Trend In DNA-binding Affinities Research Articles

Theoretical studies on interaction properties of chiral Ru(II) polypyridyl complexes with DNA

Theoretical studies on DNA-photocleavage mechanisms and abilities of chiral Ru(II) polypyridyl complexes have been carried out using the density functional theory (DFT) method. The stable DNA-docking models of chiral Ru(II) polypyridyl complexes were obtained using the docking and DFT methods. Based on the obtained DNA-docking models, the DNA-binding energies of chiral Ru(II) complexes were computed using UB3LYP and UB3LYP-D3 methods, and the trend in DNA-binding affinities of chiral Ru(II) polypyridyl complexes were reasonably explained. According to the distances between complexes and DNA, the reason of DNA-binding abilities of Δ-complexes stronger than those of Λ-complexes was also explained. In addition, the excited-state reduction potentials, electrons-transfer (ET) activation energies and intramolecular reorganization energies of chiral Ru(II) polypyridyl complexes were calculated and the DNA-photocleavage abilities were reasonably explained.

Acid–base effects, light emission, DNA-binding and photocleavage studies of oligo-homonuclear ruthenium(II) complexes and their computational study

The ground- and excited-state acid ionization constants and the DNA binding properties of mono-, di- and trinuclear ruthenium(II) polypyridine complexes have been studied by electronic absorption and fluorescence emission spectroscopy. The DNA binding abilities of the complexes increase with increasing π-electron multiplicity of phenanthroline groups and the H-bonding properties of imidazole moieties increase from the mononuclear (R1) to dinuclear (R2), followed by trinuclear (R3) complexes. In addition, the increasing surface area of the complexes relatively leads to a corresponding enhancement in binding affinity. The DNA-binding constants, Kb, of the complexes were determined systematically by spectrophotometric titration. In addition to the various ionic interactions, van der Waals interaction, hydrogen bonding, DNA-binding constants Kb and hypochromism of Ru(II) polypyridine complexes inferred the existence of intercalation mode of binding. The trend in DNA-binding affinities as well as the spectral properties of this series of complexes can be reasonably explained by applying the DFT at the B3LYP/LanL2DZ/6-31G level. The results suggest that the multiplication of complex unit has important effects on the electronic structures, a trend in the DNA-binding affinities and an improvement of spectral properties of the complexes. The binding affinity of the ruthenium complexes with biological receptors namely, G-quadraplexes from human telomeres has been investigated. The binding characteristics of complexes have been compared with each other using molecular docking. Further, these complexes tend to promote cleavage of plasmid DNA under photolytic conditions.

Influence of self-assembly on intercalative DNA binding interaction of double-chain surfactant Co(III) complexes containing imidazo[4,5-f][1,10]phenanthroline and dipyrido[3,2-d:2'-3'-f]quinoxaline ligands: experimental and theoretical study.

A new class of surfactant Co(III) complexes, cis-[Co(ip)2(C12H25NH2)2](ClO4)3 (1) and cis-[Co(dpq)2(C12H25NH2)2](ClO4)3 (2) (ip = imidazo[4,5-f][1,10]phenanthroline, dpq = dipyrido[3,2-d:2'-3'-f]quinoxaline), have been synthesized and characterized by various spectroscopic and physico-chemical techniques. The critical micelle concentration (CMC) values of these complexes in aqueous solution were obtained from conductance measurements. The specific conductivity data (at 303, 308, 313, 318 and 323 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (ΔG(0)(m), ΔH(0)(m) and ΔS(0)(m)). The trend in DNA-binding affinities and the spectral properties of a series of complexes, cis-[Co(ip)2(C12H25NH2)2](ClO4)3 (1) and cis-[Co(dpq)2(C12H25NH2)2](ClO4)3 (2), have been experimentally and theoretically investigated. The experimental results indicate that the size and shape of the intercalated ligand and hydrophobicity of the complexes have a marked effect on the binding affinity of the complexes to CT DNA in intercalation mode, and the order of their intrinsic DNA-binding constants Kb is Kb(1) < Kb(2). In addition, the influence of the extended aromatic ring and optical properties of the complexes can be reasonably explained by applying the DFT calculations. The energy gap between HOMO and LUMO indicates that these complexes are prone to interact with CT DNA. Further, molecular docking calculations have also been performed to understand the nature of binding of the complexes and the result confirms that the complexes interact with CT DNA through the alkyl chain. The cytotoxic activity of these complexes on human liver carcinoma cancer cells were determined adopting MTT assay and specific staining techniques, which revealed that the viability of the cells thus treated was significantly decreased and the cells succumbed to apoptosis as seen in the changes in the nuclear morphology and cytoplasmic features.

Mixed Ligand Copper(II) Complexes of N,N-Bis(benzimidazol-2-ylmethyl)amine (BBA) with Diimine Co-Ligands: Efficient Chemical Nuclease and Protease Activities and Cytotoxicity

A series of mononuclear mixed ligand copper(II) complexes [Cu(bba)(diimine)](ClO(4))(2)1-4, where bba is N,N-bis(benzimidazol-2-ylmethyl)amine and diimine is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) (3), or dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (4), have been isolated and characterized by analytical and spectral methods. The coordination geometry around copper(II) in 2 is described as square pyramidal with the two benzimidazole nitrogen atoms of the primary ligand bba and the two nitrogen atoms of phen (2) co-ligand constituting the equatorial plane and the amine nitrogen atom of bba occupying the apical position. In contrast, the two benzimidazole nitrogen atoms and the amine nitrogen atom of bba ligand and one of the two nitrogen atoms of 5,6-dmp constitute the equatorial plane of the trigonal bipyramidal distorted square based pyramidal (TBDSBP) coordination geometry of 3 with the other nitrogen atom of 5,6-dmp occupying the apical position. The structures of 1-4 have been optimized by using the density functional theory (DFT) method at the B3LYP/6-31G(d,p) level. Absorption spectral titrations with Calf Thymus (CT) DNA reveal that the intrinsic DNA binding affinity of the complexes depends upon the diimine co-ligand, dpq (4) > 5,6-dmp (3) > phen (2) > bpy (1). The DNA binding affinity of 4 is higher than 2 revealing that the π-stacking interaction of the dpq ring in between the DNA base pairs with the two bzim moieties of the bba ligand stacked along the DNA surface is more intimate than that of phen. The complex 3 is bound to DNA more strongly than 1 and 2 through strong hydrophobic interaction of the methyl groups on 5,6-positions of the phen ring in the DNA grooves. The extent of the decrease in relative emission intensities of DNA-bound ethidium bromide (EB) upon adding the complexes parallels the trend in DNA binding affinities. The large enhancement in relative viscosity of DNA upon binding to 3 and 4 supports the DNA binding modes proposed. Interestingly, the 5,6-dmp complex 3 is selective in exhibiting a positive induced CD band (ICD) upon binding to DNA suggesting that it induces a B to A conformational change. In contrast, 2 and 4 show induced CD responses indicating their involvement in strong DNA binding. Interestingly, only the dpq complex 4, which displays the strongest DNA binding affinity and is efficient in cleaving DNA in the absence of an activator with a rate constant of 5.8 ± 0.1 h(-1), which is higher than the uncatalyzed rate of DNA cleavage. All the complexes exhibit oxidative DNA cleavage ability, which varies as 4 > 2 > 3 > 1 (ascorbic acid) and 3 > 2 > 4 > 1 (H(2)O(2)). Also, the complexes cleave the protein bovine serum albumin in the presence of H(2)O(2) as an activator with the cleavage ability varying in the order 3 > 4 > 2 > 1. The highest efficiency of 3 to cleave both DNA and protein in the presence of H(2)O(2) is consistent with its strong hydrophobic interaction with the biopolymers. The IC(50) values of 1-4 against cervical cancer cell lines (SiHa) are almost equal to that of cisplatin, indicating that they have the potential to act as effective anticancer drugs in a time-dependent manner. The morphological assessment data obtained by using acridine orange/ethidium bromide (AO/EB) and Hoechst 33258 staining reveal that 3 induces apoptosis much more effectively than the other complexes. Also, the alkaline single-cell gel electrophoresis study (comet assay) suggests that the same complex induces DNA fragmentation more efficiently than others.

Theoretical studies on the related properties of Co(III) polypyridyl complexes interacting with DNA

Theoretical studies on the related properties of Co(III) polypyridyl complexes [Co(phen)2L]3+ (L: dppz = dipyrido[3,2-a:2′,3′-c]phenazine; phen = 1,10-phenanthroline; dione = 1,10-phenanthroline-5,6-diketone) 1–3 interacting with DNA, including the DNA-binding, DNA-photocleavage and spectral properties, have been carried out. First, the full geometry-optimizations of these three complexes in their ground states were carried out in aqueous solution. The optimized structures of these three complexes were docked into DNA-base-pairs using the Dock6.0 program. Secondly, the binding modes of complexes 1–3 were revealed in detail and the trend in DNA-binding affinities was reasonably explained. Thirdly, the electronic absorption and emission spectra of docking model of the optimal complex 1 were calculated and simulated. The experimental intense absorption and emission bands of Co(Ш) complex 1 in the presence of DNA were explained in detail, in particular, the reason why the emission spectra of complex 1 in the presence of DNA are greatly stronger than those in the absence of DNA was theoretically elucidated. Finally, the DNA-photocleavage essential of complexes was explored and the DNA photocleavage efficiencies (φ), i.e., φ(1)>φ(2)>φ(3), was also reasonably explained.

Theoretical studies on the DNA-intercalator properties of Co(III) polypyridyl complexes

Theoretical studies on the DNA-intercalator properties of Co(III) polypyridyl complexes 1 and 2 have been carried out. First, a sheared whole DNA-complex model to perform the study on DNA-interaction properties of Co(III) polypyridyl complexes was established, by using a combination method of the quantum-chemistry and the molecular mechanics as follows: The full geometric optimizations of these two complexes were carried out in aqueous solution using the restricted B3LYP method and LanL2DZ basis set, then the optimized complexes were docked into DNA-base-pairs using the docking program, and the obtained greater DNA-complex model was sheared to a simplified whole model, and finally the sheared DNA-complex model was exactly computed using the DFT/TDDFT method. Secondly, based on the computations of above-established models, via the analysis of the DNA-binding energies of complexes 1 and 2 as well as the intramolecular hydrogen bonds within the docking models, the trend in DNA-binding affinities, i.e., K b( 2) > K b( 1), can be reasonably explained. Thirdly, the electronic absorption spectra of docking models were also calculated and simulated using the TDDFT method. The simulated absorption spectra are in a satisfying agreement with experimental results, and the intense experimental absorption bands of these Co(Ш) complexes in the presence of DNA are theoretically explained in detail.

DNA binding, prominent DNA cleavage and efficient anticancer activities of Tris(diimine)iron(ii) complexes

The complexes rac-[Fe(diimine)(3)](ClO(4))(2)1-4, where diimine = 2,2'-bipyridine (bpy) 1, 1,10-phenanthroline (phen) 2, 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) 3 and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) 4, have been isolated, characterized and their interaction with calf thymus DNA studied by using a host of physical methods. The X-ray crystal structure of rac-[Fe(5,6-dmp)(3)](ClO(4))(2)3 has been determined and the packing diagram shows the presence of two enantiomeric forms of the complex cations in the same unit cell. The structures of 1-4 in solution have also been studied using UV-Visible, Cyclic Voltammetry and ESI-MS data and all data available suggests that they retain their solid state structures even in solution. The absorption spectral titrations of the iron(ii) complexes with CT DNA reveal that the DNA binding affinities of the complexes vary in the order, 4 (K(b): 9.0 × 10(3)) > 2 (6.8 × 10(3)) > 3 (4. 8 × 10(3)) > 1 (2.9 × 10(3) M(-1)). The DNA interaction of dpq complex (4) involves partial insertion of the extended phen ring in between the DNA base pairs, which is deeper than that of phen (2). The 5,6-dmp (3) complex is involved in groove binding in the major groove of DNA. The lower DNA binding affinity of 1 is due to electrostatic interaction of the cationic complexes with exterior phosphates of DNA. The EthBr displacement assay and DNA viscosity study support these DNA binding modes and the above trend in DNA binding affinities. The complexes of 1 and 2 show induced CD (ICD) upon interaction with CT DNA while 3 and 4 bound to DNA exhibit inversion in the positive band with the helicity band showing very small changes, which implies that 3 and 4 bind enantiopreferentially to DNA. The DNA cleavage abilities of 1-4 have been observed at 10 μM concentration of complexes in the presence of 100 μM H(2)O(2) and the DNA cleavage efficiency (> 90%) follows the order 3 > 1 > 2 > 4. The anticancer activity of 1-4 against human breast cancer cell line (MCF-7) has also been studied. The IC(50) values of the complexes at different incubation time intervals of 24 and 48 h follow the order, 3 (0.8, 0.6) < 4 (20.0, 17.0) < 2 (28.0, 22.0) < 1 (32.0, 29.0 μM). Interestingly, 3 exhibits anticancer activity more potent than 1, 2 and 4 and cisplatin for both 24 and 48 h. It induces cell death both through apoptosis and necrosis mechanisms, as revealed by morphological assessment data obtained by using AO/EB and Hoechst 33258 fluorescence staining methods.

Electronic structures, DNA-binding and spectral properties of Co(III) complexes [Co(bpy) 2(L)] 3+ (L=pip, odhip, hnoip)

Studies on the electronic structures and trend in DNA-binding affinities of a series of Co(Ш) complexes have been carried out, using the density functional theory (DFT) at the B3LYP/LanL2DZ level. The optimized geometric structures of these Co(Ш) complexes in aqueous solution are more close to experimental data than those in vacuo. The electronic structures of these Co(Ш) complexes were analyzed on the basis of their geometric structures optimized in aqueous solution, and the trend in the DNA-binding constants ( K b) was reasonably explained. In addition, the electronic absorption spectra of these complexes were calculated and simulated in aqueous solution using the time dependent DFT (TDDFT) at the B3LYP/LanL2DZ level. The calculated absorption spectra of these Co(Ш) complexes in aqueous solution are in satisfying agreement with experimental results, and the properties of experimental absorption bands have been theoretically explained in detail. Meanwhile, in order to explore the solvent effect on the absorption spectra of these Co(Ш) complexes, their absorption spectra in vacuo were also calculated, and the results show that the calculated absorption spectra of Co(Ш) complexes are greatly influenced by the solvent effect.

Synthesis, characterization, DNA-binding and spectral properties of complexes [Ru(L) 4(dppz)] 2+ (L = Im and MeIm)

Two new Ru(II) complexes [Ru(L) 4(dppz)] 2+ (L = imidazole (Im), 1-methylimidazole (MeIm); dppz = dipyrido[3,2- a:2′,3′- c]phenazine), have been synthesized and characterized in detail by elemental analysis, 1H NMR, Electrospray ionization mass spectrometry (ESI-MS) and UV–visible (UV–Vis) spectroscopic techniques. The interaction of these complexes with calf thymus DNA (CT-DNA) has been explored by using electronic absorption titration, competitive binding experiment, circular dichroism (CD), thermal denaturation and viscosity measurements. The experimental results show that: both the two complexes can bind to DNA in an intercalation mode; the DNA-binding affinity of complex [Ru(Im) 4(dppz)] 2+ 1 ( K b = 2.5 × 10 6 M −1) is greater than that of complex [Ru(MeIm) 4(dppz)] 2+ 2 ( K b = 1.1 × 10 6 M −1). Moreover, it is very interesting to find that the circular dichroic spectrum of DNA–complex 1 adduct, in which both bands centered at 277 nm and 236 nm are all negative, is very different from those of DNA–complex 2 adduct and other Ru(II) complexes binding to DNA in general intercalation mode. It may be due to the hydrogen-bonding effect or the contribution of induced CD signals of complex 1. Another interesting finding is that the hypochromism of the complexes is not linear relation to their DNA-binding affinities. In order to deeply study these experimental phenomena and trends, the density functional theory (DFT) and time-dependent DFT (TDDFT) computations were carried out, and on the basis of the DFT/TDDFT results and the frontier molecular orbital theory, the trend in DNA-binding affinities, the spectral properties as well as the interesting phenomena of larger extent of hypochromism but relatively smaller K b values for the title complexes have been reasonably explained.

Experimental and theoretical studies on the DNA-binding and spectral properties of water-soluble complex [Ru(MeIm) 4(dpq)] 2+

A new water-soluble Ru(II) complex [Ru(MeIm) 4(dpq)] 2+ 1, has been synthesized and characterized by elemental analysis, 1H NMR, ESI-MS and UV–Vis. The interaction of the complex with CT-DNA has been explored by using electronic absorption titration, competitive binding experiment, circular dichroic (CD) spectra, thermal denaturation and viscosity measurements. The experimental results show that: the title complex can bind to DNA in an intercalative mode and its DNA-binding affinity is weaker ( K b = 1.2 × 10 4 M −1) than that of the complex [Ru(bpy) 2(dpq)] 2+ 2 with bidentate co-ligands ( K b = 4.7 × 10 4 M −1). Here a very interesting finding is that the hypochromism of the title complex is not linear relation to its DNA-binding affinity. In addition, some significant thermodynamic parameters of the binding of the title complex to DNA, e.g., the changes of free energy at melting temperature, standard enthalpy, and standard entropy ( Δ G T 0 , Δ H 0, and Δ S 0), were determined and calculated. In order to deeply explain the experimental findings, the DFT/TDDFT computations were carried out. On the basis of the DFT/TDDFT results and the frontier molecular orbital theory, the trend in DNA-binding affinities and the spectral properties as well as the interesting phenomena of larger extent of hypochromism but relatively smaller K b value for the title complex 1 compared with complex 2 were reasonably explained.

Density Functional Theory/Time-dependent DFT Studies on the Structures, Trend in DNA-binding Affinities, and Spectral Properties of Complexes [Ru(bpy)2(p-R-pip)]2+ (R = −OH, −CH3, −H, −NO2)

Studies on the electronic structures and trend in DNA-binding affinities of a series of Ru(II) complexes [Ru(bpy)2(p-R-pip)]2+ (bpy = 2,2-bipyridine; pip = 2-phenylimidazo[4,5-f] [1,10]-phenanthroline; R = -OH, -CH3, -H, -NO2) 1-4 have been carried out, using the density functional theory (DFT) at the B3LYP/LanL2DZ level. The electronic absorption spectra of these complexes were also investigated using time-dependent DFT (TDDFT) at the B3LYP//LanL2DZ/6-31G level. The computational results show that the substituents on the parent ligand (pip) have a significant effect on the electronic structures of the complexes, in particular, on the energies of the lowest unoccupied molecular orbital (LUMO) and near some unoccupied molecular orbitals (LUMO+x, x = 1-4). With the increase in electron-withdrawing ability of the substituent in this series, the LUMO+x (x = 0-4) energies of the complexes are substantially reduced in order, for example, epsilon(LUMO)(1) approximately epsilon(LUMO)(2) > epsilon(LUMO)(3) > epsilon(LUMO)(4), whereas the pi-component populations of the LUMO+x (x = 0-4) are not substantially different. Combining the consideration of the bigger steric hindrance of complex 2, the trend in DNA-binding affinities (K(b)) of the complexes, that is, K(b)(2) < K(b)(1) < K(b)(3) < K(b)(4) can be reasonably explained. In addition, the experimental singlet metal-to-ligand charge transfer ((1)MLCT) spectra of these complexes can be well simulated and discussed by the TDDFT calculations.

Experimental and DFT studies on the DNA-binding trend and spectral properties of complexes [Ru(bpy) 2L] 2+ (L = dmdpq, dpq, and dcdpq)

The trend in DNA-binding affinities and the spectral properties of a series of Ru(II) polypyridyl complexes, [Ru(bpy) 2(dmdpq)] 2+ ( 1), [Ru(bpy) 2(dpq)] 2+ ( 2), [Ru(bpy) 2(cndpq)] 2+ ( 3) (bpy = 2,2′-bipyridine; dpq = dipyrido[3,2-d:2′,3′-f]quinoxaline; dmdpq = di-methyl-dpq; dcdpq = di-cyano-dpq), have been experimentally and theoretically investigated. The DNA-binding constants K b of the complexes were determined systematically with spectrophotometric titration. The density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were carried out for these complexes. The experimental results show that these complexes bind to DNA in intercalation mode, and the order of their intrinsic DNA-binding constants K b is K b( 1) < K b( 2) ≪ K b( 3). The substituents on the intercalative ligands of the complexes play a very important role in the control of DNA-binding affinities of the complexes, in particular, the stronger electron-withdrawing substituent (–CN) on the intercalative ligand can greatly improve the DNA-binding property of the derivative complex. The trend in DNA-binding affinities as well as the spectral properties of metal–ligand charge-transition ( 1MLCT) of this series of complexes can be reasonably explained by applying the DFT and TDDFT calculations and the frontier molecular orbital theory.

Mixed-ligand copper(II) complexes of dipicolylamine and 1,10-phenanthrolines: The role of diimines in the interaction of the complexes with DNA

Mixed-ligand copper(II) complexes of the type [Cu(dipica)(diimine)](ClO4)2, where dipica is di(2-picolyl)amine and diimine is 1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp), 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) or dipyridoquinoxaline (dpq), have been isolated and characterized by analytical and spectral methods. The copper(II) complexes exhibit a broad band in the visible region around 675 nm and axial EPR spectra in acetonitrile glass (77 K) with g∥ and A∥ values of ∼2·22 and 185 × 10−4 cm−1 respectively, suggesting the presence of a square-based coordination geometry for the CuN5 chromophore involving strong axial interaction. The interaction of the complexes with CT DNA has been studied using absorption, emission and circular dichroic spectral methods and viscosity measurements. Absorption spectral titrations reveal that the intrinsic DNA binding affinities are dependent upon the nature of the diimine ligand: dpq > 5,6-dmp > phen > 2,9-dmp. This suggests the involvement of the diimine rather than the dipica ‘face’ of the complexes in DNA binding. An intercalative mode of DNA interaction, which involves the insertion of dpq and to a lesser extent the phen ring of the complexes in between the DNA base pairs, is proposed. However, interestingly, the 5,6-dmp complex is involved in hydrophobic interaction of the 5,6-dmp ring in the grooves of DNA. The large enhancement in the relative viscosity of DNA on binding to the dpq and 5,6-dmp complexes supports the proposed DNA binding modes. Further, remarkably, the 5,6-dmp complex is selective in exhibiting a positive-induced CD band on binding to DNA suggesting the transition of the B form of CT DNA to A-like conformation. The variation in relative emission intensities of DNA-bound ethidium bromide observed upon treatment with the complexes parallels the trend in DNA binding affinities.

Electronic structures, DNA-binding and related properties of complexes [Ru(bpy) 2L] 2+ (L=ip, pip, hpip)

Theoretical and experimental studies on the electronic structures, trend in DNA-binding and related properties of a series of Ru(II) polypyridyl complexes [Ru(bpy) 2L] 2+ (L=ip, pip, hpip) have been carried out (bpy=2,2′-bipyridine; ip=imidazo[4,5-f] [1,10]-phenanthroline; pip=2-phenylimidazo [4,5-f][1,10]-phenanthroline; hpip=2-(hydroxyphenyl)imidazo[4,5-f] [1,10]-phenanthroline). The theoretical calculations were performed applying the density functional theory (DFT) method, and the DNA-binding and the related properties of the complexes were measured with an electronic absorption, emission spectroscopy, cyclic voltammetry and so on. Some interesting electronic structural characteristics of these complexes were revealed. First, the electronic structures of complexes [Ru(bpy) 2pip] 2+ 2 and [Ru(bpy) 2hpip] 2+ 3 are quite different from those of the well-known parent complex [Ru(bpy) 3] 2+ and [Ru(bpy) 2ip] 2+ 1 in the occupied frontier molecular orbitals. Second, the HOMO and NHOMO energies of the complexes obviously increase from 1 to 3, whereas their LUMO energies are not obviously varied. Third, the effect of intra-molecular hydrogen bond in complex 3 plays a very important role, it not only enlarges the planarity area of its main ligand, but also makes its LUMO energy reduce to be lower than that of 2. These electronic structural characteristics can be used to reasonably explain the experimental trend in DNA-binding affinities, as well as spectral and electrochemical properties of the complexes.