Zhou, WenhuYu, TianmengVazin, MahsaDing, JinsongLiu, Juewen2017-04-282017-04-282017-06-07http://dx.doi.org/10.1021/acs.inorgchem.6601357http://hdl.handle.net/10012/11812This document is the Accepted Manuscript version of a Published Work that appeared in final form in Inorganic Chemistry, © 2016 American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Zhou, W., Yu, T., Vazin, M., Ding, J., & Liu, J. (2016). Cr3+ Binding to DNA Backbone Phosphate and Bases: Slow Ligand Exchange Rates and Metal Hydrolysis. Inorganic Chemistry, 55(16), 8193–8200. https://doi.org/10.1021/acs.inorgchem.6601357The 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 Cr3+ for DNA binding. Recently, Cr3+ was reported to activate the Cel3d DNAzyme for RNA cleavage. Herein, the Ce13d is used to study two types of Cr3+ and DNA interactions. First, Cr3+ binds to the DNA phosphate backbone weakly through reversible electrostatic interactions, which is weakened by adding competing inorganic phosphate. However, Cr3+ coordinates with DNA nucleobases forming stable cross-links that can survive denaturing gel electrophoresis condition. The binding of Cr3+ 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 Cr3+/DNA complex cannot be dissociated by EDTA, attributable to the ultraslow ligand exchange rate of Cr3+. The binding rate follows the order of G > C > T approximate to A. Finally, Cr3+ 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 Cr3+ coordination with DNA, clarifies some inconsistency in the previous literature, and offers practically useful information for generating reproducible results.enCross-Link RepairIn-VitroChromium(III) ComplexesNucleic-AcidsAdductsCellsMechanismsDNAzymeIonsMutagenicityArticle