DNA binding studies of ruthenium(II) complexes containing asymmetric tridentate ligands

Absorption spectroscopy, fluorescence spectroscopy and viscosity measurements have been used to characterize the DNA binding of [Ru(tpy)(dppt)](2+) (tpy=2,2':6',2"-terpyridine, dppt=3-(1,10-phenanthrolin-2-yl)-5,6-diphenyl-as-triazine), [Ru(tpy)(pta)](2+) (pta=3-(1,10-phenanthrolin-2-yl)-as-triazino[5,6-f]acenaphthylene) and [Ru(tpy)(ptp)](2+) (ptp=3-(1,10-phenanthrolin-2-yl)-as-triazino[5,6-f]-phenanthrene). The results indicate that [Ru(tpy)(pta)](2+) and [Ru(tpy)(ptp)](2+) bind with CT-DNA in an intercalative mode, while [Ru(tpy)(dppt)](2+) binds with DNA by partial intercalation. The ligand planarity of the complex has a significant effect on DNA binding affinity increases in the order [Ru(tpy)(dppt)](2+)<[Ru(tpy)(pta)](2+)<[Ru(tpy)(ptp)](2+).     

Synthesis,structure and nuclease properties of several ternary copper(II) peptide complexes with 1,10-phenanthroline

Three new ternary peptide-Cu(II)-1,10-phenanthroline (phen) complexes, [Cu(L-ala-gly)(phen)].3.5H(2)O 1, [Cu(L-val-gly)(phen)] 2 and [Cu(gly-L-trp)(phen)].2H(2)O 3, have been prepared and structurally characterised. These compounds exist as distorted square pyramidal complexes with the five co-ordination sites occupied by the tridentate peptide dianion and the two heterocyclic nitrogens of the phenanthroline ligand. The bulk of the lateral chain in the peptide moiety determines the relative disposition of the phen ligand. Thus, in [Cu(L-val-gly)(phen)] 2, the phenanthroline plane is deviated towards the opposite side of the isopropyl group of the L-valine moiety. On the other hand, in [Cu(gly-L-trp)(phen)].2H(2)O 3 the absence of stacking interactions between phen and indole rings and the presence of an intramolecular CH...pi interaction should be pointed out. These complexes exhibit significant differences in their nuclease activity which depends on the nature of the peptidic moiety, the complex [Cu(gly-L-trp) (phen)].2H(2)O 3 being the most active.     

Model complexes with naturally occurring ligands (salicylglycine and imidazol) and the biometals copper and cobalt

Two new complexes [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl] (2)(2-OH-Hip)(2) (1) and [Co(2-OH-Hip)(Imz)(3)].H(2)O (2) (with Imz=Imidazol and 2-OH-Hip=2-hydroxyhippuric acid) were prepared and characterized. The molecular structures and the solution and solid state behavior of the complexes were investigated. Complex 1 crystallizes in the monoclinic space group P2(1)/c with a=16.880(1), b=8.046(1), c=24.683(1) A, beta=107.88(1) degrees, and Z=2, while complex 2 crystallizes in the orthorhombic space group Pbca with a=11.712(2), b=15.741(4), c=22.254(4) A, and Z=8. The [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl](2)(2-OH-Hip)(2) solid consists in two distinct monomeric Cu(II) complexes: one of them is neutral octahedral [Cu(Imz)(4)Cl(2)] and the other, charged square basis pyramida [Cu(Imz)(4)Cl](+). The 2-hydroxyhippuric acid, which here acts as a counter ion, is deprotonated at its carboxylic group. Cobalt(III) ion in [Co(2-OH-Hip)(Imz)(3)].H(2)O is at the center of an octahedral environment, coordinated to three Imidazol ligands and to a triply deprotonated 2-hydroxyhippuric acid molecule acting as a tridentate ligand. Aqueous solution equilibrium of the quaternary system Cu(2+)/2-OH-Hip/Imz/H(+) was studied by potentiometric titrations.     

Synthesis, characterization and DNA-binding properties of rac-[Ru(5,6-dmp)2(dppz)]2+--enantiopreferential DNA binding and co-ligand promoted exciton coupling

The new mixed ligand complex [Ru(5,6-dmp)2(dppz)]Cl2 [5,6-dmp = 5,6-dimethyl-1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine] has been isolated and its DNA-binding properties studied by employing UV-visible (UV-Vis), steady-state and time-resolved emission and circular dichroism spectral methods, viscometry, thermal denaturation and cyclic/differential pulse voltammetric techniques. The complex acts as a 'molecular light-switch' on binding to DNA, but the enhancement in emission intensity is only 75% of that of the parent complex [Ru(phen)2(dppz)]2+ (phen = 1,10-phenanthroline). The emission decay curves and quenching studies suggest two different DNA-binding modes both involving intercalation of the dppz ligand of [Ru(5,6-dmp)2(dppz)]Cl2. The characteristic red-shift of the induced CD signal, which is not observed for the phen analogue, arises from exciton coupling. The hydrophobicity and polarizability of 5,6-dmp co-ligand strongly favour the formation of a stable structural and electronic scaffold on the DNA surface for the unbound molecules to couple with the DNA-bound complexes facilitating spontaneous assembly of novel extended molecular aggregates using DNA as a helical nanotemplate. This observation is consistent with the shift in Ru(II)/Ru(III) redox potential to more positive values with a dramatic drop in peak current on binding of the 5,6-dmp complex to calf thymus (CT) DNA. Equilibrium dialysis experiments monitored by CD spectroscopy unambiguously reveal the preferential binding of the delta-enantiomer to the right-handed calf thymus (CT) DNA. The 5,6-dmp complex exhibits preferential binding to [d(AT)6]2 over [d(GC)6]2 and the complex aggregates formed consist of six [Ru(5,6-dmp)2(dppz)]2+ cations per base pair of [d(AT)6]2; however, only one [Ru(phen)2(dppz)]2+ cation per base pair is involved in DNA binding.     

Synthesis, characterization, X-ray structure and DNA photocleavage by cis-dichloro bis(diimine) Co(III) complexes

Complexes of the type [Co(LL)2Cl2]Cl, where LL = N,N'-ethylenediamine (en), 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been synthesized and characterized by elemental analyses, IR, UV-visible and NMR spectroscopy. Crystal structure of [Co(phendione)2Cl2]Cl x 0.5 HCl x 3.5 H2O has been solved and refined to R = 0.0552. The crystal is monoclinic with space group C2/c; a = 25.730(2) A, b = 12.375(1) A, c = 18.979(2) A, beta = 119.925(1) degrees and Z = 8. The DNA binding characteristics of the complexes, investigated by covalent binding assay, viscosity measurements and competitive binding fluorescence measurements show that the complexes interact with DNA covalently except the complex containing the planar dppz ligand which intercalates within the base pairs of DNA. The complexes containing en, phen and phendione cleave plasmid pBR 322 DNA upon irradiation under aerobic conditions while the complex containing the dppz ligand cleaves DNA upon irradiation under inert atmosphere. Molecular modeling studies show that the minimized structure of [Co(phendione)2Cl2]+, maintained the octahedral structure while binding to the N7 of guanines and the ligand fits into the major groove without disrupting the helical structure of the B-DNA.     

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: the novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

The coordination geometry around copper(II) in [Cu(imda)(phen)(H2O)] (1) (H2imda = iminodiacetic acid, phen = 1,10-phenanthroline) is described as distorted octahedral while those in [Cu(imda)(5,6-dmp)] (2) (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline) and [Cu(imda)(dpq)] (3) (dpq = dipyrido-[3,2-d:2',3'-f]-quinoxaline) as trigonal bipyramidal distorted square-based pyramidal with the imda anion facially coordinated to copper(II). Absorption spectral (Kb: 1, 0.60+/-0.04x10(3); 2, 3.9+/-0.3x10(3); 3, 1.7+/-0.5x10(4) M(-1)) and thermal denaturation studies (deltaTm: 1, 5.70+/-0.05; 2, 5.5+/-10; 3, 10.6+/-10 degrees C) and viscosity measurements indicate that 3 interacts with calf thymus DNA more strongly than 1 and 2. The relative viscosities of DNA bound to 1 and 3 increase while that of DNA bound to 2 decreases indicating formation of kinks or bends and/or conversion of B to A conformation as revealed by the decrease in intensity of the helicity band in the circular dichroism spectrum of DNA. While 1 and 3 are bound to DNA through partial intercalation, respectively, of phen ring and the extended planar ring of dpq with DNA base stack, the complex 2 is involved in groove binding. All the complexes show cleavage of pBR322 supercoiled DNA in the presence of ascorbic acid with the cleavage efficiency varying in the order 3 > 1 > 2. The highest oxidative DNA cleavage of dpq complex is ascribed to its highest Cu(II)/Cu(I) redox potential. Oxidative cleavage studies using distamycin reveal minor groove binding for the dpq complex but a major groove binding for the phen and 5,6-dmp complexes. Also, all the complexes show hydrolytic DNA cleavage activity in the absence of light or a reducing agent with cleavage efficiency varying in the order 1 > 3 > 2.     

Homoleptic ruthenium (II) complexes containing asymmetric tridentate 2-(benzimidazole-2-yl)-1,10-phenanthroline likes ligands: syntheses, characterization and DNA binding

Two novel homoleptic ruthenium (II) complexes containing asymmetric tridentate ligands, 2-(benzimidazole-2-yl)-1,10-phenanthroline (PHBI) and 2-(naphtho[2,3-d]imidazole-2-yl)-1,10-phenanthroline (PHNI) have been synthesized and characterized by elemental analysis, mass spectra, (1)H NMR, and electronic spectroscopy. The DNA-binding properties of the complexes have been investigated by spectroscopic methods and viscosity measurements. The results indicate that the two complexes interact with DNA via electrostatic interaction, and the mechanisms of DNA binding with the complexes have also been discussed.     

Ternary copper(II) complexes with N-carboxymethyl-l-prolinato(2-) ion and imidazole or creatinine: a comparative study of the interligand interactions influencing the molecular recognition and stability

The compounds {[Cu(CMP)(Him)].H(2)O}(n) (I) and [Cu(CMP)(crea)H(2)O].3H(2)O (II) were synthesized and characterized by X-ray diffraction, thermal, spectral and magnetic methods (CMP=N-carboxymethyl-;l-prolinato(2-) ion, Him=imidazole and crea=creatinine). Appropriate structural comparison with other compounds such as {[Cu(CMP)(H(2)O)].H(2)O}(n), [Cu(crea)(2)Cl(2)] and [Cu(dipeptide)(crea)(H(2)O)(x)].nH(2)O (x=0 or 1) have been made in order to prove that crea can act as an imidazole-like ligand (because it is able to promote the same fac- to mer-CMP tridentate conformational change in copper(II) complexes) as well as to discuss the interligand interactions which control the 'Cu(CMP) complex-crea, molecular recognition processes. In contrast to that found in related ternary complexes, we have concluded that direct CMP-crea interligand interactions are missing in the Cu-CMP-crea complex due to the inappropriate correspondence between the donor and/or acceptor H-bonding properties of these ligands. CMP can only act as H-acceptor by its two terminal carboxylate group, and crea can display H-donor and H-acceptor roles by its exocyclic -NH(2) and O moieties, respectively. That promotes the reinforcement of the Cu-N(crea) bond by a bridge -N-H(crea)...O(aqua) (2.867(3)A, 176.4 degrees).     

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.     

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.     

Copper(II)-fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability

Copper(II) complexes of fluoroquinolone antibacterial agents levofloxacin (LEV) and sparfloxacin (SPAR), containing or not a nitrogen donor heterocyclic ligand, 2,2'-bipyridine (bipy) or 1,10-phenathroline (phen), were prepared and characterized. The complexes are of the type [CuCl(2)(H(2)O)(L)], [CuCl(bipy)(L)]Cl and [CuCl(2)(phen)(L)], where L?=?LEV or SPAR. The data suggest that LEV and SPAR act as zwitterionic bidentade ligands coordinated to Cu(II) through the carboxylate and ketone oxygen atoms. The electron paramagnetic resonance spectra of the [CuCl(bipy)(L)]Cl and [CuCl(2)(phen)(L)] complexes (L?=?LEV and SPAR) in aqueous and DMSO solutions indicate mixture of mononuclear and binuclear forms. The Cu(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activity in vitro against Trypanosoma cruzi, the causative agent of Chagas disease. The assays performed against bloodstream trypomastigotes showed that all complexes were more active than their corresponding ligands. Complexes [CuCl(2)(phen)(LEV)] and [CuCl(2)(phen)(SPAR)] were revealed, among all studied compounds, to be the most active with IC(50)?=?1.6 and 4.7?μM, respectively, both presenting a superior effect than benznidazole. The interactions of fluoroquinolones and their Cu(II) complexes with calf-thymus DNA were investigated. These compounds showed binding properties towards DNA, with moderated binding constants values, suggesting that this structure may represent a parasite target.     

Zinc complexes of the biomimetic N,N,O ligand family of substituted 3,3-bis(1-alkylimidazol-2-yl)propionates: the formation of oxalate from pyruvate

The coordination chemistry of the 2-His-1-carboxylate facial triad mimics 3,3-bis(1-methylimidazol-2-yl)propionate (MIm(2)Pr) and 3,3-bis(1-ethyl-4-isopropylimidazol-2-yl) propionate (iPrEtIm(2)Pr) towards ZnCl(2) was studied both in solution and in the solid state. Different coordination modes were found depending both on the stoichiometry and on the ligand that was employed. In the 2:1 ligand-to-metal complex [Zn(MIm(2)Pr)(2)], the ligand coordinates in a tridentate, tripodal N,N,O fashion similar to the 2-His-1-carboxylate facial triad. However, the 1:1 ligand-to-metal complexes [Zn(MIm(2)Pr)Cl(H(2)O)] and [Zn(iPrEtIm(2)Pr)Cl] were crystallographically characterized and found to be polymeric in nature. A new, bridging coordination mode of the ligands was observed in both structures comprising N,N-bidentate coordination of the ligand to one zinc atom and O-monodentate coordination to a zinc second atom. A rather unique transformation of pyruvate into oxalate was found with [Zn(MIm(2)Pr)Cl], which resulted in the isolation of the new, oxalato bridged zinc coordination polymer [Zn(2)(MIm(2)Pr)(2)(ox)].6H(2)O, the structure of which was established by X-ray crystal structure determination.     

Copper(II) complexes of tridentate pyridylmethylethylenediamines: role of ligand steric hindrance on DNA binding and cleavage

Copper(II) complexes of three linear unsymmetrical tridentate ligands viz. N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L1), N,N-dimethyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L2) and N,N-dimethyl-N'-((6-methyl)pyrid-2-ylmethyl)ethylenediamine (L3) have been isolated and characterized by elemental analysis, electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes [Cu(L2)Cl2] and [Cu(L3)Cl2] have been structurally characterized by X-ray crystallography. The [Cu(L2)Cl2] complex crystallizes in the monoclinic space group P2(1)/n with a=11.566(2) A, b=7.369(1) A, c=15.703(3) A, alpha=90 degrees , beta=109.68(8) degrees , gamma=90 degrees and Z=4 while [Cu(L3)Cl2] crystallizes in the triclinic space group P1 with a=9.191(2) A, b=12.359(3) A, c=14.880(3) A, alpha=79.61(13) degrees , beta=86.64(13) degrees , gamma=87.28(8) degrees and Z=2. The coordination geometries around copper (II) in these two complexes are best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The distorted CuN3Cl basal plane in them is comprised of three nitrogen atoms of the meridionally coordinated ligand and a chloride ion and the axial position is occupied by the other chloride ion. The interaction of these complexes with Calf Thymus DNA (CT DNA) has been studied by using absorption, emission and circular dichroic spectral methods, thermal denaturation studies, viscometry and cyclic and differential pulse voltammetry. A strong blueshift in the ligand field band and a redshift in the ligand based bands of the copper(II) complexes on binding to DNA imply a covalent mode of DNA binding of the complexes, which involves coordination of most possibly guanine N7 nitrogen of DNA to form a CuN4 chromophore. This is supported by studying the interaction of the complexes with N-methylimidazole (N-meim), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine (cytd) by ligand field and EPR spectral methods, which indicate the formation of a CuN4 chromophore only in the case of the more basic N-meim and GMP. The DNA melting curves obtained in the presence of copper(II) complexes reveal a monophasic and irreversible melting of the DNA strands and the high positive DeltaTm values (12-21 degrees C) also support the formation of strong Cu-N bonds by the complexes with DNA, leading to intra- and/or interstrand crosslinking of DNA. Competitive ethidium bromide (EthBr) binding studies show that the L2 and L3 complexes are less efficient than the L1 complex in quenching EthBr emission, which is consistent with their forming DNA crosslinking preventing the displacement of the DNA-bound EthBr. A very slight decrease in relative viscosity of DNA is observed on treating the L1 and L2 complexes with CT DNA; however, a relatively significant decrease is observed for the L3 complex suggesting that the length of the DNA fiber is shortened. DNA cleavage experiments show that all the complexes induce the cleavage of pBR322 plasmid DNA, the complex of L1 being more efficient than those of sterically hindered L2 and L3 ligands.     

DNA interactions of cobalt(III) mixed-polypyridyl complexes containing asymmetric ligands

Three novel asymmetric ligands, 3-(pyridine-2-yl)-5,6-diphenyl-as-triazine (pdtb), 3-(pyridine-2-yl)-as-triazino[5,6-f]acenaphthylene (pdta) and 3-(pyridine-2-yl)-as-triazino[5,6-f]phenanthroline (pdtp) and their cobalt(III) complexes have been synthesized and characterized. Binding of the three complexes with calf thymus DNA (CT-DNA) has been investigated by spectroscopic methods, viscosity, cyclic voltammetry, and electrophoresis measurements. The experimental results indicate that the size and shape of the intercalated ligand have a marked effect on the binding affinity of complexes to CT-DNA. Complexes 2 and 3 have also been found to promote cleavage of plasmid pBR322 DNA from the supercoiled form I to the open circular form II upon irradiation.     

A comparative study of the interaction of two structurally analogue ruthenium(II) complexes with DNA

The binding of the ruthenium(II) complexes of [Ru(bpy)2(CAIP)]Cl2 and [Ru(bpy)2(HCIP)]Cl2 (where bpy=2,2'-bipyridine, CAIP=4-carboxyl-imidado[4,5-f][1,10]-phenanthroline, HCIP=3-hydroxyl-4-carboxyl-imidado[4,5-f][1,10]-phenanthroline) to calf thymus DNA (ct-DNA) has been investigated with UV-visible and emission spectroscopy, steady-state emission quenching, and viscosity measurements. The experimental results indicate that the two complexes bind to ct-DNA through an intercalative mode and [Ru(bpy)2(HCIP)]2+ intercalates into DNA more deeply than [Ru(bpy)2(CAIP)]2+ does.     

Ruthenium(II) mixed-ligand complex containing 2-(4'-benzyloxy-phenyl)imidazo[4,5-f][1,10]phenanthroline: synthesis, DNA-binding and photocleavage studies

A novel polypyridyl ligand 2-(4'-benzyloxyphenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and its complex [Ru(bpy)2(BPIP)]2+ (1) (bpy=2,2'-bipyridine) and (2) [Ru(phen)2(BPIP)]2+) (phen=1,10-phenanthroline) have been synthesized and characterized by elemental analysis, electrospray mass spectra and 1H NMR. The DNA-binding properties of the two complexes were investigated by spectroscopic and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode. Both complexes can enantioselectively interact with calf thymus DNA (CT-DNA) in a way. The Lambda enantiomer of complex 1 is slightly predominant for binding to CT-DNA to the Delta enantiomer. Under irradiation at 365 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA. Inhibitors studies suggest that singlet oxygen ((1)O2) and hydroxyl radical (*OH) play a significant role in the cleavage mechanism for both complexes. Moreover, the DNA-binding and photocleavage properties of both complexes were compared with that of [Ru(bpy)2(BPIP)]2+ and [Ru(phen)2(BPIP)]2+. The experimental results indicate that methene group existence or not have a significant effect on the DNA-binding and cleavage mechanism of these complexes.     

Reactions of the Tridentate and Tetradentate Amine Ligands di-(2-picolyl)(N-ethyl)amine and 2,5-Bis-(2-pyridylmethyl)-2,5 diazohexane with Technetium Nitrosyl Complexes

The reaction of the Tc(II) nitrosyl complex (Bu₄N)[Tc(NO)Cl₄] with di-(2-picolyl)(NEt)amine in methanol yields the neutral complex [Tc(NO)Cl(py-N(Et)-py)]. The reaction of the Tc(I) nitrosyl complex [Tc(NO)Cl₂(HOMe)(PPh₃)₂] with this tridentate ligand yields cationic [Tc(NO)Cl(py-N(Et)-py)(PPh₃)]Cl. These two complexes have been structurally characterized. The reaction of [Tc(NO)Cl₂(HOMe)(PPh₃)₂] with the tetradentate ligand 1,4-bis-(2-pyridylmethyl)-1,4-diazobutane yields a mixture of products including cationic [Tc(NO)Cl(py-NH-NH-py)]Cl and cationic [Tc(NO)Cl(PPh₃)(py-NH-NH∼py)]Cl, with a pyridyl terminus left dangling.     

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.     

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.     

Metalloantibiotics: synthesis and antibacterial activity of cobalt(II), copper(II), nickel(II) and zinc(II) complexes of kefzol

Kefzol (kzl), a beta-lactam antibiotic, possesses various donor sites for interaction with transition metal(II) ions [Co(II), Cu(II), Ni(II) and Zn(II)] to form complexes of the type [M(kzl)2]Cl2 and [M(kzl)Cl], with molar ratio of metal: ligand (M:L) of 1:2 and 1:1 respectively. These complexes were prepared and characterized by physicochemical and spectroscopic methods. Their IR and NMR spectra suggest that kefzol potentially acts as a bidentate, tridentate as well as monoanionic tetradentate ligand. The complexes have been screened for antibacterial activity and results were compared with the activity of the uncomplexed antibiotic against Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis. The metal complexes were found to be more potent against one or more bacterial species than the uncomplexed kefzol.