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X-ray powder diffraction data for the second and third polymorphs of 1-methylhydantoin

Published online by Cambridge University Press:  10 May 2022

Gerzon E. Delgado Open the ORCID record for Gerzon E. Delgado [Opens in a new window] ,
Cecilia Chacón ,
Gustavo Marroquin ,
Jonathan Cisterna  and
Iván Brito
Gerzon E. Delgado*
Affiliation:
Laboratorio de Cristalografía, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida 5101, Venezuela Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Campus Coloso, Antofagasta 240000, Chile
Cecilia Chacón
Affiliation:
Conacyt - Instituto Mexicano del Petróleo, Centro de Tecnologías para Exploración y Producción, Boca del Rio, Veracruz 94286, Mexico
Gustavo Marroquin
Affiliation:
Instituto Mexicano del Petróleo, Ciudad de México 07730, Mexico
Jonathan Cisterna
Affiliation:
Departamento de Química, Facultad de Ciencias, Universidad de Católica del Norte, Antofagasta, Chile
Iván Brito
Affiliation:
Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Campus Coloso, Antofagasta 240000, Chile
*
a)Author to whom correspondence should be addressed. Electronic mail: gerzon@ula.ve
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Abstract

X-ray powder diffraction data for the two new polymorphs of 1-methylhydantoin, C4H6N2O2, are reported. The polymorph II (MH-II) crystallizes in the orthorhombic system with space group Pna21 [a = 19.0323(7) Å, b = 3.91269(8) Å, c = 6.8311(7) Å, Z′ = 1, Z = 4, unit cell volume V = 508.70(3) Å3. Polymorph III (MH-III) crystallizes in the orthorhombic system with space group P212121 [a = a = 7.82427(5), b = 9.8230(5), c = 20.2951(4), Z′ = 3, Z = 12, unit cell volume V = 1563.5(1) Å3]. All measured lines, in each case, were indexed and are consistent with the space group.

Keywords

1-methylhydantoinpolymorphismX-ray powder diffraction
Type
Data Report
Information
Powder Diffraction , Volume 37 , Issue 2 , June 2022 , pp. 108 - 114
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of International Centre for Diffraction Data

I. INTRODUCTION

Polymorphism is the result of the different crystalline forms in the solid-state produced by different packing of the molecules (Bernstein, Reference Bernstein2002; Cruz-Cabeza and Bernstein, Reference Cruz-Cabeza and Bernstein2014). According to this definition, different polymorphs of the same compound can present different physical and chemical properties in the solid-state. Polymorphism is important in the pharmaceutical industry due to the need to control the physical and chemical properties of one specific product, such as its solubility, nonlinear optical activities, bioactivity, pharmacokinetics, and among others (Park et al., Reference Park, Evans and Myerson2003).

According to a recent report (Cruz-Cabeza et al., Reference Cruz-Cabeza, Reutzel-Edens and Bernstein2015), one out of every two organic compounds reported in the Cambridge Structural Database version 5.43, March 2022 (Groom et al., Reference Groom, Bruno, Lightfoot and Ward2016) show polymorphism and are mainly due to crystallization conditions. A particular case occurs in the 1-methylhydantoin (1-methyl-imidazolidine-2,4-dione) compound for which three different conformational polymorphs have been reported to date (Nogueira et al., Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020). Hydantoin compounds, and their analogs thiohydantoins, form a large group of derivatives widely applied in medicine and pharmacy because of their varied range of therapeutic properties (Avendaño López and González Trigo, Reference Avendaño López and González Trigo1985; Meusel and Gütschow, Reference Meusel and Gütschow2004).

Meanwhile, for 1-methylhydantoin molecule (Figure 1) have been found to have excellent anti-asthmatic and antitussive effects (Hahn et al., Reference Han, Dong and Qiu2014) and antidepressant properties (You et al., Reference You, Zhang, Wang, Shi, Guo, Shi, Hou and Liu2013). This hydantoin is produced by bacterial creatinine deaminase in the intestinal tract of uremic patients (Yang et al., Reference Yang, Liu, Li, Liu, Peng and Jiang2007) and was found as a metabolite of the intelligence affecting substance dupracetam, a nootropic drug from the racetam family (Baune and Renger, Reference Baune and Renger2014).

Figure 1. 1-Methylhydantoin structural molecule with ring atoms numbering.

1-methylhydantoin is the active ingredient in the natural product Ranae Oviductus, which is obtained from the Northeast forest frog, a wild animal found in the mountainous area of northeast China. This product is used in the traditional Chinese medicine and has been used as an antitussive, anti-inflammatory, anti-fatigue, and antilipemic drug (Wang et al., Reference Wang, Xu, Wang, Yang, Lv, Jin and Wang2017; Liu et al., Reference Liu, Chen, Lan, Ren, Wei and Lina2019; Xu et al., Reference Xu, Wang, Guo, Wang, Ni, Zhou, Wang, Bao and Wang2019).

The crystal structure of the three polymorphs of 1-methylhydantoin was studied from single-crystal X-ray diffraction. Polymorph MH-I crystallizes in the monoclinic space group P21/c (Puszynska-Tuszkanow et al., Reference Puszynska-Tuszkanow, Daszkiewicz, Maciejewska, Staszak, Wietrzyk, Filip and Cieslak-Golonka2011; Nogueira et al., Reference Nogueira, Ildiz, Canotilho, Eusébio and Fausto2014) with CSD-database refcode EWUVEY (CSD, version 5.43, March 2022), polymorph MH-II crystallizes in the orthorhombic space group Pna21, EWUEY01 (Nogueira et al., Reference Nogueira, Ildiz, Henriques, Paixão and Fausto2017) and the polymorph MH-III (Nogueira et al., Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020) crystallize in the orthorhombic space group P212121, EWUEY02. In MH-I, the molecules form dimers which then associate in chains, while in MH-II and MH-III, the molecules form chains directly (Nogueira et al., Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020).

Following our investigation on hydantoin and thiohydantoin derivative compounds (Seijas et al., Reference Seijas, Mora, Delgado, Brunelli and Fitch2010; Delgado et al., Reference Delgado, Mora, Seijas, Almeida, Chacón, Azotla-Cruz, Cisterna, Cárdenas and Brito2020, Reference Delgado, Mora, Seijas, Rincón, Marroquin, Cisterna, Cárdenas and Brito2021, Reference Delgado, Mora, Narea, Chacón, Marroquin, Hernández, Cisterna and Brito2022; Hernández et al., Reference Hernández, Narea, Cisterna, Maxwell, Cárdenas, Brito and Delgado2021) in previous work, we reported the X-ray powder diffraction data for the polymorph I of 1-methylhydantoin MH-I (Delgado et al., Reference Delgado, Mora, Contreras and Chacón2015) in the Powder Diffraction File database with code PDF-00-066-1563 (Gates-Rector and Blanton, Reference Gates-Rector and Blanton2019) and report now the X-ray powder data for the two new polymorphs MH-II and MH-III.

II. EXPERIMENTAL

1-methylhydantoin 99% was a commercial material, purchased from Aldrich. Polymorphs II and III were synthesized using previous procedures. MH-II was obtained by recrystallization from methanol (Nogueira et al., Reference Nogueira, Ildiz, Henriques, Paixão and Fausto2017), and MH-III was obtained by recrystallization from an aqueous solution of MgCl2 (Nogueira et al., Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020). MH-II crystals are colorless plates (m.p. 160–161 °C), and MH-III crystals are colorless thinner plates almost needles (m.p. 166–168 °C), both stable in air.

A. X-ray powder diffraction data

For the X-ray Powder Diffraction analyses, a small quantify of each of the two samples was ground mechanically using an agate mortar and pestle. The resulting fine powders were sieved to pass 46 (micron) and mounted on flat zero-background holders coated with a thin layer of petroleum jelly. The X-ray powder diffraction data were collected at room temperature 293(1) K, in θ/θ reflection mode using a Bruker D8 Advance diffractometer and monocromatized CuKα radiation (λ = 1.54056 Å) with Bragg-Brentano geometry with fixed slits using an LYNX-eye position sensitive detector (PSD). The specimen was scanned from 5° to 55° 2θ, with a step size of 0.02° and a counting time of 5 s per step. Silicon (SRM 640) was used as an external standard to establish 2-theta-zero. The analytical software package WinPLOTR (Roisnel and Rodríguez-Carvajal, Reference Roisnel and Rodriguez-Carvajal2001) was used to establish the positions of the peaks, background reduction, and to determine the peak intensities of the diffraction peaks.

III. RESULTS AND DISCUSSION

The X-ray powder patterns of 1-methylhydantoin polymorphs are shown in Figure 2. The first peak positions, in each case, were indexed using the program DICVOL06 (Boultif and Louër, Reference Boultif and Louër2004), which gave a unique solution in orthorhombic cells with unit cell similar to those reported by single-crystal data (see Table I) for MH-II (Nogueira et al., Reference Nogueira, Ildiz, Henriques, Paixão and Fausto2017) and MH-III (Nogueira et al., Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020), and figures of merit M 20 = 35.2 (de Wolff, Reference de Wolff1968), F 20 (36.8 (0.0077, 71) (Smith and Snyder, Reference Smith and Snyder1979), and M 17 = 31.4, F 17 (40.8 (0.0059, 71), respectively.

Figure 2. X-ray powder diffraction patterns of 1-methylhydantoin polymorphs MH-II and MH-III.

TABLE I. Crystal data for the polymorphs II and III of 1-methylhydantoin

Z′ = molecules in asymmetric unit.

To confirm the unit cell parameters, Rietveld (Rietveld, Reference Rietveld1969) refinements were carried out using the FULLPROF program (Rodríguez-Carvajal, Reference Rodriguez-Carvajal2021). The starting structure model used was that of the single-crystal structures reported for the polymorph MH-II (Nogueira et al., Reference Nogueira, Ildiz, Henriques, Paixão and Fausto2017) and polymorph MH-III (Nogueira et al., Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020). In each case, the peak profiles were described using a parametrized pseudo-Voight function (Thompson et al., Reference Thompson, Cox and Hastings1987), the background was described by the automatic interpolation of 20 points throughout the whole patterns, and the thermal motion of the atoms was described by one overall isotropic temperature factor B. The figures of merit of refinements were R exp = 4.4, R wp = 6.2 for MH-II and R exp = 4.2, R wp = 5.8 for MH-III. Figure 3 shows the very good fit between the observed and calculated patterns. These refinement results confirmed that the polymorphs MH-II and MH-III crystallize in the orthorhombic space groups Pna21 and P212121, respectively. All measured lines were indexed and were consistent with the mentioned space groups. The resulting X-ray powder diffraction data for both polymorphs of 1-methylhydantoin, together with the observed 2θ angles, the d-spacing's as well as the relative intensities of the reflections, are given in Tables II and III, respectively. Table I shows the crystal data for the polymorphs II and III of 1-methylhydantoin compared with those reported (Nogueira et al., Reference Nogueira, Ildiz, Henriques, Paixão and Fausto2017, Reference Nogueira, Milani, Ildiz, Paixão, Castiglioni and Fausto2020) in the CSD database.

Figure 3. Rietveld refinement plots of 1-methylhydantoin polymorphs (a) MH-II and (b) MH-III.

TABLE II. X-ray powder diffraction data of 1-methylhydantoin polymorph 2 (MH-II)

TABLE III. X-ray powder diffraction data of 1-methylhydantoin polymorph 3 (MH-III)

IV. DEPOSITED DATA

Cif files MH-II.cif and MH-III.cif contain the raw powder diffraction data for second and third polymorphs of 1-methylhydantoin. You may request this data from the ICDD at .

ACKNOWLEDGMENTS

This work was partially done during G.E. Delgado visit at the Universidad de Antofagasta, Chile, supported by MINUC-UA project, code ANT 1856 and FONDECYT (grant 1210689).

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Figure 0

Figure 1. 1-Methylhydantoin structural molecule with ring atoms numbering.

Figure 1

Figure 2. X-ray powder diffraction patterns of 1-methylhydantoin polymorphs MH-II and MH-III.

Figure 2

TABLE I. Crystal data for the polymorphs II and III of 1-methylhydantoin

Figure 3

Figure 3. Rietveld refinement plots of 1-methylhydantoin polymorphs (a) MH-II and (b) MH-III.

Figure 4

TABLE II. X-ray powder diffraction data of 1-methylhydantoin polymorph 2 (MH-II)

Figure 5

TABLE III. X-ray powder diffraction data of 1-methylhydantoin polymorph 3 (MH-III)