Synthesis, crystal structure and anti­cancer activity of the complex chlorido­(η2-ethyl­ene)(quinolin-8-olato-κ2N,O)platinum(II) by experimental and theoretical methods

Chi, N.T.T.; Tuan Cuong, N.; Thu Trang, T.; Van Thong, P.; Linh, N.T.B.; Ly, N.T.K.; Van Meervelt, L.

doi:10.1107/S2056989024003748

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ISSN: 2056-9890

Volume 80| Part 5| May 2024| Pages 550-554

https://doi.org/10.1107/S2056989024003748

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Synthesis, crystal structure and anticancer activity of the complex chlorido(η²-ethylene)(quinolin-8-olato-κ²N,O)platinum(II) by experimental and theoretical methods

Nguyen Thi Thanh Chi,^a ^* Ngo Tuan Cuong,^a Tran Thu Trang,^a Pham Van Thong,^a,^b Nguyen Thi Bang Linh,^a Nguyen Thi Khanh Ly ^a and Luc Van Meervelt ^c ^*

^aDepartment of Chemistry, Hanoi National University of Education, 136 Xuan Thuy, Cau Giay, Hanoi, Vietnam, ^bR&D Center, Vietnam Education and Technology Transfer JSC, Hanoi, Vietnam, and ^cDepartment of Chemistry, KU Leuven, Biomolecular Architecture, Celestijnenlaan 200F, Leuven (Heverlee), B-3001, Belgium
^*Correspondence e-mail: chintt@hnue.edu.vn, luc.vanmeervelt@kuleuven.be

Edited by S.-L. Zheng, Harvard University, USA (Received 2 April 2024; accepted 24 April 2024; online 30 April 2024)

The complex [Pt(C₉H₆NO)Cl(C₂H₄)], (I), was synthesized and structurally characterized by ESI mass spectrometry, IR, NMR spectroscopy, DFT calculations and X-ray diffraction. The results showed that the deprotonated 8-hydroxyquinoline (C₉H₆NO) coordinates with the Pt^II atom via the N and O atoms while the ethylene coordinates in the η² manner and in the trans position compared to the coordinating N atom. The crystal packing is characterized by C—H⋯O, C—H⋯π, Cl⋯π and Pt⋯π interactions. Complex (I) showed high selective activity against Lu-1 and Hep-G2 cell lines with IC₅₀ values of 0.8 and 0.4 µM, respectively, 54 and 33-fold more active than cisplatin. In particular, complex (I) is about 10 times less toxic to normal cells (HEK-293) than cancer cells Lu-1 and Hep-G2. Furthermore, the reaction of complex (I) with guanine at the N7 position was proposed and investigated using the DFT method. The results indicated that replacement of the ethylene ligand with guanine is thermodynamically more favorable than the Cl ligand and that the reaction occurs via two consecutive steps, namely the replacement of ethylene with H₂O and the water with the guanine molecule.

Keywords: platinum(II) complex; crystal structure; anticancer activity; 8-hydroxyquinoline; DFT.

CCDC reference: 2350722

1. Chemical context

8-Hydroxyquinoline (C₉H₆OH) and its complexes are well-known heterocyclic compounds in the pharmaceutical field due to their excellent biological activities (Song et al., 2015 ; Cherdtrakulkiat et al., 2016 ; Oliveri & Vecchio, 2016 ; Gupta et al., 2021 ; Prachayasittikul et al., 2013 ; Bissani Gasparin & Pilger, 2023 ). Recently, many complexes of the type [Pt(C₉H₆O)Cl(L)] (L = arylolefin, dimethyl sulfoxide, 1,3,5-triaza-7-phosphaadamantane) have been synthesized and tested for in vitro activity on many human cancer cell lines (Da et al., 2015 ; Thanh Chi et al., 2017 ; Nguyen Thi Thanh et al., 2017 ; Chi et al., 2018 ; Živković et al., 2018 ; Yang et al., 2023 ; Meng et al., 2016 ). The results illustrated that most of the complexes showed high activity on the tested cell lines. However, the crystal structure and anticancer activity of the simplest olefin-containing complexes and 8-hydroxyquinoline derivative have less information available (Al-Najjar & Al-Lohedan, 1990 ).

Complex [Pt(C₉H₆O)Cl(C₂H₄)] (I) was synthesized by the reaction between Zeise's salt and 8-hydroxyquinoline in ethanol/water solvent with the molar ratio of Zeise's salt:8-hydroxyquinoline being 1:1 (Fig. 1). The reaction was carried out at ambient temperature and complex (I) was formed in a high yield of 90% within around 3 h.

Figure 1
Synthesis of complex [Pt(C₉H₆O)Cl(C₂H₄)] (I)

from Zeize's salt and 8-hydroxyquinoline.

In the negative-mode ESI-MS spectrum of (I), a base peak with the correct isotopic pattern for [PtCl₃]⁻ was observed (Fig. S1). This anion was formed as complex (I) released the C₂H₄ and C₉H₆NO ligands and added two Cl⁻ ions. Based on the IR spectrum (Fig. S2), it is not unequivocally possible to confirm the deprotonation of the OH group of 8-hydroxyquinoline since the absorption band characteristic of ν_OH around 3500 cm⁻¹ decreased only slightly compared to the free ligand. In the ¹H NMR spectrum of (I), the resonance signal at 4.90 ppm with an intensity of 4H corresponds to the ethylenic protons (Fig. S3). Upon coordination to Pt^II, this signal has clear ¹⁹⁵Pt satellites with ²J_PtH = 60 Hz and shifts upfield in comparison to that of non-coordinated ethylene (5.28 ppm; König et al., 2012 ). Moreover, the presence of ¹⁹⁵Pt satellites at the signal of the proton, which is two sigma bond distances away from the N atom, at 9.11 ppm with ³J_PtH = 35 Hz and the absence of signal for the OH group in the spectrum are evidence for the coordination of deprotonated 8-hydroxyquinoline with Pt^II through both the N and O atoms. Notably, the chemical shift δ of the ethylene protons in complex (I) shifts downfield compared to that in the Zeise's salt (4.246 ppm; König et al., 2012), demonstrating that the C₉H₆NO ligand has weakened the Pt—(C=C) bond in complex (I). In other words, the bond order of ethylene decreases in the following order: free ethylene > complex (I) > Zeise's salt. This conclusion is further strengthened by comparing the C=C bond distances in free ethylene, complex (I) and Zeise's salt (Black et al., 1969 ), which are 1.34, 1.379 (10) and 1.44 Å, respectively. In the NOESY spectra (Fig. S4), there is no appearance of a cross peak between the protons of ethylene and the protons of 8-hydroxyquinoline. This suggests that the nitrogen heteroatom of 8-hydroxyquinoline and the ethylene are not cis but trans to one another in the Pt^II coordination sphere.

2. Structural commentary

Complex (I) crystallizes in the monoclinic space group P2₁/c with one molecule in the asymmetric unit (Fig. 2). The central Pt^II atom displays a distorted square-planar coordination with one Cl atom, the N and O atoms of quinolin-8-olate and the C=C double bond as the coordination sphere. The Pt^II atom deviates by 0.020 (3) Å from the best plane through atoms N2, Cl12, O13 and the mid-point of the double bond (r.m.s. deviation = 0.012 Å). The C=C double bond and N atom are trans with respect to each other. The deviations of atoms Pt1, Cl12 and O13 with respect to the planar quinoline ring (r.m.s. deviation = 0.013 Å) are −0.131 (1), −0.263 (2) and −0.026 (4) Å, respectively. The virtual three-membered ring Pt1–C14–C15 makes an dihedral angle of 86.9 (5)° with the quinoline plane. A short intramolecular C3—H3⋯Cl12 contact is observed (H3⋯Cl12 distance = 2.82 Å).

Figure 2
The molecular structure of complex (I)

, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.

3. Supramolecular features

The crystal packing is mainly built up by C—H⋯O and C—H⋯π interactions (Table 1, Fig. 3). One of the quinoline H atoms (H9) forms a C—H⋯O hydrogen bond with the quinolin-8-olate O atom of an adjacent complex related by a c-glide plane [H9⋯O13ⁱ = 2.58 Å; symmetry code: (i) x, −y + $[{1\over 2}]$ , z − $[{1\over 2}]$ ]. One of the ethylene H atoms (H15B) interacts with the C6–C11 aromatic ring, which results in chain formation in the a-axis direction [H15B⋯Cg1ⁱⁱ = 2.95 (6) Å; Cg1 is the centroid of the C6–C11 ring; symmetry code: (ii) x − 1, y, z]. Furthermore, the packing shows chain formation in the c-axis direction as a result of Cl⋯π and Pt⋯π interactions [Cl12⋯Cg2ⁱⁱⁱ = 3.948 (4) Å; Pt1⋯Cg1ⁱⁱⁱ = 3.647 (3) Å; Cg2 is the centroid of the N2/C3–C6/C11 pyridine ring; symmetry code: (iii) x, y, z + 1].

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C6–C11 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C9—H9⋯O13ⁱ	0.93	2.58	3.462 (7)	159
C15—H15B⋯Cg1ⁱⁱ	0.93 (5)	2.95 (6)	3.645 (8)	133 (5)
Symmetry codes: (i) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (ii) .

Figure 3
Partial packing diagram for (I)

showing the C—H⋯O, C—H⋯π, Cl⋯π and Pt⋯π interactions (orange dashed lines). Cg1 and Cg2 are the centroids of rings C6–C11 (brown) and N2/C3–C6/C11 (blue), respectively. [Symmetry codes: (i) x, −y + $[{1\over 2}]$ , z − $[{1\over 2}]$ ; (ii) x − 1, y, z; (iii) x, y, z + 1.]

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.45, update of March 2024; Groom et al., 2016 ) for Pt complexes coordinated to Cl, N, O and C=C resulted in ten hits. The average Pt—Cl (2.289 Å), Pt—N (2.060 Å) and Pt—O (2.012 Å) distances agree well with the distances in (I), which are 2.2951 (18) Å, 2.041 (5) Å and 2.004 (4) Å, respectively. The average distance between Pt and the mid-point of the C=C double bond of 2.040 Å is also comparable with the equivalent distance of 2.023 (5) in (I).

Except for chloro-(pentafluorophenolato)(η²-o-vinyl-N,N-dimethylaniline)platinum(II) (refcode PFPVAP; Cooper et al., 1978 ) and cis-chloro(sarcosine-N,O)-(η²-2-methyl-3-buten-2-ol)platinum(II) (SOLCAX; Erickson et al., 1991 ), the double bond and the N atom are in a trans position with respect to each other.

Similar to the title compound, the N and O atoms are part of 8-hydroxyquinoline in three structures: chloro(5,7-dichloroquinolin-8-olato){2-methoxy-4-[prop-2-en-1-yl]phenol}platinum(II) (SEMXEQ; Nguyen Thi Thanh et al., 2017), chloro(propyl{2-methoxy-4-[prop-2-en-1-yl]phenoxy}acetate)(quinolin-8-olato)platinum(II) (HISBAP; Chi et al., 2018) and chloro(propan-2-yl{2-methoxy-4-[prop-2-en-1-yl]phenoxy}acetate)(quinolin-8-olato)platinum(II) (HISBET; Chi et al., 2018).

For 1095 Pt complexes with a double bond as a ligand for Pt, the average distance from Pt to the mid-point of the double bond is 2.071 Å, with minimum and maximum values 1.837 and 2.435 Å, respectively.

5. In vitro cytotoxicity

The in vitro anticancer activity of complex (I) was investigated on four human cancer cell lines, namely KB, Hep-G2, Lu-1, and MCF-7 and the normal cell line HEK-293. The results in Table 2 show that complex (I) exhibits significant activity against the Lu-1 and Hep-G2 cell lines with IC₅₀ values of 0.8 and 0.4 µM, respectively, 54 and 33-fold more active than cisplatin. Compared to the series of complexes [Pt(C₉H₆NO)Cl(arylolefin)] (arylolefin = safrole, eugenol, methyleugenol, propyl/isopropyl eugenoxyacetate), complex (I) shows equivalent activity but is more selective on the Lu-1 and Hep-G2 cell lines. Remarkably, complex (I) is approximately 10 times less toxic to normal cell (HEK-293) than cancer cells Lu-1 and Hep-G2.

Table 2
In vitro cytotoxicity of complex (I) and some reference compounds, IC₅₀^a in μM

Values highlighted in bold are the lowest values.

Complexes	KB	Lu-1	Hep-G2	MCF-7	HEK-293
[Pt(C₉H₆NO)Cl(C₂H₄)] (I)	32.1	0.8	0.4	31.1	4.48
Ellipticine	1.14	1.30	1.71	1.95	–
Cisplatin^b	15.2	42.9	13.3	45.7	–
[Pt(C₉H₆NO)Cl(arylolefin)]^c	0.39–1.45	0.44–8.17	0.38–9.58	0.61–9.04	–
Notes: (a) IC₅₀ is the concentration of the compound required to inhibit cell growth by 50%. References: (b) Nguyen Thi Thanh et al. (2017); (c) Da et al. (2015); Thanh Chi et al. (2017); Nguyen Thi Thanh et al. (2017); Chi et al. (2018).

6. Density function theory calculations

To provide information supporting the experimental study of the anticancer activity of complex (I), we performed several quantum chemical calculations using density functional theory (DFT), which is implemented in the Gaussian 09 program package (Frisch et al., 2016 ). Firstly, the geometric structure of complex (I) was optimized, followed by the frequency calculation, to ensure that the obtained structure was a minimum energy structure. The long-range corrected version of Becke Three-Parameter Hybrid Functionals (B3LYP) by Handy and colleagues using the Coulomb attenuation method, CAM-B3LYP (Yanai et al., 2004 ) was used. The contracted Gaussian basis sets with polarization and diffuse functions 6-311+G(d) (McLean & Chandler, 1980 ) were used for C, H, O, N, Cl atoms and the Dunning's correlation consistent basis sets, also with diffuse functions Aug-cc-pVDZ-PP was used for the Pt atom (Pritchard et al., 2019 ). The optimized structure is shown in Fig. S5. The bond lengths and bond angles of the coordination environment calculated by the DFT and determined by the XRD of complex (I) show a good agreement (Table S1). This also indicates that the CAM B3LYP//6-31+G(d)/ccpVDZ-PP method is suitable for investigating the complex.

Secondly, based on the mechanism of the interaction of cisplatin with DNA (Johnstone et al., 2016 ), the reaction of complex (I) with guanine at the N7 position was proposed and investigated. Two possible reaction routes were considered:

(1) [Pt(C₉H₆NO)Cl(C₂H₄)] + guanine → [Pt(C₉H₆NO)(C₂H₄)(guanine)]⁺ + Cl⁻

(2) [Pt(C₉H₆NO)Cl(C₂H₄)] + guanine → [Pt(C₉H₆NO)Cl(guanine)] + C₂H₄

In order to know which reaction is thermodynamically more favorable, we optimized the geometric structures of the products [Pt(C₉H₆NO)(C₂H₄)(guanine)]⁺ and [Pt(C₉H₆NO)Cl(guanine)], as well as all species in the two reaction pathways, also followed by the frequency calculations, using the same functional and basis set as for complex (I). Then, the enthalpy changes and Gibbs free energy of the two reaction pathways were evaluated; the results are listed in Table S2.

The calculations show that reaction route (2), which corresponds to replacement of the neutral molecule C₂H₄, which has a small negative ΔG⁰₂₉₈ of −8.9 kJ mol⁻¹, is thermodynamically more favorable than route (1), which corresponds to replacement of a Cl⁻ anion by a guanine molecule with a largely positive ΔG⁰₂₉₈ of 392.7 kJ mol⁻¹.

Complex (I) could undergo a substitution reaction by replacing the Cl or C₂H₄ ligands with a water molecule. Each of the above reaction pathways (1) and (2) can therefore take place simultaneously in two reaction steps, which are represented by the following chemical equations:

(1a) [Pt(C₉H₆NO)Cl(C₂H₄)] + H₂O → [Pt(C₉H₆NO)(C₂H₄)(H₂O)]⁺ + Cl⁻

(1b) [Pt(C₉H₆NO)(C₂H₄)(H₂O)]⁺ + guanine → [Pt(C₉H₆NO)(C₂H₄)(guanine)]⁺ + H₂O

and

(2a) [Pt(C₉H₆NO)Cl(C₂H₄)] + H₂O → [Pt(C₉H₆NO)Cl(H₂O)] + C₂H₄;

(2b) [Pt(C₉H₆NO)Cl(H₂O)] + guanine → [Pt(C₉H₆NO)C(lguanine)] + H₂O.

Using the same types of calculations as for reaction paths (1) and (2) above, the enthalpy changes and Gibbs free energies of reaction steps (1a), (1b), (2a) and (2b) were evaluated (Table S3). The results indicate that steps (1a) and (2a) with ΔG⁰₂₉₈ = 511.6 and 36.2 kJ mol⁻¹, respectively, are thermodynamically unfavorable compared to steps (1b) and (2b) with ΔG⁰₂₉₈ = −118. 9 and −45.1 kJ mol⁻¹, respectively. Substitution of the Cl ligand by water, step (1a), is significantly unfavorable compared to substitution of the C₂H₄ ligand, step (2a).

The transition states connecting reactants and products for reaction steps (2a) and (2b) were obtained with the same CAM B3LYP//6-31+G(d)/ccpVDZ-PP method, each of them has one imaginary frequency only, which corresponds to the stretching vibration mode where H₂O replaces the C₂H₄ molecule for reaction step (2a), and guanine replaces the H₂O molecule for reaction step (2b). The activation energy E_a for each reaction step was then evaluated, namely 123.7 kJ mol⁻¹ for step (2a) (Fig. S6) and ca 51.4 kJ mol⁻¹ for step (2b) (Fig. S7).

7. Synthesis and crystallization

A solution of 8-hydroxyquinoline (73 mg, 0.5 mmol) in 5 mL of ethanol was slowly added to a solution of Zeise's salt (193 mg, 0.5 mmol) in 10 mL of water while being stirred at ambient temperature for 15 min. After continuing to stir for another 2 h, the reaction mixture was left undisturbed for 30 min. The yellow precipitate was then filtered off and washed consecutively with water (2 × 5 mL) and cold ethanol (1 × 3 mL), and finally dried under vacuum at 318 K for 3 h. The yield was 181 mg (90%). Yellow crystals suitable for X-ray diffraction were obtained by slow evaporation over 24 h from a saturated chloroform/ethanol solution (1:1, v/v) at ambient temperature. ¹H NMR (CDCl₃, 500 MHz): δ 9.11 (dd, ³J = 5.0 Hz, ⁴J = 1.0 Hz, ³J_PtH = 35 Hz, 1H, Ar-H), 8.47 (dd, ³J = 8.0 Hz, ⁴J = 1.0 Hz, 1H, Ar-H), 7.58 (dd, ³J = 8.0 Hz, 5.0 Hz, 1H, Ar-H), 7.46 (t, ³J = 8.0 Hz, 1H, Ar-H), 7.09 (d, ³J = 8.0 Hz, 1H, Ar-H), 7.06 (d, ³J = 8.0 Hz, 1H, Ar-H), 4.90 (s, ²J_PtH = 60 Hz, 4H, C₂H₄). –ESI MS (m/z, intensity): 302, 100%, [M – C₉H₆NO – C₂H₄ + 2Cl]⁻. FT-IR (KBr pellet, cm⁻¹): 3052, 2969 (CH), 1575, 1500 (C=C).

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. The ethylene hydrogen atoms were located in difference-Fourier maps and were refined isotropically with a C—H distance restraint of 0.93 (2) Å. Other hydrogen atoms were included as riding contributions in idealized positions with isotropic displacement parameters U_iso(H) = 1.2U_eq(C).

Table 3
Experimental details

Crystal data
Chemical formula	[Pt(C₉H₆NO)Cl(C₂H₄)]
M_r	402.74
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	7.9462 (5), 26.5977 (12), 5.1860 (2)
β (°)	100.613 (5)
V (Å³)	1077.31 (9)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	13.24
Crystal size (mm)	0.35 × 0.3 × 0.05

Data collection
Diffractometer	SuperNova, Single source at offset/far, Eos
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.014, 0.516
No. of measured, independent and observed [I > 2σ(I)] reflections	10730, 2197, 1836
R_int	0.071
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.076, 1.09
No. of reflections	2197
No. of parameters	152
No. of restraints	4
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.93, −1.54
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT2014/5 (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 2350722

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989024003748/oi2006sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989024003748/oi2006Isup2.hkl

DFT calculation (tables, figures). DOI: https://doi.org/10.1107/S2056989024003748/oi2006sup3.pdf

checkCIF report

Computing details top

Chlorido(η²-ethylene)(quinolin-8-olato-κ²N,O)platinum(II) top

Crystal data top

[Pt(C₉H₆NO)Cl(C₂H₄)]	F(000) = 744
M_r = 402.74	D_x = 2.483 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 7.9462 (5) Å	Cell parameters from 5770 reflections
b = 26.5977 (12) Å	θ = 2.8–28.5°
c = 5.1860 (2) Å	µ = 13.24 mm⁻¹
β = 100.613 (5)°	T = 293 K
V = 1077.31 (9) Å³	Plate, yellow
Z = 4	0.35 × 0.3 × 0.05 mm

Data collection top

SuperNova, Single source at offset/far, Eos diffractometer	2197 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Mo) X-ray Source	1836 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.071
Detector resolution: 15.9631 pixels mm^-1	θ_max = 26.4°, θ_min = 2.6°
ω scans	h = −9→9
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018)	k = −32→33
T_min = 0.014, T_max = 0.516	l = −6→6
10730 measured reflections

Refinement top

Refinement on F²	4 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.033	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.076	w = 1/[σ²(F_o²) + (0.0303P)²] where P = (F_o² + 2F_c²)/3
S = 1.09	(Δ/σ)_max = 0.001
2197 reflections	Δρ_max = 0.93 e Å⁻³
152 parameters	Δρ_min = −1.54 e Å⁻³

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Pt1	0.38307 (3)	0.36276 (2)	0.72718 (5)	0.03174 (12)
N2	0.5701 (7)	0.40559 (19)	0.6148 (10)	0.0357 (13)
C3	0.6158 (9)	0.4525 (3)	0.6764 (14)	0.0418 (17)
H3	0.563022	0.469543	0.796241	0.050*
C4	0.7414 (11)	0.4772 (3)	0.5669 (16)	0.054 (2)
H4	0.768667	0.510536	0.609190	0.065*
C5	0.8231 (10)	0.4519 (3)	0.3978 (14)	0.0471 (19)
H5	0.905763	0.468137	0.322614	0.057*
C6	0.7829 (9)	0.4010 (2)	0.3358 (12)	0.0354 (15)
C7	0.8637 (10)	0.3712 (3)	0.1672 (14)	0.0432 (19)
H7	0.950317	0.384603	0.089508	0.052*
C8	0.8121 (9)	0.3227 (3)	0.1209 (13)	0.0411 (17)
H8	0.863222	0.303451	0.006866	0.049*
C9	0.6837 (9)	0.3004 (2)	0.2395 (11)	0.0348 (15)
H9	0.654280	0.266856	0.206976	0.042*
C10	0.6030 (8)	0.3283 (2)	0.4021 (11)	0.0283 (14)
C11	0.6566 (9)	0.3790 (2)	0.4520 (11)	0.0310 (15)
Cl12	0.2795 (3)	0.42475 (7)	0.9633 (4)	0.0571 (6)
O13	0.4778 (6)	0.31029 (15)	0.5162 (8)	0.0339 (11)
C14	0.2577 (10)	0.3057 (3)	0.9145 (14)	0.0394 (18)
C15	0.1476 (10)	0.3214 (3)	0.6918 (15)	0.0408 (17)
H15A	0.140 (10)	0.302 (2)	0.540 (9)	0.07 (2)*
H14A	0.227 (8)	0.319 (2)	1.066 (8)	0.031 (18)*
H15B	0.055 (6)	0.343 (2)	0.675 (12)	0.037 (19)*
H14B	0.338 (9)	0.280 (2)	0.914 (16)	0.10 (3)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Pt1	0.0326 (2)	0.03370 (18)	0.03123 (17)	0.00135 (10)	0.01189 (13)	0.00116 (9)
N2	0.046 (4)	0.032 (3)	0.033 (3)	0.000 (3)	0.017 (3)	0.000 (2)
C3	0.038 (5)	0.040 (4)	0.047 (4)	−0.002 (3)	0.007 (3)	−0.004 (3)
C4	0.057 (6)	0.036 (4)	0.070 (5)	−0.009 (4)	0.014 (5)	−0.015 (4)
C5	0.034 (5)	0.052 (5)	0.058 (5)	−0.016 (4)	0.017 (4)	0.001 (4)
C6	0.032 (4)	0.039 (4)	0.036 (3)	−0.002 (3)	0.007 (3)	0.004 (3)
C7	0.040 (5)	0.052 (5)	0.039 (4)	−0.004 (3)	0.012 (3)	−0.001 (3)
C8	0.033 (4)	0.053 (5)	0.039 (4)	−0.003 (3)	0.011 (3)	−0.008 (3)
C9	0.039 (4)	0.032 (3)	0.034 (3)	−0.001 (3)	0.008 (3)	−0.003 (3)
C10	0.021 (4)	0.036 (3)	0.029 (3)	−0.001 (3)	0.007 (3)	0.003 (3)
C11	0.032 (4)	0.032 (3)	0.028 (3)	−0.005 (3)	0.002 (3)	−0.001 (3)
Cl12	0.0660 (15)	0.0478 (11)	0.0678 (13)	0.0010 (10)	0.0389 (12)	−0.0107 (9)
O13	0.036 (3)	0.028 (2)	0.043 (2)	−0.006 (2)	0.021 (2)	−0.0002 (19)
C14	0.041 (5)	0.044 (4)	0.038 (4)	0.005 (4)	0.021 (4)	0.006 (3)
C15	0.025 (4)	0.051 (5)	0.045 (4)	0.003 (3)	0.003 (3)	0.001 (4)

Geometric parameters (Å, º) top

Pt1—N2	2.041 (5)	C6—C11	1.390 (9)
Pt1—Cl12	2.2951 (18)	C7—H7	0.9300
Pt1—O13	2.004 (4)	C7—C8	1.363 (9)
Pt1—C14	2.143 (7)	C8—H8	0.9300
Pt1—C15	2.149 (8)	C8—C9	1.414 (9)
N2—C3	1.321 (8)	C9—H9	0.9300
N2—C11	1.378 (8)	C9—C10	1.368 (8)
C3—H3	0.9300	C10—C11	1.424 (8)
C3—C4	1.399 (10)	C10—O13	1.336 (7)
C4—H4	0.9300	C14—C15	1.379 (10)
C4—C5	1.362 (10)	C14—H14A	0.93 (2)
C5—H5	0.9300	C14—H14B	0.94 (2)
C5—C6	1.414 (9)	C15—H15A	0.93 (2)
C6—C7	1.418 (9)	C15—H15B	0.93 (2)

N2—Pt1—Cl12	95.90 (15)	C8—C7—H7	120.6
N2—Pt1—C14	161.5 (3)	C7—C8—H8	118.7
N2—Pt1—C15	158.4 (3)	C7—C8—C9	122.6 (6)
O13—Pt1—N2	82.32 (19)	C9—C8—H8	118.7
O13—Pt1—Cl12	178.18 (12)	C8—C9—H9	120.1
O13—Pt1—C14	90.4 (2)	C10—C9—C8	119.9 (6)
O13—Pt1—C15	90.3 (2)	C10—C9—H9	120.1
C14—Pt1—Cl12	91.4 (2)	C9—C10—C11	117.8 (6)
C14—Pt1—C15	37.5 (3)	O13—C10—C9	123.4 (6)
C15—Pt1—Cl12	91.2 (2)	O13—C10—C11	118.8 (5)
C3—N2—Pt1	129.8 (5)	N2—C11—C6	122.1 (6)
C3—N2—C11	119.1 (6)	N2—C11—C10	115.5 (5)
C11—N2—Pt1	111.1 (4)	C6—C11—C10	122.3 (6)
N2—C3—H3	119.0	C10—O13—Pt1	112.2 (4)
N2—C3—C4	122.0 (7)	Pt1—C14—H14A	109 (4)
C4—C3—H3	119.0	Pt1—C14—H14B	98 (5)
C3—C4—H4	120.4	C15—C14—Pt1	71.5 (4)
C5—C4—C3	119.3 (7)	C15—C14—H14A	112 (4)
C5—C4—H4	120.4	C15—C14—H14B	123 (5)
C4—C5—H5	119.8	H14A—C14—H14B	124 (7)
C4—C5—C6	120.3 (7)	Pt1—C15—H15A	106 (5)
C6—C5—H5	119.8	Pt1—C15—H15B	110 (4)
C5—C6—C7	124.4 (6)	C14—C15—Pt1	71.0 (4)
C11—C6—C5	117.0 (6)	C14—C15—H15A	118 (5)
C11—C6—C7	118.5 (6)	C14—C15—H15B	130 (4)
C6—C7—H7	120.6	H15A—C15—H15B	110 (6)
C8—C7—C6	118.8 (6)

Pt1—N2—C3—C4	−175.9 (6)	C7—C6—C11—N2	−178.9 (6)
Pt1—N2—C11—C6	175.9 (5)	C7—C6—C11—C10	−1.7 (10)
Pt1—N2—C11—C10	−1.5 (7)	C7—C8—C9—C10	1.9 (11)
N2—C3—C4—C5	−2.1 (12)	C8—C9—C10—C11	−2.0 (9)
C3—N2—C11—C6	−4.5 (10)	C8—C9—C10—O13	178.3 (6)
C3—N2—C11—C10	178.1 (6)	C9—C10—C11—N2	179.4 (6)
C3—C4—C5—C6	−0.7 (12)	C9—C10—C11—C6	2.0 (9)
C4—C5—C6—C7	−178.5 (7)	C9—C10—O13—Pt1	−177.4 (5)
C4—C5—C6—C11	0.8 (11)	C11—N2—C3—C4	4.6 (11)
C5—C6—C7—C8	−179.3 (7)	C11—C6—C7—C8	1.4 (11)
C5—C6—C11—N2	1.8 (10)	C11—C10—O13—Pt1	2.9 (7)
C5—C6—C11—C10	179.0 (6)	O13—C10—C11—N2	−0.9 (8)
C6—C7—C8—C9	−1.5 (11)	O13—C10—C11—C6	−178.3 (6)

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the C6–C11 ring.

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9···O13ⁱ	0.93	2.58	3.462 (7)	159
C15—H15B···Cg1ⁱⁱ	0.93 (5)	2.95 (6)	3.645 (8)	133 (5)

Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) x−1, y, z.

In vitro cytotoxicity of complex (I) and some reference compounds, IC₅₀^a in µM top

Values highlighted in bold are the lowest values.

Complexes	KB	Lu-1	Hep-G2	MCF-7	HEK-293
[Pt(C₉H₆NO)Cl(C₂H₄)] (I)	32.1	0.8	0.4	31.1	4.48
Ellipticine	1.14	1.30	1.71	1.95	–
Cisplatin	15.2	42.9	13.3	45.7	–
[Pt(C₉H₆NO)Cl(arylolefin)]	0.39–1.45	0.44–8.17	0.38–9.58	0.61–9.04	–

Notes: (a) IC₅₀ is the concentration of the compound required to inhibit cell growth by 50%. References: (b) Nguyen Thi Thanh et al. (2017); (c) Da et al. (2015); Thanh Chi et al. (2017); Nguyen Thi Thanh et al. (2017); Chi et al. (2018). To which entries do (b) and (c) apply?

Acknowledgements

The authors sincerely thank the Vietnam Ministry of Education and Training for sponsoring this work under project No. B2024-SPH-17, and thank Hanoi National University of Education for providing a fruitful working environment. LVM thanks the Hercules Foundation for supporting the purchase of the diffractometer through project AKUL/09/0035.

Funding information

Funding for this research was provided by: Herculesstichting (grant No. AKUL/09/0035 to LVM); Vietnam Ministry of Education and Training (grant No. B2024-SPH-17).

References

Al-Najjar, I. M. & Al-Lohedan, H. A. (1990). Orient. J. Chem. 6, 196–201. CAS Google Scholar
Bissani Gasparin, C. & Pilger, D. A. (2023). ChemistrySelect 8, e202204219. CrossRef Google Scholar
Black, M., Mais, R. H. B. & Owston, P. G. (1969). Acta Cryst. B25, 1753–1759. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Cherdtrakulkiat, R., Boonpangrak, S., Sinthupoom, N., Prachayasittikul, S., Ruchirawat, S. & Prachayasittikul, V. (2016). Biochem. Biophys. Rep. 6, 135–141. PubMed Google Scholar
Chi, N. T. T., Thong, P. V., Mai, T. T. C. & Van Meervelt, L. (2018). Acta Cryst. C74, 1732–1743. Web of Science CSD CrossRef IUCr Journals Google Scholar
Cooper, M. K., Hair, N. J. & Yaniuk, D. W. (1978). J. Organomet. Chem. 150, 157–170. CrossRef CAS Google Scholar
Da, T. T., Hong Hai, L. T., Meervelt, L. V. & Dinh, N. H. (2015). J. Coord. Chem. 68, 3525–3536. Web of Science CSD CrossRef CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Erickson, L. E., Jones, G. S., Blanchard, J. L. & Ahmed, K. J. (1991). Inorg. Chem. 30, 3147–3155. CrossRef CAS Google Scholar
Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J. A., Peralta, J. E. Jr, Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, J. M., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, Ö., Foresman, J. B., Ortiz, J. V., Cioslowski, J. & Fox, D. J. (2016). GAUSSIAN09. Revision D. 01. Gaussian Inc., Wallingford, CT, USA. Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Gupta, R., Luxami, V. & Paul, K. (2021). Bioorg. Chem. 108, 104633. CrossRef PubMed Google Scholar
Johnstone, T. C., Suntharalingam, K. & Lippard, S. J. (2016). Chem. Rev. 116, 3436–3486. Web of Science CrossRef CAS PubMed Google Scholar
König, A., Bette, M., Bruhn, C. & Steinborn, D. (2012). Eur. J. Inorg. Chem. pp. 5881–5895. Google Scholar
McLean, A. D. & Chandler, G. S. (1980). J. Chem. Phys. 72, 5639–5648. CrossRef CAS Web of Science Google Scholar
Meng, T., Tang, S. F., Qin, Q. P., Liang, Y. L., Wu, C. X., Wang, C. Y., Yan, H. T., Dong, J. X. & Liu, Y. C. (2016). Med. Chem. Commun. 7, 1802–1811. Web of Science CSD CrossRef CAS Google Scholar
Nguyen Thi Thanh, C., Truong Thi Cam, M., Pham Van, T., Nguyen, L., Nguyen Ha, M. & Van Meervelt, L. (2017). Acta Cryst. C73, 1030–1037. CrossRef IUCr Journals Google Scholar
Oliveri, V. & Vecchio, G. (2016). Eur. J. Med. Chem. 120, 252–274. CrossRef CAS PubMed Google Scholar
Prachayasittikul, V., Prachayasittikul, S., Prachayasittikul, S. & Ruchirawat, S. (2013). Drug. Des. Dev. Ther. pp. 1157–1178. CrossRef Google Scholar
Pritchard, B. P., Altarawy, D., Didier, B., Gibson, T. D. & Windus, T. L. (2019). J. Chem. Inf. Model. 59, 4814–4820. Web of Science CrossRef CAS PubMed Google Scholar
Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England. Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Song, Y., Xu, H., Chen, W., Zhan, P. & Liu, X. (2015). Med. Chem. Commun. 6, 61–74. CrossRef CAS Google Scholar
Thanh Chi, N. T., Da, T. T., Ha, N. V. & Dinh, N. H. (2017). J. Coord. Chem. 70, 1008–1019. CrossRef Google Scholar
Yanai, T., Tew, D. & Handy, N. (2004). Chem. Phys. Lett. 393, 51–57. CrossRef CAS Google Scholar
Yang, Y., Du, L. Q., Huang, Y., Liang, C. J., Qin, Q. P. & Liang, H. (2023). J. Inorg. Biochem. 241, 112152. CrossRef PubMed Google Scholar
Živković, M. D., Kljun, J., Ilic-Tomic, T., Pavic, A., Veselinović, A., Manojlović, D. D., Nikodinovic-Runic, J. & Turel, I. (2018). Inorg. Chem. Front. 5, 39–53. Google Scholar

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