I. INTRODUCTION
Electronic cigarettes are becoming more and more popular. Nicotine salts are important parts of e-liquids and meet the need for more effective and appealing e-cigarette products to provide satisfying alternatives to smoking (Grant et al., Reference Grant, Pritchard, Prue, Thompson, Verron, Graf and Walele2019). 3,5-Dihydroxybenzoic acid is synthesized from benzoic acid, and the value of LD50 intravenous in mouse is 2 g kg−1 (Adams and Cobb, Reference Adams and Cobb1967), generally considered safe. The lattice parameters (100 K single-crystal structure determination) and powder diffraction pattern for nicotine 3,5-dihydroxybenzoate were given by Dull et al. (Reference Dull, Car and Sharp2015, Reference Dull, Carr and Sharp2017) (US9738622B2; WO2015183801A1). However, hydrates are usually the more stable form. As far as we know, the crystal structure of nicotine 3,5-dihydroxybenzoate dihydrate has not been reported. In this study, nicotine 3,5-dihydroxybenzoate dihydrate was synthesized. The single-crystal X-ray diffraction and detailed X-ray powder diffraction data of nicotine 3,5-dihydroxybenzoate dihydrate were measured at room temperature and are reported here.
II. EXPERIMENTAL
A. Sample preparation
0.95 g of 3,5-dihydroxybenzoic acid was dissolved in 5 ml of ethanol. 1.01 g of nicotine was added in 40 °C. The ultrasound reaction took 4 h at 40 °C. The solution was left at room temperature and dark. After 2 months, the crystals of nicotine 3,5-dihydroxybenzoate dihydrate were obtained. Then, part of yellowish blocky crystals were dried and ground into powders. The powders were collected after passing through 200 mesh sieve.
B. Powder diffraction data collection and reduction
X-ray powder diffraction measurement was performed at room temperature using an Empyrean diffractometer (PANalytical Co., Ltd., Netherlands) with a PIXcel3D detector and CuKα radiation (generator setting: 40 kV and 40 mA). The diffraction data were collected over the angular range from 4 to 50° 2θ with a step size of 0.013° 2θ and a counting time of 30 ms step−1. The powder XRD pattern is shown in Figure 1.
Figure 1. XRD pattern of nicotine 3,5-dihydroxybenzoate dihydrate using Cu-Kα radiation (red line) and the simulated pattern of ours (black line).
The software package Material Studio 8.0 (Accelrys Co., Ltd., San Diego, CA, USA) was used to process the data in the Analytical & Testing Center (Sichuan University, Chengdu, China). The X-ray powder diffraction pattern was pretreated by subtracting the background, smoothing, and stripping off the Kα2 component by Material Studio. The automatic indexing results, obtained by X-Cell algorithm (Neumann, Reference Neumann2003), were then refined using the Pawley method (Pawley, Reference Pawley1981), which involves the assignment of Miller indices (h, k, l) to each observed peak in the experimental powder XRD pattern. No unindexed lines were observed.
C. Single-crystal X-ray diffraction
The single-crystal X-ray diffraction data for nicotine 3,5-dihydroxybenzoate dihydrate were collected on an Xcalibur, Eos diffractometer. The crystal was kept at 293.15 K during data collection. The structure was solved with Olex2 (Dolomanov et al., Reference Dolomanov, Bourhis, Gildea, Howard and Puschmann2009), a structure solution program using intrinsic phasing, and refined with the ShelXL (Sheldrick, Reference Sheldrick2008) refinement package using least squares minimization (Sheldrick, Reference Sheldrick2015). There are no holes and unaccounted positive electron density in the difference map.
III. RESULTS
The Pawley refinement results confirmed that the title compound is monoclinic with space group P21 and unit-cell parameters: a = 8.424(1) Å, b = 13.179(8) Å, c = 8.591(1) Å, α = 90°, β = 102.073(8)°, γ = 90°, unit-cell volume V = 932.765(3) Å3, Z = 2, and ρ cal = 1.256 g⋅cm−3. The values of 2θ obs, d obs, I obs, h, k, l, 2θ cal, d cal, Δ2θ are listed in Table I. The Smith-Snyder figure of merit, F (30) = 62, characterizes these results as highly reliable. In addition, the average magnitude of Δ2θ is 0.016 and Nposs is 30 when the value of n is 30. The results were in good agreement with single-crystal data [a = 8.4365(6) Å, b = 13.1486(11) Å, c = 8.6019(5) Å, α = 90°, β = 101.976(6)°, γ = 90°, unit-cell volume V = 933.42(12) Å3, Z = 2, and ρ cal = 1.254 g⋅cm−3]. The principal acquisition parameters and structure refinement values for single-crystal nicotine 3,5-dihydroxybenzoate dihydrate compound are listed in Supplementary Table SI. The structural formula of 3,5-dihydroxybenzoate dihydrate is shown in Figure 2. The minimum repeating unit contains one nicotine ion, one 3,5-dihydroxybenzoate ion, and two water molecules. The nicotine ion is linked to the 3,5-dihydroxybenzoate ion by an ionic bond. One of the water molecules is attached to the 3,5-dihydroxybenzoate ion by a hydrogen bond O2–H2B … O5. The other water molecule is attached to the nicotine ion by a hydrogen bond O6–H6A … N1 and to the 3,5-dihydroxybenzoate ion by a hydrogen bond O1–H1 … O6. The water content of the sample was determined by a Karl Fischer coulometer. The measured value of 9.407% is close to the theoretical value (10.225%). Crystallographic data for nicotine 3,5-dihydroxybenzoate dihydrate were deposited with the Cambridge Crystallographic Data Center (CCDC) with a supplementary publication number of CCDC-2031502. The comparison of the experimental powder XRD pattern with the simulated pattern of ours is shown in Figure 1. The simulated XRD pattern was calculated using Mercury software based on the single-crystal data. Results showed that both single-crystal and powder diffraction methods are consistent with each other.
TABLE I. Indexed X-ray powder diffraction data for nicotine 3,5-dihydroxybenzoate dihydrate. The d-values were calculated using CuKα 1 radiation (λ = 1.5405981 Å.
(M), Multiple indexing of a given observed line.
Figure 2. Structural formula of nicotine 3,5-dihydroxybenzoate dihydrate. Gray for carbon atoms, white for hydrogen atoms, blue for nitrogen atoms, and red for oxygen atoms.
SUPPLEMENTARY MATERIAL
The supplementary material for this article can be found at https://doi.org/10.1017/S0885715621000014.
