Publications by authors named "Kortney M Kersten"

6 Publications

  • Page 1 of 1

Pharmaceutical solvate formation for the incorporation of the antimicrobial agent hydrogen peroxide.

Chem Commun (Camb) 2018 Aug;54(67):9286-9289

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.

Antimicrobial functionality is introduced into a pharmaceutical formulation of miconazole while improving solubility. The work leverages hydrate formation propensity in order to produce hydrogen peroxide solvates. The ubiquity of hydrate formation suggests that hydrogen peroxide can be broadly deployed in pharmaceuticals, rendering a liquid excipient suitable for solid pharmaceutical formulations.
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http://dx.doi.org/10.1039/c8cc04530eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163058PMC
August 2018

Solid-State Insight Into the Action of a Pharmaceutical Solvate: Structural, Thermal, and Dissolution Analysis of Indinavir Sulfate Ethanolate.

J Pharm Sci 2018 10 28;107(10):2731-2734. Epub 2018 Jun 28.

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055; Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109-1055. Electronic address:

The crystal structure of indinavir sulfate, a pharmaceutical administered as an ethanol solvate, is presented, revealing a unique channel/ionic solvate structure to be characteristic of the compound. The properties of the material with regard to thermal treatment and water adsorption follow closely from the structure. The in situ amorphization of the pharmaceutical upon contacting liquid water is observed and highlights the unique dissolution enhancement of marketing the crystalline solvate dosage. Through survey of published crystal structures, an ambiguous sulfate/bisulfate ionization state is also observed in the crystal, which challenges the general understanding of the pharmaceutical. This study provides a solid-state insight into the function of a special multicomponent crystalline pharmaceutical form.
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http://dx.doi.org/10.1016/j.xphs.2018.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170162PMC
October 2018

Electrostatic Constraints Assessed by H MAS NMR Illuminate Differences in Crystalline Polymorphs.

J Phys Chem Lett 2017 Sep 25;8(17):4253-4257. Epub 2017 Aug 25.

Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.

Atomically resolved crystal structures not only suffer from the inherent uncertainty in accurately locating H atoms but also are incapable of fully revealing the underlying forces enabling the formation of final structures. Therefore, the development and application of novel techniques to illuminate intermolecular forces in crystalline solids are highly relevant to understand the role of hydrogen atoms in structure adoption. Novel developments in H NMR MAS methodology can now achieve robust measurements of H chemical shift anisotropy (CSA) tensors which are highly sensitive to electrostatics. Herein, we use H CSA tensors, measured by MAS experiments and characterized using DFT calculations, to reveal the structure-driving factors between the two polymorphic forms of acetaminophen (aka Tylenol or paracetamol) including differences in hydrogen bonding and the role of aromatic interactions. We demonstrate how the H CSAs can provide additional insights into the static picture provided by diffraction to elucidate rigid molecules.
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http://dx.doi.org/10.1021/acs.jpclett.7b01650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295661PMC
September 2017

Role of Anomalous Water Constraints in the Efficacy of Pharmaceuticals Probed by H Solid-State NMR.

ChemistrySelect 2017 Aug 16;2(23):6797-6800. Epub 2017 Aug 16.

Department of Chemistry, University of Michigan, 930 N. University Ave., Ann Arbor, MI 48109-1055, USA.

Water plays a complex and central role in determining the structural and reactive properties in numerous chemical systems. In crystalline materials with structural water, the primary focus is often to relate hydrogen bonding motifs to functional properties such as solubility, which is highly relevant in pharmaceutical applications. Nevertheless, understanding the full electrostatic landscape is necessary for a complete structure-function picture. Herein, a combination of tools including H magic angle spinning NMR and X-ray crystallography are employed to evaluate the local landscape of water in crystalline hydrates. Two hydrates of an anti-leukemia drug mercaptopurine, which exhibit dramatically different dehydration temperatures (by 90°C) and a three-fold difference in the bioavailability, are compared. The results identify an electrosteric caging mechanism for a kinetically trapped water in the hemihydrate form, which is responsible for the dramatic differences in properties.
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http://dx.doi.org/10.1002/slct.201701547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754108PMC
August 2017

Improved pharmacokinetics of mercaptopurine afforded by a thermally robust hemihydrate.

Chem Commun (Camb) 2016 Apr 22;52(30):5281-4. Epub 2016 Mar 22.

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.

Structural and thermal data were obtained for a novel hemihydrate of 6-mercaptopurine. The hemihydrate shows increased solubility and bioavailability when compared to the monohydrate form, better stability against conversion in aqueous media than the anhydrate form, and a dehydration temperature of 240 °C, the highest of any known hydrate crystal.
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http://dx.doi.org/10.1039/c6cc00424eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965881PMC
April 2016

Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines.

Med Chem Res 2015 Jul 13;24(7):2838-2861. Epub 2015 Feb 13.

Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.

The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents.
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http://dx.doi.org/10.1007/s00044-015-1330-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593509PMC
July 2015