Cargando…

The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms

[Image: see text] After years of controversy over the solid state structure of the essential amino acid l-phenylalanine, four different polymorphic forms were published recently. The common form I has symmetry P2(1) with four molecules in the asymmetric unit (Z′ = 4), similar to form III, but with a...

Descripción completa

Detalles Bibliográficos
Autores principales: Cuppen, Herma M., Smets, Mireille M. H., Krieger, Annika M., van den Ende, Joost A., Meekes, Hugo, van Eck, Ernst R. H., Görbitz, Carl Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410616/
https://www.ncbi.nlm.nih.gov/pubmed/30872978
http://dx.doi.org/10.1021/acs.cgd.8b01655
_version_ 1783402281106931712
author Cuppen, Herma M.
Smets, Mireille M. H.
Krieger, Annika M.
van den Ende, Joost A.
Meekes, Hugo
van Eck, Ernst R. H.
Görbitz, Carl Henrik
author_facet Cuppen, Herma M.
Smets, Mireille M. H.
Krieger, Annika M.
van den Ende, Joost A.
Meekes, Hugo
van Eck, Ernst R. H.
Görbitz, Carl Henrik
author_sort Cuppen, Herma M.
collection PubMed
description [Image: see text] After years of controversy over the solid state structure of the essential amino acid l-phenylalanine, four different polymorphic forms were published recently. The common form I has symmetry P2(1) with four molecules in the asymmetric unit (Z′ = 4), similar to form III, but with a different arrangement of molecular bilayers. Form II, obtained from the hydrate at very low humidity, is unrelated to forms I and III, as is the high-density form IV. The present investigation demonstrates that this prototype aromatic amino acid has two additional high-temperature phases Ih and IIIh obtained from form I and form III above 458 and 440 K, respectively, when flipping between two alternative side-chain conformations becomes dynamic and causes pairs of molecules, initially crystallographically independent, to become equivalent above a sharp transition temperature. These abrupt and reversible phase changes occur with a reduction of Z′ from 4 (low T) to 2 (high T) and modified crystal symmetry. We furthermore experienced an example of disappearing polymorph for form I which after growing form III in one of our laboratories could no longer be crystallized at room temperature. In contrast, form III crystals may be irreversibly converted to form I crystals as a result of sliding of molecular bilayers in the crystal at elevated temperature. No conversions between the high-temperature forms Ih and IIIh were found. The remarkable crystallographic results are here corroborated by Molecular Dynamics and metadynamics simulations of the form I – form III system.
format Online
Article
Text
id pubmed-6410616
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-64106162019-03-12 The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms Cuppen, Herma M. Smets, Mireille M. H. Krieger, Annika M. van den Ende, Joost A. Meekes, Hugo van Eck, Ernst R. H. Görbitz, Carl Henrik Cryst Growth Des [Image: see text] After years of controversy over the solid state structure of the essential amino acid l-phenylalanine, four different polymorphic forms were published recently. The common form I has symmetry P2(1) with four molecules in the asymmetric unit (Z′ = 4), similar to form III, but with a different arrangement of molecular bilayers. Form II, obtained from the hydrate at very low humidity, is unrelated to forms I and III, as is the high-density form IV. The present investigation demonstrates that this prototype aromatic amino acid has two additional high-temperature phases Ih and IIIh obtained from form I and form III above 458 and 440 K, respectively, when flipping between two alternative side-chain conformations becomes dynamic and causes pairs of molecules, initially crystallographically independent, to become equivalent above a sharp transition temperature. These abrupt and reversible phase changes occur with a reduction of Z′ from 4 (low T) to 2 (high T) and modified crystal symmetry. We furthermore experienced an example of disappearing polymorph for form I which after growing form III in one of our laboratories could no longer be crystallized at room temperature. In contrast, form III crystals may be irreversibly converted to form I crystals as a result of sliding of molecular bilayers in the crystal at elevated temperature. No conversions between the high-temperature forms Ih and IIIh were found. The remarkable crystallographic results are here corroborated by Molecular Dynamics and metadynamics simulations of the form I – form III system. American Chemical Society 2019-01-09 2019-03-06 /pmc/articles/PMC6410616/ /pubmed/30872978 http://dx.doi.org/10.1021/acs.cgd.8b01655 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Cuppen, Herma M.
Smets, Mireille M. H.
Krieger, Annika M.
van den Ende, Joost A.
Meekes, Hugo
van Eck, Ernst R. H.
Görbitz, Carl Henrik
The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms
title The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms
title_full The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms
title_fullStr The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms
title_full_unstemmed The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms
title_short The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms
title_sort rich solid-state phase behavior of l-phenylalanine: disappearing polymorphs and high temperature forms
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410616/
https://www.ncbi.nlm.nih.gov/pubmed/30872978
http://dx.doi.org/10.1021/acs.cgd.8b01655
work_keys_str_mv AT cuppenhermam therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT smetsmireillemh therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT kriegerannikam therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT vandenendejoosta therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT meekeshugo therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT vaneckernstrh therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT gorbitzcarlhenrik therichsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT cuppenhermam richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT smetsmireillemh richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT kriegerannikam richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT vandenendejoosta richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT meekeshugo richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT vaneckernstrh richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms
AT gorbitzcarlhenrik richsolidstatephasebehavioroflphenylalaninedisappearingpolymorphsandhightemperatureforms