Arch Pharm Chem Life Sci. 2019;e1900187. wileyonlinelibrary.com/journal/ardp © 2019 Deutsche Pharmazeutische Gesellschaft | 1 of 7
https://doi.org/10.1002/ardp.201900187
Received: 3 July 2019
|
Revised: 30 August 2019
|
Accepted: 7 September 2019
DOI: 10.1002/ardp.201900187
FULL PAPER
New morpholine‐liganded palladium(II) N‐heterocyclic
carbene complexes: Synthesis, characterization, crystal
structure, and DNA‐binding studies
Ferhat Türker
1
| Canbolat Gürses
2
| Duygu Barut Celepci
3
| Aydı n Aktaş
1
|
Burhan Ateş
1
| Yetkin Gök
1
1
Department of Chemistry, Faculty of Science,
İnönü University, Malatya, Turkey
2
Department of Molecular Biology and
Genetics, Faculty of Science, İnönü University,
Malatya, Turkey
3
Department of Physics, Faculty of Science,
Dokuz Eylül University, Buca, Izmir, Turkey
Correspondence
Aydın Aktaş, Department of Chemistry, Inonu
University, 44280 Malatya, Turkey.
Email: aydinaktash@hotmail.com
Funding information
Inonu University Research Fund, Grant/Award
Number: FYL‐2019‐1446; Dokuz Eylül
University, Grant/Award Number:
2010.KB.FEN.13
Abstract
A series of the morpholine‐liganded palladium(II) complexes (1a–e) bearing
N‐heterocyclic carbene (NHC) functionalized by benzonitrile were synthesized. These
complexes were synthesized from (NHC)Pd(II)(pyridine) complexes (PEPPSI) and
morpholine. The new complexes were fully characterized by using
1
H NMR,
13
C NMR,
Fourier‐transform infrared spectroscopy, and elemental analysis techniques. Single‐
crystal X‐ray diffraction was used to determine the structure of a derivative. The
DNA‐binding studies of the new (NHC)Pd(II)morpholine complexes were examined
using the pBR322 plasmid. The 2,4,6‐trimethylbenzyl derivative compound has the
most DNA binding activity. In addition, for the 3‐methylbenzyl derivative compound,
oxidation effects were observed at concentrations higher than 100 μg/ml. Also, the
molecular and crystal structures of the complex 3‐methylbenzyl derivative compound
were recorded by using a single‐crystal X‐ray diffraction method.
KEYWORDS
DNA binding, N‐heterocyclic carbene, structure elucidation, substituent effect, synthesis
1 | INTRODUCTION
Organometallic compounds are used as drugs in the treatment of
many diseases, particularly cancer. For example, cisplatin is one of
the most widely used drugs in the treatment of cancer. Since the
discovery of cisplatin in the late 1960s by Rosenberg et al.,
[1]
studies
on the medical applications of organometallic compounds have
increased. The discovery of cisplatin allowed the development of
other metal‐based cancer drugs and the improvement of cisplatin‐
like drugs. The newly developed organometallic drugs have a less
toxic effect and are targeted to overcome drug resistance in
cancer.
[2]
Metal N‐heterocyclic carbene (M‐NHC) complexes are
one of the most important classes of these organometallic
compounds. In fact, in the early days when the M‐NHC complexes
were discovered, chemists focused on the catalytic applications of
these complexes. Recently, the number of studies on the catalytic
activities of M‐NHC complexes has increased.
[3–9]
Furthermore, the
publication of the studies on the medical applications of M‐NHC
complexes containing metals such as Pt,
[10,11]
Ru,
[12,13]
Ag,
[14,15]
Pd,
[16,17]
Rh,
[18]
Ir,
[19]
Ni,
[20]
and Cu
[21]
is increasing.
Pd(II)NHC complexes, which are one of the most important
compounds of M‐NHC complexes, have recently attracted considerable
attention. The Pd(II)NHC complexes are noteworthy for their activity in
catalytic reactions when compared with other M‐NHC complexes.
[3–9]
Besides this, significant studies have also been published in the medical
applications of Pd(II)NHC complexes. In recent years, studies on
medicinal applications such as anticancer,
[22,23]
antimicrobial and
cytotoxicity,
[24]
antitumor,
[25]
DNA interaction,
[26]
and the enzyme
inhibition effect
[17]
have been carried out for Pd(II)NHC complexes.
Also, it was reported that NHC complexes had marked inhibition effects
on some metabolic enzymes linked to global health diseases.
[27–32]
The significant outcome of M‐NHC complexes in medical applica-
tions is due to the unique electronic and structural properties of the
NHC ligands used. NHC ligands have been used as the perfect ligand for