A high throughput screening method for the nano-crystallization of salts of organic cations

Chemical Science
Philipp P NievergeltBernhard Spingler

Abstract

The generation of solid salts of organic molecules is important to the chemical and pharmaceutical industry. Commonly used salt screening methods consume a lot of resources. We employed a combination of ion exchange screening and vapour diffusion for crystallization. This technique is semi-automatic and requires just nanoliters of the solution of the analyte to be crystallized. This high throughput screening yielded single crystals of sufficient size and quality for single-crystal X-ray structure determination using an in-house X-ray diffractometer. The broad scope of our method has been shown by challenging it with 7 very different organic cations, whose aqueous solubilities vary by a factor of almost 1000. At least one crystal structure for 6 out of 7 tested cations was determined; 4 out of the successful 6 ones had never been crystallized before. Our method is extremely attractive for high throughput salt screening, especially for active pharmaceutical ingredients (APIs), as about 40% of all APIs are cationic salts. Additionally, our screening is a new and very promising procedure for the crystallization of salts of organic cations.

References

May 20, 2006·Acta Crystallographica. Section B, Structural Science·Edwin A CollierRon J Roberts
Apr 25, 2007·Journal of Pharmaceutical Sciences·Simon N BlackRon J Roberts
Dec 7, 2007·Journal of Medicinal Chemistry·G Steffen PaulekuhnChristoph Saal
Dec 7, 2007·Drug Discovery Today·Lokesh KumarArvind K Bansal
Jun 18, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Peter B TarsaJörg Berghausen
Jul 1, 2010·Journal of Pharmaceutical Sciences·Stephen R ByrnXiaoming Sean Chen
Oct 23, 2010·Bioorganic & Medicinal Chemistry Letters·Jeff DeFalcoMatthew A J Duncton
Oct 1, 2011·Lab on a Chip·Michael R ThorsonPaul J A Kenis
Feb 16, 2012·Current Opinion in Gastroenterology·Mariano Malaguarnera
Mar 3, 2012·Drug Development and Industrial Pharmacy·Benjamin M CollmanAnthony C Blackburn
Nov 28, 2012·International Journal of Pharmaceutics·David P ElderHeidi Lopez de Diego
Feb 5, 2013·Chemical Communications : Chem Comm·Michael A BertucciMichel R Gagné
Mar 30, 2013·Nature·Yasuhide InokumaMakoto Fujita
Jan 15, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Alexander McPherson, Jose A Gavira
Dec 30, 2014·Acta Crystallographica. Section A, Foundations and Advances·Timothy R RamadharJon Clardy
Mar 24, 2016·IUCrJ·Manabu HoshinoMakoto Fujita
Apr 7, 2016·Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials·Colin R GroomSuzanna C Ward
Aug 20, 2016·Science·Seungkyu LeeOmar M Yaghi
Sep 9, 2017·Chemistry : a European Journal·Fumie SakuraiMakoto Fujita

❮ Previous
Next ❯

Citations

Apr 4, 2019·Chemistry : a European Journal·Robin BolligerRoger Alberto
Jul 3, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Ricardo AlvarezBernhard Spingler
Jul 18, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Deepak GuptaSheeba Varghese Gupta
Nov 4, 2020·Chemical Communications : Chem Comm·Riccardo RubbianiBernhard Spingler
Feb 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jolanta JaśkowskaEdyta Pindelska
Jan 13, 2021·Angewandte Chemie·Ivan A AndreevIgor V Trushkov
Oct 6, 2021·Acta Crystallographica. Section C, Structural Chemistry·Duyen N K PhamDavid R Manke

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.