Graph-Set Analysis Helps to Understand Charge Transfer in a Novel Ionic Cocrystal When the δp Ka Rule Fails

Oisín N. Kavanagh; Gavin Walker; Matteo Lusi

doi:10.1021/acs.cgd.9b00770

Graph-Set Analysis Helps to Understand Charge Transfer in a Novel Ionic Cocrystal When the δp K_a Rule Fails

Oisín N. Kavanagh, Gavin Walker, Matteo Lusi

Department of Chemical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

The cocrystallization of lamotrigine and valproic acid affords an ionic cocrystal with improved dissolution rate and mechanical properties. The multidrug crystal has a stoichiometry that is known to positively impact the pharmacokinetics of the parent compounds. As such, the new form is a suitable epileptic treatment. From a crystal engineering perspective, the structure is sustained by a complex multimolecular motif that includes each conformer in both the protonated and deprotonated state. Statistical and computational analysis reveals that the presence of ancillary H-bond donors in an R1²(4)DD (or R2²(8)DD) fashion is critical to the ionization state of the components.

Original language	English
Pages (from-to)	5308-5313
Number of pages	6
Journal	Crystal Growth and Design
Volume	19
Issue number	9
DOIs	https://doi.org/10.1021/acs.cgd.9b00770
Publication status	Published - 4 Sep 2019

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title = "Graph-Set Analysis Helps to Understand Charge Transfer in a Novel Ionic Cocrystal When the δp Ka Rule Fails",

abstract = "The cocrystallization of lamotrigine and valproic acid affords an ionic cocrystal with improved dissolution rate and mechanical properties. The multidrug crystal has a stoichiometry that is known to positively impact the pharmacokinetics of the parent compounds. As such, the new form is a suitable epileptic treatment. From a crystal engineering perspective, the structure is sustained by a complex multimolecular motif that includes each conformer in both the protonated and deprotonated state. Statistical and computational analysis reveals that the presence of ancillary H-bond donors in an R12(4)DD (or R22(8)DD) fashion is critical to the ionization state of the components.",

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AB - The cocrystallization of lamotrigine and valproic acid affords an ionic cocrystal with improved dissolution rate and mechanical properties. The multidrug crystal has a stoichiometry that is known to positively impact the pharmacokinetics of the parent compounds. As such, the new form is a suitable epileptic treatment. From a crystal engineering perspective, the structure is sustained by a complex multimolecular motif that includes each conformer in both the protonated and deprotonated state. Statistical and computational analysis reveals that the presence of ancillary H-bond donors in an R12(4)DD (or R22(8)DD) fashion is critical to the ionization state of the components.

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Graph-Set Analysis Helps to Understand Charge Transfer in a Novel Ionic Cocrystal When the δp K_a Rule Fails

Abstract

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