A bifunctional molecule as an artificial flavin mononucleotide cyclase and a chemosensor for selective fluorescent detection of flavins

J Am Chem Soc. 2009 Jul 29;131(29):10107-12. doi: 10.1021/ja9018012.

Abstract

Flavins, comprising flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and riboflavin (RF, vitamin B(2)), play important roles in numerous redox reactions such as those taking place in the electron-transfer chains of mitochondria in all eukaryotes and of plastids in plants. A selective chemosensor for flavins would be useful not only in the investigation of metabolic processes but also in the diagnosis of diseases related to flavins; such a sensor is presently unavailable. Herein, we report the first bifunctional chemosensor (PTZ-DPA) for flavins. PTZ-DPA consists of bis(Zn(2+)-dipicolylamine) and phenothiazine. Bis(Zn(2+)-dipicolylamine) (referred to here as XyDPA) was found to be an excellent catalyst in the conversion of FAD into cyclic FMN (riboflavin 4',5'-cyclic phosphate, cFMN) under physiological conditions, even at pH 7.4 and 27 degrees C, with less than 1 mol % of substrate. Utilizing XyDPA's superior function as an artificial FMN cyclase and phenothiazine as an electron donor able to quench the fluorescence of an isoalloxazine ring, PTZ-DPA enabled selective fluorescent discrimination of flavins (FMN, FAD, and RF): FAD shows ON(+), FMN shows OFF(-), and RF shows NO(0) fluorescence changes upon the addition of PTZ-DPA. With this selective sensing property, PTZ-DPA is applicable to real-time fluorescent monitoring of riboflavin kinase (RF to FMN), alkaline phosphatase (FMN to RF), and FAD synthetase (FMN to FAD).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemistry
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / metabolism
  • Chemistry Techniques, Analytical / methods*
  • Flavin Mononucleotide / analysis
  • Flavin Mononucleotide / metabolism
  • Flavins / analysis*
  • Fluorescence*
  • Fluorescent Dyes / analysis
  • Fluorescent Dyes / chemistry
  • Luminescent Measurements
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Phosphorus-Oxygen Lyases / metabolism*
  • Picolinic Acids / chemistry
  • Zinc / chemistry

Substances

  • 2,2'-dipicolylamine
  • Amines
  • Flavins
  • Fluorescent Dyes
  • Organometallic Compounds
  • Picolinic Acids
  • Flavin Mononucleotide
  • Phosphorus-Oxygen Lyases
  • FMN cyclase
  • Zinc