Confirmation of molecular planarity disruption effect on aqueous solubility improvement of β-naphthoflavone analogs

Yuji Fujita, Mitsuhiro Yonehara, Katsushi Kitahara, Jun Shimokawa, Yuichi Hashimoto, Minoru Ishikawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We have reported that increasing the dihedral angle of bicyclic molecules by ortho-substitution leads to increased aqueous solubility, which is extremely important for drug candidates. Here, we investigated in detail the improvement of aqueous solubility of β-naphthoflavone analogs by means of this approach as candidate aryl hydrocarbon receptor (AhR) agonists. To confirm the contribution of molecular planarity disruption to the increased solubility, we compared the effect of ortho-substitution with that of meta-or para-substitution with the same substituent. We also compared the wavelengths of maximum UV absorption to evaluate molecular planarity in solution, and determined the X-ray crystal structures to assess molecular planarity and crystal packing. The results support the idea that disruption of molecular planarity by substituent-induced increase of the dihedral angle results in a decrease of the crystal packing energy and a lower melting point, with a consequent increase of solubility.

Original languageEnglish
Pages (from-to)2563-2575
Number of pages13
JournalHeterocycles
Volume83
Issue number11
DOIs
Publication statusPublished - 2011 Oct 31
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

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