Convergent preparation and photophysical characterization of dimaleimide dansyl fluorogens: elucidation of the maleimide fluorescence quenching mechanism

J Am Chem Soc. 2007 Oct 3;129(39):11969-77. doi: 10.1021/ja0738125. Epub 2007 Sep 12.

Abstract

Dimaleimide fluorogens are being developed for application to fluorescent protein labeling. In this method, fluorophores bearing two maleimide quenching groups do not fluoresce until both maleimide groups have undergone thiol addition reactions with the Cys residues of the target protein sequence [J. Am. Chem. Soc. 2005, 127, 559-566]. In this work, a new convergent synthetic route was developed that would allow any fluorophore to be attached via a linker to a dimaleimide moiety in a modular fashion. Series of dimaleimide and dansyl derivatives were thus prepared conveniently and used to elucidate the mechanism of maleimide quenching. Intersystem crossing was ruled out as a potential quenching pathway, based on the absence of a detectable triplet intermediate by laser flash photolysis. Stern-Volmer rate constants were measured with exogenous dimaleimide quenchers and found to be close to the diffusion-controlled limits, consistent with electron transfer being thermodynamically favorable. The thermodynamic feasibility of the photoinduced electron transfer (PET) quenching mechanism was verified by cyclic voltammetry. The redox potentials measured for dansyl and maleimide confirm that electron transfer from the dansyl excited state to a pendant maleimide group is exergonic and is responsible for fluorescence quenching of the fluorogens studied herein. Taking this PET quenching mechanism into account, future fluorogenic protein labeling agents will be designed with spacers of variable length and rigidity to probe the structure-property PET efficiency relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dansyl Compounds / chemical synthesis
  • Dansyl Compounds / chemistry*
  • Fluorescence
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Kinetics
  • Maleimides / chemical synthesis
  • Maleimides / chemistry*
  • Photochemistry
  • Quantum Theory
  • Spectrometry, Fluorescence / methods

Substances

  • Dansyl Compounds
  • Fluorescent Dyes
  • Maleimides
  • 5-dimethylaminonaphthalene-1-sulfonamide