TY - JOUR

T1 - Water soluble palladium(ii) and platinum(ii) acyclic diaminocarbene complexes

T2 - Solution behavior, DNA binding, and antiproliferative activity

AU - Serebryanskaya, Tatiyana V.

AU - Kinzhalov, Mikhail A.

AU - Bakulev, Vladimir

AU - Alekseev, Georgii

AU - Andreeva, Anastasiya

AU - Gushchin, Pavel V.

AU - Protas, Aleksandra V.

AU - Smirnov, Andrey S.

AU - Panikorovskii, Taras L.

AU - Lippmann, Petra

AU - Ott, Ingo

AU - Verbilo, Cyril M.

AU - Zuraev, Alexander V.

AU - Bunev, Alexander S.

AU - Boyarskiy, Vadim P.

AU - Kasyanenko, Nina A.

PY - 2020/4/21

Y1 - 2020/4/21

N2 - Bis-ADC complexes cis-[Pd{C(NHC6H4NH2)N(H)R}2]Cl2 (R = Xyl 4a, Cy 4b, C6H4-4-F 4c) and cis-[Pt{C(NHC6H4NH2)N(H)R}2]Cl2 (R = Xyl 5a, Cy 5b, C6H4-4-F 5c) were synthesized via the metal-mediated coupling of two isocyanide ligands in cis-[MCl2(CNR)2] (M = Pd, Pt; R = Xyl, Cy, C6H4-4-F) and 1,2-diaminobenzene. New compounds 4c and 5a-c were characterized by HR ESI+-MS, IR, and 1H, 13C{1H} and 195Pt{1H} NMR spectroscopy; the structures of 4a and 5a were elucidated by single-crystal X-ray diffraction. The stability of the ADC complexes in aqueous media (5 mM NaCl) was monitored by UV absorption spectroscopy, HR ESI+ mass spectrometry, and 195Pt{1H} NMR spectroscopy (for 5a). Molar conductivity measurements in MeOH (ΛM = 167-173 Ω-1 mol-1 cm2) indicate that, in this solvent, the ADC complexes exist as dicationic species of [A][Q]2 type. The ADC complexes binding to CT DNA was investigated by means of spectroscopic and hydrodynamic techniques including UV absorption and circular dichroism spectroscopy, fluorescence spectroscopy, low-gradient viscometry, flow birefringence, and AFM imaging. As a result, complexes 4a and 5a were shown to bind double-stranded DNA predominantly via the formation of monofunctional adducts in the major groove of the macromolecule. Binding of the ADC complexes also provokes the formation of a large number of intermolecular DNA-DNA contacts in solution. The antiproliferative activity of all prepared ADC complexes 4a-c and 5a-c was evaluated in vitro against three human carcinoma cell lines (HT-29, MDA-MB-231, and MCF-7) and two non-tumorigenic cell lines (L929 and RC-124) and compared to that of cisplatin. Among the compounds studied, complexes 4a and 5a appeared to be the most active species with IC50 values in MCF-7 cells of about 10 μM.

AB - Bis-ADC complexes cis-[Pd{C(NHC6H4NH2)N(H)R}2]Cl2 (R = Xyl 4a, Cy 4b, C6H4-4-F 4c) and cis-[Pt{C(NHC6H4NH2)N(H)R}2]Cl2 (R = Xyl 5a, Cy 5b, C6H4-4-F 5c) were synthesized via the metal-mediated coupling of two isocyanide ligands in cis-[MCl2(CNR)2] (M = Pd, Pt; R = Xyl, Cy, C6H4-4-F) and 1,2-diaminobenzene. New compounds 4c and 5a-c were characterized by HR ESI+-MS, IR, and 1H, 13C{1H} and 195Pt{1H} NMR spectroscopy; the structures of 4a and 5a were elucidated by single-crystal X-ray diffraction. The stability of the ADC complexes in aqueous media (5 mM NaCl) was monitored by UV absorption spectroscopy, HR ESI+ mass spectrometry, and 195Pt{1H} NMR spectroscopy (for 5a). Molar conductivity measurements in MeOH (ΛM = 167-173 Ω-1 mol-1 cm2) indicate that, in this solvent, the ADC complexes exist as dicationic species of [A][Q]2 type. The ADC complexes binding to CT DNA was investigated by means of spectroscopic and hydrodynamic techniques including UV absorption and circular dichroism spectroscopy, fluorescence spectroscopy, low-gradient viscometry, flow birefringence, and AFM imaging. As a result, complexes 4a and 5a were shown to bind double-stranded DNA predominantly via the formation of monofunctional adducts in the major groove of the macromolecule. Binding of the ADC complexes also provokes the formation of a large number of intermolecular DNA-DNA contacts in solution. The antiproliferative activity of all prepared ADC complexes 4a-c and 5a-c was evaluated in vitro against three human carcinoma cell lines (HT-29, MDA-MB-231, and MCF-7) and two non-tumorigenic cell lines (L929 and RC-124) and compared to that of cisplatin. Among the compounds studied, complexes 4a and 5a appeared to be the most active species with IC50 values in MCF-7 cells of about 10 μM.

KW - NUCLEAR-MAGNETIC-RESONANCE

KW - INTERSTRAND CROSS-LINKING

KW - CARBENE COMPLEXES

KW - METAL-COMPLEXES

KW - ORGANOMETALLIC COMPOUNDS

KW - DEOXYRIBONUCLEIC-ACID

KW - HETEROCYCLIC CARBENES

KW - CIRCULAR-DICHROISM

KW - COPPER-FREE

KW - LIGANDS

UR - http://www.scopus.com/inward/record.url?scp=85083916925&partnerID=8YFLogxK

U2 - 10.1039/d0nj00060d

DO - 10.1039/d0nj00060d

M3 - Article

AN - SCOPUS:85083916925

VL - 44

SP - 5762

EP - 5773

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

IS - 15

ER -