TY - JOUR
T1 - Organoplatinum(II) Complexes Self-Assemble and Recognize AT-Rich Duplex DNA Sequences
AU - Zamora, Ana
AU - Wachter, Erin
AU - Vera, María
AU - Heidary, David K.
AU - Rodríguez, Venancio
AU - Ortega, Enrique
AU - Fernández-Espín, Vanesa
AU - Janiak, Christoph
AU - Glazer, Edith C.
AU - Barone, Giampaolo
AU - Ruiz, José
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against gene-related diseases. Here, we demonstrate that amphiphilic PtII complexes of the type [Pt(dmba)(NΛN)]NO3 (dmba = N,N-dimethylbenzylamine-κN, κC; NΛN = dpq (3), dppz (4), and dppn (5)) recognize AT-rich oligonucleotides over other types of DNA, RNA, and model proteins. The crystal structure of 4 shows the presence of significant π-stacking interactions and a distorted coordination sphere of the d8 PtII atom. Complex 5, containing the largest π-conjugated ligand, forms supramolecular assemblies at high concentrations under aqueous environment. However, its aggregation can be promoted in the presence of DNA at concentrations as low as 10 μM in a process that "turns on"its excimer emission around 600 nm. Viscometry, gel electrophoresis, and theoretical calculations demonstrate that 5 binds to minor groove when self-assembled, while the monomers of 3 and 4 intercalate into the DNA. The complexes also inhibit cancer cell growth with low-micromolar IC50 values in 2D tissue culture and suppress tumor growth in 3D tumor spheroids with a multicellular resistance (MCR) index comparable to that of cisplatin.
AB - The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against gene-related diseases. Here, we demonstrate that amphiphilic PtII complexes of the type [Pt(dmba)(NΛN)]NO3 (dmba = N,N-dimethylbenzylamine-κN, κC; NΛN = dpq (3), dppz (4), and dppn (5)) recognize AT-rich oligonucleotides over other types of DNA, RNA, and model proteins. The crystal structure of 4 shows the presence of significant π-stacking interactions and a distorted coordination sphere of the d8 PtII atom. Complex 5, containing the largest π-conjugated ligand, forms supramolecular assemblies at high concentrations under aqueous environment. However, its aggregation can be promoted in the presence of DNA at concentrations as low as 10 μM in a process that "turns on"its excimer emission around 600 nm. Viscometry, gel electrophoresis, and theoretical calculations demonstrate that 5 binds to minor groove when self-assembled, while the monomers of 3 and 4 intercalate into the DNA. The complexes also inhibit cancer cell growth with low-micromolar IC50 values in 2D tissue culture and suppress tumor growth in 3D tumor spheroids with a multicellular resistance (MCR) index comparable to that of cisplatin.
UR - http://www.scopus.com/inward/record.url?scp=85100785996&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100785996&partnerID=8YFLogxK
U2 - 10.1021/acs.inorgchem.0c02648
DO - 10.1021/acs.inorgchem.0c02648
M3 - Article
C2 - 33502194
AN - SCOPUS:85100785996
SN - 0020-1669
VL - 60
SP - 2178
EP - 2187
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 4
ER -