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The mutagenic and carcinogenic properties of chromium(VI) complexes have been ascribed to the formation of ternary Cr(III)-small molecule-DNA complexes. As part of these laboratories efforts to establish the structure and properties of discrete binary and ternary adducts of Cr(III) and DNA at a molecular level, the properties of Cr(III)-histidine-DNA complexes formed from Cr(III) were examined. These studies determined the composition of previously described "prereacted" chromium histidinate and reveal the reaction of "prereacted" chromium histidinate with DNA does not form ternary complexes as previously proposed. The products instead are chromium histidinate complexes weakly bound, probably in the minor groove, to DNA. These weakly bound adducts cannot be responsible for the mutagenic and carcinogenic properties ascribed to ternary Cr(III)-histidine-DNA adducts. The results of biological studies where "ternary adducts" of Cr(III), histidine, and DNA were made from "prereacted" chromium histidinate must, therefore, be interpreted with caution.

The mutagenic and carcinogenic properties of chromium(VI) complexes have been ascribed to the formation of ternary Cr(III)-small molecule-DNA complexes. As part of these laboratories efforts to establish the structure and properties of discrete binary and ternary adducts of Cr(III) and DNA at a molecular level, the properties of Cr(III)-histidine-DNA complexes formed from Cr(III) were examined. These studies determined the composition of previously described "prereacted" chromium histidinate and reveal the reaction of "prereacted" chromium histidinate with DNA does not form ternary complexes as previously proposed. The products instead are chromium histidinate complexes weakly bound, probably in the minor groove, to DNA. These weakly bound adducts cannot be responsible for the mutagenic and carcinogenic properties ascribed to ternary Cr(III)-histidine-DNA adducts. The results of biological studies where "ternary adducts" of Cr(III), histidine, and DNA were made from "prereacted" chromium histidinate must, therefore, be interpreted with caution.

Chromium(VI) is a carcinogen and mutagen, and its mechanisms of action are proposed to involve binding of its reduction product, chromium(III), to DNA. The manner in which chromium(III) binds DNA has not been established, particularly at a molecular level. Analysis of oligonucleotide duplex DNAs by NMR, EPR, and IR spectroscopies in the presence of chromium(III) allows the elucidation of the Cr binding site. The metal centers were found to interact exclusively with guanine N7 positions. No evidence of chromium interactions with other bases or backbone phosphates nor of Cr forming intra-strand crosslinks between neighboring guanine residues was observed.