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 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.     

Interaction of copper(II) with the non-steroidal anti-inflammatory drugs naproxen and diclofenac: synthesis, structure, DNA- and albumin-binding

Copper(II) complexes with the non-steroidal anti-inflammatory drugs (NSAIDs) naproxen and diclofenac have been synthesized and characterized in the presence of nitrogen donor heterocyclic ligands (2,2′-bipyridine, 1,10-phenanthroline or pyridine). Naproxen and diclofenac act as deprotonated ligands coordinated to Cu(II) ion through carboxylato oxygens. The crystal structures of (2,2′-bipyridine)bis(naproxenato)copper(II), , (1,10-phenanthroline)bis(naproxenato)copper(II), and bis(pyridine)bis(diclofenac)copper(II), have been determined by X-ray crystallography. The UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA with (2,2′-bipyridine)bis(naproxenato)copper(II) exhibiting the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) indicates that the complexes can displace the DNA-bound EB suggesting strong competition with EB. The cyclic voltammograms of the complexes recorded in the presence of CT DNA have shown that the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The NSAID ligands and their complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the previously reported complexes [Cu₂(naproxenato)₄(H₂O)₂], [Cu₂(diclofenac)₄(H₂O)₂] and [Cu(naproxenato)₂(pyridine)₂(H₂O)] have been also evaluated. The dinuclear complexes exhibit similar affinity for CT DNA as the 2,2′-bipyridine or 1,10-phenanthroline containing complexes. The pyridine containing complexes exhibit the lowest affinity for CT DNA and the lowest ability to displace EB from its EB-DNA complex.     

DNA-binding studies of mixed-ligand (ethylenediamine)ruthenium(II) complexes

A series of mixed-ligand ruthenium(II) complexes of the type [Ru(en)(2)bpy](2+) (bpy=2,2-bipyridine; 1), [Ru(en)(2)phen](2+) (phen=1,10-phenantroline; 2), [Ru(en)(2)IP](2+) (IP=imidazo[4,5-f][1,10]phenanthroline; 3), and [Ru(en)(2)PIP](2+) (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline; 4) have been isolated and characterized by UV/VIS, IR, and (1)H-NMR spectral methods. The binding of the complexes with calf thymus DNA has been investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photo-cleavage. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (=calf thymus DNA) by groove mode. Complex 2 binds more avidly to CT DNA than complex 1, complexes 3 and 4 bind to CT DNA by intercalation mode, 4 binds more avidly to CT DNA than 3. Noticeably, the four complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.     

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 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.     

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 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.     

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.     

Indirect molecular diagnosis of copper toxicosis in Bedlington terriers is complicated by haplotype diversity

Positional cloning recently identified the mutation causing copper toxicosis (CT) in Bedlington terriers. Isolation of the MURR1 gene will be of great value in developing a reliable diagnostic test for the breeding of a copper toxicosis-free stock. It will replace the current diagnostic test using the CT-linked marker, C04107, which is located in intron 1 of the MURR1 gene with a distance of approximately 8 kb from the exon 2 deletion. Despite the short distance between C04107 and the CT mutation, possible recombinant dogs have been reported with C04107. Although these dogs have a normal phenotype, they carry the C04107 allele 2, which is associated with CT. To study the origin of this possible recombination event we collected a pedigree consisting of two unaffected American Bedlington terriers and their litter of four pups, which were all homozygous for the C04107 2,2 genotype. Mutation analysis showed that two dogs were heterozygous for the CT exon 2 deletion mutation, whereas four dogs were homozygous for the wild-type (WT) allele. Haplotype analysis was performed using two DNA markers in the MURR1 gene and four DNA markers flanking the gene and spanning a region of approximately 600 kb. Surprisingly, we identified a new haplotype (haplotype C) that contains allele 2 of marker C04107 in combination with the WT MURR1 allele. Analysis of the flanking markers suggests there are different genetic backgrounds in the Bedlington terrier population.     

DNA-binding and photocleavage studies of cobalt(III) mixed-polypyridyl complexes containing 2-(2-chloro-5-nitrophenyl)imidazo [4,5-f][1,10]phenanthroline

The ligand 2-(2-chloro-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline(CNOIP) and its complexes [Co(bpy)(2)(CNOIP)](3+) (1) and [Co(phen)(2)(CNOIP)](3+) (2) (bpy=2,2'-bipyridine; phen=1,10-phenanthroline) have been synthesized and characterized. Binding of the two complexes with calf thymus DNA has been investigated by spectroscopic methods, cyclic voltammetry, viscosity, and electrophoresis measurements. The experimental results indicate that both complexes bind to DNA through an intercalative mode. In comparison with their parent complexes containing PIP ligand (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline), the introduction of NO(2) and Cl groups to the PIP ligand decreased the binding affinity of complexes 1 and 2 to CT DNA. Both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA, the hydroxyl radical (OH*) is suggested to be the reactive species responsible for the cleavage.     

Electrochemical characterization and DNA-binding property of dipyridophenazine complexes of osmium (II).

Novel dipyridophenazine (DPPZ) complexes of osmium (II), [Os(L)2(DPPZ)]2+ [L = 2,2'-bipyridyl (bpy)(1), 4,4'-diamino-2,2'-bipyridyl (DA-bpy)(2), 4,4'-dimethyl-2,2'-bipyridyl(DM-bpy)(3), and 4,4'-dicarboxyl-2,2'-bipyridyl (DC-bpy)(4)] have been synthesized and characterized. The DNA-binding properties of the complexes were studied by electrochemical methods. As the results, complex 2 shows higher affinity to DNA than other osmium complexes. The binding constant, K of complex 2 to calf thymus DNA has been determined to be 2.3 x 10(7) M-1 by normal pulse voltammetry (NPV).     

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.     

Synthesis, characterization and DNA binding studies of two mixed ligand complexes of ruthenium(II)

Two mixed ligand complexes [Ru(bpy)(2)(DMHBT)]Cl(2)(1) and [Ru(phen)(2)(DMHBT)]Cl(2) (2) (where DMHBT is 11,13-dimethyl-13H-4,5,9,11,14-hexaaza-benzo[b]triphenylene-10,12-dione) have been synthesized and characterized by electrospray ionization (ESI) mass, (1)H-(1)H correlation spectroscopy (COSY), electronic spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Spectroscopic titration and viscosity changes of calf thymus (CT)-DNA in the presence of incremental amount of complexes 1 and 2 clearly demonstrate that both these complexes bind intercalatively to DNA, with binding constant 2.87+/-0.20 x 10(4)M(-1) and 1.01+/-0.20 x 10(5)M(-1) for complexes 1 and 2, respectively. All the experimental evidences suggest that the ancillary ligand 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) influences the intercalative binding of these complexes to DNA.     

Study on the interaction between 4-(2-diethylamino-ethylamino)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile and DNA by molecular spectra

The binding geometry of a heterocyclic compound, 4-(2-diethylamino-ethylamino)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (A1) to CT DNA was studied by molecular spectroscopy. Deduced from SYBR Green-DNA melt curve, UV-vis spectroscopy, and fluorescence studies, there were two different interaction mechanisms involved in the whole interaction process depending on the R-value (R, the molar ratio of A1 to CT DNA base pairs). The value R = 0.20 was the turning point. The induced circular dichroism (ICD) spectra of A1 complexed with CT DNA, poly[(G-C)2] and poly[(A-T)2] showed when R < or = 0.20, A1 intercalated into CT DNA and the intercalation orientation of A1 to the dyad axis of DNA double-helix was heterogeneous. When R > 0.20, stacking of A1 on surface helix of DNA occurred driven by the protonation of amidogen group in the N,N-diethyldiamine substitution of A1, which was illustrated by the changes of A1-DNA geometry in different pH solutions. The intrinsic circular dichroism (CD) spectra showed the conformation of DNA converted from the B-form to A-like conformation due to the A1 intercalation.     

Family shuffling of soil DNA to change the regiospecificity of Burkholderia xenovorans LB400 biphenyl dioxygenase

Previous work has shown that the C-terminal portion of BphA, especially two amino acid segments designated region III and region IV, influence the regiospecificity of the biphenyl dioxygenase (BPDO) toward 2,2'-dichlorobiphenyl (2,2'-CB). In this work, we evolved BPDO by shuffling bphA genes amplified from polychlorinated biphenyl-contaminated soil DNA. Sets of approximately 1-kb DNA fragments were amplified with degenerate primers designed to amplify the C-terminal portion of bphA. These fragments were shuffled, and the resulting library was used to replace the corresponding fragment of Burkholderia xenovorans LB400 bphA. Variants were screened for their ability to oxygenate 2,2'-CB onto carbons 5 and 6, which are positions that LB400 BPDO is unable to attack. Variants S100, S149, and S151 were obtained and exhibited this feature. Variant S100 BPDO produced exclusively cis-5,6-dihydro-5,6-dihydroxy-2,2'-dichlorobiphenyl from 2,2'-CB. Moreover, unlike LB400 BPDO, S100 BphA catalyzed the oxygenation of 2,2',3,3'-tetrachlorobiphenyl onto carbons 5 and 6 exclusively and it was unable to oxygenate 2,2',5,5'-tetrachlorobiphenyl. Based on oxygen consumption measurements, variant S100 oxygenated 2,2'-CB at a rate of 16 +/- 1 nmol min(-1) per nmol enzyme, which was similar to the value observed for LB400 BPDO. cis-5,6-Dihydro-5,6-dihydroxy-2,2'-dichlorobiphenyl was further oxidized by 2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase (BphB) and 2,3-dihydroxybiphenyl dioxygenase (BphC). Variant S100 was, in addition, able to oxygenate benzene, toluene, and ethyl benzene. Sequence analysis identified amino acid residues M237 S238 and S283 outside regions III and IV that influence the activity toward doubly ortho-substituted chlorobiphenyls.     

Intercalation into the DNA double helix and in vivo biological activity of water-soluble planar [Pt(diimine)(N,N-dihydroxyethyl-N'-benzoylthioureato)]+Cl- complexes: a study of their thermal stability, their CD spectra and their gel mobility

The interaction of newly synthesised water-soluble planar complexes of general structure [Pt(diimine)(N,N-dihydroxyethyl-N'-benzoylthioureato)]+Cl- with DNA was investigated by means of DNA melting studies, CD spectroscopy, and DNA gel mobility studies. Addition of stoichometric amounts of [Pt(diimine)H2L-S,O]Cl complexes to polynucleotides caused a significant increase in the melting temperature of poly(dA-dT) and calf-thymus DNA, respectively, indicating that these complexes interacted with DNA and stabilised the double helical structure. The CD spectra confirmed the relatively strong binding of three related Pt(II) complexes ([Pt(2,2'-bipyridine)H2L-S,O]Cl, [Pt(4,4'-dimethyl-2,2'-bipyridine)H2L-S,O]Cl, and [Pt(1,10-phenanthroline)H2L-S,O]Cl), to DNA. Comparison with the published CD spectra of ethidium bromide/DNA complex suggests a similar intercalation mode of binding. cis-[(4,4'-di-tert-butyl-2,2'-bipyridyl)N,N-di(2-hydroxyethyl)-N'-benzoylthioureatoplatinum(II)] chloride, with its very bulky tert-butyl groups, did not intercalate into the polynucleotide double helix. In DNA mobility studies in the presence of the four [Pt(diimine)H2L-S,O]Cl complexes, only [Pt(2,2'-bipyridine)H2L-S,O]Cl affected the DNA mobility to any detectable extent. Finally, in vivo studies on the biological activity of the complexes, using an Escherichia coli DNA excision repair deficient uvrA mutant strain, indicated that only the [Pt(2,2'-bipyridine)H2L-S,O]Cl complex showed significant cellular toxicity and that this was, in part, linked to DNA damage.     

Effect of platinum(II) chemotherapeutic agents on properties of DNA liquid crystals

We have investigated the X-ray and optical properties (CD spectra and polarization microscopy) of liquid-crystalline phases and dispersions formed on pretreatment of low molecular weight DNA with the platinum(II) coordination complexes, cis-diammine-dichloroplatinum(II) (DDP), 2,2'-bipyridinedichloroplatinum(II) (1) and 2,2'-bipyridineethylenediammineplatinum(II) (2). It is demonstrated that the platination of DNA leads to the ordering of neighbouring molecules of DNA in liquid-crystalline phases being diminished. The intense bands observed in the CD spectra of liquid-crystalline dispersions prepared from DNA pretreated with 1 or 2 can be used to determine the orientation of the latter compounds with respect to the helical axis of the DNA and to detect distortions in the secondary structure of DNA. The possible causes of the appearance of the intense bands in the CD spectra of liquid-crystalline phases and alterations in the manner of packing of the molecules of DNA within them are discussed.     

Synthesis and antioxidant capacities of hydroxyl derivatives of cinnamoylphenethylamine in protecting DNA and scavenging radicals

Cinnamoylphenethylamine (CNPA) derivatives including feruloylphenethylamine (FRPA), caffeoylphenethylamine (CFPA), cinnamoyltyramine (CNTA), feruloyltyramine (FRTA) and caffeoyltyramine (CFTA) were synthesized in order to investigate the influence of the number and position of hydroxyl group on Cu(2+)/glutathione (GSH) and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. The radical-scavenging properties of these CNPA derivatives were also evaluated by trapping 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonate) cationic radical (ABTS(+?)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and galvinoxyl radical. In addition, these CNPA derivatives were tested by linoleic acid (LH)-β-carotene-bleaching experiment. The chemical kinetic was employed to treat the results from AAPH-induced oxidation of DNA and gave the order of antioxidant ability as CFTA > CFPA > FRTA > FRPA. CFTA and CFPA also possessed high abilities to inhibit Cu2(+)/GSH-mediated degradation of DNA, whereas FRPA and FRTA can protect LH against the auto-oxidation efficiently. Finally, CFPA and FRPA exhibited high activity in trapping ABTS(+?), DPPH and galvinoxyl radicals. Therefore, the cinnamoyl group bearing ortho-dihydroxyl or hydroxyl with ortho-methoxyl benefited for CNPA derivatives to protect DNA, while hydroxyl in tyramine cannot enhance the radical-scavenging abilities of CNPA derivatives.