The Space-Group of Strychnine

Marwick, Thora C.

doi:10.1038/126438b0

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Optical crystallographic data of this anhydrous form have already been reported in the compilation of Groth in 1919 48. Lattice parameters and space group of the same phase were reported in 1930 by Marwick (CSD-Refcode: ZZZUEE),49 followed by full structure determinations performed by Golver (ZZZUEE01),50 Mostad (ZZZUEE02),51 Messerschmidt (ZZZUEE03- ZZZUEE06),52 and Zharylgasina (ZZZUE07) 53. In contrast, brucine shows a rich solid form landscape: two anhydrates (MAJRIZ54 – a low temperature anhydrate AH LT and MAJRIZ0155– the commercially available AH ), twelve solvates with organic solvents (JIFWEB,56 JIFWIF, 56 JIFWOL,56 JIFWUR,56 PIGNUP,56 PIGPAX,56 PIGPEB,56 PIGPIF,56 PIGPOL,56 PIGPUR,56 PIGQAY56 and MAJROF54), four heterosolvates (‘mixed’ solvates) with water and organic solvent molecules (DAFFUL,50 MAJRUL,54 HIDGOS57 and HIDGUY57), and four hydrates ( HyA : dihydrate, CIKDOQ58; HyB : tetrahydrate, ZZZPRW01;59 HyC : 3.86-hydrate, YOYZIX55 ; a 5.25-hydrate: UCOJIG59).…”

Section: Introductionmentioning

confidence: 99%

Why Do Hydrates (Solvates) Form in Small Neutral Organic Molecules? Exploring the Crystal Form Landscapes of the Alkaloids Brucine and Strychnine

Braun

Griesser

2016

Crystal Growth & Design

View full text Add to dashboard Cite

Computational methods were used to generate and explore the crystal structure landscapes of the two alkaloids strychnine and brucine. The computed structures were analyzed and rationalized by correlating the modelling results to a rich pool of available experimental data. Despite their structural similarity, the two compounds show marked differences in the formation of solid forms. For strychnine only one anhydrous form is reported in the literature and two new solvates from 1,4-dioxane were detected in the course of this work. In contrast, 22 solid forms are so far known to exist for brucine, comprising two anhydrates, four hydrates (HyA -HyC and a 5.25-hydrate), twelve solvates (alcohols and acetone) and four heterosolvates (mixed solvates with water and alcohols). For strychnine it is hard to produce any solid form other than the stable anhydrate while the formation of specific solid state forms of brucine is governed by a complex interplay between temperature and relative humidity/water activity and it is rather a challenging to avoid hydrate formation. Differences in crystal packing and the high tendency for brucine to form hydrates are not intuitive from the molecular structure alone, as both molecules have hydrogen bond acceptor groups but lack hydrogen bond donor groups. Only the evaluation of the crystal energy landscapes, in particular the close-packed crystal structures and high-energy open frameworks containing voids of molecular (water) dimensions, allowed us to unravel the diverse solid state behavior of the two alkaloids at a molecular level. In this study we demonstrate that expanding the analysis of anhydrate crystal energy landscapes to higher energy structures and calculating the solventaccessible volume can be used to estimate non-stoichiometric or channel hydrate (solvate) formation, without explicitly computing the hydrate/solvate crystal energy landscapes. Keywords brucine; strychnine; hydrates; crystal structure prediction; void analysis * Author to whom correspondence should be addressed: Dr. Doris E. Braun, Institute of Pharmacy, University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria, Tel: +43(0)512 507 58653, doris.braun@uibk.ac.at. Associated ContentComputational search for guest-free strychnine and brucine forms (anhydrates); experimental screen for strychnine solvates/hydrates; strychnine 1,4-dioxane solvates: powder X-ray diffraction and thermogravimetric analysis; IR spectra of strychnine and brucine solid forms. This information is available free of charge via the Internet at http://pubs.acs.org/.

show abstract