TY - JOUR
T1 - Reactivity of a nitrosyl ruthenium complex and its potential impact on the fate of DNA – An in vitro investigation
AU - Martins, Patrícia H.R.
AU - Romo, Adolfo I.B.
AU - da Silva, Francisco O.N.
AU - Nascimento, Otaciro R.
AU - Rodríguez-López, Joaquín
AU - Diógenes, Izaura C.N.
AU - Lopes, Luiz G.F.
AU - Sousa, Eduardo H.S.
N1 - The authors are thankful to the Brazilian agencies CAPES, CNPq (L. G. F. Lopes 303355/2018-2, E. H. S. Sousa 309010/2021-7, I. C. N. Diógenes 311274/2020-0, Edital Universal 01/2016 403866/2016-2), FUNCAP (PPSUS12535691-9, PRONEX PR2-0101-00030.01.00/15 SPU No: 3265612/2015), FINEP (CV. 01.22.0174.00). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001, CAPES/PROEX ( 23038.000509/2020-82 ). We are also thankful to the JRL lab in the University of Illinois at Urbana-Champaign, IL – USA.
The authors are thankful to the Brazilian agencies CAPES, CNPq (L. G. F. Lopes 303355/2018-2, E. H. S. Sousa 309010/2021-7, I. C. N. Diógenes 311274/2020-0, Edital Universal 01/2016 403866/2016-2), FUNCAP (PPSUS12535691-9, PRONEX PR2-0101-00030.01.00/15 SPU No: 3265612/2015), FINEP (CV. 01.22.0174.00). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001, CAPES/PROEX (23038.000509/2020-82). We are also thankful to the JRL lab in the University of Illinois at Urbana-Champaign, IL – USA.
PY - 2023/1
Y1 - 2023/1
N2 - The role of metal complexes on facing DNA has been a topic of major interest. However, metallonitrosyl compounds have been poorly investigated regarding their reactivities and interaction with DNA. A nitrosyl compound, cis-[Ru(bpy)2(SO3)(NO)](PF6)(A), showed a variety of promising biological activities catching our attention. Here, we carried out a series of studies involving the interaction and damage of DNA mediated by the metal complex A and its final product after NO release, cis-[Ru(bpy)2(SO3)(H2O](B). The fate of DNA with these metal complexes was investigated upon light or chemical stimuli using electrophoresis, electronic absorption spectroscopy, circular dichroism, size-exclusion resin, mass spectrometry, electron spin resonance (ESR) and viscometry. Since many biological disorders involve the production of oxidizing species, it is important to evaluate the reactivity of these compounds under such conditions as well. Indeed, the metal complex B exhibited important reactivity with H2O2 enabling DNA degradation, with detection of an unusual oxygenated intermediate. ESR spectroscopy detected mainly the DMPO-OOH adduct, which only emerges if H2O2 and O2 are present together. This result indicated HOO• as a key radical likely involved in DNA damage as supported by agarose gel electrophoresis. Notably, the nitrosyl ruthenium complex did not show evidence of direct DNA damage. However, its aqua product should be carefully considered as potentially harmful to DNA deserving further in vivo studies to better address any genotoxicity.
AB - The role of metal complexes on facing DNA has been a topic of major interest. However, metallonitrosyl compounds have been poorly investigated regarding their reactivities and interaction with DNA. A nitrosyl compound, cis-[Ru(bpy)2(SO3)(NO)](PF6)(A), showed a variety of promising biological activities catching our attention. Here, we carried out a series of studies involving the interaction and damage of DNA mediated by the metal complex A and its final product after NO release, cis-[Ru(bpy)2(SO3)(H2O](B). The fate of DNA with these metal complexes was investigated upon light or chemical stimuli using electrophoresis, electronic absorption spectroscopy, circular dichroism, size-exclusion resin, mass spectrometry, electron spin resonance (ESR) and viscometry. Since many biological disorders involve the production of oxidizing species, it is important to evaluate the reactivity of these compounds under such conditions as well. Indeed, the metal complex B exhibited important reactivity with H2O2 enabling DNA degradation, with detection of an unusual oxygenated intermediate. ESR spectroscopy detected mainly the DMPO-OOH adduct, which only emerges if H2O2 and O2 are present together. This result indicated HOO• as a key radical likely involved in DNA damage as supported by agarose gel electrophoresis. Notably, the nitrosyl ruthenium complex did not show evidence of direct DNA damage. However, its aqua product should be carefully considered as potentially harmful to DNA deserving further in vivo studies to better address any genotoxicity.
KW - DNA interaction
KW - Hydrogen peroxide
KW - Nitric oxide donor
KW - Radical species
KW - Ruthenium
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UR - http://www.scopus.com/inward/citedby.url?scp=85142447113&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2022.112052
DO - 10.1016/j.jinorgbio.2022.112052
M3 - Article
C2 - 36334365
AN - SCOPUS:85142447113
SN - 0162-0134
VL - 238
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
M1 - 112052
ER -