Six new derivatives of ciprofloxacin compounds and their copper(II) complexes were synthesized, characterized by spectroscopic methods (ultraviolet–visible [UV–vis], Fourier transform infrared [FTIR], nuclear magnetic resonance [NMR], mass spectrometry [MS], and electron paramagnetic resonance [EPR]), and tested for antibacterial activities against gram‐negative and gram‐positive bacteria. The data showed that ciprofloxacin derivatives act as bidentate ligands and the metal ions coordinate through the pyridone carbonyl and the carboxylate oxygen atoms. Tetragonally distorted octahedral ligand fields were assumed for all complexes based on their spectral studies. Copper(II) complexes of the synthesized ciprofloxacin derivatives revealed higher antibacterial activities against gram‐positive and gram‐negative bacterial species than the parent ciprofloxacin antibiotic. Furthermore, three‐dimensional quantitative structure–activity relationship (3D‐QSAR) models were evaluated by studying 30 antibiotic compounds of the quinolone class. Density function theory (DFT) calculations were applied to evaluate the optimized geometrical structures using the B3LYP method and 6‐311G(d,p) basis set. The 3D‐QSAR study revealed that there are eight optimum parameters that give the best predictive modulation with good reliability (R2 = 0.996, F = 12.004, sigma = 0.426). In silico molecular docking was also performed on the derivatives, and the results revealed the presence of two types of interactions between the Escherichia coli and the derivatives, H‐bonding and Van der Waals interactions, and an effective inhibition at the docked site.

The Schiff base 3-(3-hydroxypyridin-2-ylimino)-1-phenylbutan-2-one (HPIB) was synthesized and characterized by elemental analysis and IR spectra. The proton-ligand dissociation constant of HPIB and the stepwise stability constants of its metal complexes with Cu 2+ , Ni 2+ , Co 2+ , and Mn 2+ were determined potentiometrically in a 40 % (v/v) ethanol-water mixture in the presence of 0.100 M KCl under nitrogen. The stabilities of the complexes follow the order Cu 2+ > Ni 2+ > Co 2+ > Mn 2+ . The dissociation constants of HPIB and the stability constants, log K, of its metal complexes were determined at different temperatures, and the corresponding thermodynamic parameters are derived and discussed. The proton-ligand dissociation is found to be nonspontaneous, endothermic, and entropically unfavorable. The values of ∆G 0 and ∆H 0 accompanying the complex formation are related to the ionic radius, the electronegativity, the ionization enthalpy, and the hydration enthalpy of the metal ion. The order of -∆G 0 and -∆H 0 was found to obey Mn 2+ < Co 2+ < Ni 2+ < Cu 2+ , in agreement with the Irving-Williams order. The different thermodynamic parameters suggest that the complex formation is an enthalpydriven process. The speciation of the complexes is determined.

A series of ruthenium (II) complexes derived from the reaction between cis-bis (2,2 0 -bipyridine) dichloro ruthenium (II) dihydrate and enaminone derivatives of ciprofloxacin were synthesized and fully characterized using elemental analysis, cyclic voltammetry and different spectroscopic techniques (Uv-vis, FTIR, NMR, mass spectroscopy, and X-ray photoelectron spectrometry (XPS)). The isolated compounds were tested for their antibacterial and antifungal activities against gram-negative and gram-positive bacteria. The FTIR data revealed that ciprofloxacin derivatives act as bidentate ligands through the pyridone carbonyl and the carboxylate oxygen atom. The UV-visible data showed that the charge transfer CT band is blue shifted upon the coordination of the ciprofloxacin derivatives compared to the CT band of the parent complex. The XPS results revealed the characteristic peaks of Ru 3p3/2 and Ru 3p1/2 as well as Ru 3d5/2 and Ru 3d3/2 , which confirmed the assembly of the ruthenium (II) ciprofloxacin derivative complexes. Cyclic voltammetry data showed that the ciprofloxacin enaminone derivatives have a similar reduction potential for the Ru (II)/Ru (III) redox couple, and it revealed that the coordination of the ruthenium (II) ion altered the redox property of the ligands and enhanced their electron transfer rate. The electrochemical and the UV-visible results suggest that the ciprofloxacin derivative ligands are π-acceptor ligands. Further, the complexes showed higher antibacterial activities than the parent ciprofloxacin antibiotic and did not show antifungal activities among the tested fungi strains.

Aspects of the molecular and supramolecular structure of the new dinuclear [Ag(L)(NO3)]2 complex, where L is 2-((E)-(((E)-1-(thiazol-2-yl)ethylidene)hydrazono)methyl)phenol, were discussed. The complex was crystallized in the monoclinic crystal system and P21/n space group. The unit cell parameters are a = 10.3274(2) Å, b = 11.4504(3) Å, c = 12.7137(3) Å and β = 108.2560(10)°. The asymmetric unit comprised one [Ag(L)(NO3)] formula in which the azine and nitrate ligand groups act as NN- and OO-bidentate chelates, respectively. The coordination environment of the Ag(I) is completed by one weak Ag-O bond with another [Ag(L)(NO3)] unit, leading to the dinuclear formula [Ag(L)(NO3)]2. This was clearly revealed by Hirshfeld analysis. Additionally, the Ag…C, O…H and C…C intermolecular interactions played an important role in the molecular packing of the studied complex. The antimicrobial, antioxidant and cytotoxic activities of the [Ag(L)(NO3)]2 complex and the free ligand (L) were discussed. While the [Ag(L)(NO3)]2 complex showed very weak antioxidant activity, the results of the antifungal and cytotoxic activities were promising. The inhibition zone diameters (IZD) and the minimum inhibitory concentration (MIC) values were determined to be 31 mm and 20 μg/mL, respectively, against A. fumigatus, which is compared to 17 mm and 156 μg/mL, respectively, for the positive control Ketoconazole. Generally, the Ag(I) complex has better antimicrobial activities than the free ligand against all microbes except for S. aureus, where the free ligand has higher activity. Additionally, the IC50 value against colon carcinoma (HCT-116 cell line) was determined to be 12.53 ± 0.69 µg/mL, which is compared to 5.35 ± 0.49 µg/mL for cis-platin. Additionally, the Ag(I) complex displays better cytotoxicity than the free ligand (L) (242.92 ± 8.12 µg/mL).

Reactions of 2‐(1‐hydrazonoethyl)pyridine with silver salts AgX (X = NO3¯ or ClO4¯) proceeded via the hydrolysis of the pyridine ligand and the formation of the dinuclear [AgL1]2(ClO4)2 (1) and [AgL1(NO3)]2 (2) complexes of the azine ligand, 1,2‐bis(1‐(pyridin‐2‐yl)ethylidene)hydrazine (L1). The structures of the obtained complexes were determined by single crystal X‐ray diffraction. The azine ligand (L1) is acting as a bidentate ligand and connects the two Ag‐sites via the pyridine and the azine nitrogen atoms. In complex 1, the Ag(I) ion is tetra‐coordinated, while in complex 2 the Ag(I) ion is penta‐coordinated due to the presence of additional interaction with one of the oxygen atoms of the nitrate ion. As a result, the azine ligand is significantly twisted in complex 2 compared to complex 1. The optimized geometries of three conformers of L1 were calculated using DFT calculations, and their kinetic and thermodynamic stability were analyzed. It was found that a free rotation of L1 is required prior to the chelation of the Ag(I) ion. The packing in complex 1 is controlled by H…H, O…H, and Ag…O interactions, but in complex 2, the O…H and N…H interactions are the most significant. Complex 2 has better antifungal activity against Aspergillus fumigatus and Candida albicans than the antifungal drug Ketoconazole. Also, the nitrato complex 2 has a promising antioxidant activity compared to the perchlorate complex 1. The cytotoxicity against colon carcinoma HCT‐116 cell line is higher for complex 1 (IC50 = 19.72 ± 0.94 μg/ml) than complex 2 (IC50 = 68.31 ± 2.97 μg/ml).