Low-dimensional com­pounds containing bioactive ligands. XXII. First crystal structure, cytotoxic activity and DNA and HSA binding of a zirconium(IV) com­plex with 8-hy­droxy­quinoline-2-carb­oxy­lic acid

Harmošová, M.; Vilková, M.; Kello, M.; Smolko, L.; Samol'ová, E.; Šebová, D.; Potočňák, I.

doi:10.1107/S2053229623005971

Low-dimensional compounds containing bioactive ligands. XXII. First crystal structure, cytotoxic activity and DNA and HSA binding of a zirconium(IV) complex with 8-hydroxyquinoline-2-carboxylic acid

M. Harmošová, M. Vilková, M. Kello, L. Smolko, E. Samol'ová, D. Šebová and I. Potočňák

A new zirconium(IV) complex, diaquabis(8-hydroxyquinoline-2-carboxylato-κ³N,O²,O⁸)zirconium(IV) dimethylformamide disolvate, [Zr(C₁₀H₅NO₃)₂(H₂O)₂]·2C₃H₇NO or [Zr(QCa)₂(H₂O)₂]·2DMF (1) (HQCaH is 8-hydroxyquinoline-2-carboxylic acid and DMF is dimethylformamide), was prepared and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray structure analysis. Complex 1 is a mononuclear complex in which the Zr^IV atoms sit on the twofold axis and they are octacoordinated by two N and six O atoms of two tridentate anionic QCa²⁻ ligands, and two aqua ligands. Outside the coordination sphere are two DMF molecules bound to the complex unit by hydrogen bonds. The structure and stability of complex 1 in dimethyl sulfoxide were verified by NMR spectroscopy. The cytotoxic properties of 1 and HQCaH were studied in vitro against eight cancer cell lines, and their selectivity was tested on the BJ-5ta noncancerous cell line. Both the complex and HQCaH exhibited low activity, with IC₅₀ > 200 µM. DNA and human serum albumin (HSA) binding studies showed that 1 binds to calf thymus (CT) DNA via intercalation and is able to bind to the tryptophan binding site of HSA (Trp-214).

Keywords: crystal structure; cytotoxicity; Zr^IV complex; 8-hydroxyquinoline-2-carboxylic acid; low-dimensional; bioactive ligand; DNA binding; HSA binding.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229623005971/dg3041sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229623005971/dg3041Isup2.hkl Contains datablock I
	Portable Document Format (PDF) file https://doi.org/10.1107/S2053229623005971/dg3041sup3.pdf IR and NMR spectra

CCDC reference: 2280560

Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b) in WinGX (Farrugia, 2012); molecular graphics: DIAMOND (Brandenburg, 2014); software used to prepare material for publication: SHELXL2018 (Sheldrick, 2015b) and PLATON (Spek, 2020).

Diaquabis(8-hydroxyquinoline-2-carboxylato-κ³N,O²,O⁸)zirconium(IV) dimethylformamide disolvate top

Crystal data top

[Zr(C₁₀H₅NO₃)₂(H₂O)₂]·2C₃H₇NO	F(000) = 664
M_r = 647.74	D_x = 1.576 Mg m⁻³
Monoclinic, P2/n	Mo Kα radiation, λ = 0.71073 Å
a = 11.3873 (5) Å	Cell parameters from 7970 reflections
b = 9.0517 (4) Å	θ = 2.3–26.4°
c = 14.4136 (7) Å	µ = 0.47 mm⁻¹
β = 113.225 (1)°	T = 100 K
V = 1365.28 (11) Å³	Block, yellow
Z = 2	0.18 × 0.17 × 0.15 mm

Data collection top

Bruker APEXII TXS Artemis diffractometer	2802 independent reflections
Radiation source: Micro Focus Rotating Anode	2554 reflections with I > 2σ(I)
Detector resolution: 7.9 pixels mm^-1	R_int = 0.027
ω and φ scans	θ_max = 26.4°, θ_min = 2.0°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −14→12
T_min = 0.619, T_max = 0.647	k = −11→11
13542 measured reflections	l = −18→18

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.022	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.055	w = 1/[σ²(F_o²) + (0.022P)² + 0.9586P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
2802 reflections	Δρ_max = 0.37 e Å⁻³
196 parameters	Δρ_min = −0.24 e Å⁻³
0 restraints

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.

Refinement. The data collection for 1 was performed using a Bruker APEX II diffractometer equipped with a Bruker APEXII CCD detector. Data were integrated using the Bruker SAINT V8.40B Software program and scaled using the SADABS software program (SADABS, 2016). The structure was solved with SHELXT (Sheldrick, 2015a) and refined by subsequent Fourier syntheses with SHELXL2018 (Sheldrick, 2015b), implemented in WinGX program suit (Farrugia, 2012). Geometric analysis was performed with SHELXL2018, PLATON (Spek, 2009) was used to analyze the π–π interaction, while DIAMOND (Brandenburg, 2014) was used for molecular graphics.

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

	x	y	z	U_iso*/U_eq
Zr1	0.750000	0.32719 (2)	0.750000	0.01198 (7)
O2	0.71344 (10)	0.42621 (12)	0.60036 (8)	0.0153 (2)
O4	0.89979 (12)	0.49079 (13)	0.76534 (9)	0.0183 (3)
O1	0.66547 (11)	0.16143 (12)	0.80984 (8)	0.0174 (2)
O3	0.60148 (11)	0.45120 (13)	0.43466 (8)	0.0190 (2)
O5	0.97262 (12)	0.60919 (15)	0.63249 (9)	0.0271 (3)
N1	0.57147 (12)	0.23096 (14)	0.62244 (10)	0.0150 (3)
C10	0.62027 (15)	0.39356 (17)	0.51694 (11)	0.0151 (3)
N5	0.92669 (15)	0.68600 (17)	0.47237 (11)	0.0248 (3)
C14	0.39775 (16)	0.05558 (18)	0.57564 (13)	0.0214 (4)
C11	0.53278 (15)	0.27651 (17)	0.52780 (12)	0.0159 (3)
C19	0.50732 (15)	0.12427 (17)	0.64791 (13)	0.0173 (3)
C13	0.35762 (17)	0.10721 (19)	0.47538 (13)	0.0230 (4)
H13	0.284101	0.065307	0.424136	0.028*
C15	0.34366 (17)	−0.0610 (2)	0.61059 (15)	0.0274 (4)
H15	0.269909	−0.110827	0.565264	0.033*
C51	0.89798 (17)	0.62167 (19)	0.54316 (13)	0.0223 (4)
H51	0.814344	0.582384	0.524080	0.027*
C12	0.42340 (16)	0.21698 (18)	0.45110 (13)	0.0199 (3)
H12	0.395641	0.252214	0.383732	0.024*
C18	0.56296 (16)	0.08473 (17)	0.75187 (13)	0.0185 (3)
C17	0.50635 (17)	−0.03032 (19)	0.78212 (14)	0.0238 (4)
H17	0.539905	−0.061042	0.850695	0.029*
C16	0.39787 (18)	−0.1023 (2)	0.71023 (15)	0.0281 (4)
H16	0.361238	−0.182513	0.732000	0.034*
C52	1.05252 (19)	0.7488 (2)	0.49536 (15)	0.0315 (4)
H52A	1.047296	0.856800	0.496430	0.047*
H52B	1.083289	0.718483	0.443616	0.047*
H52C	1.111826	0.713425	0.561540	0.047*
C53	0.8346 (2)	0.6942 (2)	0.36867 (14)	0.0357 (5)
H53A	0.754360	0.647924	0.363207	0.053*
H53B	0.868324	0.642192	0.324761	0.053*
H53C	0.819039	0.797891	0.347962	0.053*
H1O4	0.914 (2)	0.527 (2)	0.7183 (18)	0.036 (6)*
H2O4	0.959 (2)	0.512 (3)	0.8176 (19)	0.043 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Zr1	0.01018 (12)	0.01315 (11)	0.01008 (11)	0.000	0.00130 (8)	0.000
O2	0.0136 (6)	0.0185 (5)	0.0101 (5)	−0.0015 (4)	0.0006 (5)	−0.0011 (4)
O4	0.0175 (7)	0.0233 (6)	0.0096 (6)	−0.0069 (5)	0.0008 (5)	0.0012 (5)
O1	0.0140 (6)	0.0176 (6)	0.0190 (6)	−0.0018 (4)	0.0049 (5)	0.0014 (4)
O3	0.0174 (6)	0.0245 (6)	0.0118 (5)	0.0028 (5)	0.0022 (5)	0.0009 (4)
O5	0.0275 (7)	0.0366 (7)	0.0166 (6)	−0.0100 (6)	0.0080 (5)	−0.0006 (5)
N1	0.0122 (7)	0.0136 (6)	0.0181 (7)	0.0007 (5)	0.0047 (6)	−0.0035 (5)
C10	0.0135 (8)	0.0161 (7)	0.0146 (8)	0.0042 (6)	0.0043 (7)	−0.0027 (6)
N5	0.0228 (8)	0.0338 (8)	0.0175 (7)	−0.0050 (6)	0.0074 (6)	0.0006 (6)
C14	0.0128 (8)	0.0194 (8)	0.0306 (9)	−0.0008 (6)	0.0070 (8)	−0.0067 (7)
C11	0.0130 (8)	0.0166 (7)	0.0163 (8)	0.0030 (6)	0.0040 (7)	−0.0044 (6)
C19	0.0135 (8)	0.0136 (7)	0.0250 (9)	0.0011 (6)	0.0077 (7)	−0.0035 (6)
C13	0.0138 (9)	0.0234 (9)	0.0270 (9)	−0.0018 (7)	0.0028 (7)	−0.0106 (7)
C15	0.0161 (9)	0.0245 (9)	0.0404 (11)	−0.0059 (7)	0.0097 (8)	−0.0067 (8)
C51	0.0213 (9)	0.0244 (9)	0.0225 (9)	−0.0051 (7)	0.0100 (8)	−0.0022 (7)
C12	0.0155 (9)	0.0215 (8)	0.0182 (8)	0.0021 (7)	0.0020 (7)	−0.0060 (6)
C18	0.0137 (8)	0.0164 (8)	0.0261 (9)	0.0008 (6)	0.0085 (7)	−0.0007 (6)
C17	0.0196 (9)	0.0212 (8)	0.0321 (10)	−0.0004 (7)	0.0116 (8)	0.0043 (7)
C16	0.0225 (10)	0.0226 (9)	0.0432 (11)	−0.0048 (7)	0.0172 (9)	0.0015 (8)
C52	0.0297 (11)	0.0392 (11)	0.0290 (10)	−0.0090 (9)	0.0153 (9)	0.0015 (8)
C53	0.0317 (11)	0.0510 (13)	0.0213 (10)	−0.0007 (9)	0.0073 (9)	0.0047 (9)

Geometric parameters (Å, º) top

Zr1—O1ⁱ	2.1393 (11)	C14—C13	1.412 (3)
Zr1—O1	2.1393 (11)	C14—C19	1.415 (2)
Zr1—O4ⁱ	2.2031 (12)	C11—C12	1.406 (2)
Zr1—O4	2.2032 (12)	C19—C18	1.423 (2)
Zr1—O2	2.2182 (10)	C13—C12	1.370 (3)
Zr1—O2ⁱ	2.2182 (10)	C13—H13	0.9500
Zr1—N1ⁱ	2.3074 (13)	C15—C16	1.373 (3)
Zr1—N1	2.3074 (13)	C15—H15	0.9500
O2—C10	1.2856 (19)	C51—H51	0.9500
O4—H1O4	0.82 (2)	C12—H12	0.9500
O4—H2O4	0.81 (3)	C18—C17	1.383 (2)
O1—C18	1.332 (2)	C17—C16	1.419 (3)
O3—C10	1.2347 (19)	C17—H17	0.9500
O5—C51	1.237 (2)	C16—H16	0.9500
N1—C11	1.323 (2)	C52—H52A	0.9800
N1—C19	1.346 (2)	C52—H52B	0.9800
C10—C11	1.504 (2)	C52—H52C	0.9800
N5—C51	1.323 (2)	C53—H53A	0.9800
N5—C53	1.450 (2)	C53—H53B	0.9800
N5—C52	1.453 (2)	C53—H53C	0.9800
C14—C15	1.411 (2)

O1ⁱ—Zr1—O1	90.93 (6)	C15—C14—C13	127.01 (16)
O1ⁱ—Zr1—O4ⁱ	152.20 (4)	C15—C14—C19	116.62 (16)
O1—Zr1—O4ⁱ	93.34 (4)	C13—C14—C19	116.31 (15)
O1ⁱ—Zr1—O4	93.34 (4)	N1—C11—C12	121.51 (15)
O1—Zr1—O4	152.20 (4)	N1—C11—C10	111.21 (13)
O4ⁱ—Zr1—O4	95.53 (7)	C12—C11—C10	127.28 (15)
O1ⁱ—Zr1—O2	80.39 (4)	N1—C19—C14	122.01 (15)
O1—Zr1—O2	137.20 (4)	N1—C19—C18	113.79 (14)
O4ⁱ—Zr1—O2	77.87 (4)	C14—C19—C18	124.16 (15)
O4—Zr1—O2	70.55 (4)	C12—C13—C14	120.82 (16)
O1ⁱ—Zr1—O2ⁱ	137.20 (4)	C12—C13—H13	119.6
O1—Zr1—O2ⁱ	80.39 (4)	C14—C13—H13	119.6
O4ⁱ—Zr1—O2ⁱ	70.55 (4)	C16—C15—C14	119.84 (17)
O4—Zr1—O2ⁱ	77.87 (4)	C16—C15—H15	120.1
O2—Zr1—O2ⁱ	132.33 (6)	C14—C15—H15	120.1
O1ⁱ—Zr1—N1ⁱ	70.21 (4)	O5—C51—N5	124.45 (17)
O1—Zr1—N1ⁱ	78.99 (4)	O5—C51—H51	117.8
O4ⁱ—Zr1—N1ⁱ	137.54 (5)	N5—C51—H51	117.8
O4—Zr1—N1ⁱ	76.69 (5)	C13—C12—C11	118.75 (16)
O2—Zr1—N1ⁱ	134.10 (4)	C13—C12—H12	120.6
O2ⁱ—Zr1—N1ⁱ	67.00 (4)	C11—C12—H12	120.6
O1ⁱ—Zr1—N1	78.99 (4)	O1—C18—C17	126.67 (16)
O1—Zr1—N1	70.21 (4)	O1—C18—C19	116.46 (14)
O4ⁱ—Zr1—N1	76.69 (5)	C17—C18—C19	116.87 (15)
O4—Zr1—N1	137.54 (5)	C18—C17—C16	119.70 (17)
O2—Zr1—N1	67.00 (4)	C18—C17—H17	120.2
O2ⁱ—Zr1—N1	134.10 (4)	C16—C17—H17	120.2
N1ⁱ—Zr1—N1	135.64 (7)	C15—C16—C17	122.79 (17)
C10—O2—Zr1	125.85 (10)	C15—C16—H16	118.6
Zr1—O4—H1O4	125.2 (16)	C17—C16—H16	118.6
Zr1—O4—H2O4	125.2 (17)	N5—C52—H52A	109.5
H1O4—O4—H2O4	108 (2)	N5—C52—H52B	109.5
C18—O1—Zr1	122.35 (10)	H52A—C52—H52B	109.5
C11—N1—C19	120.58 (14)	N5—C52—H52C	109.5
C11—N1—Zr1	122.30 (11)	H52A—C52—H52C	109.5
C19—N1—Zr1	117.12 (10)	H52B—C52—H52C	109.5
O3—C10—O2	124.59 (15)	N5—C53—H53A	109.5
O3—C10—C11	121.78 (14)	N5—C53—H53B	109.5
O2—C10—C11	113.63 (13)	H53A—C53—H53B	109.5
C51—N5—C53	121.29 (16)	N5—C53—H53C	109.5
C51—N5—C52	121.18 (16)	H53A—C53—H53C	109.5
C53—N5—C52	117.52 (15)	H53B—C53—H53C	109.5

Symmetry code: (i) −x+3/2, y, −z+3/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C51—H51···O2	0.95	2.35	3.097 (2)	135
C51—H51···O3	0.95	2.55	3.473 (2)	165
O4—H1O4···O5	0.82 (2)	1.79 (2)	2.5991 (17)	170 (2)
O4—H2O4···O3ⁱⁱ	0.81 (3)	1.85 (3)	2.6619 (16)	175 (2)

Symmetry code: (ii) x+1/2, −y+1, z+1/2.

¹H and ¹³C NMR data of free ligand and the complex 1 top

Atom number	Free ligand		Complex 1*
	δ_C (ppm)	δ_H (ppm)	δ_C (ppm)	δ_H (ppm)
2	144.3	–	147.1	–
		–	146.9	–
		–	144.6	–
3	120.0	8.14 (d, 8.5)	119.6	8.04 (d, 8.4)
			119.5	8.04 (overlapped)
			118.9	7.84 (d, 8.3)
4	138.4	8.56 (d, 8.5)	140.2	8.68 (d, 8.4)
			140.2	8.68 (overlapped)
			140.0	8.65 (d, 8.3)
5	117.6	7.53 (dd, 8.3, 1.2)	112.6	7.27 (d, 8.0)
			112.8	7.29 (d, 8.0))
			111.9	7.31 (d, 8.3)
6	130.3	7.63 (t, 8.4)	132.0	7.43 (t, 8.0)
			132.0	7.43 (overlapped)
			132.5	7.66 (t, 8.0)
7	112.0	7.21 (dd, 7.7, 1.2)	111.3	6.47 (d, 7.8)
			111.1	6.47 (overlapped)
			111.7	6.86 (d, 7.8)
8	153.8	–	163.8	–
		–	164.9	–
		–	163.6	–
4a	130.0	–	130.0	–
		–	130.0	–
		–	130.7	–
8a	136.5	–	139.8	–
	136.5	–	139.6	–
	136.5	–	140.0	–
9	165.1	–	169.5	–
		–	170.0	–
		–	169.5	–
8-OH	–	12.98 (br s)	–	–

Notes: (*) DMF: 7.95 (s, H), 2.89 (s, CH₃), 2.73 (s, CH₃) ppm.

Cg···Cg distance and angles (Å, °) characterizing π–π interactions in 1 top

Cg(I)···Cg(J)^a	Cg···Cg	α^b	β	γ
Cg_py1···Cg_py1ⁱ	3.5965 (10)	0.00 (8)	23.4	23.4

Symmetry code: (i) -x+1, -y, -z+1.

Notes: (a) Cg_py1 represents centroid of the pyridine ring containing the N1 atom; (b) α is the dihedral angle between planes I and J. β is the angle between the Cg(I)···Cg(J) vector and the normal to plane I. γ is the angle between the Cg(I)···Cg(J) vector and normal to plane J.

CT DNA and HSA binding parameters top

CT DNA	HSA
K_SV (M^-1)	F/F₀ [% '[%' %]]	K_SV (M^-1)	F/F₀ (%)
3.20 (16) × 10⁴	55.21	3.13 (11) × 10⁶	60.66

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Low-dimensional com­pounds containing bioactive ligands. XXII. First crystal structure, cytotoxic activity and DNA and HSA binding of a zirconium(IV) com­plex with 8-hy­droxy­quinoline-2-carb­oxy­lic acid

Supporting information

Low-dimensional compounds containing bioactive ligands. XXII. First crystal structure, cytotoxic activity and DNA and HSA binding of a zirconium(IV) complex with 8-hydroxyquinoline-2-carboxylic acid