New advances in the study on the interaction of [Cr(phen)2(dppz)]3+ complex with biological models; association to transporting proteins

The present study reports a detailed investigation with the interaction of [Cr(phen)₂(dppz)]³⁺ with serum albumins, the key protein for the transport of drugs in the blood plasma, which allows us to understand further the role of [Cr(phen)₂(dppz)]³⁺ as sensitizer in Photodynamic Therapy (PDT).Chromium(III) complex [Cr(phen)₂(dppz)]³⁺, (dppz = dipyridophenazine and phen = 1,10-phenanthroline), where dppz is a planar bidentate ligand with an extended π system, has been found to bind strongly with bovine and human serum albumins (BSA and HSA) with an intrinsic binding constants, K_b, of (1.7 ± 0.3) × 10⁵ M^− 1 and (2.2 ± 0.3) × 10⁵ M^− 1 at 295 K, respectively. The interactions of serum albumins with [Cr(phen)₂(dppz)]³⁺ were assessed employing fluorescence spectroscopy, circular dichroism and UV-vis absorption spectroscopy. The serum albumins-[Cr(phen)₂(dppz)]³⁺ interactions caused conformational changes with the loss of helical stability of the protein and local perturbation in the domain IIA binding pocket. The relative fluorescence intensity of the albumin (BSA or HSA) bound to the Cr(III) complex decreased, suggesting that perturbation around the Trp 214 residue took place. The analysis of the thermodynamic parameters ΔG, ΔH, ΔS indicated that the hydrophobic interactions played a major role in both BSA-Cr(III) and HSA-Cr(III) association processes. The binding distances and transfer efficiencies for BSA-Cr(III) and HSA-Cr(III) binding reactions were calculated according to the Föster theory of non-radiation energy transfer. All these experimental results suggests that [Cr(phen)₂(dppz)]³⁺ binds to serum albumins, by which these proteins could act as carriers of this complex for further applications in PDT.     

New insights in the DNA-[Cr(phen)2(dppz)] binding and photocleavage properties by the complex with an intercalating ligand

Due to the key role of DNA in cell life and pathological processes, the design of specific chemical nucleases, DNA probes and alkylating agents is an important research area for the development of new therapeutic agents and tools in Biochemistry. Hence, the interaction of small molecules with DNA has attracted in particular a great deal of attention.The aim of this study was to investigate the ability of [Cr(phen)₂(dppz)]³⁺ to associate with DNA and to characterize it as photocleavage reagent for Photodynamic Therapy (PDT).Chromium(III) complex [Cr(phen)₂(dppz)]³⁺, (dppz = dipyridophenazine, phen = 1,10-phenanthroline), where dppz is a planar bidentate ligand with an extended π system, has been found to bind strongly to double strand oligonucleotides (ds-oligo) and plasmid DNA with intrinsic DNA binding constants, K_b, of (3.9 ± 0.3) × 10⁵ M⁻¹ and (1.1 ± 0.1) × 10⁵ M⁻¹, respectively. The binding properties to DNA were investigated by UV-visible (UV-Vis) absorption spectroscopy and electrophoretic studies. UV-Vis absorption data provide clearly that the chromium(III) complex interacts with DNA intercalatively. Competitive binding experiments show that the enhancement in the emission intensity of ethidium bromide (EthBr) in the presence of DNA was quenched by [Cr(phen)₂(dppz)]³⁺, indicating that the Cr(III) complex displaces EthBr from its binding site in plasmid DNA. Moreover, [Cr(phen)₂(dppz)]³⁺, non-covalently bound to DNA, promotes the photocleavage of plasmid DNA under 457 nm irradiation. We also found that the irradiated Cr(III)-plasmid DNA association is able to impair the transforming capacity of bacteria. These results provide evidence confirming the responsible and essential role of the excited state of [Cr(phen)₂(dppz)]³⁺ for damaging the DNA structure. The combination of DNA, [Cr(phen)₂(dppz)]³⁺ and light, is necessary to induce damage. In addition, assays of the photosensitization of transformed bacterial suspensions suggest that Escherichia coli may be photoinactivated by irradiation in the presence of [Cr(phen)₂(dppz)]³⁺. In sum, our results allow us to postulate the [Cr(phen)₂(dppz)]³⁺ complex as a very attractive candidate for DNA photocleavage with potential applications in Photodynamic Therapy (PDT).     

A theoretical study of Ru(II) polypyridyl DNA intercalators: Structure and electronic absorption spectroscopy of [Ru(phen)2(dppz)] and [Ru(tap)2(dppz)] complexes intercalated in guanine-cytosine base pairs

The structural and spectroscopic properties of [Ru(phen)₂(dppz)]²⁺ and [Ru(tap)₂(dppz)]²⁺ (phen = 1,10-phenanthroline; tap = 1,4,5,8-tetraazaphenanthrene; dppz = dipyridophenazine ) have been investigated by means of density functional theory (DFT), time-dependent DFT (TD-DFT) within the polarized continuum model (IEF-PCM) and quantum mechanics/molecular mechanics (QM/MM) calculations. The model of the Δ and Λ enantiomers of Ru(II) intercalated in DNA in the minor and major grooves is limited to the metal complexes intercalated in two guanine-cytosine base pairs. The main experimental spectral features of these complexes reported in DNA or synthetic polynucleotides are better reproduced by the theoretical absorption spectra of the Δ enantiomers regardless of intercalation mode (major or minor groove). This is especially true for [Ru(phen)₂(dppz)]²⁺. The visible absorption of [Ru(tap)₂(dppz)]²⁺ is governed by the MLCT_tap transitions regardless of the environment (water, acetonitrile or bases pair), the visible absorption of [Ru(phen)₂(dppz)]²⁺ is characterized by transitions to metal-to-ligand-charge-transfer MLCT_dppz in water and acetonitrile and to MLCT_phen when intercalated in DNA. The response of the IL_dppz state to the environment is very sensitive. In vacuum, water and acetonitrile these transitions are characterized by significant oscillator strengths and their positions depend significantly on the medium with blue shifts of about 80 nm when going from vacuum to solvent. When the complex is intercalated in the guanine-cytosine base pairs the ¹IL_dppz transition contributes mainly to the band at 370 nm observed in the spectrum of [Ru(phen)₂(dppz)]²⁺ and to the band at 362 nm observed in the spectrum of [Ru(tap)₂(dppz)]²⁺.     

Synthesis and DNA threading properties of quaternary ammonium [Ru(phen)2(dppz)] derivatives

Ruthenium complexes with one dipyrido[3,2-a:2′-3′-c]phenazine (dppz) ligand, e.g. [Ru(phen)₂(dppz)]²⁺ (phen = phenanthroline), shows strong binding to double helical DNA and are well-known DNA “light-switch” molecules. We have here investigated four new [Ru(phen)₂(dppz)]²⁺ derivatives with different bulky quaternary ammonium substituents on the dppz ligand to find relationships between molecular structure and intercalation kinetics, which is considered to be of importance for antitumor applicability. Linear dichroism spectroscopy shows that the enantiomers of the new complexes exhibit very similar binding geometries (intercalation of dppz moiety between adjacent DNA base pairs) as the enantiomers of the parent [Ru(phen)₂(dppz)]²⁺ complex. Absorption spectra and luminescence properties provide further evidence for a final intercalative binding mode which has to be reached by threading of a bulky moiety between the strands of the DNA. Δ-enantiomers of all the new complexes show much slower association and dissociation kinetics than that of a reference complex without a cationic substituent. Kinetics were not very different whether the bulky quaternary group was derived from hexamethylene tetramine or 1,4-diazabicyclo-(2,2,2)octane (DABCO) or whether it had one or two positive charges. However, a complex in which the hexamethylene tetramine substituent is attached via a phenyl group showed a lowered association rate, in addition to an improved quantum yield of luminescence. A second positive charge on the DABCO substituent resulted in a much slower dissociation rate, suggesting that the distance from the Ru-centre and the amount of charge are both important for threading intercalation kinetics.     

DNA photocleavage activity of cobalt(III) polypyridyl complexes containing dpq ligand

Four cobalt(III) polypyridyl complexes, [Co(phen)_3−n(dpq)_n]³⁺ (phen = 1,10-phenanthroline, dpq = dipyrido[3,2-f:2′,3′-h]-quinoxaline) (n = 0, 1, 2, and 3) were synthesized and the influences of the dpq ligand on the photophysical properties, electrochemical properties, DNA binding affinities, as well as photonuclease activities of the complexes, were examined in detail. The presence of dpq ligand increases the DNA binding affinities of the corresponding complexes remarkably with respect to [Co(phen)₃]³⁺. With the sequential substitution of phen ligand by dpq ligand, the ¹O₂ quantum yields of the corresponding complexes are enhanced greatly. As a result, the photonuclease activities follow the order of [Co(dpq)₃]³⁺ > [Co(phen)(dpq)₂]³⁺ > [Co(phen)₂(dpq)]³⁺ ? [Co(phen)₃]³⁺. It was found all the examined complexes can generate OH upon UV irradiation, and OH is also involved in DNA photocleavage as reactive oxygen species.     

Synthesis, characterization and photophysical properties of mixed ligand tris(polypyridyl)chromium(III) complexes, [Cr(phen)2L]

A series of new heteroleptic, tris(polypyridyl)chromium(III) complexes, [Cr(phen)₂L]³⁺ (L = substituted phenanthrolines or bipyridines), has been prepared and characterized, and their photophyical properties in a number of solvents have been investigated. X-ray crystallography measurements confirmed that the cationic (3+) units contain only one ligand L plus two phenanthroline ligands. Electrochemical and photophysical data showed that both ground state potentials and lifetime decays are sensitive to ligand structure and the nature of the solvent with the exception of compounds containing L = 5-amino-1,10-phenanthroline (aphen) and 2,2′-bipyrimidine (bpm). Addition of electron-donating groups in the ligand structure shifts redox potentials to more negative values than those observed for the parent compound, [Cr(phen)₃]³⁺. Emission decays show a complex dependence with the solvent. The longest lifetime was observed for [Cr(phen)₂(dip)]³⁺ (dip = 4,7-diphenylphenanthroline) in air-free aqueous solutions, τ = 273 μs. Solvent effects are explained in terms of the affinity of hydrophobic complexes for non-polar solvent molecules and the solvent microstructure surrounding chromium units.     

The relationship between the structures of periphery ligands and the DNA binding mode of [Ru(II)(1,10-phenanthroline)(L1L2)dipyrido[3,2-a:2',3'-c]phenazine](n+) (L1=Cl or pyridine and L2=pyridine, n=1,2)

The binding modes of the [Ru(II)(1,10-phenanthroline)(L₁L₂) dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ {[Ru(phen)(py) Cl dppz]⁺ (L₁ = Cl, L₂ = pyridine) and ([Ru(phen)(py)₂dppz]²⁺ (L₁ = L₂ = pyridine)} to native DNA is compared to that of the [Ru(II)(1,10-phenanthroline)₂dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ complex ([Ru(phen)₂dppz]²⁺) by various spectroscopic and hydrodynamic methods including electric absorption, linear dichroism (LD), fluorescence spectroscopy, and viscometric titration. All measured properties, including red-shift and hypochromism in the dppz absorption band, nearly perpendicular molecular plane of the dppz ligand with respect to the local DNA helix axis, prohibition of the ethidium binding, the light switch effect and binding stoichiometry, increase in the viscosity upon binding to DNA, increase in the melting temperature are in agreement with classical intercalation of dppz ligand of the [Ru(phen)₂dppz]²⁺ complex, in which both phenanthroline ligand anchored to the DNA phosphate groups by electrostatic interaction. [Ru(phen)(py)₂ dppz]²⁺ and [Ru(phen)(py) Cl dppz]⁺ complexes had one of the phenanthroline ligand replaced by either two pyridine ligands or one pyridine plus a chlorine ion. They exhibited similar protection from water molecules, interaction with DNA bases, and occupying site that is common with ethidium. The dppz ligand of these two Ru(II) complex were greatly tilted relative to the DNA helix axis, suggesting that the dppz ligand resides inside the DNA and is not perpendicular relative to the DNA helix axis. These observation suggest that anchoring the [Ru(phen)₂dppz]²⁺complex by both phenanthroline is essential for the dppz ligand to be classically intercalated between DNA base-pairs.     

Synthesis, structure, DNA binding and photocleavage activity of a ruthenium(II) complex with 11-(9-acridinyl)dipyrido[3,2-a:2′,3′-c]phenazine ligand

In our search for new DNA intercalating ligands, a novel bifunctional intercalator 11-(9-acridinyl)dipyrido[3,2-a:2′,3′-c]phenazine, acdppz (has two potentially effective intercalators via dipyridophenazine(dppz) and acridine which are linked together via C-C bond) and its corresponding Ru(II) polypyridyl complex [Ru(phen)₂(acdppz)]²⁺ (where phen = 1,10-phenanthroline) have been synthesized and characterized. The electrochemical behaviors of the ligand and its complex have been thoroughly examined. The structure of acdppz and [Ru(phen)₂(acdppz)]²⁺ were determined by X-ray crystallography. From the crystal structure of the complex, we found that the dppz moiety is not coplanar with the acridine ring, having a dihedral angle of 64.79 in the acdppz. The selected bond lengths and angles for the crystal structure of [Ru(phen)₂(acdppz)]²⁺ were compared to the geometry-optimized molecular structure of [Ru(phen)₂(acdppz)]²⁺ derived by Gaussian. The interaction of [Ru(phen)₂(acdppz)]²⁺ with calf-thymus (CT) DNA was investigated by absorption and viscometry titration, thermal denaturation studies. The above measurements indicated that the complex binds less strongly with the CT DNA due to the intercalation by the ruthenium bound acdppz with an intrinsic binding constant of 2.6 × 10⁵ M⁻¹. Molecular-modeling studies also support an intercalative mode of binding of the complex to the model duplex d(CGCAATTGCG)₂ possibly from the major groove with a slight preference for GC rich region. Additionally, the title complex promotes the cleavage of plasmid pBR322 DNA upon irradiation under aerobic conditions.     

[Ru(phen)2(dppz)] as an efficient optical probe for staining nuclear components

The ‘molecular light switch’ complexes [Ru(bpy)₂(dppz)]²⁺ (1) and [Ru(phen)₂(dppz)]²⁺ (2), where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and dppz = dipyrido[3,2-a:2′,3′-c]phenazine, have been explored as probes for diagnosing and staining nuclear components. The phen complex acts as a better staining agent for nonviable cells than for viable cells and exhibits a staining efficiency in tail region of comet more specific and stronger than the already known dye Hoechst 33258.     

DNA binding and bending by dinuclear complexes comprising ruthenium polypyridyl centres linked by a bis(pyridylimine) ligand

The interaction of enantiomerically pure dinuclear complexes of the form [Ru₂(L-L)₄L¹]⁴⁺ (where L-L = 2,2^′-bipyridine (bpy) or 1,10-phenanthroline (phen) and L¹ = bis(pyridylimine) ligand ((C₅H₄N)CN(C₆H₄))₂CH₂)) with ct-DNA have been investigated by absorbance, circular dichroism, fluorescence displacement assays, thermal analysis, linear dichroism and gel electrophoresis. The complexes all bind more strongly to DNA than ethidium bromide, stabilise DNA and have a significant bending effect on DNA. The data for Δ,Δ-[Ru₂(bpy)₄L¹]⁴⁺ are consistent with it binding to DNA outside the grooves wrapping the DNA about it. By way of contrast the other complexes are groove-binders. The phen complexes provide a chemically and enantiomerically stable alternative to the DNA-coiling di-iron triple-helical cylinder previously studied. In contrast to the di-iron helicates, the phen complexes show DNA sequence effects with Δ,Δ-[Ru₂(phen)₄L¹]⁴⁺ binding preferentially to GC and Λ,Λ-[Ru₂(phen)₄L¹]⁴⁺ to AT.     

The interaction of native calf thymus DNA with Fe(III)-dipyrido[3,2-a:2',3'-c]phenazine

The mono and bis dipyrido[3,2-a:2′,3′-c]phenazine (dppz) adducts of iron(III) chloride, i.e. [Fe(dppz)]Cl₃ and [Fe(dppz)₂]Cl₃, have been synthesized and characterized. The interaction of the Fe^IIIdppz hydrolyzed aquo complex with native calf thymus DNA has been monitored as a function of the metal complex-DNA molar ratio, by variable temperature UV absorption spectrophotometry, circular dichroism (CD) and fluorescence spectroscopy. The results obtained in solution at various ionic strength values give support for a tight intercalative binding of the Fe^IIIdppz cation with DNA. In particular, the appearance of induced CD bands, caused by the addition of Fe^IIIdppz, indicate the existence of a rigid metal complex-DNA-binding leading to dominating chiral organization of Fe^IIIdppz species within the DNA double helix. The trend of selected CD bands with the molar concentration of Fe^IIIdppz emphasizes that the presence of high amounts of metal complex induces also the formation of DNA-Fe^IIIdppz supramolecular aggregates in solution. The analysis of fluorescence measurements allowed us to calculate a value of the intercalative binding constant comparable to that obtained by UV spectrophotometric titration. Finally, the temperature dependence of the absorbance at 258 nm shows that the metal complex strongly increases the DNA melting temperature already at metal complex-DNA molar ratio equal to 0.25 suggesting that metal complex intercalation effectively hinders DNA denaturation. Overall, the results of the present study point out that the Fe^IIIdppz aquo complex has DNA-binding properties analogous to those previously reported for the tris-chelate Fe^II(phen)₂dppz complex (phen = 1,10-phenantroline).     

Preparation, crystal structures and spectroscopic properties of novel [MCl3 − n(P)3 + n] (M = Co, Rh; n = 0, 1, 2 or 3) series of complexes containing tripodal tridentate phosphine, 1,1,1-tris(dimethylphosphinomethyl)ethane

Cobalt(III) and rhodium(III) complexes of the series of [M^IIICl_3 − n(P)_3 + n]ⁿ⁺ (M = Co or Rh; n = 0, 1, 2 or 3) have been prepared with the use of 1,1,1-tris(dimethylphosphinomethyl)ethane (tdmme) and mono- or didentate phosphines. The single-crystal X-ray analyses of both series of complexes revealed that the M-P and M-Cl bond lengths were dependent primarily on the strong trans influence of the phosphines, and secondarily on the steric congestion around the metal center resulting from the coordination of several phosphine groups. In fact, the M-P(tdmme) bonds became longer in the order of [MCl₃(tdmme)] < [MCl₂(tdmme)(PMe₃)]⁺ < [MCl(tdmme)(dmpe)]²⁺ (dmpe = 1,2-bis(dimethylphosphino)ethane) < [M(tdmme)₂]³⁺ for both Co^III and Rh^III series of complexes, while the M-Cl bond lengths were shortened in this order (except for [M(tdmme)₂]³⁺). Such a steric congestion around the metal center can also account for the structural and spectroscopic characteristics of the series of complexes, [MCl(tdmme)(dmpm, dmpe or dmpp)]²⁺ (dmpm = bis(dimethylphosphino)methane, dmpp = 1,3-bis(dimethylphosphino)propane). The X-ray analysis for [CoCl(tdmme)(dmpm or dmpe)](BF₄)₂ showed that all Co-P bonds in the dmpm complex were shorter by 0.03-0.04 Å than those in the dmpe complex. Furthermore, the first d-d transition energy of the Co^III complexes and the ¹J_Rh-P(tdmme) coupling constants observed for the Rh^III complexes indicated an unusual order in the coordination bond strengths of the didentate diphosphines, i.e., dmpm > dmpe > dmpp.     

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.     

Vibrational and structural mapping of [Os(bpy)3] and [Os(phen)3]

Structural changes between [Os^IIL₃]²⁺ and [Os^IIIL₃]³⁺ (L: 2,2′-bipyridine; 1,10-phenanthroline) and molecular and electronic structures of the Os^III complexes [Os^III(bpy)₃]³⁺ and [Os^III(phen)₃]³⁺ are discussed in this paper. Mid-infrared spectra in the ν(bpy) and ν(phen) ring stretching region for [Os^II(bpy)₃](PF₆)₂, [Os^III(bpy)₃](PF₆)₃, [Os^II(phen)₃](PF₆)₂, and [Os^III(phen)₃](PF₆)₃ are compared, as are X-ray crystal structures. Absorption spectra in the UV region for [Os^III(bpy)₃](PF₆)₃ and [Os^III(phen)₃](PF₆)₃ are dominated by very intense absorptions (ε = 40 000-50 000 M⁻¹ cm⁻¹) due to bpy and phen intra-ligand π → π^∗ transitions. In the visible region, relatively narrow bands with vibronic progressions of ∼1500 cm⁻¹ appear, and have been assigned to bpy or phen-based, spin-orbit coupling enhanced, ¹π → ³π^∗ electronic transitions. Also present in the visible region are ligand-to-metal charge transfer bands (LMCT) arising from π(bpy) → t_2g(Os^III) or π(phen) → t_2g(Os^III) transitions. In the near infrared, two broad absorption features appear for oxidized forms [Os^III(bpy)₃](PF₆)₃ and [Os^III(phen)₃](PF₆)₃ arising from dπ-dπ interconfigurational bands characteristic of dπ⁵Os^III. They are observed at 4580 and 5090 cm⁻¹ for [Os^III(bpy)₃](PF₆)₃ and at 4400 and 4990 cm⁻¹ for [Os^III(phen)₃](PF₆)₃. The bpy and phen infrared vibrational bands shift to higher energy upon oxidation of Os(II) to Os(III). In the cation structure in [Os^III(bpy)₃](PF₆)₃, the Os^III atom resides at a distorted octahedral site, as judged by ∠N-Os-N, which varies from 78.78(22)° to 96.61(22)°. Os-N bond lengths are also in general longer for [Os^III(bpy)₃](PF₆)₃ compared to [Os^II(bpy)₃](PF₆)₂ (0.010 Å), and for [Os^III(phen)₃](PF₆)₃ compared to [Os^II(phen)₃](PF₆)₂ (0.014 Å). Structural changes in the ligands between oxidation states are discussed as originating from a combination of dπ(Os^II) → π^∗ (bpy or phen) backbonding and charge redistribution on the ligands as calculated by natural population analysis.     

Searching for switchable molecular conductors: Salts of [M(dcbdt)2] (M = Ni, Au) anions with [Fe(sal2-trien)] and [Fe(phen)3]

Salts of [Fe^III(sal₂-trien)]⁺and [Fe^II(phen)₃]²⁺ cations and M[(dcbdt)₂]⁻ anions with M = Ni and Au (dcbdt = dicyanobenzenedithiolate) with formula [Fe(sal₂-trien)] [M(dcbdt)₂] and [Fe(phen)₃] [M(dcbdt)₂]₂ were obtained and characterized by single X-ray diffraction and magnetic measurements. None of these salts shows a clear spin crossover behaviour and their magnetic properties are due essentially to the cations in a high spin S = 5/2 and low spin states for the Fe^III and Fe^II salts respectively. The magnetic Ni sublattices in both compounds appear to have a negligible direct contribution to the magnetization but enhance the AF interactions in the cation sublattice.     

Synthesis and electrochemical studies of octahedral nickel β-diketonate complexes

The reaction of [Ni(tmhd)₂] and [Ni(dbm)₂] with N-donor chelating ligands in dichloromethane and acetone, respectively, yields the complexes [Ni(tmhd)₂(L-L)] (L-L = 2,2′-bpy 1, phen 2 and dmae 3) and [Ni(dbm)₂(L-L)] (L-L = 2,2′-bpy 4, phen 5, dmae 6). UV-Vis spectroscopy shows very strong bands in the UV region consistent with ligand centred π → π^∗ transitions. The electrochemical studies of 1-6 reveal oxidation to Ni(III). The [Ni(tmhd)₂(L-L)] 1-3 are more easily oxidized by ca. 300 mV and are quasi-reversible whereas for the [Ni(dbm)₂(L-L)] series only complex 6 shows significant reversibility. X-ray crystallographic studies have been conducted in the case of [Ni(dbm)₂(phen)] 5 and [Ni(dbm)₂(dmae)] 6. The structures both show that the nickel metal centre is octahedral with an O₄N₂ coordination environment. In the structures the β-diketonate ligands exhibit a cis-arrangement, with the metal displaced out of the planar chelate ring.     

Electronic effects on the interactions of complexes [Ru(phen)2(p-L)] (L=MOPIP, HPIP, and NPIP) with DNA

In order to explore the electronic effects of Ru(II) complexes binding to DNA, a series of Ru(II) complexes [Ru(phen)₂ (p-MOPIP)]²⁺ (1), [Ru(phen)₂ (p-HPIP)]²⁺ (2), and [Ru(phen)₂(p-NPIP)]²⁺ (3) were synthesized and characterized by elementary, ¹H NMR, and ES-MS analysis. The binding properties of these complexes to CT-DNA were investigated with spectroscopic methods and viscosity experiments. Furthermore, the computations for these complexes applying the density functional theory (DFT) method have also been performed. The results show that all of these complexes can well bind to DNA in intercalation mode and DNA-binding affinity of these complexes is greatly influenced by electronic effects of intercalating ligands. The intrinsic binding constants for 1, 2, and 3 are 0.20, 0.69, and 1.56 × 10⁵ M⁻¹, respectively. This order is in accordance with that of the electron-withdrawing ability of substituent [-OR < -OH < -NO₂]. Such a trend in electronic effects of Ru(II) complexes binding to DNA can be reasonably explained by the DFT calculations.     

Photocytotoxicity and near-IR light DNA cleavage activity of oxovanadium(IV) Schiff base complexes having phenanthroline bases

Oxovanadium(IV) complexes [VO(L)(B)] (1-3), where H₂L is a Schiff base ligand 2-(2-hydroxybenzylideneamino)phenol and B is 1,10-phenanthroline (phen for 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq for 2) or dipyrido[3,2-a:2′,3′-c]phenazine (dppz for 3), have been prepared, characterized and their DNA binding property and photo-induced DNA cleavage activity studied. Complex 3 which is structurally characterized by X-ray crystallography shows the presence of an oxovanadium(IV) moiety in a six coordinate VO₃N₃ coordination geometry. The complexes show a d-d band within 800-850 nm in DMF. The complexes display an oxidative response near 0.7 V versus SCE for V(V)-V(IV) and a reductive response within −1.1 to −1.3 V due to V(IV)-V(III) couple in DMF-0.1 M TBAP. The complexes are avid binders to calf thymus DNA giving binding constant values of 4.2 × 10⁴ to 1.2 × 10⁵ M⁻¹. The complexes do not show any “chemical nuclease” activity in dark. The dpq and dppz complexes are photocleavers of plasmid DNA in UV-A light of 365 nm via ¹O₂ pathway and in near-IR light (752.5 to 799.3 nm IR optics) by HO^• pathway. Complex 3 exhibits significant photocytotoxicity in visible light in HeLa cells giving IC₅₀ value of 13 μM, while it is less toxic in dark (IC₅₀ = 97 μM).     

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.     

Solution studies of lanthanide (III) complexes based on 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and 1,10-phenanthroline Part-I: Synthesis, H NMR, 4f-4f absorption and photoluminescence

Solution studies on the complexes of the type [Ln(hfaa)₃(phen)₂] (Ln = La, Pr and Nd) and [Ln(hfaa)₃phen] (Ln = Nd, Ho, Er and Yb; hfaa stands for the anion of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione and phen stands for 1,10-phenanthroline) are presented. These complexes are synthesized in high yields by an in situ method in which hfaa, ammonium hydroxide, lanthanide chlorides and phen were allowed to react in 3:3:1:1 molar ratio in ethanol. In the case of neodymium both eight- and ten-coordinate complexes are isolated. The paramagnetic shifts of the methine protons of β-diketone have their sign opposed to those of paramagnetic shifts of phen protons and the shifts are dominated by dipolar interactions. The inter- and intramolecular shift ratios have been calculated and discussed. The 4f-4f absorption spectra of the complexes of Pr, Nd, Ho and Er are analyzed. The eight- and ten-coordinate neodymium complexes display distinctively different band shapes of the ⁴G_5/2,²G_7/2 ← ⁴I_9/2 hypersensitive transition. The efficient energy transfer from ligand to Pr(III) is reflected by strong red luminescence of this complex at room temperature.