Dual Functioning Thieno-Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance

Chem Asian J. 2015 Jun;10(6):1335-43. doi: 10.1002/asia.201500140. Epub 2015 Apr 23.

Abstract

We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure-photophysical property relationship, we prepared SBDPiR analogs with electron-withdrawing groups at the para-position of the phenyl groups. The electron-withdrawing groups increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of brightness (82290 m(-1) cm(-1) ) and phototoxic power (99170 m(-1) cm(-1) ) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1) cm(-1) ) and balanced decay (Φflu =0.39 and ΦΔ =0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor.

Keywords: BODIPY; fluorescence imaging; photodynamic therapy; singlet oxygen generation; theranostics.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Boron Compounds / chemistry*
  • Boron Compounds / toxicity
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Drug Design
  • Fluorescent Dyes / chemistry
  • Halogens / chemistry
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Heterocyclic Compounds, 4 or More Rings / toxicity
  • Humans
  • Lasers
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Conformation
  • Neoplasms / drug therapy
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use
  • Photosensitizing Agents / toxicity
  • Pyrroles / chemistry*
  • Quantum Theory
  • Singlet Oxygen / chemistry
  • Singlet Oxygen / metabolism*
  • Spectroscopy, Near-Infrared
  • Structure-Activity Relationship
  • Transplantation, Heterologous

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • 5,5-difluoro-2,8-diphenyl-11-(trifluoromethyl)-5H-thieno(2',3'-4,5)pyrrolo(1,2-c)thieno(2',3'-4,5)pyrrolo(2,1-f)(1,3,2)diazaborinin-4-ium-5-uide
  • Boron Compounds
  • Fluorescent Dyes
  • Halogens
  • Heterocyclic Compounds, 4 or More Rings
  • Photosensitizing Agents
  • Pyrroles
  • Singlet Oxygen