Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes by FAD and Flavoproteins

Angew Chem Int Ed Engl. 2018 Mar 12;57(12):3143-3147. doi: 10.1002/anie.201800288. Epub 2018 Feb 15.

Abstract

Recent advances in bioorthogonal catalysis promise to deliver new chemical tools for performing chemoselective transformations in complex biological environments. Herein, we report how FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), and four flavoproteins act as unconventional photocatalysts capable of converting PtIV and RuII complexes into potentially toxic PtII or RuII -OH2 species. In the presence of electron donors and low doses of visible light, the flavoproteins mini singlet oxygen generator (miniSOG) and NADH oxidase (NOX) catalytically activate PtIV prodrugs with bioorthogonal selectivity. In the presence of NADH, NOX catalyzes PtIV activation in the dark as well, indicating for the first time that flavoenzymes may contribute to initiating the activity of PtIV chemotherapeutic agents.

Keywords: bioorthogonal chemistry; flavoproteins; metal-based prodrugs; photocatalysis; photochemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Catalysis
  • Coordination Complexes / chemistry*
  • Flavin Mononucleotide / chemistry
  • Flavin-Adenine Dinucleotide / chemistry*
  • Flavoproteins / chemistry*
  • Light
  • Models, Molecular
  • Molecular Structure
  • Photochemical Processes
  • Platinum / chemistry*
  • Ruthenium / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Flavoproteins
  • Flavin-Adenine Dinucleotide
  • Platinum
  • Flavin Mononucleotide
  • Ruthenium