Mononuclear Fe(II)-N4Py complexes in oxidative DNA cleavage: structure, activity and mechanism

Dalton Transactions : an International Journal of Inorganic Chemistry
Qian LiGerard Roelfes

Abstract

A series of monotopic N4Py (N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine, 1) derived ligands have been prepared and evaluated in the iron catalyzed oxidative cleavage of pUC18 DNA, in the presence and absence of external reducing agent DTT. The mononuclear iron(II) complexes induce efficient DNA cleavage in air with a low catalyst loading. It was demonstrated that covalent attachment of 9-aminoacridine, ammonium group or 1,8-naphthalimide leads to increased DNA cleavage activity in the presence of a reductant. Also some complexes displayed a small degree of double-strand DNA cleavage activity. In contrast, in the absence of reducing agent, no beneficial effect of the covalently attached DNA binding moieties was observed, which was attributed to the reduction from Fe(III) to Fe(II), which is required for oxygen activation, becoming rate limiting. Mechanistic investigations revealed an important role for superoxide radicals. A proposed mechanism involves the formation of an Fe(III)-OOH intermediate as the active species or precursor.

References

Oct 1, 1977·Nucleic Acids Research·L F PovirkF Hutchinson
Jan 1, 1990·Chemico-biological Interactions·D H PeteringW E Antholine
Jul 21, 1987·Journal of Theoretical Biology·R CowanG W Grigg
Feb 26, 1982·Biochemical and Biophysical Research Communications·L O Rodriguez, S M Hecht
Jun 24, 1980·Biochemistry·S A LeskoP O Ts'o
Feb 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·J E RepineD E Pettijohn
Jan 29, 2000·Journal of Natural Products·S M Hecht
Feb 24, 2001·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·C HemmertB Meunier
Oct 24, 2001·Inorganic Chemistry·Gerard RoelfesBen L. Feringa
Dec 26, 2001·Chemical Reviews·E R Jamieson, S J Lippard
Dec 26, 2001·Chemical Reviews·K E ErkkilaJ K Barton
Nov 7, 1996·Chemical Reviews·G. Charles Dismukes
Feb 19, 2002·Chemical Reviews·Wendy Knapp Pogozelski, Thomas D. Tullius
Feb 19, 2002·Chemical Reviews·Richard M. Burger
Dec 16, 2003·Chemical Society Reviews·M Eugenio VázquezJ L Mascareñas
Feb 12, 2004·Chemical Reviews·Derek JantzJeremy M Berg
Feb 12, 2004·Chemical Reviews·Amy J WuVincent L Pecoraro
Apr 9, 2004·Journal of the American Chemical Society·Elisa BoseggiaGiuseppe Zagotto
Feb 3, 2005·Nature Reviews. Cancer·Jingyang Chen, JoAnne Stubbe
Feb 16, 2005·Accounts of Chemical Research·Helen T Chifotides, Kim R Dunbar
Apr 7, 2005·Current Opinion in Chemical Biology·Andrea Decker, Edward I Solomon
Jun 9, 2005·Journal of the American Chemical Society·Yan Jin, J A Cowan
Sep 15, 2005·Chemical Communications : Chem Comm·Ella Lai-Ming WongNianyong Zhu
Jul 13, 2006·Journal of the American Chemical Society·Raymond M DossPeter B Dervan
Dec 21, 2006·Chemical Communications : Chem Comm·Tieme A van den BergGerard Roelfes
Feb 1, 2007·Chemical Society Reviews·Michael J Hannon
Feb 28, 2007·Chemical Society Reviews·Adair D Richards, Alison Rodger
Mar 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kristie D GoodwinMillie M Georgiadis
Jul 3, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Mithun RoyAkhil R Chakravarty
Aug 9, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Juan HeLiang-Nian Ji
Jan 6, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·D Roeland BoerMiquel Coll
Jan 9, 2009·Chemistry : a European Journal·Rik P MegensGerard Roelfes
May 20, 2009·Journal of the American Chemical Society·Luis González-Bulnes, José Gallego
Jan 27, 2010·Chemical Reviews·Marguerite Pitié, Geneviève Pratviel

❮ Previous
Next ❯

Citations

Jan 10, 2012·Inorganic Chemistry·Apparao DraksharapuWesley R Browne
Apr 7, 2015·Molecular Oncology·Monique G P van der WijstMarianne G Rots
Feb 18, 2014·ACS Chemical Biology·Qian LiGerard Roelfes
Aug 5, 2015·Journal of Inorganic Biochemistry·Wei WangCheal Kim
Nov 10, 2010·Inorganic Chemistry·Qian LiGerard Roelfes

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.