Oligomerization of indole-3-carbinol in aqueous acid

Chem Res Toxicol. Mar-Apr 1992;5(2):188-93. doi: 10.1021/tx00026a007.

Abstract

Indole-3-carbinol [I3C, also called 3-(hydroxymethyl)indole] is a naturally occurring modulator of carcinogenesis with a biological activity that is at least partially dependent on its conversion to active substances in acidic media. We compared the identities of the major oligomeric products of I3C produced under conditions approximating those found in gastric juice with the reported identities of products of 3-substituted indoles produced under enzymatic and other nonenzymatic conditions. After a 10-min treatment in aqueous HCl solution, I3C was converted in 18% yield to a mixture of acetonitrile-soluble products, the major components of which (as determined by HPLC) were diindol-3-ylmethane (5.9%), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8-b"]triindo le (2.0%), and [2-(indol-3-ylmethyl)indol-3-yl]indol-3-ylmethane (5.9%). Tentative assignments were made for 3,3-bis(indol-3-ylmethyl)indolenine (0.59%), a symmetrical cyclic tetramer (0.64%), and a linear tetramer (1.1%). Indolo[3,2-b]carbazole (ICZ) was formed slowly in aqueous acidic solutions in low yields (2.0 ppm) which increased to greater than 90 ppm following addition of an organic solvent [tetrahydrofuran (THF) or dimethylformamide (DMF)] to a neutralized solution. Relative yields of trimers vs dimer increased with decreasing pH and with decreasing starting concentration of I3C. Evidence is presented that ICZ formation may not involve radical intermediates as is characteristic of photodynamic processes. A mechanistic rationale is presented for the formation of the identified products.

MeSH terms

  • Carbazoles / chemistry*
  • Carcinogens / toxicity
  • Chromatography, High Pressure Liquid
  • Hydrogen-Ion Concentration
  • Indoles / chemistry*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Polymers

Substances

  • Carbazoles
  • Carcinogens
  • Indoles
  • Polymers
  • indolo(3,2-b)carbazole
  • indole-3-carbinol