Forming a chromium-based interstrand DNA crosslink: Implications for carcinogenicity.

The reduction of the carcinogen chromate has been proposed to lead to three Cr(III)-containing DNA lesions: binary adducts (Cr(III) and DNA), interstrand crosslinks, and ternary adducts (Cr(III) linking DNA to a small molecule or protein). Although the structures of binary adducts have recently been elucidated, the structures of interstrand crosslinks and ternary adducts are not known. Analysis of Cr(III) binding to an oligonucleotide duplex containing a 5'-CG site allows elucidation of the structure of an oxide- or hydroxide-bridged binuclear Cr(III) assembly bridging the two strands of DNA. One Cr(III) is directly coordinated by the N-7 atom of a guanine residue, and the complex straddles the helix to form a hydrogen bond between another guanine residue and a Cr(III)-bound aquo ligand. No involvement of the phosphate backbone was observed. The properties and stability of this Cr-O(H)-Cr-bridged complex differ significantly from those reported for Cr-induced interstrand crosslinks, suggesting that interstrand crosslinks resulting from chromate reduction may be organic in nature.

Examining the Potential Formation of Ternary DNA Complexes with Chromium­Cysteine, Chromium-Ascorbate, and Chromium-Glutathione and Implications for Their Carcinogenicity.

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)-cysteine-DNA, Cr(III)-ascorbate-DNA, and Cr(III)-glutathione-DNA complexes formed from Cr(III) were examined. These studies determined the composition of previously described "pre-reacted" chromium cysteinate and chromium glutathione. Neither of these complexes nor "chromium ascorbate" form ternary complexes with DNA as previously proposed. In fact, these Cr(III) compounds do not measurably bind to DNA and cannot be responsible for the mutagenic and carcinogenic properties ascribed to ternary Cr(III)-cysteine-DNA and Cr(III)-ascorbate-DNA adducts. The results of biological studies where "ternary adducts" of Cr(III), cysteine, glutathione, or ascorbate and DNA were made from "pre-reacted" chromium cysteinate or chromium glutathione or from "chromium ascorbate" must, therefore, be interpreted with caution.

Substituent effects on indole universal bases in DNA.

A series of eleven 5-substituted-indole nucleoside residues were synthesized and incorporated into 15-mer oligodeoxynucleotide duplexes with each of the four natural bases (A, G, C, T) paired with the non-natural residues. The universal base properties of these residues were evaluated by comparing the stabilities of these complexes determined by UV thermal denaturation experiments. All of the substituted indoles were more stable than an unsubstituted indole residue, and measures of electronic influences of substituents on the indole pi system correlate with stability. Several residues were more promiscuous than the previously studied 5-nitroindole residue, but the relationship between substituents and selectivity is not clear.

Verification and Temperature-Dependent Rectification by HBQ, the Smallest Unimolecular Donor-Acceptor Rectifier.

Five years ago, rectification of electrical current was found in 4'-bromo-3,4-dicyano-2',5'-dimethoxy-[1,1'-biphenyl]-2,5-dione (1), a hemibiquinone (which we will call either 1 or HBQ) that has a very small working length (1.1 nm). Monolayers of HBQ on AuTS were detected by "nanodozing" atomic force microscopy (AFM) and were contacted with two types of top electrodes: either cold Au or eutectic Ga-In. Here, we describe cyclic voltammetry of a self-assembled monolayer (SAM) of HBQ and its orientation on a gold substrate with angle-resolved X-ray photoelectron spectroscopy. New measurements of its rectification as a monolayer as a function of bias range and temperature confirm and prove that HBQ is truly the smallest donor-acceptor rectifier and provide some insight into the mechanism of rectification.

Examining the Potential Formation of Ternary Chromium-Histidine-DNA Complexes and Implications for Their Carcinogenicity.

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.

Molecular Structure of Binary Chromium(III)-DNA Adducts.

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.

Crystal structure of 4'-bromo-2',5'-dimeth-oxy-2,5-dioxo-[1,1'-biphen-yl]-3,4-dicarbo-nitrile [BrHBQ(CN)2] benzene hemisolvate.

In the crystal of the title compound, C16H9BrN2O4·0.5C6H6, the mol-ecules stack in a centrosymmetric unit cell in a 2:1 stoichiometry with co-crystallized benzene solvent mol-ecules and inter-act via various weak inter-actions. This induces a geometry different from that predicted by theory, and is unique among the hemibi-quinones heretofore reported.

Crystal structure of 4'-bromo-2,5-dihy-droxy-2',5'-dimeth-oxy-[1,1'-biphen-yl]-3,4-dicarbo-nitrile.

In the crystal of the title substituted hemibi-quinone derivative, C16H11BrN2O4 or [BrHBQH2(CN)2], the substituted benzene rings are rotated about the central C-C bond, forming a dihedral angle of 53.59 (7)°. The ring systems inter-act through an intra-molecular O-H⋯Ometh-oxy hydrogen bond, which induces a geometry quite different from those in previously reported hemibi-quinone structures. In the crystal, the mol-ecules associate through an inter-molecular O-H⋯Nnitrile hydrogen bond, forming chains which extend along [100] and are inter-linked through very weak C-H⋯N hydrogen bonds, giving a overall two-dimensional structure lying parallel to (010).

Surprisingly Big Rectification Ratios for a Very Small Unimolecular Rectifier.

To shrink electrical circuits beyond the looming practical limits of Moore's "Law", it has been a common goal to create carbon-based components. Here is the first example of a new class of donor-σ-acceptor rectifiers: hemibiquinones (HBQs). HBQs possess donor and acceptor moieties that are electronically isolated by inter-ring torsion. A HBQ-dinitrile self-assembles on a template-stripped gold surface through directed chemisorption, forming a 1.1 nm-thick monolayer. Rectification is measured through the monolayer or single molecules by using three different top electrode arrangements. Even though the HBQs are composed of relatively weak electrophores, rectification ratios ranging from 5 to 160 were observed at 2.5 V.

Crystal structure of 4,4'-di-bromo-2',5'-dimeth-oxy-[1,1'-biphen-yl]-2,5-dione (BrHBQBr).

In the title compound, C14H10Br2O4, the dihedral angle between the aromatic rings is 67.29 (19)°. Both meth-oxy-group C atoms lie close to the plane of their attached ring [deviations = -0.130 (4) and 0.005 (5) Å]. In the crystal, mol-ecules pack in a centrosymmetric fashion and inter-act via a mixture of weak π-π stacking inter-actions [centroid-centoid separations = 4.044 (2) and 4.063 (3) Å], weak C-H⋯O hydrogen bonding, and Br⋯Br halogen bonding. This induces a geometry quite different than that predicted by theory.

Polarization of charge-transfer bands and rectification in hexadecylquinolinium 7,7,8-tricyanoquinodimethanide and its tetrafluoro analog.

A Langmuir-Blodgett (LB) multilayer film of the unimolecular rectifier hexadecyl-gamma-quinolinium-7,7,8-tricyanoquinodimethanide (C(16)H(33)gammaQ-3CNQ) has two distinct polarized charge-transfer bands, one at lower film pressures (28 mN m(-1)) with a peak at 530 nm, due to an intramolecular charge transfer or intervalence transfer (IVT); past the collapse point (32 to 35 mN m(-1)), this band disappears, and a new intermolecular charge-transfer band appears with peak at 570 nm. An LB multilayer film of the tetrafluoro analogue, hexadecyl-gamma-quinolinium-2,3,5,6-tetrafluoro-7,7,8-tricyanoquinodimethanide (C(16)H(33)gammaQ-3CNQF(4)) shows, for all film pressures, only one IVT band with a peak at 504 nm; when sandwiched between gold electrodes, (C(16)H(33)gammaQ-3CNQF(4) is also an LB monolayer electrical rectifier.

Fluoroaromatic universal bases in peptide nucleic acids.

Fluoroaromatic peptide nucleic acid residues were found to possess little base discrimination when incorporated into PNA.DNA double helices.