Biological evaluation of cobalt(II) complexes with non-steroidal anti-inflammatory drug naproxen

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug naproxen in the presence or absence of nitrogen-donor heterocyclic ligands (pyridine, 2,2′-bipyridine or 1,10-phenanthroline) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated naproxen acts as monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structure of [bis(aqua)bis(naproxenato)bis(pyridine)cobalt(II)], 2 has been determined by X-ray crystallography. The EPR spectrum of complex 2 in frozen solution reveals that it retains its structure. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [(2,2′-bipyridine)bis(methanol)bis(naproxenato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Naproxen and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin proteins having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals.     

Nickel-quinolones interaction. Part 5-Biological evaluation of nickel(II) complexes with first-, second- and third-generation quinolones

The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N′-donor heterocyclic ligand 2,2′-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2′-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2′-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)₂(2,2′-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)₂(H₂O)₂], [Ni(quinolonato)₂(2,2′-bipyridine)] and [Ni(quinolonato)₂(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase.     

Non-steroidal anti-inflammatory drug diflunisal interacting with Cu(II). Structure and biological features

Copper(II) complexes with the non-steroidal anti-inflammatory drug diflunisal in the presence of N,N-dimethylformamide or nitrogen donor heterocyclic ligands (pyridine, 1,10-phenanthroline, 2,2′-bipyridine or 2,2′-bipyridylamine) have been synthesized and characterized. The deprotonated diflunisal ligands are coordinated to Cu(II) ion through carboxylato oxygen atoms. The crystal structures of [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] 1 and [bis(diflunisal)bis(pyridine)copper(II)], 2 have been determined by X-ray crystallography and are the first reported crystal structures of diflunisal complexes. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) suggests binding of the complexes to CT DNA with the dinuclear [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] compound exhibiting the highest binding constant, K_b. Intercalative binding mode may also be concluded using cyclic voltammetry and solution viscosity measurements of the complexes in the presence of CT DNA. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting competition with EB. Diflunisal and its complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values.     

Nickel-quinolones interaction. Part 2 - Interaction of nickel(II) with the antibacterial drug oxolinic acid

The mononuclear nickel(II) complexes with the first-generation quinolone antibacterial agent oxolinic acid in the presence or absence of nitrogen-donor heterocyclic ligands (2,2′-bipyridine, 1,10-phenanthroline or pyridine) have been synthesized and characterized. The experimental data suggest that oxolinic acid acts as deprotonated bidentate ligand coordinated to Ni(II) ion through the ketone and carboxylato oxygens. The crystal structure of (2,2′-bipyridine)bis(oxolinato) nickel(II), 2 has been determined by X-ray crystallography. The cyclic voltammograms of the complexes recorded in dmso solution and in 1/2 dmso/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of calf-thymus DNA (CT DNA) they can bind to CT DNA by the intercalative binding mode. UV study of the interaction of the complexes with CT DNA has shown that the complexes bind to CT DNA and bis(aqua)bis(oxolinato) nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.     

Nickel-quinolones interaction: Part 3 — Nickel(II) complexes of the antibacterial drug flumequine

Nickel(II) complexes with the first-generation quinolone antibacterial agent flumequine in the presence or absence of nitrogen donor heterocyclic ligands (4-benzylpyridine, pyridine, 2,2′-bipyridine or 1,10-phenanthroline) have been structurally characterized by physicochemical and spectroscopic techniques. The experimental data suggest that flumequine acts as deprotonated bidentate ligand coordinated to Ni(II) through the carboxylato and ketone oxygen atoms. The crystal structures of bis(4-benzylpyridine)bis(flumequinato)nickel(II) 2, (2,2′-bipyridine)bis(flumequinato)nickel(II) 4 and (1,10-phenanthroline)bis(flumequinato)nickel(II) 5 have been determined by X-ray crystallography and are the first crystal structures of flumequinato complexes reported. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes bind to CT DNA and bis(aqua)bis(flumequinato)nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in DMSO solution and in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they bind to CT DNA by the intercalative binding mode. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.     

Nickel-quinolones interaction. Part 4. Structure and biological evaluation of nickel(II)-enrofloxacin complexes compared to zinc(II) analogues

The nickel(II) complexes with the second-generation quinolone antibacterial agent enrofloxacin in the presence or absence of the nitrogen-donor heterocyclic ligands 1,10-phenanthroline, 2,2′-bipyridine or pyridine have been synthesized and characterized. Enrofloxacin acts as bidentate ligand coordinated to Ni(II) ion through the ketone oxygen and a carboxylato oxygen. The crystal structure of (1,10-phenanthroline)bis(enrofloxacinato)nickel(II) has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and bis(pyridine)bis(enrofloxacinato)nickel(II) exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the corresponding Zn(II) enrofloxacinato complexes as well as Ni(II) complexes with the first-generation quinolone oxolinic acid.     

Zinc complexes of the antibacterial drug oxolinic acid: Structure and DNA-binding properties

The neutral mononuclear zinc complexes with the quinolone antibacterial drug oxolinic acid in the absence or presence of a nitrogen donor heterocyclic ligand 2,2′-bipyridine or 1,10-phenanthroline have been synthesized and characterized. The experimental data suggest that oxolinic acid is on deprotonated mode acting as a bidentate ligand coordinated to the metal ion through the ketone and one carboxylato oxygen atoms. The crystal structures of (chloro)(oxolinato)(2,2′-bipyridine)zinc(II), 2, and bis(oxolinato)(1,10-phenanthroline)zinc(II), 3, have been determined with X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV and fluorescence spectroscopies. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA and the DNA-binding constants have been calculated. Competitive studies with ethidium bromide (EB) have shown that complex 3 exhibits the ability to displace the DNA-bound EB indicating that it binds to DNA in strong competition with EB.     

Nickel-quinolones interaction. Part 1 - Nickel(II) complexes with the antibacterial drug sparfloxacin: Structure and biological properties

The mononuclear nickel(II) complexes with the third-generation quinolone antibacterial agent sparfloxacin in the absence or presence of nitrogen donor heterocyclic ligands (1,10-phenanthroline or 2,2′-bipyridine) have been synthesized and characterized. The experimental data suggest that sparfloxacin acts as deprotonated bidentate ligand coordinated to Ni(II) ion through the ketone and carboxylato oxygens. The crystal structure of (1,10-phenanthroline)bis(sparfloxacinato) nickel(II), 2 has been determined by X-ray crystallography. The cyclic voltammograms of the complexes recorded in dmso solution and in 1/2 dmso/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they can bind to CT DNA by the intercalative binding mode. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and 2 exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The antimicrobial activity of the complexes has been tested on three different microorganisms and has revealed that the inhibition provided by the complexes is slightly decreased in comparison to free sparfloxacin. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values.     

Zinc(II) complexes of the second-generation quinolone antibacterial drug enrofloxacin: Structure and DNA or albumin interaction

Zinc mononuclear complexes with the second-generation quinolone antibacterial drug enrofloxacin in the absence or presence of a nitrogen donor heterocyclic ligand 1,10-phenanthroline or 2,2′-bipyridine have been synthesized and characterized. Enrofloxacin is on deprotonated mode acting as a bidentate ligand coordinated to zinc ion through the ketone and a carboxylato oxygen atoms. The crystal structure of bis(enrofloxacinato)(1,10-phenanthroline)zinc(II), 2, has been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV and fluorescence spectroscopies. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA and the DNA binding constants have been calculated. Competitive studies with ethidium bromide (EB) have shown that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values.     

Mixed ligand ruthenium(II) complexes of 5,6-dimethyl-1,10-phenanthroline: The role of ligand hydrophobicity on DNA binding of the complexes

A series of mixed ligand Ru(II) complexes of 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) as primary ligand and 1,10-phenanthroline (phen), 2,2′-bipyridine (bpy), pyridine (py) and NH₃ as co-ligands have been prepared and characterized by X-ray crystallography, elemental analysis and ¹H NMR and electronic absorption spectroscopy. The X-ray crystal structure of the complex [Ru(phen)₂(bpy)]Cl₂ reveals a distorted octahedral coordination geometry for the RuN₆ coordination sphere. The DNA binding constants obtained from the absorption spectral titrations decrease in the order, tris(5,6-dmp)Ru(II) > bis(5,6-dmp)Ru(II) > mono(5,6-dmp)Ru(II), which is consistent with the trend in apparent emission enhancement of the complexes on binding to DNA. These observations reveal that the DNA binding affinity of the complexes depend upon the number of 5,6-dmp ligands and hence the hydrophobic interaction of 5,6-dimethyl groups on the DNA surface, which is critical in determining the DNA binding affinity and the solvent accessibility of the exciplex. Among the bis(5,6-dmp)Ru(II) complexes, those with monodentate py (4) or NH₃ (5) co-ligands show DNA binding affinities slightly higher than the bpy and phen analogues. This reveals that they interact with DNA through the co-ligands while both the 5,6-dmp ligands interact with the exterior of the DNA surface. All these observations are supported by thermal denaturation and viscosity measurements. Two DNA binding modes - surface/electrostatic and strong hydrophobic/partial intercalative DNA interaction - are suggested for the mixed ligand complexes on the basis of time-resolved emission measurements. Interestingly, the 5,6-dmp ligands promote aggregation of the complexes on the DNA helix as a helical nanotemplate, as evidenced by induced CD signals in the UV region. The ionic strength variation experiments and competitive DNA binding studies on bis(5,6-dmp)Ru(II) complexes reveal that EthBr and the partially intercalated and kinetically inert [Ru(phen)₂(dppz)]²⁺ (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) complexes revert the CD signals induced by exciton coupling of the DNA-bound complexes with the free complexes in solution.     

Ruthenium(II) mixed-ligand complexes containing 2-(6-methyl-3-chromonyl)imidazo[4,5-f][1,10]-phenanthroline: Synthesis, DNA-binding and photocleavage studies

Two novel Ru(II) complexes [Ru(bpy)₂(MCMIP)]²⁺ (1) and [Ru(phen)₂(MCMIP)]²⁺ (2) (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline; MCMIP = 2-(6-methyl-3-chromonyl)imidazo[4,5-f][1,10]-phenanthroline) have been synthesized and characterized by elemental analysis, mass spectra and ¹H NMR. The DNA-binding properties of the complexes were investigated by absorption, emission, melting temperature and viscosity measurements. Experimental results indicate that the two complexes can intercalate into DNA base pairs. Upon irradiation at 365 nm, two Ru(II) complexes were found to promote the cleavage of plasmid pBR 322 DNA from supercoiled form I to nicked form II, and the mechanisms for DNA cleavage by the complexes were also investigated.     

Mononuclear copper(II) complexes with quinolones and nitrogen-donor heterocyclic ligands: Synthesis, characterization, biological activity and interaction with DNA

The neutral mononuclear copper(II) complexes with the quinolone antibacterial drugs, pipemidic acid and N-propyl-norfloxacin, in the presence or absence of nitrogen-donor heterocyclic ligands, 2,2′-bipyridine, 1,10-phenanthroline or 2,2′-dipyridylamine, have been prepared and characterized spectroscopically. The interaction of copper(II) with the deprotonated quinolone ligand leads to the formation of the neutral mononuclear complexes of the type [Cu(quinolone)₂(H₂O)] (1)–(2) while the presence of the N-donor ligand leads to the formation of the neutral mononuclear complexes of the type [Cu(quinolone)(N-donor)Cl] (3)–(8). In all the complexes, copper(II) is pentacoordinate having a distorted square pyramidal geometry. The electron paramagnetic resonance spectra of 1 and 2 are typical of mononuclear Cu(II) complexes, while for the mixed-ligands complexes 3–8 a mixture of dimeric and monomeric species is indicated. The interaction of the complexes with calf-thymus DNA has been investigated with diverse spectroscopic techniques and has shown that the complexes can be bound to calf-thymus DNA by the intercalative mode. The antimicrobial activity of the complexes has been tested on three different microorganisms. All the complexes show an increased biological activity in comparison to the corresponding free quinolone ligand.     

Synthesis, characterization and properties of series coordination polymers constructed from a biphenyl dicarboxylate and nitrogen-containing mixed ligands

A series of coordination polymers have been prepared by the combination of flexible ligand 1,1′-biphenyl-2,2′-dicarboxylic acid (H₂dpa) and different types of nitrogen-containing ligands, with various metal ions such as Co(II), Zn(II) and Cd(II). The single-crystal structure analyses reveal that the above complexes possess different structure features with the introduction of different nitrogen-containing ligands. When auxiliary linear ligand 4,4′-bipyridine (4,4′-bpy) is introduced, two-dimensional layered complex, [Co₂(dpa)₂(4,4′-bpy)₂(H₂O)]_n (1) is formed. Whereas if chelating ligand, 1,10-phenanthroline (1,10′-phen) and 2,2′-bipyridine (2,2′-bpy) are introduced, one-dimensional complex [Zn(dpa)(1,10′-phen)]_n (2) and discrete complexes [Co₂(dpa)₂(2,2′-bpy)₂(H₂O)₂] (3), [Co₃(dpa)₃(1,10′-phen)₆(H₂O)₂] (4), [Cd(dpa)(1,10′-phen)₂][(H₂dpa)₂(H₂O)₂] (5) are synthesized. To our interest, 1 and 2 crystallize in homochiral spacegroup. Furthermore, the magnetic property of complex 1 and the fluorescent properties of complexes 2 and 5 are studied.     

DNA-binding and photocleavage studies of mixed polypyridyl ruthenium(II) complexes with calf thymus DNA

New mixed polypyridyl {NMIP = 2′-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo-[4′,5′-f][1,10]-phenanthroline, dmb = 4,4′-dimethyl-2,2′-bipyridine, bpy = 2,2′-bipyridine} ruthenium(II) complexes [Ru(dmb)₂(NMIP)]²⁺ (1) and [Ru(bpy)₂(NMIP)]²⁺ (2) have been synthesized and characterized. The binding of these complexes to calf thymus DNA (CT-DNA) has been investigated with spectroscopic methods, viscosity and electrophoresis measurements. The experimental results indicate that both complexes could bind to DNA via partial intercalation from the minor/major groove. In addition, both complexes have been found to promote the single-stranded cleavage of plasmid pBR 322 DNA upon irradiation. Under comparable experimental conditions compared with [Ru(phen)₂(NMIP)]²⁺, during the course of the dialysis at intervals of time, the CD signals of both complexes started from none, increased to the maximum magnitude, then no longer changed, and the activity of effective DNA cleavage dependence upon concentration degree lies in the following order: [Ru(phen)₂NMIP]²⁺ > complex 2 > complex 1.     

Synthesis, characterization, photophysics and intramolecular energy transfer process in bimetallic rhenium(I)-ruthenium(II) complexes

Two new heterobimetallic complexes of rhenium(I) and ruthenium(II) [(CO)₃(NN)Re(4,4′-bpy)Ru(NN)₂Cl](PF₆)₂ and already known monometallic complexes [Cl(NN)₂Ru(4,4′-bpy)](PF₆) and [(CO)₃(NN)Re(4,4′-bpy)](PF₆) and bimetallic complexes [Cl(NN)₂Ru(4,4′-bpy)Ru(NN)₂Cl](PF₆)₂, [(CO)₃(NN)Re(4,4′-bpy)Re(NN)(CO)₃](PF₆)₂ (NN = 2,2′-bipyridine, 1,10-phenanthroline; 4,4′-bpy = 4,4′-bipyridine) are synthesized and characterized by spectral techniques. The photophysical properties of all the complexes are studied. It is found that attachment of rhenium(I) altered the photophysical characteristics of ruthenium(II). Excited state energy transfer from the rhenium(I) chromophore to the ruthenium(II) is observed upon excitation at 355 nm.     

Synthesis and characterization of two novel [Ru(bpy)2(phen)]2+-based electrochemiluminescent labels

Two novel electrochemiluminescent labels, bis(2,2′-bipyridine)[5-(3-carboxylic acid-propionamido)-1,10-phenanthroline]ruthenium(II) hexafluorophosphate dihydrate and bis(2,2′-bipyridine)[5-(4-carboxylic acid-butanamido)-1,10-phenanthroline]ruthenium(II) hexafluorophosphate dihydrate, were synthesized and confirmed by IRelemental analysis, and ¹H-NMR spectra were completely assigned using the ¹H-¹H COSY technique. Cyclic voltammograms with different scan rates showed quasi-reversible electrochemical behaviour of the two Ru (II) complex labels in MeCN solution. Electronic absorption, photoluminescence and electrochemiluminescence of Ru(II) complexes were also characterized. Copyright © 2000 John Wiley & Sons, Ltd.     

Synthesis and characterization of tris(heteroleptic) diimine complexes of chromium(III)

A preparative procedure of potentially wide applicability is described for the synthesis of previously unreported tris(heteroleptic) [Cr(diimine)₃]³⁺ complexes. The synthetic scheme involves the sequential addition of three different diimine ligands, and employs CrCl₃ · 6H₂O as the initial Cr(III) reagent. The synthesis and characterization of the complexes [Cr(TMP)(phen)(diimine′)]³⁺ are reported (where TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline, phen = 1,10-phenanthroline; and diimine′ is either bpy = 2,2′-bipyridine, Me₂bpy = 4,4′-dimethyl-2,2′-bipyridine, 5-Clphen = 5-chloro-1,10-phenanthroline, or DPPZ = dipyridophenazine). Chiral capillary electrophoresis and electrospray mass spectrometry were essential aids in determining the presence or absence of diimine ligand scrambling. Utilizing emission and electrochemical data obtained on these compounds, the oxidizing power of the lowest lying excited state (²E_g(O_h)) was calculated, and was found to vary in a systematic fashion with diimine ligand type.     

Analysis of the DNA Interaction of Copper Compounds Belonging to the Casiopeínas® Antitumoral Series

Casiopeínas® are mixed-chelate copper complexes with antitumor tested potential. Their activity, both in vitro and in vivo, as antiproliferative, cytotoxic, and genotoxic drugs has been assessed. Biological results of these copper compounds have deserved some of them entering clinical trials. Significant efforts have been devoted to the in-depth identification of their mechanism of action. Using gel electrophoresis analysis, we have previously shown that the interaction of the Casiopeínas® Cas II-gly, [Cu(4,7-dimethyl-1,10-phenanthroline)(glycinate)]NO₃ with DNA, triggers the cleavage of the biomolecule by a free radical mechanism. In this work, we further study the behavior of different complexes of the same Casiopeínas® series also including glycinate as co-ligand {Cas VI-gly (5,6 dimethyl-1,10-phenanthroline glycinato copper(II) nitrate), Cas VII-gly (1,10-phenanthroline glycinato copper(II) nitrate), and Cas IX-gly (2,2′-bipyridine glycinato copper(II) nitrate)} and of a Casiopeínas® with a different co-ligand (Cas III-Cs; 4,7-dimethyl-1,10-phenanthroline salicylaldehydato-copper(II) nitrate). While all of them produce DNA degradation, the performance in the presence of a radical scavenger suggests the existence of differences in their mechanism of interaction with DNA.     

One pot synthesis of Cu(II) 2,2'-bipyridyl complexes of 5-hydroxy-hydurilic acid and alloxanic acid: synthesis, crystal structure, chemical nuclease activity and cytotoxicity

A barbiturate derivative [1,5-dihydro-5-[5-pyrimidine-2,4(1H,3H)-dionyl]-2H-chromeno[2,3-d] pyrimidine-2,4(3H)-dione] (LH₄) was allowed to react with 2,2′-bipyridyl-dinitrato-Copper(II)-dihydrate which provides two complexes, characterized as [Cu(bpy)(L1)]·3H₂O () and [Cu(bpy)(L2)]·H₂O (), where bpy = 2,2′-bipyridine, L1 = 5-hydroxy-hydurilic acid and L2 = alloxanic acid. In a separate reaction of LH₄ with Cu(NO₃)₂·H₂O another type of complex [Cu(LH₃)₂·(H₂O)₂]·4H₂O () is formed. The complexes were characterized by single crystal X-ray crystallography, physicochemical and electrochemical studies. The interaction of complexes 1 and 3 with DNA was monitored using absorption and emission titrations as well as circular dichroism spectroscopy. The complexes were found to cleave supercoiled plasmid DNA to nicked circular and linear DNA. Complexes 1 and 3 were also tested against T-cell lymphoma (Dalton lymphoma DL) and showed significant cytotoxic activity with IC₅₀ values of ~ 9.0 nM and 0.6 nM.