Synthesis, crystal structure and biological properties of a cis-di­chlorido­bis­(di­imine)­copper(II) complex

The mechanisms of inter­action of inorganic complexes with DNA are important in the design and development of new metal-based drug mol­ecules. The limitations of cis-platin have encouraged the design and development of new metal-based target-specific anti­cancer drugs having reduced side effects. The com­plex cis-di­chlorido­bis­(1,2,5-thia­diazolo[3,4-f][1,10]phenanthroline-κ²N¹,N¹⁰)copper(II), [CuCl₂(C₁₂H₆N₄S)₂], has been synthesized and characterized. The complex crystallizes in the monoclinic space group C2/c. The covalent binding of the complex with DNA was studied by absorption spectroscopy. The anti­cancer activity of the complex on the Human Lung Carcinoma (A549) cell line was investigated by MTT assay. The complex exhibits higher toxicity than cis-platin and induces an apoptotic mode of cell death.

Computing details

Data collection: SMART (Bruker, 2014); cell refinement: SMART (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

cis-Dichloridobis(1,2,5-thiadiazolo[3,4-f][1,10]phenanthroline-κ²N¹,N¹⁰)copper(II)

Crystal data

[CuCl2(C12H6N4S)2]	F(000) = 1228
Mr = 610.98	Dx = 1.775 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.181 (4) Å	Cell parameters from 4383 reflections
b = 12.168 (5) Å	θ = 3.0–25.7°
c = 22.99 (1) Å	µ = 1.41 mm^−1
β = 92.197 (7)°	T = 298 K
V = 2286.8 (17) Å^3	Plate, blue
Z = 4	0.28 × 0.24 × 0.16 mm

Data collection

Bruker SMART CCD area detector diffractometer	1974 reflections with I > 2σ(I)
phi and ω scans	Rint = 0.033
Absorption correction: empirical (using intensity measurements) sadabs	θmax = 26.1°, θmin = 1.8°
Tmin = 0.694, Tmax = 0.806	h = −10→10
11562 measured reflections	k = −14→14
2250 independent reflections	l = −28→28

Refinement

Refinement on F^2	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.043	H-atom parameters constrained
wR(F^2) = 0.116	w = 1/[σ^2(Fo^2) + (0.059P)^2 + 4.722P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
2250 reflections	Δρmax = 0.59 e Å^−3
168 parameters	Δρmin = −0.60 e Å^−3
0 restraints

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cu1	0.5000	0.57810 (5)	0.7500	0.0462 (2)
Cl1	0.66036 (11)	0.72346 (9)	0.80884 (4)	0.0685 (3)
S1	0.66218 (14)	0.34721 (8)	0.45450 (4)	0.0648 (3)
N1	0.6788 (3)	0.5646 (2)	0.69073 (10)	0.0417 (6)
N2	0.3942 (3)	0.4572 (2)	0.68896 (12)	0.0530 (7)
N3	0.7753 (4)	0.4210 (2)	0.49855 (11)	0.0518 (7)
N4	0.5045 (4)	0.3292 (2)	0.49399 (13)	0.0588 (7)
C5	0.6413 (3)	0.5034 (2)	0.64287 (12)	0.0362 (6)
C4	0.7471 (3)	0.4960 (2)	0.59694 (12)	0.0372 (6)
C11	0.6915 (4)	0.4333 (2)	0.54656 (12)	0.0400 (6)
C6	0.4837 (3)	0.4471 (2)	0.64110 (13)	0.0391 (6)
C3	0.8977 (4)	0.5490 (3)	0.60191 (13)	0.0454 (7)
H3	0.9707	0.5449	0.5720	0.054*
C7	0.4298 (4)	0.3880 (2)	0.59198 (14)	0.0441 (7)
C12	0.5365 (4)	0.3814 (2)	0.54411 (13)	0.0446 (7)
C1	0.8235 (4)	0.6141 (3)	0.69432 (13)	0.0484 (7)
H1	0.8500	0.6556	0.7273	0.058*
C2	0.9369 (4)	0.6071 (3)	0.65127 (14)	0.0508 (8)
H2	1.0382	0.6414	0.6559	0.061*
C8	0.2742 (4)	0.3401 (3)	0.5925 (2)	0.0632 (10)
H8	0.2323	0.3020	0.5603	0.076*
C10	0.2498 (5)	0.4079 (3)	0.6886 (2)	0.0701 (12)
H10	0.1886	0.4122	0.7218	0.084*
C9	0.1856 (4)	0.3503 (3)	0.6409 (2)	0.0759 (13)
H9	0.0822	0.3188	0.6421	0.091*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cu1	0.0457 (3)	0.0633 (4)	0.0304 (3)	0.000	0.0113 (2)	0.000
Cl1	0.0583 (5)	0.0901 (7)	0.0585 (5)	0.0259 (5)	0.0216 (4)	0.0145 (5)
S1	0.0986 (8)	0.0612 (6)	0.0344 (4)	0.0161 (5)	−0.0014 (4)	−0.0080 (4)
N1	0.0422 (13)	0.0533 (14)	0.0300 (12)	0.0028 (11)	0.0043 (10)	−0.0009 (10)
N2	0.0418 (14)	0.0692 (18)	0.0493 (16)	0.0116 (13)	0.0177 (12)	0.0173 (13)
N3	0.0660 (18)	0.0557 (16)	0.0345 (13)	0.0086 (13)	0.0153 (12)	0.0011 (11)
N4	0.0701 (19)	0.0513 (16)	0.0538 (16)	0.0059 (14)	−0.0147 (14)	−0.0089 (13)
C5	0.0359 (14)	0.0429 (15)	0.0301 (13)	0.0053 (11)	0.0051 (10)	0.0030 (11)
C4	0.0362 (14)	0.0425 (15)	0.0331 (14)	0.0039 (11)	0.0061 (11)	0.0031 (11)
C11	0.0446 (16)	0.0428 (15)	0.0329 (14)	0.0064 (12)	0.0050 (12)	0.0024 (11)
C6	0.0334 (14)	0.0443 (15)	0.0400 (15)	0.0052 (11)	0.0079 (11)	0.0077 (12)
C3	0.0359 (15)	0.0567 (18)	0.0444 (17)	0.0031 (13)	0.0116 (12)	0.0035 (13)
C7	0.0365 (15)	0.0390 (15)	0.0568 (18)	0.0014 (12)	−0.0008 (13)	0.0071 (13)
C12	0.0499 (17)	0.0393 (15)	0.0442 (16)	0.0050 (13)	−0.0046 (13)	−0.0002 (13)
C1	0.0472 (17)	0.0589 (19)	0.0388 (16)	−0.0002 (14)	−0.0021 (13)	−0.0054 (14)
C2	0.0375 (16)	0.0615 (19)	0.0532 (19)	−0.0056 (14)	0.0004 (14)	0.0007 (16)
C8	0.0439 (18)	0.0489 (19)	0.096 (3)	−0.0049 (15)	−0.0023 (18)	0.0049 (19)
C10	0.048 (2)	0.077 (3)	0.088 (3)	0.0127 (18)	0.032 (2)	0.032 (2)
C9	0.0360 (18)	0.061 (2)	0.131 (4)	−0.0055 (16)	0.015 (2)	0.024 (2)

Geometric parameters (Å, º)

Cu1—Cl1	2.5579 (14)	C4—C11	1.446 (4)
Cu1—Cl1^i	2.5579 (14)	C4—C3	1.391 (4)
Cu1—N1	2.043 (2)	C11—C12	1.415 (4)
Cu1—N1^i	2.043 (2)	C6—C7	1.396 (4)
Cu1—N2	2.189 (3)	C3—H3	0.9300
Cu1—N2^i	2.189 (3)	C3—C2	1.365 (4)
S1—N3	1.617 (3)	C7—C12	1.433 (4)
S1—N4	1.620 (4)	C7—C8	1.401 (4)
N1—C5	1.354 (4)	C1—H1	0.9300
N1—C1	1.329 (4)	C1—C2	1.385 (4)
N2—C6	1.350 (4)	C2—H2	0.9300
N2—C10	1.324 (5)	C8—H8	0.9300
N3—C11	1.330 (4)	C8—C9	1.356 (6)
N4—C12	1.333 (4)	C10—H10	0.9300
C5—C4	1.394 (4)	C10—C9	1.387 (6)
C5—C6	1.460 (4)	C9—H9	0.9300
Cl1^i—Cu1—Cl1	92.51 (6)	N3—C11—C4	124.6 (3)
N1^i—Cu1—Cl1	93.93 (8)	N3—C11—C12	114.0 (3)
N1—Cu1—Cl1^i	93.93 (8)	C12—C11—C4	121.4 (3)
N1—Cu1—Cl1	92.44 (8)	N2—C6—C5	116.1 (3)
N1^i—Cu1—Cl1^i	92.44 (8)	N2—C6—C7	122.8 (3)
N1—Cu1—N1^i	170.78 (15)	C7—C6—C5	121.0 (3)
N1^i—Cu1—N2	95.62 (10)	C4—C3—H3	120.4
N1—Cu1—N2^i	95.62 (10)	C2—C3—C4	119.2 (3)
N1—Cu1—N2	78.11 (10)	C2—C3—H3	120.4
N1^i—Cu1—N2^i	78.11 (10)	C6—C7—C12	117.9 (3)
N2—Cu1—Cl1	170.44 (7)	C6—C7—C8	117.7 (3)
N2—Cu1—Cl1^i	86.76 (8)	C8—C7—C12	124.4 (3)
N2^i—Cu1—Cl1^i	170.44 (7)	N4—C12—C11	113.1 (3)
N2^i—Cu1—Cl1	86.76 (8)	N4—C12—C7	125.8 (3)
N2—Cu1—N2^i	95.52 (15)	C11—C12—C7	121.0 (3)
N3—S1—N4	99.95 (14)	N1—C1—H1	118.4
C5—N1—Cu1	116.15 (19)	N1—C1—C2	123.2 (3)
C1—N1—Cu1	125.5 (2)	C2—C1—H1	118.4
C1—N1—C5	118.3 (3)	C3—C2—C1	118.9 (3)
C6—N2—Cu1	111.7 (2)	C3—C2—H2	120.5
C10—N2—Cu1	129.8 (3)	C1—C2—H2	120.5
C10—N2—C6	117.7 (3)	C7—C8—H8	120.5
C11—N3—S1	106.3 (2)	C9—C8—C7	119.0 (4)
C12—N4—S1	106.6 (2)	C9—C8—H8	120.5
N1—C5—C4	121.6 (3)	N2—C10—H10	118.5
N1—C5—C6	116.9 (2)	N2—C10—C9	123.0 (4)
C4—C5—C6	121.5 (3)	C9—C10—H10	118.5
C5—C4—C11	117.1 (3)	C8—C9—C10	119.7 (3)
C3—C4—C5	118.8 (3)	C8—C9—H9	120.1
C3—C4—C11	124.1 (3)	C10—C9—H9	120.1

Symmetry code: (i) −x+1, y, −z+3/2.