Direct Determination of Metal Complexes' Interaction with DNA by Atomic Telemetry and Multiscale Molecular Dynamics.
The lack of molecular mechanistic understanding of the interaction between metal complexes and biomolecules hampers their potential medical use. Herein we present a robust procedure combining resonant X-ray emission spectroscopy and multiscale molecular dynamics simulations, which allows for straightforward elucidation of the precise interaction mechanism at the atomic level. The report unveils an unforeseen hydrolysis process and DNA binding of [Pt{N(p-HC6F4)CH2}2py2] (Pt103), which showed potential cytotoxic activity in the past. Pt103 preferentially coordinates to adjacent adenine sites, instead of guanine sites as in cisplatin, because of its hydrogen bond ability. Comparison with previous research on cisplatin suggests that selective binding to guanine or adenine may be achieved by controlling the acidity of the compound.
Institute of Nuclear Physics, Polish Academy of Sciences , PL-31342 Krakow, Poland.|Paul Scherrer Institute (PSI) , 5232 Villigen, Switzerland.
Joanna
http://orcid.org/0000-0001-7706-0296
J
Czapla-Masztafiak
University of Vienna , Faculty of Chemistry, Institute of Theoretical Chemistry, Währinger Str. 17, A-1090 Vienna, Austria.
Juan J
JJ
Nogueira
Institute of Nuclear Physics, Polish Academy of Sciences , PL-31342 Krakow, Poland.|ETH Zurich , Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
Ewelina
E
Lipiec
Institute of Nuclear Physics, Polish Academy of Sciences , PL-31342 Krakow, Poland.
Wojciech M
WM
Kwiatek
Centre for Biospectroscopy, School of Chemistry, Monash University , 3800 Victoria, Australia.
Bayden R
BR
Wood
School of Chemistry, Faculty of Science, Monash University , 3800 Victoria, Australia.
Glen B
GB
Deacon
Paul Scherrer Institute (PSI) , 5232 Villigen, Switzerland.
Yves
http://orcid.org/0000-0002-0301-2918
Y
Kayser
Department of Chemistry-Ånsgtröm Laboratory, Uppsala University , 751 20 Uppsala, Sweden.
Daniel L A
DL
Fernandes
Department of Chemistry-Ånsgtröm Laboratory, Uppsala University , 751 20 Uppsala, Sweden.
Mariia V
MV
Pavliuk
Paul Scherrer Institute (PSI) , 5232 Villigen, Switzerland.|Institute of Physics, Jan Kochanowski University in Kielce , Świętokrzyska 15 St., 25-406 Kielce, Poland.
Jakub
J
Szlachetko
University of Vienna , Faculty of Chemistry, Institute of Theoretical Chemistry, Währinger Str. 17, A-1090 Vienna, Austria.
Leticia
http://orcid.org/0000-0001-5112-794X
L
González
Department of Chemistry-Ånsgtröm Laboratory, Uppsala University , 751 20 Uppsala, Sweden.|Institute of Physical Chemistry, Polish Academy of Sciences , ul. Kasprzaka 44/52, 01-224 Warsaw, Poland.
Jacinto
J
Sá
D000225:Adenine / Q000737:chemistry; D002945:Cisplatin / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009944:Organoplatinum Compounds / Q000737:chemistry; D013052:Spectrometry, X-Ray Emission; D013686:Telemetry
D056831:Coordination Complexes; D009944:Organoplatinum Compounds; C448661:platinum 103; D006147:Guanine; D004247:DNA; D000225:Adenine; D002945:Cisplatin