.0175 (15)0.0133 (13)−0.0003 (10)−0.0001 (10)−0.0047 (11)
N20.0168 (12)0.0151 (14)0.0160 (13)−0.0017 (10)0.0009 (10)−0.0055 (11)
N30.0150 (13)0.0179 (14)0.0124 (12)0.0033 (10)0.0007 (10)−0.0008 (10)
N40.0141 (13)0.0180 (14)0.0125 (12)0.0046 (11)−0.0020 (10)−0.0016 (10)
C10.0145 (14)0.0168 (16)0.0163 (16)−0.0015 (12)−0.0001 (12)−0.0074 (13)
C20.0159 (14)0.0156 (16)0.0143 (15)−0.0015 (12)−0.0017 (12)−0.0040 (13)
C30.0139 (14)0.0174 (17)0.0199 (15)−0.0003 (12)−0.0012 (12)−0.0085 (13)
C40.0164 (15)0.0220 (17)0.0167 (15)−0.0043 (12)0.0015 (12)−0.0071 (12)
C50.0197 (15)0.0195 (17)0.0140 (15)−0.0025 (12)−0.0010 (12)−0.0044 (12)
C60.0151 (14)0.0195 (17)0.0170 (15)0.0018 (12)−0.0030 (12)−0.0068 (13)
C70.0140 (14)0.0127 (16)0.0139 (14)−0.0014 (11)0.0000 (12)−0.0048 (12)
C80.0159 (15)0.0149 (16)0.0133 (16)0.0006 (12)−0.0048 (12)−0.0039 (13)
C90.0162 (15)0.0176 (17)0.0152 (16)−0.0007 (12)−0.0014 (12)−0.0056 (13)
C100.0155 (15)0.0176 (17)0.0158 (15)0.0010 (12)−0.0013 (12)−0.0056 (12)
Geometric parameters (Å, º) top
O1—C91.217 (3)C1—C61.414 (4)
O2—C101.224 (4)C1—C21.422 (4)
N1—C71.321 (4)C2—C31.420 (4)
N1—C11.372 (4)C3—C41.368 (4)
N2—C81.318 (4)C3—H30.9500
N2—C21.358 (4)C4—C51.407 (4)
N3—C101.372 (4)C4—H40.9500
N3—C91.381 (4)C5—C61.364 (4)
N3—H3N0.92 (3)C5—H50.9500
N4—C101.369 (4)C6—H60.9500
N4—C71.377 (4)C7—C81.423 (4)
N4—H4N0.90 (3)C8—C91.483 (4)
C7—N1—C1115.5 (3)C5—C4—H4120.0
C8—N2—C2116.9 (3)C6—C5—C4122.0 (3)
C10—N3—C9127.3 (3)C6—C5—H5119.0
C10—N3—H3N113 (2)C4—C5—H5119.0
C9—N3—H3N119 (2)C5—C6—C1119.5 (3)
C10—N4—C7123.5 (3)C5—C6—H6120.2
C10—N4—H4N116 (2)C1—C6—H6120.2
C7—N4—H4N121 (2)N1—C7—N4118.0 (3)
N1—C1—C6119.7 (3)N1—C7—C8123.0 (3)
N1—C1—C2121.5 (3)N4—C7—C8119.0 (3)
C6—C1—C2118.8 (3)N2—C8—C7122.0 (3)
N2—C2—C3118.8 (3)N2—C8—C9118.3 (3)
N2—C2—C1121.1 (3)C7—C8—C9119.8 (3)
C3—C2—C1120.1 (3)O1—C9—N3121.7 (3)
C4—C3—C2119.5 (3)O1—C9—C8124.5 (3)
C4—C3—H3120.3N3—C9—C8113.8 (3)
C2—C3—H3120.3O2—C10—N4121.8 (3)
C3—C4—C5120.1 (3)O2—C10—N3121.6 (3)
C3—C4—H4120.0N4—C10—N3116.6 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3N···O2i0.92 (3)2.00 (4)2.883 (3)162 (3)
N4—H4N···N1ii0.90 (3)2.22 (3)3.114 (3)176 (3)
C3—H3···N2iii0.952.583.520 (4)173
C6—H6···O2ii0.952.213.158 (4)173
Symmetry codes: (i) −x, −y+1, −z+2; (ii) −x, −y+2, −z+1; (iii) −x+2, −y+1, −z+1.
 

Funding information

The authors acknowledge the support from the National Institutes of Health (NIH) through the National Institute of General Medical Sciences (NIGMS) Institutional Development Award (IDeA) grant No. P20 GM103424–21 and the US Department of Education (US DoE; Title III, HBGI Part B grant No. P031B040030). Its contents are solely the responsibility of authors and do not represent the official views of NIH, NIGMS, or US DoE. The upgrade of the diffractometer was made possible by grant No. LEQSF(2011–12)-ENH-TR-01, administered by the Louisiana Board of Regents.

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Journal logoIUCrDATA
ISSN: 2414-3146
Volume 8| Part 1| January 2023| x221223
https://doi.org/10.1107/S2414314622012238