Crystal structure of mono-β-alanine hydrochloride 61 D O I: 1 0. 15 82 6/ ch im te ch .2 02 0. 7. 2. 03 Dmitry S. Tsvetkov, Maxim O. Mazurin Chimica Techno Acta. 2020. Vol. 7, no. 2. P. 61–70. ISSN 2409–5613 Dmitry S. Tsvetkov*, Maxim O. Mazurin Institute of Natural Sciences and Mathematics, Ural Federal University, 620002, 19 Mira St., Ekaterinburg, Russia *e-mail: Dmitry.Tsvetkov@urfu.ru Crystal structure of mono-β-alanine hydrochloride Crystal structure of mono-β-alaninium chloride has been studied by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic system. The space group is Pbca, with the following lattice constants: a = 9.7414(5) Å, b = 7.4671(6) Å, c = 16.5288(11) Å, V = 1202.31(14) Å3, Z = 8. The asym- metric unit contains one β-alaninium cation (+NH3CH2CH2COOH) and one chloride anion. The structure was shown to consist of layers stacked along the c-axis and connected with each other by weak van der Waals forces. Each layer consists of two halves linked by hydrogen bonds between carbonyl and NH3 + groups and, also, between NH3 + groups and Cl– anions. Fourier transform infrared spectrum of β-alaninium chloride was recorded and analyzed. The spectroscopic results were found to support the conclusions of the structural study. Keywords: β-alanine; amino acids; X-ray diffraction; FTIR Received: 20.04.2020. Accepted: 28.05.2020. Published: 30.06.2020. © Dmitry S. Tsvetkov, Maxim O. Mazurin, 2020 Introduction β-alanine, NH2CH2CH2COOH, is  the  simplest and the  only naturally occurring β-amino acid participating (as a constituent of carnosine and anser- ine dipeptides as well as pantothenic acid) in some important biochemical processes in muscle and brain tissues of mammals, including humans [1]. The crystal struc- ture of β-alanine and some of its deriva- tives has already been studied [1–9]. How- ever, this is not the case for the simplest salts of  β-alanine such as  halides which can be considered as  promising precur- sors for the  development of  new hybrid organic-inorganic materials. To  the  best of our knowledge, the vibrational spectra of  these compounds also have not been reported yet, except in the narrow range of 1400–1500 cm–1 [10] for β-alanine hy- drochloride (β-ALA·HCl). Therefore, the  main aim of  this work was to  study the  crystal structure of  β-ALA·HCl and its vibrational properties in the wider range of frequencies. Experimental The single crystals and the polycrystal- line powder of β-ALA·HCl were prepared by the following technique. 3.5 ml of con- centrated hydrochloric acid, HCl, (mass fraction 36 wt. %, purity >99.99 wt.%), were combined with solution of  3.54 g of  β-alanine (purity >98 wt.%) in  20 ml of  distilled water. The  resulting solution 62 was evaporated to the final volume of 10 ml and left for cooling and crystallization in the Petri dish for several days. After this, the crystals of β-ALA·HCl were filtered out using glass filter. The largest crystals with the size up to 0.5×0.5×0.5 mm3 were hand- picked, carefully dried by filter paper and left in the desiccator under P2O5 for 24 h. The precipitate containing smaller crystals was washed with small amount of acetone (purity >99 wt.%), dried under vacuum at  100 °C for 3–4 h, carefully powdered using an agate mortar and pestle and stored in the desiccator under P2O5. IR spectra of  the  powdered sample of  β-ALA·HCl were recorded at  room temperature in  the  range from 400 cm–1 to  3500 cm–1 using Nicolet 6700 FTIR spectrometer (Thermo Scientific, USA) equipped with diamond Smart Orbit ATR sampling accessory. X-ray data for β-ALA·HCl single crys- tal were collected using four-circle dif- fractometer Xcalibur Sapphire3 (Oxford Diffraction Limited, UK) equipped with fine-focus sealed Mo tube, graphite mono- chromator and Sapphire3 CCD plate detec- tor. The crystal structure of β-ALA·HCl was solved by direct methods as implemented in SHELXS-97 program [11] and refined by the full matrix least squares method on all F2 data using the SHELXL-97 programs [12]. The  non-hydrogen atoms were re- fined anisotropically, by means of the full- matrix least squares procedure. The  hy- drogen atoms of  the  methylene groups (–CH2–) were placed at  calculated posi- tions (C–H = 0.97 Å) and treated as riding on their parent atoms, with Uiso(H) values set at 1.2–1.5 Ueq(C). The rest of the H at- oms (i.e. those corresponding to  –NH3 + and –COOH groups) were found from difference Fourier maps and constrained with N–H ≤ 1.03 Å (similar to ammonia) and O–H ≤ 0.98 Å, and their displace- ment factors were refined isotropically. The basic crystallographic data and details of  the  measurement and refinement are summarized in Table 1. A list of the ob- served and calculated structural factors and the anisotropic displacement factors is available in Supplementary. Table 1 Basic crystallographic data, data collection and refinement parameters Empirical formula C3H8NO2Cl a 9.7414(5) Å b 7.4671(6) Å c 16.5288(11) Å V 1202.31(14) Å3 Z 8 D (calc.) 1.387·103 kg·m–3 Crystal system orthorhombic Space group Pbca Mr 125.55 Cell parameters from 1876 reflections, θ = 4.165–29.036 T 293 K μ(Mo Kα) 0.534 mm–1 63 Results and discussion β-ALA·HCl, as  indicated in  Table  1, crystallizes in  the  orthorhombic space group Pbca with eight formula units per elementary cell. The refined atomic coordi- nates and atomic displacement parameters are given in Tables 2 and 3, and the bond lengths and angles are summarized in Ta- ble 4. The asymmetric unit of β-ALA·HCl cont ains one β-a laninium cat ion (+NH3CH2CH2COOH) and one chloride anion. The arrangement of these species in the elementary cell is shown in Fig. 1. The crystal structure may be considered as consisting of double layers connected with each other by  weak van der Waals forces and stacked along the c-axis, as can be seen in Fig. 2. Each double layer con- sists of two halves which are mirror images of each other. They are shifted against each other along the a-axis by about one half of the translation. As a result, the –C=O groups of the one half layer are almost di- rectly facing the –NH3 + groups of the oth- er half layer. Therefore, the  two halves of  the  double layer are linked together by the hydrogen bonds, whose length var- ies from 2.680 to 2.998 Å, formed by –C=O and –NH3 + groups. In  addition,  –NH3 + groups of the one half layer form hydro- gen bonds (length 2.613 Å) with the clos- F(000) 528 Crystal dimensions and shape, color 0.45 × 0.35 × 0.25 mm3 prism, colorless Data collection Diffractometer and radiation used Xcalibur Sapphire3, Mo Kα, λ= 0.71073 Å Scan technique ω — 2θ θ Range 3.65°–30.91° Index ranges  — 11≤h≤13, — 10≤k≤10, — 22≤l≤22 Absorption correction multi-scan, CrysAlisPro 1.171.39.38a (Rigaku Oxford Diffraction, 2017). Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm Tmin, Tmax 0.75985, 1.00000 No. of measured, independent and observed [I > 2σ(I)] reflections 7329, 1573, 1124 Rint 0.0315 Refinement R[F2>2σ(F2)], wR(F2), S 0.0669, 0.1724, 1.003 No. of reflections 1573 No. of parameters 80 No. of restraints 0 Δρmax, Δρmin (e·Å 3) 0.311, –0.335 End of table 1 64 est Cl– anions of the other half layer. This is drawn in greater details in Fig. 3. Fur- thermore, each half layer itself is stabilized by  the  multidirectional hydrogen bonds between the Cl– anions, on the one side, and both the closest –NH3 + groups (length 2.546 Å) and the –OH part of the carboxyl group (–C(=O)OH) (length 2.316 Å), on the other, as seen in Fig. 4. There is also an intramolecular hydrogen bond (length 2.548 Å) between the  –NH3 + and –C=O groups of the same β-alaninium cation. IR spectrum of β-ALA·HCl is shown Fig.  5. The  observed vibrational bands were tentatively assigned on the  basis of the comparison with published IR spec- tra of β-alanine [13], β-ALA·HNO3 [5] and 2(β-ALA)·HCl [9]. Table 2 Fractional atomic coordinates and isotropic or equivalent displacement parameters Atom site x y z Ueq * / Å 2 Cl1 0.57555(6) 0.14434(9) 0.40265(3) 0.0481(3) N1 0.8957(2) 0.2305(3) 0.44022(12) 0.0470(5) H1A 0.894(3) 0.369(5) 0.433(2) 0.068(9) H1B 0.815(3) 0.203(4) 0.4584(19) 0.060(8) H1C 0.952(3) 0.216(4) 0.472(2) 0.071(10) C1 1.1833(2) 0.1496(3) 0.37117(14) 0.0453(6) C2 1.0566(2) 0.1977(4) 0.32491(14) 0.0520(6) H2A 1.0628 0.1459 0.2712 0.062 H2B 1.0532 0.3268 0.3188 0.062 C3 0.9247(2) 0.1359(4) 0.36360(17) 0.0507(7) H3A 0.8494 0.1557 0.3263 0.061 H3B 0.9304 0.0083 0.3741 0.061 O1 1.18503(18) 0.0817(3) 0.43693(11) 0.0605(5) O2 1.2945(2) 0.1964(3) 0.33036(12) 0.0645(6) H2 1.357(4) 0.173(5) 0.349(2) 0.076(11) * *1 3eq ij i j i j U U a a∗ = ∑∑ a ai j Table 3 Atomic displacement parameters Atom site U11 / Å 2 U22 / Å 2 U33 / Å 2 U23 / Å 2 U13 / Å 2 U12 / Å 2 Cl1 0.0354(4) 0.0540(6) 0.0549(4) 0.0009(2) 0.00071(19) 0.0004(2) C1 0.0397(11) 0.0542(16) 0.0418(11) –0.0072(9) 0.0000(8) 0.0028(9) C2 0.0393(11) 0.0741(19) 0.0426(11) –0.0032(11) –0.0012(8) 0.0078(10) C3 0.0395(12) 0.057(2) 0.0559(14) –0.0115(10) –0.0057(9) –0.0007(9) O1 0.0486(10) 0.0808(15) 0.0522(10) 0.0070(9) –0.0030(7) 0.0085(9) O2 0.0358(9) 0.1009(18) 0.0567(10) 0.0063(10) 0.0010(8) 0.0041(9) N1 0.0355(10) 0.0585(17) 0.0469(10) –0.0009(8) 0.0005(8) –0.0033(9) 65 The wide absorption band in the range 3300–2500 cm–1 is characteristic of stretch- ing vibrations of the N–H and O–H groups, involved into the system of hydrogen bonds [5, 9]. Stretching vibrations of CH2 are su- perimposed on top of the N–H and O–H bands [5, 9]. The  weak bands observed from ~2650 to  ~1850 cm–1 seem to  cor- respond to  the  overtones and combina- tion bands of the fundamental vibrations. The  C=O stretching vibration is  located at about 1711 cm–1, confirming the exist- ence of the β-alaninium cation in the lat- tice of β-ALA·HCl. Interestingly, this ab- sorption band, in fact, seems to be splitted with the second minimum lying at about 1722 cm–1 and a shoulder — at 1680 cm–1. This may be related to  the  participation the C=O-groups in the hydrogen bonding. The  rest of  the  observed vibrational bands and their assignments are sum- marized in  Table  5. In  general, it can be Table 4 Geometric parameters Bond lengths, Å Bond Value Bond Value C1–O1 1.199(3) O2–H2 0.71(4) C1–O2 1.323(3) N1–H1A 1.04(3) C1–C2 1.496(3) N1–H1B 0.87(3) C3–N1 1.477(3) N1–H1C 0.77(3) C3–C2 1.507(3) C2–H2A 0.9700 C3–H3A 0.9700 C2–H2B 0.9700 C3–H3B 0.9700 Angles, ° Angle Value Angle Value O1–C1–O2 124.2(2) C3–N1–H1B 111(2) O1–C1–C2 125.2(2) H1A–N1–H1B 105(2) O2–C1–C2 110.6(2) C3–N1–H1C 112(3) N1–C3–C2 112.4(2) H1A–N1–H1C 103(3) N1–C3–H3A 109.1 H1B–N1–H1C 113(3) C2–C3–H3A 109.1 C1–C2–C3 114.4(2) N1–C3–H3B 109.1 C1–C2–H2A 108.7 C2–C3–H3B 109.1 C3–C2–H2A 108.7 H3A–C3–H3B 107.9 C1–C2–H2B 108.7 C1–O2–H2 115(3) C3–C2–H2B 108.7 C3–N1–H1A 112.7(19) H2A–C2–H2B 107.6 Torsion angles, ° Angle Value Angle Value O1–C1–C2–C3 –6.3(4) N1–C3–C2–C1 67.5(3) O2–C1–C2–C3 175.3(2) 66 concluded that the character of the meas- ured IR-spectrum of  β-ALA·HCl, in- dicating the  compound containing β-alaninium cations involved in hydrogen bonds, is  in  agreement with the  results of the structural study. Fig. 1. The elementary cell of β-ALA·HCl in three projections. White balls — H, red balls — O, grey balls — C, blue balls — N, green balls — Cl Fig. 2. The structure of the β-ALA·HCl in three projections with hydrogen bonds indicated as dashed blue lines and clearly seen stacking of double layers along the c-axis. Color interpretation is the same as in Fig. 1 67 Fig. 3. The arrangement of the two halves of the double layer in the structure of β-ALA·HCl: (a) view along the b-axis; (b) hydrogen bonds between the halves of the layer; (c) the half of the double layer with intrinsic hydrogen bonds. Color interpretation is the same as in Fig. 1 Fig. 4. Different views of the half layer with its intrinsic hydrogen bonds: (a) view along the b-axis as in Fig. 3; (b) projection on the ab-plane. Color interpretation is the same as in Fig. 1 68 Fig. 5. IR spectrum of β-ALA·HCl at room temperature Table 5 Vibrational bands observed in the IR-spectrum of β-ALA·HCl at room temperature ν, cm–1 Assignment 3421 2×ν(C=O) 3172 νs(NH3 +), νa(CH2), νs(CH2), ν(N-H···O), ν(O-H···Cl) 3122 3048 3016 2965 2947 2925–2902 2854 2834 2706 Overtones, combinations 2607 2521 2490 2432 2395 2285 1981 1903 1830 1722 νa(C=O), νs(C=O) 1711 1680 69 Conclusions Mono-β-alanine hydrochloride was found to crystallize in the orthorhombic space group Pbca with eight formula units per elementary cell. The  structure was shown to  consist of  double layers con- nected with each other by  weak van der Waals forces and stacked along the  c-ax- is. Each double layer, in  turn, consists of  two halves linked by hydrogen bonds between –C=O and –NH3 + groups. In ad- dition, –NH3 + groups of the one half layer form hydrogen bonds with the  closest Cl– anions of the other half layer. The re- sults of  the  IR-spectroscopy were found to  be consistent with these conclusions. The IR-active vibrational bands were iden- tified and their preliminary assignment was carried out based on the comparison with similar compounds reported previously. Acknowledgements The authors would like to acknowledge Dr. P. A. Slepukhin (I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, Ekaterinburg, Russia) ν, cm–1 Assignment 1587 δa(NH3 +) 1572 δa(NH3 +) 1493 δs(NH3 +) 1473 δs(CH2) 1402 νs(C-O) 1394 δ(CH2), ω(CH2) 1327 ω(CH2) 1306 τ(CH2) 1257 1186 ν(C–C), ρ(NH3 +) 1130 ρ(NH3 +) 1100 ρ(NH3 +) 1086 ν(C–C) 1053 νs(C-N) 953 ρ(NH3 +) 912 ρ(NH3 +) 860 ν(C–C) 831 ν(C-N), ν(C–C) 800 ρ(CH2) 636 δ(COO) 567 ω(COO) 509 τ(NH3 +) End of table 5 70 for his help in collecting the single crystal XRD data and Dr. N. V. Lakiza (Ural Federal University, Ekaterinburg, Russia) for spectroscopic measurements. This work was supported by the Russian Science Foundation (Grant No. 18-73-10059). References 1. Fleck M., Petrosyan AM. Salts of Amino Acids. 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