title: Cr(3+) Binding to DNA Backbone Phosphate and Bases: Slow Ligand Exchange Rates and Metal Hydrolysis.
abstract: The interaction between chromium ions and DNA is of great interest in inorganic chemistry, toxicology, and analytical chemistry. Most previous studies focused on in situ reduction of Cr(VI), producing Cr(3+) for DNA binding. Recently, Cr(3+) was reported to activate the Ce13d DNAzyme for RNA cleavage. Herein, the Ce13d is used to study two types of Cr(3+) and DNA interactions. First, Cr(3+) binds to the DNA phosphate backbone weakly through reversible electrostatic interactions, which is weakened by adding competing inorganic phosphate. However, Cr(3+) coordinates with DNA nucleobases forming stable cross-links that can survive denaturing gel electrophoresis condition. The binding of Cr(3+) to different nucleobases was further studied in terms of binding kinetics and affinity by exploiting carboxyfluorescein-labeled DNA homopolymers. Once binding takes place, the stable Cr(3+)/DNA complex cannot be dissociated by EDTA, attributable to the ultraslow ligand exchange rate of Cr(3+). The binding rate follows the order of G > C > T ≈ A. Finally, Cr(3+) gradually loses its DNA binding ability after being stored at neutral or high pH, attributable to hydrolysis. This hydrolysis can be reversed by lowering the pH. This work provides a deeper insight into the bioinorganic chemistry of Cr(3+) coordination with DNA, clarifies some inconsistency in the previous literature, and offers practically useful information for generating reproducible results.
authors.affiliation: School of Pharmaceutical Sciences, Central South University , Changsha, Hunan 410013, China.|Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Wenhu
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Tianmeng
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Vazin
authors.affiliation: School of Pharmaceutical Sciences, Central South University , Changsha, Hunan 410013, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ding
authors.affiliation: School of Pharmaceutical Sciences, Central South University , Changsha, Hunan 410013, China.|Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Juewen
authors.initials: J
authors.lastname: Liu
mesh_terms: D002712:Chlorides / Q000737:chemistry; D002857:Chromium / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D021881:DNA, Catalytic / Q000737:chemistry / Q000378:metabolism; D004492:Edetic Acid / Q000737:chemistry / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism
chemical_list: D002712:Chlorides; D003432:Cross-Linking Reagents; D021881:DNA, Catalytic; D005452:Fluoresceins; D005456:Fluorescent Dyes; D010710:Phosphates; D002857:Chromium; C024098:6-carboxyfluorescein; D004247:DNA; D004492:Edetic Acid