DNA interaction studies of a cobalt(III) complex containing ß-amino alcohol ligand by spectroscopic and molecular docking methods.

In the present research, the feasibility of a Cobalt(III) complex containing ß-amino alcohol ligands for affinity with the target calf thymus DNA is demonstrated. In the title complex, [Co(C11H15N2O2)2]Cl, the Co(III) atom is six-coordinated with four N atoms and two O atoms from (2-[(E)-({2-[(2-Hydroxyethyl) amino]ethyl}imino)methyl]phenol) ligand (L). To investigate the molecular interaction between the synthesized complex and DNA, some multi-spectroscopic approaches associated with molecular docking were employed in the physiological buffer (pH 7.4). The results indicated that the Co(III) complex proved to be a minor groove binder with a preference for the A-T region, which was substantiated by displacement studies with Hoechst33258 and Methylene blue (MB) as minor groove binder and intercalator. In addition, the results of the molecular docking study revealed that the Co(III) complex approached the gap between the DNA minor grooves near the spot where the Hoechst was. Furthermore, the results of the cytotoxicity and apoptosis tests for the MCF-7 cell line were also indicative of the positive effects of the complex on controlling the growth and viability of breast cancer.Communicated by Ramaswamy H. Sarma.

In vitro cytotoxicity, antibacterial activity and HSA and ct-DNA interaction studies of chlorogenic acid loaded on γ-Fe2O3@SiO2 as new nanoparticles.

In this study, nanoparticles with both anticancer and antibacterial features were synthesized through loading chlorogenic acid (CGA) of essential oils on magnetic nanoparticles (MNPs). Characterization of γ-Fe2O3@SiO2-CGA MNPs was performed using Fourier transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM) that show effective coating of the MNPs with SiO2 and CGA ligand and spherical shape of the nanoparticles with a mean diameter of 16 nm, respectively. The cytotoxicity study demonstrated that γ-Fe2O3@SiO2-CGA MNPs had fewer toxic effects on normal cells (Huvec) than on cancerous cells (U-87 MG, A-2780 and A-549), and could be a new potential candidate for use in biological and pharmaceutical applications. The interaction of calf thymus deoxyribonucleic acid (ct-DNA) with γ-Fe2O3@SiO2-CGA MNPs indicated that the anticancer activity might be associated with the DNA binding properties of γ-Fe2O3@SiO2-CGA MNPs. Moreover, the interaction of γ-Fe2O3@SiO2-CGA MNPs with human serum albumin (HSA) suggests that the native conformation of HSA was preserved at the level of secondary structure, indicating that the γ-Fe2O3@SiO2-CGA MNPs do not show any cytotoxicity effect when they are injected into the blood. Antibacterial tests were performed and represented γ-Fe2O3@SiO2-CGA MNPs attained better antibacterial function than CGA as free.

Synthesis, characterization, in vitro cytotoxicity and DNA interaction studies of antioxidant ferulic acid loaded on γ-Fe2O3@SiO2 nanoparticles.

In this investigation, Fe3O4 magnetic nanoparticles (MNPs) were prepared via a chemical coprecipitation reaction, and the surface of Fe3O4 MNPs was coated with silica by a sol-gel process. The surface of Fe3O4@SiO2 MNPs was modified by an antioxidant agent, trans-ferulic acid, to achieve water-soluble MNPs for biological applications. Fourier transform infrared spectroscopy (FT-IR) showed that the MNPs were successfully coated with SiO2 and ferulic acid (FA) ligand. The morphology of γ-Fe2O3@SiO2-FA MNPs was found to be spherical in images of transmission electron microscopy (TEM) and showed a uniform size distribution with an average diameter of 21 nm. The in vitro cytotoxic activity of γ-Fe2O3@SiO2-FA MNPs and FA were investigated against the human cancer cells (MCF-7, PC-3, U-87 MG, A-2780, and A-549) by MTT colorimetric assay. The cytotoxic effect of MNPs on all cancer cell lines was several times of magnitude higher compared to free FA except for A-549 cell lines. Furthermore, in vitro DNA binding studies were investigated by UV-vis and circular dichroism spectroscopies.

Antimicrobial, cytotoxicity, molecular modeling and DNA cleavage/binding studies of zinc-naproxen complex: switching DNA binding mode of naproxen by coordination to zinc ion.

The intercalation DNA binding mode of the naproxen, a non-steroidal anti-inflammatory drug, has been reported previously. In this study, calf thymus deoxyribonucleic acid (CT-DNA) binding of zinc-naproxen complex, [Zn(naproxen)2(MeOH)2], at physiological pH has been investigated by multi-spectroscopic techniques and molecular docking. Zinc-naproxen complex displays significant binding property to the CT-DNA (Kb = 0.2 × 105 L.mol-1). All of the experimental results; relative increasing in viscosity of CT-DNA and fluorimetric studies using ethidium bromide (EB) and Hoechst 33258 probes, are indicative of groove binding mode of zinc-naproxen complex to CT-DNA. These results show that the coordination of naproxen to zinc metal switches the mode of binding from intercalation to groove. The molecular modeling also shows that the complex binds to the AT-rich region of minor groove of DNA. Structural and topography changes of DNA in interaction with the complex by atomic force microscopy (AFM) indicated that CT-DNA becomes swollen after interaction. The pUC18 plasmid DNA cleavage ability of zinc-naproxen complex by gel electrophoresis experiments revealed that zinc-naproxen complex cleaved supercoiled pUC18 plasmid DNA to nicked DNA. The cytotoxicity of the zinc complex performed by MTT method on HT29 and MCF7 cancer cell lines and on HEK 293 normal cell lines indicates that zinc complex has no cytotoxic effect on both HT29 and MCF7 cell lines but has better cytotoxicity effect on HEK 293 cell lines compared to cisplatin standard drug. The antimicrobial activity of the complex against Staphylococcus aureus and Escherichia coli bacteria revealed the high antimicrobial activity of the complex.Communicated by Ramaswamy H. Sarma.

In vitro cytotoxicity studies of smart pH-sensitive lamivudine-loaded CaAl-LDH magnetic nanoparticles against Mel-Rm and A-549 cancer cells.

In this study, an effective nano-drug delivery system was prepared by the co-precipitation method via two steps; the preparation of Fe3O4 magnetic nanoparticles and its surface modification with layered double hydroxide (LDH) and loading lamivudine on this nanocarrier (Fe3O4@CaAl-LDH@Lamivudine). The developed nanoparticles (NPs) were characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray analysis, Fourier-transformed infrared spectroscopy, vibrating-sample magnetometry, thermogravimetric analysis, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller. The prepared system demonstrated an average size of 130 nm. Also, the drug entrapment efficiency was estimated at ∼70%. In vitro, drug release investigations showed a controlled and pH-dependent lamivudine release over 300 min. The in vitro cytotoxic activity of Fe3O4@CaAl-LDH@Lamivudine NPs was explored against Mel-Rm and A-549 cancer cell lines in comparison with lamivudine and nanocarrier using lactate dehydrogenase colorimetric and MTT assay. The results of the MTT assay revealed that the Fe3O4@CaAl-LDH@Lamivudine NPs significantly inhibited the proliferation of Mel-Rm and A-549 cells in a dose-dependent manner. The influences of Fe3O4@CaAl-LDH@Lamivudine on the cancer cell lines by different therapeutic investigation illustrated the remarkable effect in comparison with free drug. Finally, the achieved consequences confirm the anticancer properties of Fe3O4@CaAl-LDH@Lamivudine and indicate that they may be a cost-effective substitute in the treatment of lung and skin cancer.Communicated by Ramaswamy H. Sarma.

Synthesis, characterization and in vitro cytotoxicity studies of novel Cu(II) complex containing zonisamide drug: DNA interaction by multi spectroscopic and molecular docking methods.

In this study, the Cu(II) complex with Zonisamide (ZNS) and 1, 10-Phenanthroline (Phen) ligands as an anticancer metallodrug was synthesized and characterized successfully by FT-IR, mass spectrometry, TGA, XPS, AAS, CHNSO, magnetic susceptibility and electrical conductivity. The interaction of Cu(II) complex with DNA was explored through a multi-spectroscopic approach such as fluorescence, UV-vis spectrophotometry, CD spectroscopy, and viscosity measurements. Molecular docking simulation was carried out to gain a deeper insight into the target site of DNA which interacted with the mentioned complex. The competitive binding tests with Hoechst 33258 showed that [CuCl2(ZNS)(Phen)EtOH].H2O can bind to the groove site of DNA. The calculated thermodynamic parameters, ΔS° = +201.15 J mol-1K-1 and ΔH° = +41.32 kJ mol-1 confirm that the hydrophobic forces and hydrogen bonding play an essential role in the binding process. The experimental and molecular modeling results demonstrate that the Cu(II) complex binds to DNA through major groove binding. Moreover, the in vitro cytotoxic effects of [CuCl2(ZNS)(Phen)EtOH].H2O against B92 cancer cell lines showed better activity in Cu(II) complex in comparison to free ZNS. Therefore, [CuCl2(ZNS)(Phen)EtOH].H2O can open a new horizon in the treatment of glioma cancer by ZNS metallodrugs.Communicated by Ramaswamy H. Sarma.

Selenium nanoparticles: Synthesis, in-vitro cytotoxicity, antioxidant activity and interaction studies with ct-DNA and HSA, HHb and Cyt c serum proteins.

The aim of this study was the synthesis of selenium nanoparticles (SeNPs) employing vitamin C as a biocompatible and low toxic reducing agent. The synthesized selenium nanoparticles were characterized by using UV-vis, FT-IR, SEM-EDX, TEM, DLS, and zeta potential measurements. The results of the DPPH free radical scavenging assay demonstrate that this synthesized nano-selenium has strong potentials to scavenge the free radicals and cytotoxicity against MCF-7 and Raji Burkitt's lymphoma cancer cell lines. The interaction of calf thymus DNA (ct-DNA) with SeNPs indicated that the anticancer activity might be associated with the DNA-binding properties of nano-selenium. Finally, it was found that the synthesized nano-selenium can bind to the most important blood proteins such as human serum albumin (HSA), human hemoglobin (HHb), and Cytochrome c (Cyt c). The results showed that the secondary structure of these proteins remains unchanged, suggesting that the synthesized nano-selenium could be employed as a carrier in the drug delivery system without any cytotoxicity effect.

Direct effects of low-energy electrons on including sulfur bonds in proteins: a second-order Møller-Plesset perturbation (MP2) theory approach.

In an attempt to describe how low-energy electrons (LEEs) damage the polypeptide chain at disulfide bridges, ab initio electronic structure estimates on LEE interactions with cysteine-cysteine (Cys-Cys) disulfide bond model have been performed. Here, the fundamental mechanisms in LEE impression on S-S and C-S bond ruptures in the Cys-Cys model have been discussed. The electronic energy was calculated using the MP2 method with a Hartree-Fock exchange during the SCF and the Møller-Plesset correlation energy correction on the converged HF orbitals with 6-311++G(d,p) atomic orbital basis set. Further, six more sets of diffuse s and p functions with extra basis on the sulfur and relevant carbon atoms were used to describe the added electron to located away as much as possible from the nuclei in anions. The bonds rupture mechanisms involve the primary placement of LEEs to the π* orbital of the model to construct the shape-resonance state following by an adiabatic or nonadiabatic electron migration to either S-S or C-S bond σ* orbital. The formed radical anion undergoes S-S or C-S bonds cleavage by energy barriers of ca. 5.68 and 9.19 kcal/mol, respectively, to produce either (2-amino-2-carboxyethyl) sulfanyl (cysteine radical), aziridine-2-carboxylic acid or mercapto-L-cysteine lesions. In SMD solvent, calculations suggest electronically stable of the formed π* and σ* states by solvation, something that induces either S-S or C-S bond break even when the electron energy is near zero. The required barrier energy of only 0 to < 0.4 eV indicates a high kinetic favorable fragmentation for involved sulfur polypeptides with LEEs.Communicated by Ramaswamy H. Sarma.

Multispectroscopic analysis, atomic force microscopy, molecular docking and molecular dynamic simulation studies of the interaction between [SnMe2Cl2(Me2phen)] complex and ct-DNA in the presence of glucose.

In this study, the spectroscopic methods (UV-vis, fluorimetric), Atomic force microscopy, and computational studies (molecular docking and molecular dynamic simulation) were used to investigate the interaction of [SnMe2Cl2(Me2phen)] complex with CT-DNA in the presence of glucose. The results showed the complex in the medium containing glucose has less effect on calf thymus DNA (ct-DNA) than the medium without glucose. Cytotoxicity of [SnMe2Cl2(Me2phen)] complex on MCF-7 cells was examined and showed Sn(IV) complex possesses potential cytotoxicity against this cell line. Molecular docking study showed that Sn(IV) complex interacts with DNA by groove binding mode. Radius of gyration (Rg) was smaller upon binding of the Sn(IV) complex suggesting a more compact structure of DNA in the presence of Sn(IV) complex.Communicated by Ramaswamy H. Sarma.

Binding Studies of AICAR and Human Serum Albumin by Spectroscopic, Theoretical, and Computational Methodologies.

The interactions of small molecule drugs with plasma serum albumin are important because of the influence of such interactions on the pharmacokinetics of these therapeutic agents. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) is one such drug candidate that has recently gained attention for its promising clinical applications as an anti-cancer agent. This study sheds light upon key aspects of AICAR's pharmacokinetics, which are not well understood. We performed in-depth experimental and computational binding analyses of AICAR with human serum albumin (HSA) under simulated biochemical conditions, using ligand-dependent fluorescence sensitivity of HSA. This allowed us to characterize the strength and modes of binding, mechanism of fluorescence quenching, validation of FRET, and intermolecular interactions for the AICAR-HSA complexes. We determined that AICAR and HSA form two stable low-energy complexes, leading to conformational changes and quenching of protein fluorescence. Stern-Volmer analysis of the fluorescence data also revealed a collision-independent static mechanism for fluorescence quenching upon formation of the AICAR-HSA complex. Ligand-competitive displacement experiments, using known site-specific ligands for HSA's binding sites (I, II, and III) suggest that AICAR is capable of binding to both HSA site I (warfarin binding site, subdomain IIA) and site II (flufenamic acid binding site, subdomain IIIA). Computational molecular docking experiments corroborated these site-competitive experiments, revealing key hydrogen bonding interactions involved in stabilization of both AICAR-HSA complexes, reaffirming that AICAR binds to both site I and site II.

In vitro interaction of nucleoside reverse transcriptase inhibitor, didanosine with calf-thymus DNA: Insights from spectroscopic studies.

Many antivirals interact with DNA and alter their expression profile. Thus, it is necessary to understand the binding mode. Didanosine, a nucleoside reverse transcriptase inhibitor, is used to treat HIV infection in patients with or without acquired immunodeficiency syndrome. Understanding the mechanism of interaction of this nucleoside reverse transcriptase inhibitor with DNA can prove useful in the development of a rational drug designing system. In vitro studies (UV-vis, fluorescence, and viscometry techniques) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) show that didanosine drug interacts with calf-thymus DNA (ct-DNA) via partial intercalative binding mode. UV-visible spectroscopy confirmed the formation didanosine-DNA complex with a binding strength of about 1.5 × 105 M-1 thus indicating their biological worth. Dye displace experiments and viscometry confirmed that didanosine partially intercalates toward DNA molecules. Negative value of Gibb's-free energy change revealed that the process is spontaneous. The thermodynamic parameters such as enthalpy change (ΔH) and entropy change (ΔS) showed that the acting forces between didanosine and ct-DNA mainly included hydrophobic interactions.

Equilibrium and site selective analysis for DNA threading intercalation of a new phosphine copper(I) complex: Insights from X-ray analysis, spectroscopic and molecular modeling studies.

To clarify the interaction of phosphine copper(I) complex with DNA, our study reports the synthesis of a new phosphine copper(I) complex, along with a detailed analysis of the geometry characterization and its interaction with double-stranded DNA. The triclinic phase Cu(PPh3)2(L)(I) with a tetrahedral geometry was identified as the product of the reaction of copper(I) iodide with (E,E)-N,N'-1,2-Ethanediylbis[1-(3-pyridinyl)methanimine] ligand and triphenylphosphine by single-crystal X-ray analysis. Molecular interaction of the synthesized complex with the calf thymus deoxyribonucleic acid (ct-DNA) was investigated in the physiological buffer (pH 7.4) by multi-spectroscopic approaches associated with a competitive displacement towards Hoechst 33258 and methylene blue (MB) as groove and intercalator probes. The fluorescence and UV/Vis results detected the formation of a complex-DNA adduct in the ground-state with a binding affinity in order of 104 M-1, which is in keeping with both groove binders and intercalators. The thermodynamic parameters, ΔS0 = -200.31 ± 0.08 cal/mol·K and ΔH0 = -63.11 ± 0.24 kcal/mol, confirmed that the van der Waals interaction is the main driving force for the binding process. Moreover, the ionic strength and pH effect experiments demonstrated the electrostatic interactions between the complex and DNA is negligible. Analysis of the molecular docking simulation declared the flat (E,E)-N,N'-1,2-Ethanediylbis[1-(3-pyridinyl)methanimine] part of the complex was inserted between the sequential A…T/A…T base pairs, while the phosphine substituents were located in the groove, i.e. threading intercalation. Besides, the cytotoxicity of the complex against the MCF-7 human breast cancer cells was detected at IC50 = 10 µg/mL.

Design, synthesis and DNA interaction studies of new fluorescent platinum complex containing anti-HIV drug didanosine.

Forming coordination complexes with nucleoside analogues may be helpful in studying anti-tumour activity of them. Therefore, to improve the clinical efficacy of nucleoside analogue and design new ones, a new fluorescent platinum (Pt) complex with anti-human immunodeficiency virus drug didanosine (ddI); K[PtCl(OCH3)2(ddI)]; was synthesized and characterized. The ultraviolet-visible (UV-vis) spectroscopy, infrared, thermogravimetric analysis, mass assignments and elemental analysis confirmed the preparation of the complex. The molecular ion peaks seen at the positive mass spectrum of Pt complex confirm coordination of the drug to metal centre. The interaction of this complex with calf thymus DNA (ct-DNA) was studied using several spectroscopic techniques such as UV absorption, fluorescence spectroscopy and dynamic viscosity measurements. Hyperchromism of the band in the UV-vis spectra and the intrinsic binding constant (0.56 ± 0.25) × 104 M-1, decreasing in Hoechst-DNA fluorescence by adding Pt complex concentration and also relatively small changes in DNA viscosity indicated that this complex could interact as a groove-binder. According to the UV spectra and the fluorescence quenching of the complex in our case seems to be primarily caused by complex formation between the Pt complex and DNA. The thermodynamic parameters showed that hydrogen bond and van der Waals interactions play main roles in the binding of Pt complex to ct-DNA. The free energy values are negative, showing the spontaneity of the Pt complex-DNA binding. The docking simulation was performed and the results confirm a preference of groove site of synthesized complex on DNA helix. The knowledge gained from this study will be helpful to further understand the DNA binding mechanism and can also provide much fruitful information for designing a new type of anti-cancer drugs.Communicated by Ramaswamy H. Sarma.

Molecular docking and spectroscopic studies on the interaction of new fifth-generation antibacterial drug ceftobiprole with calf thymus DNA.

The interaction of the cefobiprole drug with calf thymus DNA (ct-DNA) at physiological pH was investigated by UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, circular dichroism spectroscopy and molecular modeling. The binding constant obtained of UV-visible was 4 × 104 L mol-1. Moreover, the results of circular dichroism (CD) and viscosity measurements displayed that the binding of the cefobiprole to ct-DNA can change the conformation of ct-DNA. Furthermore, thermodynamic parameters indicated that hydrogen bond and van der waals play main roles in the binding of cefobiprole to ct-DNA. Optimal results of docking, it can be concluded that ceftobiprole-DNA docked model is in approximate correlation with our experimental results.

Antiproliferative effects of new magnetic pH-responsive drug delivery system composed of Fe3O4, CaAl layered double hydroxide and levodopa on melanoma cancer cells.

In this study, an efficient drug delivery system composed of Fe3O4, CaAl layered double hydroxide (LDH) and l-Dopa has been synthesized through hydrogen bonds between l-Dopa and CaAl-LDH encapsulated Fe3O4 nanoparticles (Fe3O4@CaAl-LDH@l-Dopa). The structural features of Fe3O4@CaAl-LDH@l-Dopa were characterized using XRD, SEM, TEM, EDX, FT-IR, VSM, TGA, XPS, zeta potential analysis and BET. All of the characterization techniques show the uniform high surface area core-shell structure with about 120 nm in average size. Also, the obtained results clearly indicate that this drug delivery system possess high potent for adsorption of l-Dopa (52 wt%) and high drug encapsulation efficiency (71%). The amount of l-Dopa release in low pHs (53.8%) which simulates the environment of cancer cells is greater than higher pHs. The in vitro cytotoxic and anticancer activities of Fe3O4@CaAl-LDH@l-Dopa were investigated against Mel-Rm Cells Melanoma (NCIt: C3224) using LDH colorimetric assay and differential staining cell death assay. The results showed Fe3O4@CaAl-LDH@l-Dopa with a lower concentration of l-Dopa, illustrate a higher cytotoxicity and anticancer activity.

A novel sensitive laccase biosensor using gold nanoparticles and poly L-arginine to detect catechol in natural water.

In this study, the simple, green, and fast layer-by-layer modification of the glassy carbon electrode was mainly performed by electrodeposition of gold nanoparticles and then, poly-l-arginine, and finally, laccase was covalently bonded to poly-l-arginine using glutaraldehyde. This type of fabrication is used for the first time for catechol detection, which provides a bioelectrocatalytic cycle for electron transport in the presence of laccase that results in sensitive and fast detection of catechol. The scanning electron microscopy, Fourier-transform infrared spectroscopy, and electrochemical studies were performed to confirm successful immobilization of the enzyme. The biosensor response was linear in a wide range of catechol trace concentrations, 24.90-274.00 nM, with the detection limit of 18.00 nM. Values of Km , α, n, and Ks for the immobilized enzyme were calculated to be 1.25 × 10-2  µM, 0.56, 3.19, and 0.28 Sec-1 , respectively. It was examined in real sample successfully confirming it is capable of measuring catechol in natural water.

DNA binding and cytotoxicity studies of magnetic nanofluid containing antiviral drug oseltamivir.

In this work, the possibility of preparing a nanoparticle with improved treatment properties was investigated. In this regard, synthesis, characterization, in vitro cytotoxicity and DNA binding of Fe3O4@oleate/oseltamivir magnetic nanoparticles (MNPs) were investigated. Fe3O4 nanoparticles were synthesized via chemical co-precipitation and coated by oleate bilayers. Then, Fe3O4@OA MNPs were functionalized with an antiviral drug (oseltamivir), for better biological applications. The MNPs were subsequently characterized by zeta sizer and Zeta potential measurements, Fourier transform infrared (FT-IR) spectroscopy, vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) analyses. The TEM image demonstrated that average sizes of Fe3O4@OA/oseltamivir MNPs were about 8 nm. The in vitro cytotoxicity of Fe3O4@OA/oseltamivir MNPs was studied against cancer cell lines (MCF-7 and MDA-MB-231) and compared with oseltamivir drug. The results illustrated that Fe3O4@OA/oseltamivir magnetic nanoparticles have better antiproliferative effects on the mentioned cell lines as compared with oseltamivir. Also, in vitro DNA binding studies were done by UV-Vis, circular dichroism, and Fluorescence spectroscopy. The results indicated that Fe3O4@OA/oseltamivir MNPs bound to DNA via groove binding. Moreover, this magnetic nanofluid has potential for magnetic hyperthermia therapy due to magnetic core of its nanoparticles. Communicated by Ramaswamy H. Sarma.

Intercalation of a Zn(II) complex containing ciprofloxacin drug between DNA base pairs.

In this study, an attempt has been made to study the interaction of a Zn(II) complex containing an antibiotic drug, ciprofloxacin, with calf thymus DNA using spectroscopic methods. It was found that Zn(II) complex could bind with DNA via intercalation mode as evidenced by: hyperchromism in UV-Vis spectrum; these spectral characteristics suggest that the Zn(II) complex interacts with DNA most likely through a mode that involves a stacking interaction between the aromatic chromophore and the base pairs of DNA. DNA binding constant (Kb = 1.4 × 104 M-1) from spectrophotometric studies of the interaction of Zn(II) complex with DNA is comparable to those of some DNA intercalative polypyridyl Ru(II) complexes 1.0 -4.8 × 104 M-1. CD study showed stabilization of the right-handed B form of DNA in the presence of Zn(II) complex as observed for the classical intercalator methylene blue. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and Van der Waals play main roles in this binding prose. Competitive fluorimetric studies with methylene blue (MB) dye have shown that Zn(II) complex exhibits the ability of this complex to displace with DNA-MB, indicating that it binds to DNA in strong competition with MB for the intercalation.

DNA binding affinity of a macrocyclic copper(II) complex: Spectroscopic and molecular docking studies.

The interaction of a novel macrocyclic copper(II) complex, ([CuL(ClO4)2] that L is 1,3,6,10,12,15-hexaazatricyclo[13.3.1.16,10]eicosane) with calf thymus DNA (ct-DNA) was investigated by various physicochemical techniques and molecular docking at simulated physiological conditions (pH = 7.4). The absorption spectra of the Cu(II) complex with ct-DNA showed a marked hyperchroism with 10 nm blue shift. The intrinsic binding constant (Kb) was determined as 1.25 × 104 M-1, which is more in keeping with the groove binding with DNA. Furthermore, competitive fluorimetric studies with Hoechst33258 have shown that Cu(II) complex exhibits the ability to displace the ct-DNA-bound Hoechst33258 indicating that it binds to ct-DNA in strong competition with Hoechst33258 for the groove binding. Also, no change in the relative viscosity of ct-DNA and fluorescence intensity of ct-DNA-MB complex in the present of Cu(II) complex is another evidence to groove binding. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the binding reaction. The experimental results were in agreement with the results obtained via molecular docking study.

DNA-binding study of anticancer drug cytarabine by spectroscopic and molecular docking techniques.

The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 104 L mol-1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure -20.61 KJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.