Spectroscopic investigation into the interaction of a diazacyclam-based macrocyclic copper(ii) complex with bovine serum albumin.

Cyclam-based ligands and their complexes are known to show antitumor activity. This study was undertaken to examine the interaction of a diazacyclam-based macrocyclic copper(II) complex with bovine serum albumin (BSA) under physiological conditions. The interactions of different metal-based drugs with blood proteins, especially those with serum albumin, may affect the concentration and deactivation of metal drugs, and thereby influence their availability and toxicity during chemotherapy. In this vein, several spectral methods including UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy techniques were used. Spectroscopic analysis of the fluorescence quenching confirmed that the Cu(II) complex quenched BSA fluorescence intensity by a dynamic mechanism. In order to further determine the quenching mechanism, an analysis of Stern-Volmer plots at various concentrations of BSA was carried out. It was found that the KSV value increased with the BSA concentration. It was suggested that the fluorescence quenching process was a dynamic quenching rather than a static quenching mechanism. Based on Förster's theory, the average binding distance between the Cu(II) complex and BSA (r) was found to be 4.98 nm; as the binding distance was less than 8 nm, energy transfer from BSA to the Cu(II) complex had a high possibility of occurrence. Thermodynamic parameters (positive ΔH and ΔS values) and measurement of competitive fluorescence with 1-anilinonaphthalene-8-sulphonic acid (1,8-ANS) indicated that hydrophobic interaction plays a major role in the Cu(II) complex interaction with BSA. A Job's plot of the results confirmed that there was one binding site in BSA for the Cu(II) complex (1:1 stoichiometry). The site marker competitive experiment confirmed that the Cu(II) complex was located in site I (subdomain IIA) of BSA. Finally, CD data indicated that interaction of the Cu(II) complex with BSA caused a small increase in the α-helical content. Copyright © 2016 John Wiley & Sons, Ltd.

Analysis of the binding mechanism for a water-soluble Pd(II) complex containing ß-amino alcohols with HSA applying experimental and computational methods.

In the study ahead, the binding interactions of the [Pd (HEAC) Cl2] complex with human serum albumin (HSA) protein have been assayed in vitro (pH= 7.40) utilizing computational and experimental procedures. The mentioned complex was synthesized as a water-soluble complex from {2-((2-((2-hydroxyethyl)amino)ethyl)amino) cyclohexanol} ligand = HEAC. The results of electronic absorption and circular dichroism investigations illustrated that the hydrophobicity of the Tryptophan microenvironment in HSA undergoes the changes by binding to the Pd(II) complex without substantial perturbations on the protein secondary structure. The fluorescence emission spectroscopy analysis revealed that with rising temperature, the quenching constant (Ksv) in the Stern-Volmer's relation decreases; so, it can be said that the interaction process is along with a static quenching mechanism. The values of 2.88 × 105 M-1, and 1.26 represent the binding constant (Kb) and the number of the binding sites (n), respectively. The Job graph showed the maximum point at χ = 0.5, which means organizing a new set with 1:1 stoichiometry. Thermodynamic profile (ΔH < 0, ΔS < 0, and ΔG < 0) has affirmed that van der Waals forces and hydrogen bonds have a basic function in the Pd(II) complex-albumin bindings. The ligand-competitive displacement studies utilizing warfarin and ibuprofen have represented that Pd(II) complex interacts with albumin by site II (subdomain IIIA). The computational molecular docking theory approved the results of the site-competitive tests; also, it indicated the existence of hydrogen bonds and van der Waals forces in Pd(II) complex-albumin interactions.Communicated by Ramaswamy H. Sarma.

Molecular interaction of antiviral drug penciclovir with DNA and HSA insights from experimental and docking studies.

One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. During recent decades, penciclovir (PNV) has been frequently utilized as a potent antiviral drug, in particular against infections caused by herpes viruses. Many antivirals interact with DNA and change their expression level, so determining the binding mode is of great importance. In our laboratory, we have focused our attention to design improved drugs that target cellular DNA, to understand the mechanism of action at the molecular level, and also to investigate the effect of antiviral drugs as anticancer agents. The results of ct-DNA-PNV interactions at physiological pH using fluorescence spectroscopy, UV-visible absorption spectroscopy, and molecular modeling reveal this drug binds well to ct-DNA through groove binding. The circular dichroism measurements displayed that PNV caused a slight change in the DNA structure which affirmed that the binding of PNV with the DNA occurs through the groove mode. Besides, multi-spectroscopic and molecular docking were used to evaluate how PNV interacts with human serum albumin under physiological conditions. The findings of fluorescence quenching suggested that static quenching was involved in the spontaneous development of HSA-PNV complex through hydrophobic force. The docking simulation results validated the findings of spectroscopic techniques.Communicated by Ramaswamy H. Sarma.

A high-efficiency decomposition method for mono and dimethylmercury induced by low-energy electron attachment (<≈7 eV): A computational insight into the decomposition mechanism of extremely toxic mercury compounds.

Dimethylmercury (DMM) and monomethylmercury (MMM) are extremely toxic and dangerous environmental contaminants. Unfortunately, there is no effective way to remove these substances from the environment. This study looks into the efficient decomposition of DMM and MMM by low-energy electrons. The calculated quantum scattering properties reveal the presence of metastable electronic states in both molecules. An examination of the spatial features of the electronic resonances, as well as the computation and characterization of the vibrational normal modes, suggests possible bond break pathways of the metastable electronic states. Most electronic resonances result in the release of Hg(0), which is easily transported to the gas phase due to its low solubility in water and high volatility.

A binuclear Cu(I)-phosphine complex as a specific HSA site I binder: synthesis, X-ray structure determination, and a comprehensive HSA interaction analysis.

In this research, we present a method for synthesis and a detailed description of geometry characterization of a novel binuclear Cu(I) phosphine complex, along with analysis of its interaction with HSA using spectroscopic and simulation methods. The Cu atoms are coordinated in a tetrahedral geometry, which results in coordination by two nitrogen atoms from the N,N'-(ethane-1,2-diyl)bis(1-(pyridin-2-yl)methanimine ligand (L), a chloride, and a PPh3. The complex binding constant to HSA in a biochemical environment was determined to be ∼106, which is indicative of a strong interaction. The fluorescence of HSA is significantly quenched by binding to the complex via a static mechanism, whereas the microenvironment of the tryptophan residue remains unchanged. A spontaneous binding process was indicated by a negative value for ΔG. Thermodynamic signatures reflect the dominance of hydrophobic forces during the interaction. The site marker competitive experiment combined with docking simulation analysis revealed the closeness position of the complex binding site to warfarin location in specific ligand site I of HSA. The information generated in the present study would be valuable to understand the interaction mechanistic and pharmacological behavior of Cu(I) complexes.Communicated by Ramaswamy H. Sarma.

Evaluation of DNA damage induced by acesulfame potassium: spectroscopic, molecular modeling simulations and toxicity studies.

Acesulfame potassium (Ace-K) is a widely used artificial sweetener that has been reported to interact with DNA and cause important genetic damage. However, the type of interaction mechanism is unknown. This study provides an approach to understanding the in vitro mechanism of Ace-K interaction with Ct-DNA using spectroscopic methods combined with molecular simulations. The hypochromic effect as obtained from UV-Vis spectra indicated the formation of the DNA-Ace-K complex in the minor groove. Further evidence for groove binding mode comes from the decrease in Hoechst-DNA fluorescence caused by increasing Ace-K concentrations, alongside no detectable change in MB-DNA emission band intensity. A negative value of ΔH and ΔS represents the hydrogen bonds and van der Waals forces between Ace-K and DNA. Based on the molecular docking, Ace-K was located between the guanine10 and 16 in DNA minor groove and stabilized by two hydrogen bonds and one π-Sulfur interaction. In vitro cell culture results showed that about 5 mg/mL of Ace-K caused the death of 85% of HUVEC cells after 48 h. Communicated by Ramaswamy H. Sarma.

Spectroscopic and molecular docking investigation on the interaction of a water-soluble Cu(II) complex containing diethanolamine and dipicolinic acid ligands with human serum albumin.

Under physiological conditions, spectroscopic techniques as well as molecular docking simulation have been used to investigate the binding interaction mechanism between Cu(II) complex containing Pyridine-2,6-dicarboxylic acid (PDCA) and Diethanolamine (DEA) ligands, [Cu(DEA)(PDCA)] and human serum albumin (HSA). UV spectral changes of protein in the presence of the Cu(II) complex suggested the formation of a Protein-Cu(II) complex conjugate with specific new structure. The Cu(II) complex quenches the intrinsic fluorescence of the HSA via a static mechanism in which van der Waals interactions along with hydrogen bonds are fundamental binding forces. Displacement experiments performed by warfarin and ibuprofen site probes predict that the Cu(II) complex is located in subdomain IIA, Sudlow site 1 of HSA. Molecular docking results showed close resemblance with experimental data.Communicated by Ramaswamy H. Sarma.

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.

Binding Studies of a New Water-Soluble Iron(III) Schiff Base Complex to DNA Using Multispectroscopic Methods.

A novel iron(III) complex [Fe(SF)](ClO(4))(3).2H(2)O; in which SF = N,N(0)-bis{5-[(triphenylphosphonium chloride)-methyl] salicylidene}-o-phenylenediamine) has been synthesized and characterized using different physicochemical methods. The binding of this complex with calf thymus (CT) DNA was investigated by circular dichroism, absorption studies, emission spectroscopy, voltammetric studies, and viscosity measurements. The results showed that this complex can bind to DNA via external and groove binding modes.

Structural modification of antineoplastic drug carmofur designed to the inhibition of SARS-CoV-2 main protease: A theoretical investigation.

A coherent account of the reaction mechanistic details, structural modifications, and inhibition potentials of antineoplastic drug carmofur and its modified analogs to inhibition of SARS-CoV-2 main protease (Mpro) is reported. The survey is performed by integrating the density functional based tight binding (DFTB3) with density functional theory (DFT) calculations. The inhibition process commences with nucleophilic attack from the sulfur atom on the carbonyl group, yielding a C-S bond formation, followed by a bond formation of the H-O9 by 2.07 Å, which results in a transition state contains a ring of six atoms. We found that although the direct addition of sulfhydryl group hydrogen to the N3 position is likely to happen, the proper position of the hydrogen to O9 decreases its accessibility. The thermodynamic stability of the complex was calculated to be highly sensitive to the substituent on the N11 position. Compounds with CH2NH2 and CH2F at N11 positions of carmofur revealed high thermodynamic stability to complexation with Mpro but induced no change in substrate-binding pocket comparable to carmofur. Replacing the N11 of carmofur with carbon (C-carmofur) was effective in terms of complexation stability at CH2CH2CH2F and CH2CH2CH2OH substitutions and occupation of S1 subsite by these structures in addition to the S2 subsite. Based on the resulted data, increasing the length of the carbon chain at introduced substitutions in N-carmofur almost decreases the complexation stability while in C-carmofur the trend is reversed. Throughout these information outputs, it was suggested that compounds d, e, i', and k' might be novel and more efficacious drug candidates instead of carmofur. We believe that our characterization of mechanistic details and structural modification on Mpro/carmofur complex will significantly intensify researchers' understanding of this system, and consequently help them to take advantage of results into practice and design various valuable derivatives for inhibition of SARS-CoV-2 main protease.

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.

High selective gas-phase rearrangement reaction of TCDD induced by excess electron attachment: Theoretical insight on the decomposition mechanism of one of the most toxic chemical known to science.

Dioxins are highly toxic chemicals with serious health risks, for which there is no safe level of exposure. Because of the slow decomposition of dioxins, the removal of these persistent environmental pollutants still remains a challenge. Based on theoretical studies, the present work investigates the degradation mechanism of the most toxic type of dioxin-related compounds by low-energy electron irradiation. To explore the rearrangement manner of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced by excess electron attachment, the B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/6-311++G(d,p) level of density functional theory was applied. Electron attachment resulted in a remarkable decrease in the activation barrier of the rearrangement reaction in a thermodynamically preferred reaction. An activation energy as low as 6.6 kcal/mol provides a strong demonstration that this pathway is the most effective in comparison to the neutral or radical rearrangement mechanisms. The attachment of electrons in the above energy range to C-Cl σ∗orbital is more likely than attachment to the LUMO of TCDD with π∗ orbital character. This σ∗ anion then undergoes a C-O σ bond rupture over a small barrier to produce a relatively stable intermediate, n-IM. The formed n-IM is again reactive toward a subsequent C-O bond rupture along with an intramolecular C-C coupling to produce the products, (E)-4,4',5,5'-tetrachloro-[1,1'-bi(cyclohexylidene)]-3,3',5,5'-tetraene-2,2'-dione and (Z)-4,4',5,5'-tetrachloro-[1,1'-bi(cyclohexylidene)]-3,3',5,5'-tetraene-2,2'-dione. The thermodynamic driving force for the anionic mechanism ensures the formation of the products to be irreversible enough to be purified. The purified products, with their active carbonyl groups, can react in many different ways with a wide range of nucleophile compounds.

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.

New water-soluble Fe3O4@SiO2 magnetic nanoparticles functionalized with levetiracetam drug for adsorption of essential biomolecules by case studies of DNA and HSA.

Communicated by Ramaswamy H. Sarma.

Theoretical mechanistic insight into the gabapentin lactamization by an intramolecular attack: Degradation model and stabilization factors.

PURPOSE: Gabapentin is degraded directly into a high toxicity form known as gabapentin lactam (gaba-L) with a maximizing desire in mild pH and low humidity. This study reports the lactamization process of gabapentin, along with a detailed analysis of the energy landscape, geometry, and thermodynamic and kinetic preference of the process. To investigate the effect of the acidic/basic conditions on the energy landscape, the energy profiles were investigated for both protonation and deprotonation forms of gabapentin. METHODS: All the calculations were performed by using the density functional theory (DFT) and the G4MP2 levels of theory in the conductor-like polarizable continuum model, CPCM, and water as the solvent. RESULTS: The lactamization process is an intramolecular cyclization which results in formation of gabapentin-lactam. The chemically intact gabapentin exists in two forms of a stable, R, and a relatively disordered form, R*. The conversion of stable crystalline form R to the intact unstable isomer R* is considered as the primary step in the gabapentin degradation. The results exhibited that near the unstable geometry, R*, a transition state (TS), is 41.3 kcal/mol higher in energy than the optimized ground state, R* (4.1 kcal/mol). From the intrinsic reaction coordinates (IRC) computations, it can be concluded that this transition state led to the unstable R* in one direction and to gabapentin-lactam in the other. CONCLUSIONS: The thermodynamic stability of the lactam form (-13.63 kcal/mol) clarifies the more thermal stability of gaba-L than its related gabapentin form and the experimental preference for the lactamization. The corresponding energy profile on protonation/deprotonation forms of gabapentin indicates the pH-dependent of the process and the rate reduction in out of the mild pH.

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.

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.

Synthesis, characterization and DNA binding studies of a new ibuprofen-platinum(II) complex.

The study is focused on the synthesis of a novel complex of ibuprofen and Platinum(II). The formation of the product was characterized through analytical tools including Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, ultraviolet-visible spectroscopy, mass spectrometry as well as density functional theory. Using the continuous variation method, the stoichiometry of Pt(HIb)2(Cl)2 binding on DNA (ct-DNA) determines as a single class of binding. Based on the results of Stern-Volmer analysis on the fluorescence quenching data, the quenching mechanism was determined to be static in nature. The studies indicated that the complex could bind DNA molecules via groove binding for four major reasons. Initially, the complex-DNA binding constant determined based on spectrophotometric data were found to be comparable to those of groove-binding drugs. In addition, the competitive fluorimetric based on the applications of Hoechst 33258 proved the ability of Pt(HIb)2(Cl)2 to displace with Hoechst in its DNA-bounded form, reflecting the competition between Pt(HIb)2(Cl)2 and Hoechst for groove binding. Further, no considerable changes were observed in the intensity of the methylene blue (MB)-DNA system after adding the Pt(HIb)2(Cl)2 complex, reflecting the stability of MB molecules in the DNA helix and a non-intercalative bonds of Pt(HIb)2(Cl)2 interaction on DNA. Finally, minor changes in the viscosity of DNA in the presence of Pt(HIb)2(Cl)2, indicated that changes in the length of DNA in the presence of the complex are negligible, supporting the assumption of DNA groove-binding. Also induced CD spectral changes and docking simulations were in favor of the groove mechanism for the Pt(HIb)2(Cl)2-DNA binding.Communicated by Ramaswamy H. Sarma.

Synthesis, characterization and DNA interaction studies of new copper complex containing pseudoephedrine hydrochloride drug.

A new copper(II) complex, [Cu(pse)(phen)Cl2]; in which phen = 1,10-phenanthroline and pse = pseudoephedrine hydrochloride drug; was synthesized and characterized by FT-IR, Mass and UV-Vis spectroscopy in combination with computational methods. Binding interaction of this complex with calf thymus DNA (ct-DNA) has been investigated by absorption, emission, circular dichroism, molecular docking and viscosity measurements. The complex displays significant binding properties of ct-DNA. The results of fluorescence and UV-Vis absorption spectroscopy indicated that, this complex interacted with ct-DNA in a groove-binding mode, and the binding constant was 8 × 104 L mol-1. Competitive fluorimetric studies with Hoechst 33258 have shown that Cu(II) complex exhibit the ability to displace the DNA-bound Hoechst 33258 indicating that it binds to DNA in strong competition with Hoechst 33258 for the groove binding. Furthermore, the complex induces detectable changes in the CD spectrum of ct-DNA and does not induce any changes in DNA viscosity which verified the groove-binding mode. The molecular modeling results illustrated that the complex strongly binds to groove of DNA by relative binding energy of docked structure (-27.61 kJ mol-1).

Studies on the interaction of antibiotic drug rifampin with DNA and influence of bivalent metal ions on binding affinity.

In this paper, the interaction between rifampin, a known antibiotic used against tuberculosis, and DNA helix is investigated by applying multiple biophysical and molecular modelling approaches in an aqueous solution at pH 7.4 and 5. It was proved that the fluorescence quenching of labeled probe DNA by rifampin is a result of the complex formation of rifampin in groove of DNA. Binding parameters were calculated using the logarithmic Hill equation to provide a quantitative term of the binding affinity between rifampin and DNA sites. The resulting ΔH0 = -122.76 ±â€¯0.07 kJ/mol and ΔS0 = -308.19 ±â€¯238.78 J/mol K confirms the role of the Van der Waals' forces and hydrogen bonding in the rifampin-DNA complexation. Furthermore, the influence of bivalent metal ions on the binding affinity was resulted in order of Cu(II) > Ca(II) > Co(II) > Zn(II).