Synthesis,Characterization And Biological Activities Of Metal Complexes With Quinolones

Quinolone is a kind of synthetic antibacterial agents with excellen t activity,low toxicity and special mechanism.Nowadays,quinolone has been one of the important bacteriophage in clinical practice.However,there are some difficulties in the study of the exact mechanism of the antibacterial action and the bacteria resistance,which make the further development of quinolone stalled.Based on the metal ions advantages,the synthesis of complexes or compounds of drug ligand has important meaning on study of quinolone.The interaction of complexes with deoxyribonucleic acid?DNA?and serum albumin has been key subject of bioinorganic chemistry.DNA is a carrier and passer of genetic information,as well as the main targets of some anticancer and antiviral.Besides,serum albumin directly affects the distribution,storage,transshipment,pharmacokinetics and toxic in biological body.Therefore studying the interaction of quinolone metal complexes with DNA and SA could help us to study the mechanism of quinolone,discover its potential biological activities,design and synthesi ze its complexes and derivatives.In the manuscript,we synthesized eight novel quinolone metal complexes with sarafloxacin,enrofloxacin,levofloxacin and ciprofloxacin.All eight complexes were structurally determined by infrared spectra,elemental analysis and single crystal analysis.1 is a mononuclear copper complex which the Cu^II coordinates with two oxygen atoms of sarafloxacin and two nitrogen atoms of N,N-diethyl ethylenediamine.The Cu^III is four-coordinate showing a distorted square planar geometry?space group:P-1;cell parameters:a=9.7524?14??,b=10.1785?14??,c=17.390?3??,?=77.262?4?°,?=88.694?4?°,?=77.069?4?°?.2 is a mononuclear zinc complex which the Zn^II coordinates with four oxygen atoms of two sarafloxacin and two nitrogen atoms of 1,2-propylene diamine.The Zn^II is six-coordinate showing a distorted octahedron?space group:P-1;cell parameters:a=10.1595?7??,b=10.2396?6??,c=22.5633?13??,?=79.613?2?°,?=87.923?2?°,?=84.552?2?°?.3 is a copper two-dimensional coordination polymer.Each crystallographically independent unit contains one Cu^II ion,deprotonated ciprofloxacin,as well as a water molecule.Cu^II is five-coordinate in a distorted tetragonal pyramid geometry,with three oxygen atoms of two ciprofloxacin,an oxygen atoms of a water molecule and a nitrogen atom of the third ciprofloxacin and ciprofloxacin ligand exhibits tetradentate chelating bridging,namely three oxygen atoms and a nitrogen atom,forming a 2D net structure?space group:Pbca;cell parameters:a=20.394?2??,b=8.2289?8??,c=26.027?3??,?=90°,?=90°,?=90°?.4 is a copper two-dimensional coordination polymer.Each crystallographically independent unit contains two Cu^II ions,two deprotonated ciprofloxacin ligands,a perchlorate anion,as well as a methanol and half water molecule.Three are two different coordination modes.The fisrt Cu^III is five-coordinate in a distorted tetragonal pyramid geometry with three oxygen atoms of two ciprofloxacin and and two oxygen atom of two water molecules.In this type of coordination mode,ciprofloxacin ligand exhibits terdentate chelating bridging,namely two oxygen atoms and a nitrogen atom.The second Cu^II is six-coordinate in distorted octahedral,with two oxygen atoms of a ciprofloxacin,two nitrogen atoms of two different ciprofloxacin,an oxygen atom of the water molecule and an oxygen atom of perchlorate anion.In this type of coordination mode,ciprofloxacin ligand exhibits tetradentate chelating bridging,namely three oxygen atoms and a nitrogen atom,forming a 2D net structure?space group:P2₁/c,cell parameters:a=24.748?10??,b=8.567?4??,c=20.870?8??,?=90°,?=98.848?11?°,?=90°?.5 is a mononuclear copper complex which the Cu ^III coordinates with two oxygen atoms of levofloxacin,two nitrogen atoms of2,2-pyridine and an oxygen atom of water molecule.The Cu^II is five-coordinate in a distorted tetragonal pyramid geometry?space group:P 1,cell parameters:a=10.598?3??,b=10.710?3??,c=15.085?4??,?=80.410?4?°,?=86.353?4?°,?=69.459?3?°?.6 is a mononuclear cobalt complex which the Co ^II coordinates with four oxygen atoms of two levofloxacin and two nitrogen atoms of phenanthroline.The Co^II is six-coordinate showing a distorted octahedron?space group:C2/c,cell parameters:a=20.360?11??,b=32.323?16??,c=10.184?5??,?=90°,?=109.733?6?°,?=90°?.7 is a mononuclear silver complex which the Ag ^I coordinates with two nitrogen atoms of two enrofloxacin and an oxygen atom of nitrate ion.The Ag^I is three-coordinate showing distorted plane triangle geometry?space group:P-1,cell parameters:a=9.9139?5??,b=13.3399?7??,c=15.3653?9??,?=79.672?2?°,?=78.900?2?°,?=71.914?2?°?.8 is a silver coordination polymer Each crystallographically independent unit contains a Ag^I ions,a deprotonated enrofloxacin ligand,a perchlorate anion,as well as one and a half water molecules,with two oxygen atoms of two enrofloxacin,a nitrogen atom of the third enrofloxacin and an oxygen atom of water molecule.The Ag^I is four-coordinate showing distorted tetrahedron geometry and enrofloxacin ligand exhibits terdentate chelating bridging,namely two carboxylate oxygen atoms and a nitrogen atom,forming a 1D line structure?space group:P-1,cell parameters:a=9.4912?8??,b=9.7931?8??,c=11.6908?10??,?=103.975?2?°,?=101.604?2?°,?=103.063?2?°?.Firstly,we studied the the antimicrobial activities of the complexes 1–6against four bacterial species by MTT and the results indicated that they exhibited enhanced or similar activities(MICs=0.066–1.513?g·mL^-1)to the free ligands(MICs=0.091–1.228?g·mL^-1).Besides,UV,circular dichroism?CD?spectroscopies and Fluorescence competitive studies with ethidium bromide?EB?studies of the interaction of quinolones and complexes 1–6 with calf-thymus DNA?CT DNA?showed that all complexes have higher binding constant to CT DNA(K_b=2.36×10⁴–3.32×10⁶ M^-1)than their ligands(5.7×10⁵ M^-1 for sarafloxacin,2.58×10⁵ M^-1 for ciprofloxacin and 2.36×10⁴ M^-1 for levofloxacin).Complex 4exhibits the highest binding constant to CT DNA and the results indicated they interact with DNA mainly via intercalation.In addition,we studied complexes 1–4with human or bovine serum albumin protein by fluorescence spectroscopy.The results exhibited good binding propensity(K=2.29×10⁴–2.0×10⁵ M^-1)to HSA or BSA with relatively high binding constant values and complex 1 has highest binding values to BSA and complex 4 has the highest binding values to HSA.