title: NMR spectroscopic and quantum mechanical analyses of enhanced solubilization of hesperidin by theasinensin a.
abstract: OBJECTIVE
  The use of hesperidin in the pharmaceutical field is limited by its aqueous insolubility. The effects of natural compounds in tea on the solubility of hesperidin were evaluated and the underlying mechanism was investigated by nuclear-magnetic resonance (NMR) and quantum mechanical calculations.
  
  
  METHODS
  The solubility of hesperidin was measured by liquid chromatography time-of-flight mass spectrometry; the structure of the hesperidin/theasinensin A complex was characterized by (1)H-NMR, diffusion-ordered NMR spectroscopy, and rotating frame NOE spectroscopy, as well as theoretically by quantum mechanical calculations.
  
  
  RESULTS
  Among the natural compounds in tea, theasinensin A was the most effective in improving hesperidin solubility. The complexation of hesperidin with theasinensin A led to changes in the chemical shift of protons in hesperidin (Δδ: 0.01-0.27 ppm) and diffusion coefficient (ΔD: 0.66-1.32 × 10(-10) m(2)/s) of hesperidin. ROE correlation signals between hesperidin and theasinensin A and quantum mechanical calculations revealed that two hesperidin molecules formed a stable complex with theasinensin A (2:1 complex) with a ΔG energy of -23.5 kJ/mol.
  
  
  CONCLUSIONS
  This is the first study that provides insight into the enhanced solubility of hesperidin through interactions with theasinensin A via a 2:1 complex formation between hesperidin and theasinensin A.
authors.affiliation: Division of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan.
authors.forename: Ruge
authors.initials: R
authors.lastname: Cao
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Airi
authors.initials: A
authors.lastname: Nonaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyata
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
mesh_terms: D001578:Benzopyrans / Q000737:chemistry*; D003198:Computer Simulation; D006569:Hesperidin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008962:Models, Theoretical; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D011789:Quantum Theory; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001578:Benzopyrans; D010636:Phenols; D012997:Solvents; C481298:theasinensin A; D006569:Hesperidin