Synthesis and crystal structures of three organoplatinum(II) complexes bearing natural arylolefin and quinoline derivatives

The synthesis and crystal structures of three organoplatinum(II) complexes bearing natural arylolefin and quinoline derivatives are reported.


Chemical context
In cancer chemotherapy, three generations of platinum-based drugs, namely cisplatin, carboplatin and oxaliplatin, have been approved all over the world.In addition, some other platinumbased drugs are used in Asia, such as Japan (nedaplatin), China (lobaplatin) and Korea (heptaplatin) (Johnstone et al., 2016).However, these drugs cause several undesirable side effects and are not universally effective in all types of human cancer.Recently, many organoplatinum(II) complexes possessing natural arylolefin ligands and either amine or Nheterocyclic carbene have been synthesized with the aim of minimizing toxicity and diversifying hopeful anti-cancer agents.The tested cytotoxicity results show that many of them exhibit higher activity than cisplatin on some human cancer cell lines such as KB, Lu-1, Hep G2 and MCF-7 (Da et al., 2012(Da et al., , 2015;;Thi Hong Hai et al., 2019;Nguyen Thi Thanh et al., 2017;Chi et al., 2018Chi et al., , 2020;;Van Thong et al., 2022).
The assigned results of the IR and 1 H NMR spectra (see section 5) show that the amines cleave the dimers to form monomeric complexes (I)-(III), in which the amines coordinate with Pt II through the N atoms.For QOH and QCOOH, they were deprotonated at the OH/COOH group and further bonded with Pt II via the O atom to produce the chelating complexes (I) and (II).These conclusions were further strengthened by the single-crystal XRD results.Moreover, the XRD results indicate that the donor N atoms of the amine ligands and the allyl group of arylolefin in complexes (I)-(III) are in the cis position with respect to each other.

Structural commentary
Complex (I) crystallizes in the monoclinic space group P2 1 /c with one complex and a water molecule with partial occupancy of 0.473 (11) in the asymmetric unit (Fig. 2).No hydrogen atoms could be located for this water molecule, the oxygen atom O30 is in close contact with O12 [O30� � �O12 = 2.718 (8) A ˚] and O22 [O30� � �O22 = 2.945 (8) A ˚] suggesting the likelihood that the water forms hydrogen bonds to O12 and O22.The central Pt II atom displays a distorted square-

Figure 2
The molecular structure of (I), showing the atom-labeling scheme and displacement ellipsoids at the 30% probability level.Water oxygen atom O30 [occupancy 0.473 (11)] is in close contact with atoms O12 and O22 (red dotted lines).

Figure 3
The molecular structure of (II), showing the atom-labeling scheme and displacement ellipsoids at the 30% probability level.Crystals of complex (II) crystallize in the monoclinic space group P2 1 /n with one molecule in the asymmetric unit (Fig. 3).The cis position of quinoline N atom and the allyl group and the coordination of the Pt II atom is similar to that in (I) with a deviation of Pt II of 0.033 (1) A ˚from the best plane through atoms N21, O33, C6 and the midpoint of the double bond.The dihedral angle between the best planes through the C5-C10 ring (r.m.s.deviation = 0.008 A ˚) and through the quinoline ring system (r.m.s.deviation = 0.048 A ˚) is 41.72 (16) � .
Complex (III) crystallizes in the monoclinic space group P2 1 /c with one complex in the asymmetric unit (Fig. 4).The Pt II atom was found to be disordered over two positions with refined occupancies of 0.928 (7) and 0.072 (7) and a distance between both Pt components of 0.529 (17) A ˚.In the subsequent discussion, only the main position of the disordered Pt atom is used.The distorted square-planar coordination of the Pt II atom is again characterized by a cis position of the C C double bond and atom N3.The Pt II atom deviates by 0.005 (1) A ˚from the best plane through atoms Cl2, N3, C21 and the midpoint of the double bond (r.m.s.deviation = 0.026 A ˚). Complex (III) displays a short intramolecular contact O22� � �H25B (2.40A ˚) resulting from a different orientation of the side chain at C19 compared to complexes (I) and (II).This is further illustrated by the different torsion angles determining the orientation of the side chain in the three complexes: 178.4 (4) � for C16-C15-O19-C20 in (I), 179.8 (4) � for C9-C8-O13-C14 (II), and À 69.9 (5) � for C18-C19-O24-C25 (III).Compared to the two other complexes, the C16-C21 arylolefin ring (r.m.s.deviation = 0.013 A ˚) makes a larger dihedral angle of 57.38 (18) � with the best plane through the quinoline ring system (r.m.s.deviation = 0.017 A ˚).
In the crystal, molecules of (II) are connected by C-H� � �O and C-H� � �� interactions (Fig. 6).Inversion dimers are

Figure 4
The molecular structure of (III), showing the atom-labeling scheme and displacement ellipsoids at the 30% probability level.Only the major position of the disordered Pt atom is shown.
For complex (III), the molecules are linked together by C-H� � �O, C-H� � �Cl and C-H� � �� interactions (Fig. 7, Table 3).Atoms H6 and H9 of the quinoline ring system interact with ring C16-C21 and O27, respectively.At the other end of the complex, the methoxy group links with a neighboring Cl2 atom and the propyloxy group connects with an neighboring atom O24.Again, despite the presence of aromatic rings, no �-� interactions are observed in the packing.Da et al., 2015).

Database survey
Entries LOJDEW and GACYUH are comparable to complex (I), but crystallize with different unit cells.An overlay of Pt and its coordination sphere (N, O, C, C C) gives for (I) and LOJDEW an r.m.s.deviation of 0.106 A ˚, and for (I) and GACYUH 0.120 A ˚(Fig.8a).Compared to (II) and LOJDEW, the double bond of the allyl chain in GACYUH complexes is in a different orientation with Pt.This causes also a different orientation of the aromatic ring of the arylolefin ligand.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.1.195 (5)
planar coordination with the N2 and O12 atoms of the quinolin-8-olate ligand and the C13 atom and C C double bond of the arylolefin as coordination sphere.The Pt II atom deviates by 0.012 (1) A ˚from the best plane through atoms N2, O12, C13 and the midpoint of the double bond (r.m.s.deviation = 0.005 A ˚).The C C double bond and N2 atom are cis with respect to each other.The arylolefin ring C13-C18 (r.m.s.deviation = 0.007 A ˚) makes a dihedral angle of 25.79 (11) � with the best plane through the quinoline ring system (r.m.s.deviation = 0.014 A ˚).

Table 4
Experimental details.