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Water soluble palladium() and platinum() acyclic diaminocarbene complexes: solution behavior, DNA binding, and antiproliferative activity
Bis-ADC complexes cis -[Pd{C(NHC 6 H 4 NH 2 )N(H)R} 2 ]Cl 2 (R = Xyl 4a , Cy 4b , C 6 H 4 -4-F 4c ) and cis -[Pt{C(NHC 6 H 4 NH 2 )N(H)R} 2 ]Cl 2 (R = Xyl 5a , Cy 5b , C 6 H 4 -4-F 5c ) were synthesized via the metal-mediated coupling of two isocyanide ligands in cis -[MCl 2 (CNR) 2 ] (M = Pd, Pt; R...
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Published in: | New journal of chemistry 2020-04, Vol.44 (15), p.5762-5773 |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Bis-ADC complexes
cis
-[Pd{C(NHC
6
H
4
NH
2
)N(H)R}
2
]Cl
2
(R = Xyl
4a
, Cy
4b
, C
6
H
4
-4-F
4c
) and
cis
-[Pt{C(NHC
6
H
4
NH
2
)N(H)R}
2
]Cl
2
(R = Xyl
5a
, Cy
5b
, C
6
H
4
-4-F
5c
) were synthesized
via
the metal-mediated coupling of two isocyanide ligands in
cis
-[MCl
2
(CNR)
2
] (M = Pd, Pt; R = Xyl, Cy, C
6
H
4
-4-F) and 1,2-diaminobenzene. New compounds
4c
and
5a-c
were characterized by HR ESI
+
-MS, IR, and
1
H,
13
C{
1
H} and
195
Pt{
1
H} 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
195
Pt{
1
H} NMR spectroscopy (for
5a
). Molar conductivity measurements in MeOH (Λ
M
= 167-173 Ω
−1
mol
−1
cm
2
) 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 IC
50
values in MCF-7 cells of about 10 μM.
Water soluble Pd(
ii
) and Pt(
ii
)-ADC species synthesized
via
the metal-mediated coupling of isocyanides and 1,2-diaminobenzene have demonstrated antitumor potential. |
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ISSN: | 1144-0546 1369-9261 |
DOI: | 10.1039/d0nj00060d |