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The title compound, C10H24N6O4, is the most stable type of nitric oxide (NO) donor among the broad category of discrete N-diazeniumdiolates (NO adducts of nucleophilic small mol­ecule amines). Sitting astride a crystallographic inversion center, the mol­ecule contains a symmetric dimethyl­hexane-1,6-diamine structure bearing two planar O2-methyl­ated N-di­azeniumdiolate functional groups [N(O)=NOMe]. These two groups are parallel to each other and have the potential to release four mol­ecules of NO. The methyl­ated diazenium­diolate substituent removes the negative charge from the typical N(O)=NO- group, thereby increasing the stability of the diazeniumdiolate structure. The crystal was nonmerohedrally twinned by a 180° rotation about the real [101] axis. This is the first N-based bis-diazeniumdiolate compound with a flexible aliphatic main unit to have its structure analyzed and this work demonstrates the utility of stabilizing the N-dia­zeniumdiolate functional group by methyl­­ation.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270108038420/fa3166sup1.cif
Contains datablocks global, II

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270108038420/fa3166IIsup2.hkl
Contains datablock II

CCDC reference: 718116

Comment top

Nitric oxide (NO) is an extremely reactive free radical and an important physiological gas molecule. Among a host of organic NO donor species reported to date, N-diazeniumdiolates have emerged as attractive candidates for direct use as pharmacological agents (Keefer et al., 2003) as well as dopants within polymeric materials to create more biocompatible NO release polymers (Frost et al., 2005). Discrete N-diazeniumdiolates [R'R"N—N(O)NOR, NO adducts of nucleophilic small molecule amines] have been developed and can be classified within three broad categories: intramolecularly stabilized (where R is an intramolecular protonated amine), anionic (R = cation, i.e. Na+) and protected species (where R is a substituent group, e.g. Me). O2-methylated bis-diazeniumdiolates are the most stable type of NO donors (protected species), with half-lives at physiological conditions in the order of days–months (Saavedra et al., 2002). Under similar conditions, anionic diazeniumdiolates have much shorter half-lives, ranging only from 2 s to a few minutes (Saavedra et al., 2002). Stability variation is attributed to the structural differences among the three diazeniumdiolate species.

Recently, we reported the synthesis and NO release properties of a series of bis-sodium salt N-diazeniumdiolates, one of the most useful NO donors that provides doubled NO delivery capability compared to their zwitterionic counterparts (Reynolds et al., 2005). Bis-sodium 1,1-(1-N,6-N-dimethylhexamethylenediaminyl) diazen-1-ium-1,2-diolate, (I), is one molecule in that series. Although various analytical data strongly suggested that the bis-diazeniumdiolates were formed within the molecule, exact confirmation of its structural authenticity proved to be extremely difficult due to the labile nature of such an NO donor. We therefore derivatized the compound via methylation at the O2 position of the N2O2- group. The resulting, more stable, O2-methyl-protected form, bis- O2-methyl 1,1-(1-N,6-N-dimethylhexamethylenediaminyl)diazen-1-ium-1,2-diolate [systematic name: 1,1'-dimethoxy-3,3'-dimethyl-2,2'-dioxido-3,3'-(hexane-1,6-diyl)ditriazene-

2,2'-diium], (II), enabled full characterization. The resulting data strongly supported the identification of its precursor, the bis-sodium diazeniumdiolate species, (I).

For the first time, a representative single-crystal of the N-based O2-methylated bis-diazeniumdiolate compound with a flexible dimethylhexanediamine main unit (II) has been grown and the structure analyzed. This work demonstrates the utility of stabilizing the N-diazeniumdiolate functional group by methylation. The single-crystal X-ray diffraction data (Fig. 1, Table 1) provide the strongest evidence to date verifying the proposed structures of the bis-sodium N-diazeniumdiolate (I) in an indirect, but valid way. The bis-diazeniumdiolate molecule (II) sits on a crystallographic center of symmetry, which bisects the bond between C5 and C5' (symmetry code: -x, 1 - y, 2 - z). The two methylated diazeniumdiolate moieties of the molecule, bonded with two amine N atoms, are equivalent by symmetry. The anti-disposition of the two N2O2- groups of the molecule accompanies the symmetry element (Fig. 1). The methylation occurs at the O2 positon of the diazeniumdiolate group, as previously reported for a couple of mono-diazeniumdiolate species (Keefer et al., 2001; Saavedra et al., 2004). Furthermore, the N2O2- groups are nearly planar, with an O2—N1—N2—O1 torsion angle of only 3.9 (2)°. Within the N2O2- structure, the N1—N2 and N2—O1 bond distances are short (Table 1), indicating extensive charge and double-bond delocalization. The torsion angle and bond lengths are similar to those in other structurally characterized N- or C-diazeniumdiolates (Keefer et al., 2001; Saavedra et al., 1992, 2004; Arulsamy et al., 2005, 2006). The substituted methyl group on O2 is believed to reduce the negative character from the planar [N(O)NO-] group, which prevents protonation, thereby increasing the half-life of the diazeniumdiolate structure under physiological conditions (Saavedra et al., 1992). In addition, as a consequence of the crystallographic inversion center, the two diazeniumdiolate groups are parallel to each other, with a distance between the two planes of 7.331 Å.

Related literature top

For related literature, see: Arulsamy & Bohle (2005, 2006); Blessing (1995); Frost et al. (2005); Keefer (2003); Keefer et al. (2001); Reynolds et al. (2005); Saavedra & Keefer (2002); Saavedra et al. (1992, 2004); Sheldrick (2003).

Experimental top

Compound (II) was synthesized by reacting dimethyl sulfate and bis-sodium diazeniumdiolate of dimethyl-1,6-hexanediamine, (I), which was prepared by the addition of nitric oxide to N,N'-dimethyl-1,6-hexanediamine under elevated pressure (Reynolds et al., 2005), in the presence of anhydrous sodium carbonate in anhydrous methanol at 273–298 K for about 6 h. After work-up, the crude product was purified by flash chromatography with dichloromethane/ethyl acetate (3:1) to obtain a clear oil (yield: 59%). Large, colorless, plate-like crystals of the bis-O2-methylated diazeniumdiolate of dimethyl-1,6-hexanediamine were grown by diffusion of petroleum ether into an ethyl acetate solution of the compound at 277 K (m.p. 330 K). Analysis calculated for C10H24N6O4: C 41.09, H 8.27, N 28.75%; found: C 40.98, H 8.62, N 28.56%.

Refinement top

TWINABS was used to apply post-collection corrections. Data were merged according to Laue group 2/m with the contributions of both twin components as well as overlaps used in corrections and in preparing the HKLF 5 file used in the refinement.

For the calculation of the quality-of-fit and variance/covariance values, the number of observations was taken to be the number of unique data from the dominant component rather than the total number in the twin-separated data set. There were 3692 total data and 1889 unique data after merging for Fourier.

H atoms were placed at calculated positions (methyl C—H 0.98 Å, CH2, 0.99 Å) and refined as riding atoms.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: CELL_NOW (Sheldrick, 2003); data reduction: SHELXTL (Sheldrick, 2008); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. (II) with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are omitted for clarity [C5'; symmetry code: -x, 1 - y, 2 - z].
1,1'-Dimethoxy-3,3'-dimethyl-2,2'-dioxido-3,3'-(hexane-1,6-diyl)ditriazene- 2,2'-diium top
Crystal data top
C10H24N6O4F(000) = 316
Mr = 292.35Dx = 1.283 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 6.7115 (15) ÅCell parameters from 9312 reflections
b = 9.4207 (8) Åθ = 2.8–23.2°
c = 12.1863 (11) ŵ = 0.10 mm1
β = 100.942 (2)°T = 123 K
V = 756.50 (19) Å3Plate, colorless
Z = 20.40 × 0.36 × 0.28 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
3692 independent reflections
Radiation source: fine-focus sealed tube3020 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.040
π and ω scansθmax = 28.4°, θmin = 2.8°
Absorption correction: multi-scan
(Blessing, 1995; Sheldrick, 2003)
h = 88
Tmin = 0.774, Tmax = 0.973k = 1212
4787 measured reflectionsl = 1616
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.118H-atom parameters constrained
S = 1.10 w = 1/[σ2(Fo2) + (0.0638P)2 + 0.0947P]
where P = (Fo2 + 2Fc2)/3
26771 reflections(Δ/σ)max < 0.001
94 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = 0.21 e Å3
Crystal data top
C10H24N6O4V = 756.50 (19) Å3
Mr = 292.35Z = 2
Monoclinic, P21/nMo Kα radiation
a = 6.7115 (15) ŵ = 0.10 mm1
b = 9.4207 (8) ÅT = 123 K
c = 12.1863 (11) Å0.40 × 0.36 × 0.28 mm
β = 100.942 (2)°
Data collection top
Bruker SMART CCD area-detector
diffractometer
3692 independent reflections
Absorption correction: multi-scan
(Blessing, 1995; Sheldrick, 2003)
3020 reflections with I > 2σ(I)
Tmin = 0.774, Tmax = 0.973Rint = 0.040
4787 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0360 restraints
wR(F2) = 0.118H-atom parameters constrained
S = 1.10Δρmax = 0.27 e Å3
26771 reflectionsΔρmin = 0.21 e Å3
94 parameters
Special details top

Experimental. 2653 frames x 20 sec. at 4.980 cm; 0.5° steps in ω and π

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. The molecule lies on an inversion center in the crystal lattice. The crystal was found to be a non-merohedral twin with the twin components related by a 180.0 degree rotation about the real [1 0 1] axis and twin ratio 0.603 (1)/0.397 (1).

TWINABS was used to apply post-collection corrections. Both twin components were used in corrections and overlaps in addition to the two components were included in the reflection file. An additional parameter was included on the L.S. instruction to properly calculate parameter estimated uncertainties.

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 (Å2) top
xyzUiso*/Ueq
O10.05858 (14)0.23790 (10)0.65786 (8)0.0283 (3)
O20.15601 (14)0.36791 (11)0.50092 (7)0.0271 (3)
N10.29373 (17)0.37900 (12)0.60161 (9)0.0238 (3)
N20.22394 (17)0.30293 (12)0.67301 (9)0.0214 (3)
N30.35658 (17)0.28574 (12)0.77613 (9)0.0233 (3)
C10.2283 (2)0.45615 (16)0.42034 (11)0.0283 (3)
H1A0.22680.55570.44350.042*
H1B0.14020.44430.34700.042*
H1C0.36720.42850.41570.042*
C20.5396 (2)0.37455 (16)0.78900 (12)0.0278 (3)
H2A0.62070.34620.73370.042*
H2B0.62010.36230.86440.042*
H2C0.50020.47440.77750.042*
C30.2467 (2)0.29045 (14)0.87047 (11)0.0239 (3)
H3A0.34250.26460.93980.029*
H3B0.13840.21760.85780.029*
C40.1514 (2)0.43294 (14)0.88837 (11)0.0258 (3)
H4A0.04770.45670.82170.031*
H4B0.25710.50760.89750.031*
C50.0529 (2)0.43051 (14)0.99119 (11)0.0234 (3)
H5A0.15840.41071.05800.028*
H5B0.04740.35240.98340.028*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0259 (5)0.0254 (5)0.0325 (5)0.0062 (4)0.0031 (4)0.0008 (4)
O20.0278 (5)0.0307 (6)0.0213 (5)0.0038 (4)0.0013 (4)0.0005 (4)
N10.0253 (6)0.0256 (6)0.0200 (5)0.0003 (4)0.0035 (4)0.0001 (4)
N20.0228 (5)0.0185 (5)0.0231 (6)0.0013 (4)0.0045 (4)0.0008 (4)
N30.0241 (6)0.0241 (6)0.0212 (5)0.0009 (4)0.0031 (4)0.0023 (4)
C10.0329 (7)0.0294 (7)0.0230 (7)0.0011 (6)0.0062 (6)0.0022 (5)
C20.0240 (7)0.0326 (8)0.0259 (7)0.0035 (6)0.0022 (5)0.0033 (6)
C30.0277 (7)0.0225 (6)0.0221 (6)0.0009 (5)0.0065 (5)0.0037 (5)
C40.0310 (7)0.0233 (7)0.0239 (7)0.0016 (5)0.0074 (6)0.0041 (5)
C50.0258 (7)0.0227 (7)0.0217 (6)0.0016 (5)0.0043 (5)0.0022 (5)
Geometric parameters (Å, º) top
O2—N11.3930 (13)C2—H2B0.9800
O2—C11.4393 (16)C2—H2C0.9800
O1—N21.2503 (15)C3—C41.5205 (19)
N1—N21.2825 (16)C3—H3A0.9900
N2—N31.4047 (15)C3—H3B0.9900
N3—C21.4700 (17)C4—C51.5237 (18)
N3—C31.4795 (17)C4—H4A0.9900
C1—H1A0.9800C4—H4B0.9900
C1—H1B0.9800C5—C5i1.524 (3)
C1—H1C0.9800C5—H5A0.9900
C2—H2A0.9800C5—H5B0.9900
N1—O2—C1107.72 (10)H2B—C2—H2C109.5
N2—N1—O2106.79 (10)N3—C3—C4115.04 (11)
O1—N2—N1127.01 (11)N3—C3—H3A108.5
O1—N2—N3118.01 (11)C4—C3—H3A108.5
N1—N2—N3114.85 (10)N3—C3—H3B108.5
N2—N3—C2113.88 (10)C4—C3—H3B108.5
N2—N3—C3111.53 (10)H3A—C3—H3B107.5
C2—N3—C3115.45 (11)C3—C4—C5111.39 (11)
O2—C1—H1A109.5C3—C4—H4A109.4
O2—C1—H1B109.5C5—C4—H4A109.4
H1A—C1—H1B109.5C3—C4—H4B109.4
O2—C1—H1C109.5C5—C4—H4B109.4
H1A—C1—H1C109.5H4A—C4—H4B108.0
H1B—C1—H1C109.5C4—C5—C5i112.92 (14)
N3—C2—H2A109.5C4—C5—H5A109.0
N3—C2—H2B109.5C5i—C5—H5A109.0
H2A—C2—H2B109.5C4—C5—H5B109.0
N3—C2—H2C109.5C5i—C5—H5B109.0
H2A—C2—H2C109.5H5A—C5—H5B107.8
Symmetry code: (i) x, y+1, z+2.

Experimental details

Crystal data
Chemical formulaC10H24N6O4
Mr292.35
Crystal system, space groupMonoclinic, P21/n
Temperature (K)123
a, b, c (Å)6.7115 (15), 9.4207 (8), 12.1863 (11)
β (°) 100.942 (2)
V3)756.50 (19)
Z2
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.40 × 0.36 × 0.28
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(Blessing, 1995; Sheldrick, 2003)
Tmin, Tmax0.774, 0.973
No. of measured, independent and
observed [I > 2σ(I)] reflections
4787, 3692, 3020
Rint0.040
(sin θ/λ)max1)0.669
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.118, 1.10
No. of reflections26771
No. of parameters94
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.27, 0.21

Computer programs: SMART (Bruker, 2001), CELL_NOW (Sheldrick, 2003), SHELXTL (Sheldrick, 2008).

Selected geometric parameters (Å, º) top
O2—N11.3930 (13)N2—N31.4047 (15)
O2—C11.4393 (16)N3—C21.4700 (17)
O1—N21.2503 (15)N3—C31.4795 (17)
N1—N21.2825 (16)
N1—O2—C1107.72 (10)N1—N2—N3114.85 (10)
N2—N1—O2106.79 (10)N2—N3—C2113.88 (10)
O1—N2—N1127.01 (11)N2—N3—C3111.53 (10)
O1—N2—N3118.01 (11)C2—N3—C3115.45 (11)
 

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