research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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COMMUNICATIONS
ISSN: 2056-9890

Synthesis and structure of a 1:1 co-crystal of hexa­methyl­ene­tetra­mine carb­­oxy­borane and acetamino­phen

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aDepartment of Chemistry, University of Texas Permian Basin, Odessa, Texas, USA, and bDepartment of Chemistry, State University of New York at Oswego, Oswego, New York, USA
*Correspondence e-mail: dingra_n@utpb.edu

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 4 October 2020; accepted 17 November 2020; online 24 November 2020)

Hexa­methyl­ene­tetra­mine carboacetamino­phenborane, a mol­ecule with two pharmacophores attached to a central carb­oxy­borate moiety, was synthesized and crystals were grown with an acetamino­phen co-crystal former to result in the title 1:1 co-crystal [hexa­methyl­ene­tetra­mine 4-acetamido­phenyl 2-boranyl­acetate–4-acet­amido­phenol (1/1)], C15H22BN5O3·C8H9NO2. In the first of these mol­ecules, both the borate-ester and acetyl­amino groups are considerably twisted away from the plane of the inter­vening benzene ring [dihedral angles = 76.89 (9) and 65.42 (9)°, respectively]. The extended structure of this co-crystal features N—H⋯O and O—H⋯O hydrogen bonds, which link the components into (100) sheets and weak C—H⋯O hydrogen bonds help to consolidate the structure.

1. Chemical context

Crystal structures of pure drugs are of great inter­est in the pharmaceutical industry since these structures provide an understanding of the inter­molecular inter­actions that explain the physical and chemical properties of the solid (Desiraju, 2007[Desiraju, G. R. (2007). Angew. Chem. Int. Ed. 46, 8342-8356.]). Modifications made to the active pharmaceutical ingredients to enhance the biological availability often include crystal engineering. For instance, the recrystallization of acetamino­phen, C8H9NO2 (also known as paracetamol), gives crystal form II, which displays better solubility and compressibility than form I (Naumov et al., 1998[Naumov, D. Yu., Vasilchenko, M. A. & Howard, J. A. K. (1998). Acta Cryst. C54, 653-655.]; Agnew et al., 2016[Agnew, L. R., Cruickshank, D. L., McGlone, T. & Wilson, C. C. (2016). Chem. Commun. 52, 7368-7371.]). Another approach that has been brought into attention is using crystal formers or co-formers to improve the physicochemical characteristics of the solids. Recent developments in co-crystallization show potential advantages of drug–coformer co-crystals as well as drug–drug co-crystals (Kaur et al., 2017[Kaur, R., Cavanagh, K. L., Rodríguez-Hornedo, N. & Matzger, A. J. (2017). Cryst. Growth Des. 17, 5012-5016.]; Cheney et al., 2011[Cheney, M. L., Weyna, D. R., Shan, N., Hanna, M., Wojtas, L. & Zaworotko, M. J. (2011). J. Pharm. Sci. 100, 2172-2181.]; Nugrahani et al., 2007[Nugrahani, I., Asyarie, S., Soewandhi, S. N. & Ibrahim, S. (2007). Int. J. Pharm. 3, 475-481.]; Dalpiaz et al., 2018[Dalpiaz, A., Ferretti, V., Bertolasi, V., Pavan, B., Monari, A. & Pastore, M. (2018). Mol. Pharm. 15, 268-278.]).

A group of organo–boron compounds, namely amine carb­oxy­boranes, have been studied extensively for their diverse biological effects such as anti-inflammatory, anti-neoplastic and anti-osteoporotic activities (Hall et al., 1995[Hall, I. H., Rajendran, K. G., Chen, S. Y., Wong, O. T., Sood, A. & Spielvogel, B. F. (1995). Arch. Pharm. Pharm. Med. Chem. 328, 39-44.], 1990[Hall, I. H., Spielvogel, B. F. & Sood, A. (1990). Anticancer Drugs, 1, 133-142.]; Murphy et al., 1996[Murphy, M. E., Elkins, A. L., Shrewsbury, R. P., Sood, A., Spielvogel, B. F. & Hall, I. H. (1996). Met.-Based Drugs, 3, 31-47.]). Their fundamental structure contains tetra­valent amines connected to a boron atom of the carb­oxy­borane moiety with an N—B coordinate covalent bond (Spielvogel et al., 1976[Spielvogel, B. F., Wojnowich, L., Das, M. K., McPhail, A. T. & Hargrave, K. D. (1976). J. Am. Chem. Soc. 98, 5702-5703.]). As a result of the ease of structural transformability, this group is very amenable to modification such as exchanging various amine groups and esterification on the carb­oxy­borate. Our inter­est in amine carb­oxy­boranes stemmed from their innate structure that undergoes deca­rbonylation to produce CO, H2, and the amine group when placed in aqueous solution. We have shown amine carb­oxy­boranes to be a group of mol­ecules that can be used as carbon monoxide releasers (Ayudhya et al., 2017[Ayudhya, T. I., Raymond, C. C. & Dingra, N. N. (2017). Dalton Trans. 46, 882-889.]). Moreover, we have recently reported that this process is accelerated by reactive oxygen species (ROS) increasing the rate at which CO and the amine group is released (Ayudhya et al., 2018[Ayudhya, T. I., Pellechia, P. J. & Dingra, N. N. (2018). Dalton Trans. 47, 538-543.]). Considering the amine compounds are drug mol­ecules, carb­oxy­boranes can be used as a system to deliver drugs that contain amino groups. Since we started our endeavor with drug-conjugated carb­oxy­boranes (Ayudhya et al., 2018[Ayudhya, T. I., Pellechia, P. J. & Dingra, N. N. (2018). Dalton Trans. 47, 538-543.]), we speculated that carb­oxy­boranes may be able to carry more than one drug. In addition to the amine group on the boron atom, ester and amide derivatives at the carb­oxy­borate end have been shown previously (Das et al., 1990[Das, M. K., Mukherjee, P. & Roy, S. (1990). Bull. Chem. Soc. Jpn, 63, 3658-3660.]).

[Scheme 1]

As part of this work, we now describe the crystal structure of the title co-crystal, C15H22BN5O3·C8H9NO2, (I)[link], which resulted from the synthetic concept that conjugating two different pharmacophores to the carb­oxy­borate moiety may make a mol­ecule that has multiple biological effects.

2. Structural commentary

The asymmetric unit of the resulting monoclinic crystal (space group P21/c) contains one C15H22BN5O3 ester (CORCB-1-APAP) and one C8H9NO2 acetamino­phen mol­ecule (Fig. 1[link]). The hexa­methyl­ene­tetra­amine (hmta) moiety of the ester is syn to the C9=O3 carb­oxy carbonyl group and the aromatic C3–C8 ring is approximately perpendicular to the plane of the B1/C9/O2/O3 ester carboxyl­ate group [dihedral angle = 76.89 (9)°] while the C1/C2/N1/O1 acetyl­amino group is twisted out of plane of the ring by 65.42 (9)°; the dihedral angle between the pendant groups is 11.70 (10)°.

[Figure 1]
Figure 1
The mol­ecular structure of (I)[link] with displacement ellipsoids drawn at the 50% probability level.

Based on the observed geometry, we may assume that the bonding in this difunctionalized carb­oxy­borate is very similar to that in the previously reported crystal structure of C7H15BN4O2 or CORCB-1 [Ayudhya et al., 2017[Ayudhya, T. I., Raymond, C. C. & Dingra, N. N. (2017). Dalton Trans. 46, 882-889.]; Cambridge Structural Database (Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) refcode UDAQOI]. The only significant difference is in the slightly longer C9—O2 single bond, 1.399 (2) Å in the difunctionalized title compound compared to 1.353 (3) Å in CORCB-1. This lengthening is expected to be due to the weak ester bond, which is confirmed by rapid hydrolysis. There are only small differences in B—N and B—C bond lengths between the two materials with some lengthening seen in the difunctionalized compound. In the co-crystallized acetamino­phen mol­ecule in (I)[link], the dihedral angle between the C18–C23 benzene ring and the acetyl­amino C16/C17/N6/O5 grouping is 54.61 (10)°.

3. Supra­molecular features

During crystallization, the new difunctionalized mol­ecule, CORCB-1-APAP, forms a co-crystal with acetamino­phen at a 1:1 ratio with hydrogen-bonding inter­actions (Table 1[link]) between them (Figs. 2[link] and 3[link]). In comparison to the CORCB-1 crystal reported previously, which features hydrogen bonds between the amino and carb­oxy­lic acid groups (Ayudhya et al., 2017[Ayudhya, T. I., Raymond, C. C. & Dingra, N. N. (2017). Dalton Trans. 46, 882-889.]), this new structure cannot form hydrogen bonds in the CORCB-1 region due to the replacement of carb­oxy­lic acid with an ester functional group. As a result, a co-crystal former such as acetamino­phen is needed for crystal formation to provide stable hydrogen bonds: with acetamino­phen mol­ecules flanking CORCB-1-APAP; no inter­actions are observed between these difunctionalized compounds. The co-crystal shows three classical hydrogen bonds. The first is an N6—H6N⋯O1 hydrogen bond (H⋯O = 2.00 Å) found between the N—H group of acetamino­phen and the C=O acceptor from CORCB-1-APAP. This type of bond has been previously reported in the acetamino­phen co-crystal with citric acid (Elbagerma et al., 2011[Elbagerma, M. A., Edwards, H. G. M., Munshi, T. & Scowen, I. J. (2011). CrystEngComm, 13, 1877-1884.]). Pure acetamino­phen crystals typically only form hydrogen bonds between N—H⋯O—H and O—H⋯O=C. The second inter­action N1—H1N⋯O4—H4O is between CORCB-1-APAP and another acetamino­phen mol­ecule. The bond length (2.18 Å) of this hydrogen bond is similar to the N—H⋯O—H bond (2.09 Å) from the known acetamino­phen crystal form II (Agnew et al., 2016[Agnew, L. R., Cruickshank, D. L., McGlone, T. & Wilson, C. C. (2016). Chem. Commun. 52, 7368-7371.]; Thomas et al., 2011[Thomas, L. H., Wales, C., Zhao, L. & Wilson, C. C. (2011). Cryst. Growth Des. 11, 1450-1452.]). The third hydrogen bond does not involve CORCB-1-APAP: it is exclusively formed between two acetamino­phen mol­ecules and this O4—H4O⋯O5=C17 bond (1.85 Å) is identical in length to that of acetamino­phen crystal form II (1.85 Å). Several weak C—H⋯O hydrogen bonds may help to consolidate the structure.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C10—H10A⋯O3 0.97 2.52 3.184 (2) 125
C12—H12B⋯O3 0.97 2.46 3.135 (2) 126
N1—H1N⋯O4i 0.86 2.18 3.0217 (19) 168
O4—H4O⋯O5ii 0.82 1.85 2.6619 (18) 174
N6—H6N⋯O1 0.86 2.00 2.8415 (19) 166
C10—H10B⋯O3iii 0.97 2.49 3.413 (2) 159
C15—H15A⋯O4iv 0.97 2.50 3.160 (2) 125
C20—H20⋯O5ii 0.93 2.51 3.195 (2) 130
Symmetry codes: (i) [x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]; (ii) [x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]; (iii) [-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]; (iv) [-x+1, -y+1, -z+1].
[Figure 2]
Figure 2
Unit cell packing of (I)[link] viewed down the c-axis direction, with additional mol­ecules added along the b-axis direction. Acetamino­phen mol­ecules are green; hydrogen bonds are shown as dashed yellow lines.
[Figure 3]
Figure 3
Detail of the packing of (I)[link] showing hydrogen bonds (yellow lines) between the components of the co-crystal. Three acetamino­phen mol­ecules are shown but only the two on the left are hydrogen bonded with CORCB-1-APAP. The third acetamino­phen mol­ecule, which accepts a hydrogen bond from the second, is oriented in the same way as the first and repeats the pattern.

A mol­ecular packing projection of (I)[link] is shown in Fig. 4[link] for clear representation of each pair of CORCB-1-APAP and its co-former, acetamino­phen. As noted, the observed hydrogen-bond lengths in this co-crystal are similar to those from acetamino­phen form II packing while the overall packing looks similar to form I (Naumov et al., 1998[Naumov, D. Yu., Vasilchenko, M. A. & Howard, J. A. K. (1998). Acta Cryst. C54, 653-655.]).

[Figure 4]
Figure 4
Mol­ecular packing diagram for (I)[link] viewed down [010].

4. Database survey

The crystal structures of amine carb­oxy­borane have been reported as dimers (Spielvogel et al., 1980[Spielvogel, B. F., Das, M. K., McPhail, A. T., Onan, K. D. & Hall, I. H. (1980). J. Am. Chem. Soc. 102, 6343-6344.]; Rana et al., 2002[Rana, G., Vyakaranam, K., Zheng, C., Li, S., Spielvogel, B. F. & Hosmane, N. S. (2002). Main Group Met. Chem. 25, 179-180.]; Vyakaranam et al., 2002[Vyakaranam, K., Rana, G., Chong, G., Zheng, S. L., Spielvogel, B. F. & Hosmane, N. S. (2002). Main Group Met. Chem. 25, 181-182.]). The CORCB-1 crystal structure does not show typical hydrogen bonding from carb­oxy­lic acid groups and does not show dimer formation (Ayudhya et al., 2017[Ayudhya, T. I., Raymond, C. C. & Dingra, N. N. (2017). Dalton Trans. 46, 882-889.]). Acetamino­phen co-crystallized structures to name a few are with ibuprofen (Stone et al., 2009[Stone, K. H., Lapidus, S. H. & Stephens, P. W. (2009). J. Appl. Cryst. 42, 385-391.]), citric acid (Elbagerma et al., 2011[Elbagerma, M. A., Edwards, H. G. M., Munshi, T. & Scowen, I. J. (2011). CrystEngComm, 13, 1877-1884.]), theophylline (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]) and morpholine (Oswald et al., 2002[Oswald, I. D. H., Allan, D. R., McGregor, P. A., Motherwell, W. D. S., Parsons, S. & Pulham, C. R. (2002). Acta Cryst. B58, 1057-1066.]).

5. Synthesis and crystallization

The synthesis of amine carb­oxy­borane derivatives such as methyl ester of various amine carb­oxy­borates have been described previously. Several esterification methods of amine carb­oxy­boranes with alcohols include using DCC to make 98% yield (Spielvogel et al., 1986[Spielvogel, B. F., Ahmed, F. U. & Mcphail, A. T. (1986). Synthesis, 1986, 833-835.]) and using a catalytic amount of hydrogen bromide, which provides nearly qu­anti­tative yields (Győri et al., 1995[Győri, B., Berente, Z., Emri, J. & Lázár, I. (1995). Synthesis, 1995, 191-194.]). In our process, esterification is completed before the amine exchange reaction and not vice versa. The synthesis of hexa­methyl­ene­tetra­mine carbo­acet­amino­phenborane (CORCB-1-APAP) involves several steps using tri­methyl­amine carb­oxy­borane (CORCB-3) as the starting material. Tri­methyl­amine carb­oxy­borane, synthesized by the previously reported method (Spielvogel et al., 1976[Spielvogel, B. F., Wojnowich, L., Das, M. K., McPhail, A. T. & Hargrave, K. D. (1976). J. Am. Chem. Soc. 98, 5702-5703.]) is first esterified at the carb­oxy­borate moiety with acetamino­phen (APAP). The esterification was carried out in a mixed solvent system of chloro­form and THF (1:1) at 313 to 318 K for five days and the crude product was purified by a series of recrystallizations. CORCB-1-APAP and acetamino­phen co-crystals for X-ray data collection were grown in mixed solvents of hexa­ne/chloro­form using the solution crystallization method.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All hydrogen atoms were treated as riding atoms in geometrically idealized positions [N—H = 0.86, O—H = 0.82 and C—H = 0.93–0.97 Å with Uiso(H) = 1.2Ueq(N,O,C) or 1.2Ueq(Cmeth­yl)].

Table 2
Experimental details

Crystal data
Chemical formula C15H22BN5O3·C8H9NO2
Mr 482.35
Crystal system, space group Monoclinic, P21/c
Temperature (K) 293
a, b, c (Å) 20.760 (4), 9.5527 (19), 12.045 (2)
β (°) 91.929 (4)
V3) 2387.2 (8)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.23 × 0.06 × 0.05
 
Data collection
Diffractometer Bruker APEXII CCD
No. of measured, independent and observed [I > 2σ(I)] reflections 29824, 4870, 3044
Rint 0.091
(sin θ/λ)max−1) 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.041, 0.072, 1.08
No. of reflections 4870
No. of parameters 319
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.24, −0.22
Computer programs: APEX2 and SAINT (Bruker, 2007[Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014/7 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2010).

Hexamethylenetetramine 4-acetamidophenyl 2-boranylacetate–4-acetamidophenol (1/1) top
Crystal data top
C15H22BN5O3·C8H9NO2F(000) = 1024
Mr = 482.35Dx = 1.342 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 20.760 (4) ÅCell parameters from 7373 reflections
b = 9.5527 (19) Åθ = 5.8–54.1°
c = 12.045 (2) ŵ = 0.10 mm1
β = 91.929 (4)°T = 293 K
V = 2387.2 (8) Å3Needle, colorless
Z = 40.23 × 0.06 × 0.05 mm
Data collection top
Bruker APEXII CCD
diffractometer
Rint = 0.091
Radiation source: sealed tubeθmax = 26.4°, θmin = 2.0°
phi and ω scansh = 2525
29824 measured reflectionsk = 1111
4870 independent reflectionsl = 1515
3044 reflections with I > 2σ(I)
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.041H-atom parameters constrained
wR(F2) = 0.072 w = 1/[σ2(Fo2) + (0.018P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max < 0.001
4870 reflectionsΔρmax = 0.24 e Å3
319 parametersΔρmin = 0.22 e Å3
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.05099 (9)1.08726 (18)0.86077 (16)0.0285 (5)
H1A0.01751.11250.80760.043*
H1B0.07321.17010.88590.043*
H1C0.03241.04130.92290.043*
C20.09783 (9)0.98985 (19)0.80733 (15)0.0227 (4)
O10.07872 (6)0.88651 (12)0.75419 (10)0.0260 (3)
N10.16095 (7)1.02002 (14)0.82219 (12)0.0228 (4)
H1N0.17151.08980.86400.027*
C30.21163 (8)0.94201 (17)0.77195 (15)0.0194 (4)
C40.25773 (9)0.87339 (17)0.83793 (16)0.0221 (4)
H40.25430.87270.91470.026*
C50.30902 (9)0.80567 (17)0.78963 (15)0.0217 (5)
H50.34010.76010.83370.026*
C60.31331 (8)0.80687 (17)0.67507 (16)0.0186 (4)
C70.26699 (8)0.87268 (17)0.60850 (15)0.0209 (4)
H70.27000.87180.53160.025*
C80.21585 (9)0.94021 (17)0.65765 (15)0.0214 (4)
H80.18440.98430.61340.026*
O20.36389 (6)0.73601 (11)0.62473 (10)0.0221 (3)
C90.42431 (8)0.80105 (18)0.63013 (15)0.0189 (4)
O30.42901 (6)0.91608 (12)0.67315 (10)0.0242 (3)
B10.47824 (10)0.7044 (2)0.57512 (19)0.0210 (5)
H1B10.47210.60780.59710.025*
H1B20.47350.70950.49480.025*
N20.54897 (7)0.75441 (14)0.61337 (11)0.0164 (3)
C100.55901 (8)0.75507 (18)0.73918 (14)0.0191 (4)
H10A0.52880.81980.77120.023*
H10B0.55020.66240.76790.023*
N30.62411 (7)0.79543 (14)0.77251 (12)0.0206 (4)
C110.63675 (9)0.93610 (17)0.72684 (15)0.0236 (5)
H11A0.60651.00220.75710.028*
H11B0.67990.96530.75020.028*
N40.63096 (7)0.93989 (14)0.60505 (12)0.0197 (4)
C120.56578 (8)0.89959 (17)0.57118 (15)0.0191 (4)
H12A0.56150.90080.49070.023*
H12B0.53560.96720.59970.023*
C130.59876 (8)0.65314 (17)0.56842 (15)0.0209 (4)
H13A0.59030.55970.59580.025*
H13B0.59470.65090.48800.025*
N50.66398 (7)0.69366 (14)0.60153 (12)0.0202 (4)
C140.66971 (9)0.69583 (18)0.72354 (15)0.0234 (5)
H14A0.71340.72170.74620.028*
H14B0.66150.60260.75180.028*
C150.67633 (9)0.83683 (18)0.56036 (16)0.0244 (5)
H15A0.72010.86390.58160.029*
H15B0.67250.83720.47990.029*
C160.06429 (10)0.69737 (19)0.99581 (16)0.0331 (5)
H16A0.02710.66761.03480.050*
H16B0.05280.77420.94770.050*
H16C0.09740.72671.04840.050*
C170.08889 (9)0.57733 (19)0.92747 (16)0.0244 (5)
O50.09247 (6)0.45723 (12)0.96712 (10)0.0300 (3)
N60.10633 (7)0.60827 (14)0.82433 (12)0.0243 (4)
H6N0.10480.69470.80430.029*
C180.12735 (9)0.50769 (17)0.74469 (15)0.0211 (4)
C190.08895 (9)0.39203 (18)0.71821 (15)0.0227 (4)
H190.05130.37620.75590.027*
C200.10712 (9)0.30031 (18)0.63528 (15)0.0232 (5)
H200.08200.22210.61830.028*
C210.16282 (9)0.32553 (18)0.57793 (15)0.0213 (4)
O40.17995 (6)0.24556 (12)0.48852 (11)0.0272 (3)
H4O0.15290.18430.47710.033*
C220.20183 (9)0.43896 (18)0.60524 (15)0.0242 (5)
H220.23980.45420.56810.029*
C230.18357 (9)0.53024 (18)0.68920 (15)0.0238 (5)
H230.20950.60670.70780.029*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0260 (12)0.0238 (10)0.0363 (13)0.0017 (9)0.0109 (10)0.0002 (9)
C20.0258 (12)0.0189 (10)0.0237 (12)0.0016 (9)0.0041 (9)0.0036 (9)
O10.0257 (8)0.0202 (7)0.0320 (8)0.0011 (6)0.0027 (6)0.0018 (6)
N10.0211 (9)0.0188 (8)0.0286 (10)0.0010 (7)0.0035 (8)0.0056 (7)
C30.0181 (11)0.0149 (10)0.0254 (12)0.0012 (8)0.0047 (9)0.0010 (8)
C40.0274 (12)0.0188 (10)0.0203 (11)0.0021 (9)0.0053 (9)0.0014 (8)
C50.0230 (11)0.0159 (10)0.0262 (12)0.0018 (8)0.0005 (9)0.0032 (8)
C60.0155 (10)0.0115 (9)0.0292 (12)0.0014 (8)0.0069 (9)0.0016 (8)
C70.0259 (11)0.0175 (10)0.0195 (11)0.0039 (8)0.0032 (9)0.0016 (8)
C80.0201 (11)0.0178 (10)0.0260 (12)0.0014 (8)0.0029 (9)0.0015 (8)
O20.0177 (7)0.0171 (7)0.0316 (8)0.0019 (5)0.0048 (6)0.0060 (6)
C90.0174 (10)0.0182 (10)0.0213 (11)0.0004 (8)0.0017 (9)0.0033 (8)
O30.0208 (7)0.0172 (7)0.0349 (8)0.0014 (6)0.0043 (6)0.0062 (6)
B10.0214 (13)0.0172 (11)0.0246 (13)0.0034 (9)0.0028 (10)0.0016 (9)
N20.0197 (9)0.0131 (7)0.0168 (9)0.0019 (6)0.0044 (7)0.0007 (6)
C100.0231 (11)0.0170 (9)0.0174 (11)0.0035 (8)0.0043 (9)0.0020 (8)
N30.0205 (9)0.0206 (8)0.0209 (9)0.0048 (7)0.0004 (7)0.0010 (7)
C110.0201 (11)0.0193 (10)0.0312 (12)0.0006 (8)0.0001 (9)0.0042 (9)
N40.0167 (9)0.0174 (8)0.0252 (10)0.0010 (7)0.0034 (7)0.0032 (7)
C120.0212 (11)0.0157 (9)0.0206 (11)0.0002 (8)0.0025 (9)0.0053 (8)
C130.0221 (11)0.0180 (10)0.0231 (11)0.0035 (8)0.0071 (9)0.0027 (8)
N50.0171 (9)0.0197 (8)0.0239 (10)0.0017 (7)0.0047 (7)0.0013 (7)
C140.0212 (11)0.0215 (10)0.0274 (12)0.0041 (8)0.0001 (9)0.0030 (9)
C150.0192 (11)0.0244 (11)0.0298 (12)0.0004 (8)0.0061 (9)0.0042 (9)
C160.0420 (14)0.0275 (11)0.0299 (13)0.0095 (10)0.0036 (11)0.0009 (9)
C170.0259 (12)0.0228 (11)0.0245 (12)0.0017 (9)0.0014 (10)0.0003 (9)
O50.0389 (9)0.0225 (7)0.0287 (8)0.0038 (6)0.0033 (7)0.0040 (6)
N60.0338 (10)0.0145 (8)0.0247 (10)0.0014 (7)0.0018 (8)0.0004 (7)
C180.0241 (11)0.0176 (10)0.0216 (11)0.0022 (9)0.0009 (9)0.0010 (8)
C190.0205 (11)0.0209 (10)0.0270 (12)0.0009 (8)0.0037 (9)0.0024 (9)
C200.0230 (11)0.0171 (10)0.0296 (12)0.0026 (8)0.0035 (10)0.0000 (9)
C210.0239 (11)0.0166 (10)0.0236 (12)0.0047 (8)0.0013 (9)0.0018 (8)
O40.0275 (8)0.0218 (7)0.0326 (8)0.0007 (6)0.0080 (7)0.0037 (6)
C220.0203 (11)0.0249 (11)0.0275 (12)0.0018 (9)0.0013 (9)0.0047 (9)
C230.0241 (12)0.0199 (10)0.0271 (12)0.0044 (8)0.0028 (10)0.0020 (9)
Geometric parameters (Å, º) top
C1—C21.506 (2)C11—H11B0.9700
C1—H1A0.9600N4—C121.452 (2)
C1—H1B0.9600N4—C151.477 (2)
C1—H1C0.9600C12—H12A0.9700
C2—O11.235 (2)C12—H12B0.9700
C2—N11.348 (2)C13—N51.451 (2)
N1—C31.439 (2)C13—H13A0.9700
N1—H1N0.8600C13—H13B0.9700
C3—C81.383 (2)N5—C141.471 (2)
C3—C41.388 (2)N5—C151.480 (2)
C4—C51.390 (2)C14—H14A0.9700
C4—H40.9300C14—H14B0.9700
C5—C61.386 (2)C15—H15A0.9700
C5—H50.9300C15—H15B0.9700
C6—C71.382 (2)C16—C171.511 (2)
C6—O21.404 (2)C16—H16A0.9600
C7—C81.391 (2)C16—H16B0.9600
C7—H70.9300C16—H16C0.9600
C8—H80.9300C17—O51.244 (2)
O2—C91.399 (2)C17—N61.339 (2)
C9—O31.2174 (19)N6—C181.436 (2)
C9—B11.611 (3)N6—H6N0.8600
B1—N21.597 (2)C18—C231.381 (2)
B1—H1B10.9700C18—C191.393 (2)
B1—H1B20.9700C19—C201.390 (2)
N2—C101.523 (2)C19—H190.9300
N2—C121.522 (2)C20—C211.388 (2)
N2—C131.528 (2)C20—H200.9300
C10—N31.449 (2)C21—O41.377 (2)
C10—H10A0.9700C21—C221.386 (2)
C10—H10B0.9700O4—H4O0.8200
N3—C111.479 (2)C22—C231.397 (2)
N3—C141.479 (2)C22—H220.9300
C11—N41.468 (2)C23—H230.9300
C11—H11A0.9700
C2—C1—H1A109.5C12—N4—C11108.57 (14)
C2—C1—H1B109.5C12—N4—C15108.70 (14)
H1A—C1—H1B109.5C11—N4—C15108.42 (14)
C2—C1—H1C109.5N4—C12—N2111.71 (13)
H1A—C1—H1C109.5N4—C12—H12A109.3
H1B—C1—H1C109.5N2—C12—H12A109.3
O1—C2—N1122.26 (17)N4—C12—H12B109.3
O1—C2—C1120.98 (17)N2—C12—H12B109.3
N1—C2—C1116.74 (16)H12A—C12—H12B107.9
C2—N1—C3123.69 (15)N5—C13—N2111.70 (13)
C2—N1—H1N118.2N5—C13—H13A109.3
C3—N1—H1N118.2N2—C13—H13A109.3
C8—C3—C4119.91 (17)N5—C13—H13B109.3
C8—C3—N1119.80 (16)N2—C13—H13B109.3
C4—C3—N1120.24 (16)H13A—C13—H13B107.9
C5—C4—C3120.23 (17)C13—N5—C14108.77 (14)
C5—C4—H4119.9C13—N5—C15108.97 (13)
C3—C4—H4119.9C14—N5—C15108.22 (14)
C6—C5—C4119.25 (17)N5—C14—N3112.10 (14)
C6—C5—H5120.4N5—C14—H14A109.2
C4—C5—H5120.4N3—C14—H14A109.2
C7—C6—C5120.97 (17)N5—C14—H14B109.2
C7—C6—O2118.98 (16)N3—C14—H14B109.2
C5—C6—O2120.00 (16)H14A—C14—H14B107.9
C6—C7—C8119.33 (17)N4—C15—N5111.96 (14)
C6—C7—H7120.3N4—C15—H15A109.2
C8—C7—H7120.3N5—C15—H15A109.2
C3—C8—C7120.29 (17)N4—C15—H15B109.2
C3—C8—H8119.9N5—C15—H15B109.2
C7—C8—H8119.9H15A—C15—H15B107.9
C9—O2—C6116.62 (13)C17—C16—H16A109.5
O3—C9—O2118.65 (16)C17—C16—H16B109.5
O3—C9—B1130.19 (16)H16A—C16—H16B109.5
O2—C9—B1111.15 (14)C17—C16—H16C109.5
N2—B1—C9110.79 (14)H16A—C16—H16C109.5
N2—B1—H1B1109.5H16B—C16—H16C109.5
C9—B1—H1B1109.5O5—C17—N6123.05 (17)
N2—B1—H1B2109.5O5—C17—C16120.52 (17)
C9—B1—H1B2109.5N6—C17—C16116.43 (16)
H1B1—B1—H1B2108.1C17—N6—C18124.75 (15)
C10—N2—C12107.66 (13)C17—N6—H6N117.6
C10—N2—C13106.47 (13)C18—N6—H6N117.6
C12—N2—C13107.04 (13)C23—C18—C19119.95 (17)
C10—N2—B1112.47 (14)C23—C18—N6119.97 (16)
C12—N2—B1113.27 (13)C19—C18—N6119.95 (16)
C13—N2—B1109.56 (13)C20—C19—C18119.82 (18)
N3—C10—N2111.84 (14)C20—C19—H19120.1
N3—C10—H10A109.2C18—C19—H19120.1
N2—C10—H10A109.2C21—C20—C19119.93 (17)
N3—C10—H10B109.2C21—C20—H20120.0
N2—C10—H10B109.2C19—C20—H20120.0
H10A—C10—H10B107.9O4—C21—C20122.30 (16)
C10—N3—C11108.32 (13)O4—C21—C22117.09 (16)
C10—N3—C14108.77 (14)C20—C21—C22120.50 (17)
C11—N3—C14108.20 (14)C21—O4—H4O109.5
N4—C11—N3112.61 (14)C21—C22—C23119.29 (17)
N4—C11—H11A109.1C21—C22—H22120.4
N3—C11—H11A109.1C23—C22—H22120.4
N4—C11—H11B109.1C18—C23—C22120.47 (17)
N3—C11—H11B109.1C18—C23—H23119.8
H11A—C11—H11B107.8C22—C23—H23119.8
O1—C2—N1—C34.5 (3)C11—N4—C12—N258.36 (17)
C1—C2—N1—C3176.59 (16)C15—N4—C12—N259.38 (18)
C2—N1—C3—C864.0 (2)C10—N2—C12—N456.54 (17)
C2—N1—C3—C4118.63 (19)C13—N2—C12—N457.59 (18)
C8—C3—C4—C51.6 (3)B1—N2—C12—N4178.46 (14)
N1—C3—C4—C5175.82 (15)C10—N2—C13—N557.80 (17)
C3—C4—C5—C60.4 (3)C12—N2—C13—N557.13 (18)
C4—C5—C6—C70.9 (3)B1—N2—C13—N5179.67 (14)
C4—C5—C6—O2178.39 (15)N2—C13—N5—C1459.31 (18)
C5—C6—C7—C80.9 (2)N2—C13—N5—C1558.47 (18)
O2—C6—C7—C8178.43 (15)C13—N5—C14—N359.61 (18)
C4—C3—C8—C71.5 (3)C15—N5—C14—N358.64 (18)
N1—C3—C8—C7175.85 (15)C10—N3—C14—N559.51 (19)
C6—C7—C8—C30.3 (3)C11—N3—C14—N557.96 (18)
C7—C6—O2—C9105.80 (17)C12—N4—C15—N559.85 (19)
C5—C6—O2—C976.6 (2)C11—N4—C15—N557.99 (18)
C6—O2—C9—O33.1 (2)C13—N5—C15—N459.57 (19)
C6—O2—C9—B1176.90 (15)C14—N5—C15—N458.56 (18)
O3—C9—B1—N217.3 (3)O5—C17—N6—C184.0 (3)
O2—C9—B1—N2162.61 (14)C16—C17—N6—C18176.28 (16)
C9—B1—N2—C1056.76 (19)C17—N6—C18—C23130.07 (19)
C9—B1—N2—C1265.61 (19)C17—N6—C18—C1954.1 (2)
C9—B1—N2—C13174.96 (14)C23—C18—C19—C200.5 (3)
C12—N2—C10—N356.73 (17)N6—C18—C19—C20175.33 (16)
C13—N2—C10—N357.78 (17)C18—C19—C20—C211.1 (3)
B1—N2—C10—N3177.79 (13)C19—C20—C21—O4173.96 (16)
N2—C10—N3—C1158.28 (17)C19—C20—C21—C222.3 (3)
N2—C10—N3—C1459.11 (17)O4—C21—C22—C23174.61 (15)
C10—N3—C11—N460.21 (18)C20—C21—C22—C231.8 (3)
C14—N3—C11—N457.55 (18)C19—C18—C23—C221.0 (3)
N3—C11—N4—C1260.24 (18)N6—C18—C23—C22174.86 (16)
N3—C11—N4—C1557.68 (18)C21—C22—C23—C180.2 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C10—H10A···O30.972.523.184 (2)125
C12—H12B···O30.972.463.135 (2)126
N1—H1N···O4i0.862.183.0217 (19)168
O4—H4O···O5ii0.821.852.6619 (18)174
N6—H6N···O10.862.002.8415 (19)166
C10—H10B···O3iii0.972.493.413 (2)159
C15—H15A···O4iv0.972.503.160 (2)125
C20—H20···O5ii0.932.513.195 (2)130
Symmetry codes: (i) x, y+3/2, z+1/2; (ii) x, y+1/2, z1/2; (iii) x+1, y1/2, z+3/2; (iv) x+1, y+1, z+1.
 

Acknowledgements

The authors thank M. Zeller for the X-ray data collection and the NSF for funding the diffractometer (DMR-1337296) at Youngstown State University.

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