Molecular and Crystal Structure of N-Allylamide-9-Nitrocytisine
- PDF / 241,336 Bytes
- 5 Pages / 594 x 792 pts Page_size
- 47 Downloads / 288 Views
Pharmaceutical Chemistry Journal, Vol. 54, No. 6, September, 2020 (Russian Original Vol. 54, No. 6, June, 2020)
STRUCTURE OF CHEMICAL COMPOUNDS, METHODS OF ANALYSIS AND PROCESS CONTROL MOLECULAR AND CRYSTAL STRUCTURE OF N-ALLYLAMIDE-9-NITROCYTISINE A. F. Smol’yakov,1,* A. V. Shapovalov,1 A. A. Lashakov,1 P. R. Petrova,2 A. V. Koval’skaya,2 and I. P. Tsypysheva2 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 6, pp. 60 – 64, June, 2020.
Original article submitted December 9, 2019. X-ray diffraction measurements and quantum-chemical calculations of the crystal structures of nitromethylcytisines were performed. N-allylamide-9-nitrocytisine (III) was compared to previously studied N-methyl9-nitrocytisine (II). The crystal structure of III was stabilized as a result of participation of the amide in relatively strong N–H···OH-bonds. The packing density of crystals of III was higher than that of II. Compound III had a significantly higher melting point, in agreement with our previously suggested positive correlation between the packing density and melting point. Compound III was readily soluble in water, in contrast to II, because of a substantial role of specific solvation effects. Keywords: nitromethylcytisines, crystal packing, x-ray crystal structure analysis, quantum chemistry.
Cytisine derivatives possess antiviral and analeptic activity [1-3]. Furthermore, unsubstituted cytisine and its halogenated derivatives are nicotine antagonists [4, 5]. Recently, amide derivatives of cytisine were shown to possess nootropic activity like piracetam [6-8]. Previously, x-ray crystal structure analyses (XSAs) of two methylcytisine derivatives (I and II, Fig. 1) with potential antiviral activity were performed by us. A comparison of their crystal packings showed that these compounds in the crystals had energetically different intermolecular interactions that were responsible for different dissolution kinetics and bioavailabilities. An explanation for their different melting points was also given [9]. The present work determined the crystal structure of N-allylamide-9-nitrocytisine (III, Fig. 1) and compared the crystal packings of II and III to find relationships between 1 2 *
the types and energies of intermolecular interactions and hydration energies during dissolution. EXPERIMENTAL PART Compound III was synthesized by the published method [10]. Single crystals were obtained by slow evaporation of a CHCl3 solution of III. The single crystals of III (C15H18N4O4) at 120 K were orthorhombic, a = 7.1986(3), b = 10.4366(5), and c = 19.6336(10) Å; V = 1475.05(12) Å3; Z = 4; space group P212121; dcryst = 1.433 g/cm3. Intensities of reflections (9,879) were measured on a SMART APEX2 CCD diffractometer (lMo-Ka = 0.71073 Å, graphite monochromator, w-scanning, 2q < 60°). The starting dataset of measured intensities was processed using the SAINT and SADABS programs embedded in the APEX2 software [11]. The structure was solved by direct methods and refined by anisotropic full-matrix least-squares (LS) methods for nonhydr
Data Loading...
