Ternary copper(II) complexes of levofloxacin and phenanthroline derivatives: In-vitro antibacterial, DNA interactions, and SOD-like activity

Figures & data

Table 1.  Analytical and physical data of the complexes.

Empirical formula for complexes	Elemental analysis % required (found)					mp (°C)	% Yield	µeff. BM	Formula weight (g/mol)
	C	H	N	Cu	Cl
C32H41ClCuFN5O9 (1)	50.73 (50.66)	5.45 (5.63)	9.24 (9.17)	8.39 (8.35)	4.68 (4.34)	> 300	64.52	1.83	757.69
C44H49ClCuFN5O9 (2)	58.08 (58.02)	5.43 (5.37)	7.70 (7.62)	6.98 (6.91)	3.90 (3.98)	245	73.89	1.79	909.89
C30H38ClCuFN5O10 (3)	48.26 (48.30)	5.13 (5.04)	9.38 (9.29)	8.51 (8.44)	4.75 (4.66)	> 300	66.76	1.88	746.65
C30H35ClCuFN5O11 (4)	47.43 (47.36)	4.64 (4.71)	9.22 (9.28)	8.37 (8.43)	4.67 (4.72)	293	54.62	1.82	759.62
C30H36ClCuFN6O11 (5)	46.51 (46.56)	4.68 (4.74)	10.85 (10.88)	8.20 (8.16)	4.58 (4.50)	286	77.82	1.77	774.64

BM, Bohr Magneton.

Figure 1.  Basic sketch for square pyramidal copper(II) complexes derived from levofloxacin (LFLH); uninegative bidentate OO- donating, and phenanthrolines; neutral bidentate NN- donating ligands.

Table 2.  Characteristic IR bands (4000–400 cm⁻¹) of LFLH and their complexes.

Compound	ν(C=O)pyridone	ν(H–O)Carboxyl	ν(COO)asym	ν(COO)sym	Δν	ν(M–N)	ν(M–O)
LFLH	1728	3519	1634	1316	318	—	—
(1)	1628	—	1584	1350	234	534	520
(2)	1627	—	1588	1362	226	533	519
(3)	1624	—	1572	1333	239	544	522
(4)	1621	—	1576	1341	235	537	527
(5)	1626	—	1579	1348	231	542	511

IR, infrared; LFLH, levofloxacin.

Figure 2.  Fast atom bombardment (FAB)-mass spectrum of complex 1, i.e. [Cu(LFL)(A¹)Cl]·5H₂O recorded on Jeol SX 102/Da–600 mass spectrophotometer/Data system using Argon/Xenon (6 kV, 10 mA) as the FAB gas at accelerating voltage of 10 kV.

Table 3.  Antimicrobial activities of LFLH, phenanthrolines and their complexes in terms of minimum inhibitory concentration (MIC; µM).

Compounds	Gram-positive		Gram-negative.
	S. aureus	B. subtilis	S. marcescens	P. aeruginosa	E. coli
CuCl2 2H2O	2698.00	2815.00	2756.00	2404.00	3402.00
LFLH	1.70	2.20	1.70	1.70	1.00
A^1	130.00	250.00	506.00	154.00	129.00
A^2	194.00	169.00	272.00	255.00	278.00
A^3	631.00	670.00	604.00	725.00	758.00
A^4	829.00	733.00	771.00	738.00	762.00
A^5	578.00	631.00	609.00	658.00	591.00
(1)	0.68	0.66	0.43	0.73	0.48
(2)	0.88	0.44	0.44	0.88	0.83
(3)	0.63	0.54	0.40	0.58	0.45
(4)	0.35	0.46	0.38	0.33	0.40
(5)	0.33	0.40	0.32	0.61	0.37

LFLH, levofloxacin.

Table 4.  Binding constant (K_b) and 50% inhibitory concentration (IC₅₀) values of the complexes.

Complexes	Kb (M^−1)	IC50 (µM)
(1)	0.613 × 10^4	1.5000
(2)	0.584 × 10^4	1.7432
(3)	0.767 × 10^4	1.1154
(4)	0.823 × 10^4	0.9795
(5)	1.123 × 10^4	0.7917

Figure 3.  Absorption spectral traces on addition of Herring Sperm DNA to the solution of complex 1 after incubating it for 10 min at room temperature in phosphate buffer at 7.2 pH. (shown by arrow). Inset: plot of [DNA]/(ϵ_a-ϵ_f) versus [DNA] for absorption titration of Herring Sperm DNA with complex 1.

Figure 4.  Effect of increasing amount of ethidium bromide (EtBr), levofloxacin (LFLH) and complexes on the relative viscosity of Herring Sperm DNA at 27 ± 0.1°C.

Table 5.  Percentage of all the three forms of plasmid separated on agarose gel, when subjection to different synthesized complexes at 200 µM concentration.

Lane No.	Compounds	Form I (SC)	Form II (OC)	Form III (LC)
1	Control	89	11	—
2	CuCl2·2H2O	84	16	—
3	Levofloxacin	38	51	11
4	(1)	32	44	24
5	(2)	38	40	22
6	(3)	29	49	22
7	(4)	25	42	33
8	(5)	16	58	26

SC, Super coiled; OC, Open Circular; LC, Linear.

Figure 5.  Gel electrophoresis diagram showing the cleavage of SC pUC19 DNA(300 µg/mL) with as series of copper(II) complex (200 µM) in a final volume of 15 µL, incubated at 37°C, using 1% agarose gel, at 50 mV for 1.5 h. Lane 1, DNA control; Lane 2, DNA + CuCl₂·2H₂O; Lane 3, DNA + LFLH; Lane 4, DNA + [Cu(LFL)(A¹)Cl].5H₂O; Lane 5, DNA + [Cu(LFL)(A²)Cl].5H₂O; Lane 6, DNA + [Cu(LFL)(A³)Cl].5H₂O; Lane 7, DNA + [Cu(LFL)(A⁴)Cl].5H₂O; Lane 8, DNA + [Cu(LFL)(A⁵)Cl].5H₂O.

Figure 6.  Oxygen radical production by NBT/NADH/PMS system and its scavenging; Proposed mechanism for superoxide dismutase-like activity of complex checked in NBT/NADH/PMS system.