Intercalative Mode Research Articles

Copper-assisted anticancer activity of hydroxycinnamic acid terpyridine conjugates on triple-negative breast cancer.

The development of active therapeutic agents to treat highly metastatic cancer while minimizing damage to healthy cells is of utmost importance. Due to potential antioxidant properties, hydroxycinnamic acid derivatives (caffeic acid and p-coumaric acids) were found to inhibit highly metastatic breast cancer cell growth both in vitro and in vivo without much effect on normal cells. Especially due to the structure-activity relationships, ester and amide derivatives of hydroxycinnamic acids are reported to gain much higher radical scavenging ability than their naked hydroxycinnamic acid analogs like caffeic acid and p-coumaric acid. These results prompted us to design a set of ligands by incorporating an amide moiety on caffeic acid and p-coumaric acid to achieve the least toxicity towards healthy cell lines. Further, the Cu(II) complexes of amide-coupled caffeic acid and p-coumaric acid ligands have been explored for their therapeutic activity on triple-negative breast cancer and other cancer cells like colon, and prostate cancer. The Cu(II) complexes (4 & 5) were characterized by UV-Vis spectroscopy, FTIR, and X-band EPR spectroscopy. The trigonal bipyramidal geometry of complexes was confirmed by the X-band EPR spectra recorded in solution state at liquid N2 temperature. The purity of the complexes was determined by elemental analysis and HPLC traces. Initially, Calf thymus DNA (ct-DNA) binding studies with the complexes were explored. The results suggested the complexes (4 & 5) bind majorly through an intercalative mode of binding with ct-DNA, whereas no significant binding was observed for the bare organic ligands (2 & 3). The intercalation binding modes of 4 and 5 were further supported by UV-visible spectroscopy, ct-DNA melting point analysis, and CD spectroscopy. Moreover, these complexes showed better activity towards cisplatin-resistant TNBC cell lines (4T1, a TNBC cell line derived from the mammary gland tissue of a mouse). The combination of antioxidants and Cu(II) as the metal center made the complexes more cytotoxic toward cancer cell lines (4T1) (IC50 ∼ 3.5 ± 2.5 μM) and the least toxic toward healthy cells (L929) (IC50 ∼ 15 ± 5 μM). Finally, the mechanism of cell death was studied using JC-1 staining and a cell colony formation assay. These studies might help in designing safer anticancer drugs for treating more aggressive types of cancer.

Interacting Characteristics of Chrysene with Free DNA in vitro

Deoxyribonucleic acid (DNA), an important material in life science, is considered a natural and highly specific functional biopolymer. Various analytical techniques were used to analyze the interaction of chrysene with free DNA in vitro, and based on this interaction, we studied the removal of chrysene from contaminated water by DNA via magnetic beads-based separation. The results of UV-visible spectroscopy, DNA thermal denaturation measurement, circular dichroism (CD) spectroscopy, and fluorescence microscopy showed that chrysene interacted with DNA through an intercalating mode. The results of fluorescence spectroscopy demonstrated that DNA had a static quenching effect on chrysene, indicating the formation of a stable complex between chrysene and DNA. Thermodynamic studies revealed that the interaction of chrysene with free DNA was spontaneous in vitro. In addition, chrysene could be efficiently removed from contaminated water by DNA via DNA-intercalation and magnetic bead-based separation. The chrysene removal efficiency of DNA was better than that of activated carbon even when the amount of activated carbon was 400 times more than that of DNA. The results of this study provide insights into the development of new chrysene elimination processes based on DNA-intercalation in water pollution.

Design, structural characterization, DNA interaction studies, antibacterial, antioxidant, and cytotoxicity studies of Co(II), Ni(II), Cu((II), Zn((II) complexes containing 2-methoxy 5-trifluoromethyl benzenamine Schiff base

The bivalent Co(II), Ni(II), Cu(II), and Zn(II) complexes (A, B, C, D) of novel Schiff base ligand such as 2-((E)-(5-(trifluoromethyl)-2-methoxyphenylimino)methyl)-4-chlorophenol (HL1) have been synthesized. The structural analysis have been carried by elemental analysis, NMR, FTIR, ESI-mass, UV–Visible, ESR, TGA and these results confirmed that Ni(II) and Cu(II) complexes were exhibit square planar geometry, whereas Co(II) and Zn(II) complexes exhibits octahedral geometry. DNA binding interaction studies such as UV absorption, viscosity, fluorescence techniques revealed that the mode of binding of complexes with DNA is intercalative mode. DNA cleavage studies revealed that all the complexes were cleaved into Form I & II. The pathological studies of all the complexes were screened against microbial strains in-vitro, which revealed that Cu(II) complexes are more potent compared to other complexes and free ligands. The antidiabetic and antioxidant activity studies revealed that Cu(II) complex exhibit slight higher activity. Cytotoxicity studies on cell lines (KB3 & MCF7 cell lines) revealed that the all synthesized complexes were showed superior activity compared to the ligand.

Synthesis, crystal structure, DNA binding, and anticancer activity of the cobalt(II), nickel(II), and copper(II) complexes of 9-benzothiazolanthrahydrazone

In the present study, we synthesized and extensively characterized a novel ligand, 9-THA, based on 9-benzothiazolanthrahydrazone, along with its three corresponding transition metal complexes: 9-THA-Co (1), 9-THA-Ni (2), and 9-THA-Cu (3). The crystallographic analysis revealed distinct coordination geometries - six-coordinate for 9-THA-Co and 9-THA-Ni, binding three and two 9-THA ligands, respectively, and four-coordinate for 9-THA-Cu, binding one 9-THA ligand. In vitro anticancer screening demonstrated that 9-THA-Cu exhibited significant growth inhibition in HeLa-229, NCI-H460, and SK-OV-3 cancer cells with IC50 values of 12.10 ± 0.54, 12.12 ± 0.58, and 17.65 ± 0.66 μM, respectively. Moreover, it displayed comparable cytotoxicity to cisplatin on HL-7702 normal liver cells. In contrast, 9-THA and 9-THA-Co/9-THA-Ni did not exhibit significant growth inhibition in the tested cancer cells, suggesting that Cu(II) played a pivotal role in its anticancer mechanism. Further investigation revealed the intercalative DNA binding mode of 9-THA-Cu by UV–Vis and fluorescent spectral analyses. It also exhibited competitive binding with two typical DNA intercalators, Gel-red (GR) and ethidium bromide (EB). Cell cycle and cell apoptosis experiments indicated that 9-THA-Cu at a concentration of 22 μM could induce cell cycle arrest in the S phase in 40 % of HeLa-229 cancer cells. Simultaneously, it induced 33.2 % apoptosis in HeLa-229 cells, suggesting that 9-THA-Cu may employ multiple mechanisms to exert its anticancer effects.

Synthesis, crystal structures, CT-DNA/BSA binding modes and antibacterial activities of Zn(II) and Cr(III) with an acylhydrazone ligand

Two salicylaldehyde-4-hydroxy phenylacetyl acylhydrazone transition metal complexes ZnL2·H2O (I) and [CrL2]NO3·EtOH (II) were synthesized by C15H14N2O3 (HL) with Zn(NO3)2·6H2O and Cr(NO3)3·9H2O. Structures of HL, I and II were characterized by single crystal X-ray diffraction. With the ligand HL belonging to the monoclinic crystal system and the P21/c space group, the coordinating atoms (N and O atoms) in both two complexes I and II exhibited a six-coordinated octahedral geometry centered on the metal ion. Thermal stabilities of the two complexes were analyzed by TG-DTG techniques, which illustrated the maximum thermal decomposition peak temperatures of two complexes were both higher than 170 °C, exhibiting strong thermal stabilities. UV–vis absorption spectroscopy and microcalorimetry were used to determine interaction patterns of I and II with CT-DNA, showing that I and II effectively bound to CT-DNA through the intercalation mode and the interactions processes of I and II with CT-DNA were spontaneous, exothermic entropy reduction reactions. Fluorescence spectroscopy and microcalorimetry were used to determine the interactions of I and II with BSA, presenting that the two complexes can effectively bind to BSA and form non-fluorescent matrix complexes and the interactions processes were spontaneous exothermic and entropy reducing, and each of interaction duration was within 48 min. In addition, the antimicrobial activities of complexes I and II against S. aureus, P. aeruginosa, B. subtilis and E. coli were determined, revealing II exhibited stronger inhibition activity against P. aeruginosa than gentamicin sulfate at 0.5 mg·L-1. Complexes I and II were expected to be used as alternative drugs of gentamicin sulfate in the future.

Refashioning of the drug-properties of fluoroquinolone through the synthesis of a levofloxacin-imidazole cobalt (II) complex and its interaction studies on with DNA and BSA biopolymers, antimicrobial and cytotoxic studies on breast cancer cell lines

Levofloxacin (HLVX), a quinolone antimicrobial agent, when deprotonated (LVX−) behaves as a bidentate ligand, and it coordinates to Co2+ through the pyridone oxygen and the carboxylate oxygen. Along with two imidazole (ImH) ligands, levofloxacin forms a Co(II)-Levofloxacin-imidazole complex, [CoCl(LVX)(ImH)2(H2O)]·3H2O (abbreviated henceforth as CoLevim) which was isolated and characterized by 1H and 13C NMR spectroscopy, UV–visible and FT-IR spectroscopy, powder X-ray diffraction and thermal analysis methods. CoLevim shows promise in its antimicrobial activities when tested against microorganisms (Bacillus cereus, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli). Fluorescence competitive studies with ethidium bromide (EB) revealed that CoLevim can compete with EB and displace it to bind to CT-DNA through intercalative binding mode. In addition, CoLevim exhibited a good binding propensity to BSA proteins with relatively high binding constants. The antioxidant activities of the free ligands and CoLevim were determined in vitro using ABTS+ radical (TEAC assay). The Co-complex showed a better antioxidant capacity with inhibitory concentrations (IC50) of 40 μM than the free ligands. CoLevim also showed noteworthy apoptotic potential and behaved as an efficient resistant modifying agent when its antiproliferative potential was examined by MTT assay using the breast cancer cell lines (MCF7, MCF7Dox/R and MCF7Pacli/R cells).

Synthesis, structure and biological activity of silver(I) complexes containing triphenylphosphine and non-steroidal anti-inflammatory drug ligands

Two Ag(I) complexes containing triphenylphosphine and non-steroidal anti-inflammatory drug ligands were synthesized and investigated using various spectroscopic studies and single crystal X-ray crystallography. The binding properties of tolfenamic acid, ibuprofen and the two complexes with DNA and BSA were investigated using UV or fluorescence spectroscopy. The results showed that two Ag(I) complexes bound to DNA by the intercalation mode and interacted with BSA using a static quenching procedure. Furthermore, the results of fluorescence titration suggested that the complexes had good affinity for BSA and one binding site close to BSA. The in vitro cytotoxicity of tolfenamic acid, ibuprofen, and the two complexes against four human carcinoma cell lines (MCF-7, HepG-2, A549, and HeLa cells) was tested using an MTT assay. Complex 1 had higher cytotoxicity against HeLa cells. The intracellular reactive oxygen species (ROS) assay showed complex 1 induced the ROS generation in HeLa cells in a concentration dependent manner. Flow cytometry analysis showed complex 1 could suppress the HeLa cells growth during the G0/G1 phase and induce apoptosis in dose-depended manner.

A DNA biosensor strategy in monitoring of Vinorelbine breast cancer drug using catalytic effect of Pt–Pd–ZnO/SWCNTs

The present research work introduced a new electrocatalyst (Pt–Pd–ZnO/SWCNTs in this case) to the fabrication of a powerful DNA biosensor in the monitoring of Vinorelbine anticancer drug. The characterization information confirms the high purity of Pt–Pd–ZnO/SWCNTs nanocomposite and an intercalation reaction between Vinorelbine anticancer drug and the guanine base of DNA in an aqueous solution. The reducing signal of DNA after interaction with Vinorelbine drug showed a linear analytical range of 0.1–120 μM with a detection limit of 0.05 μM. The biosensor was fabricated by layer-by-layer modification of glassy carbon electrode with ds-DNA and Pt–Pd–ZnO/SWCNTs nanocomposite and used as the working electrode to sensing of vinorelbine drug in pharmaceutical and other real samples with acceptable recovery data. The preferential intercalation mode for the binding of vinorelbine anticancer drug into the ds-DNA receptor is clarified using the molecular docking study.

Antibacterial and ct-DNA binding studies of new synthesized ruthenium (III) hydroxamate complexes: Design, synthesis, DFT calculations and in-vitro study

Ruthenium (III) complexes (1–5) with general composition [Ru(L1–4)3] and [Ru(HL5)3Cl3] where L1 = benzohydroximato (1), L2 = salicylhydroximato (2), L3 = acetohydroximato (3), L4 = hydroxyureato (4), HL 5 = N‑hydroxy-N-phenylbenzamide (5) were synthesized by reacting RuCl3·3H2O with respective hydroxamic acids in 1:3 molar ratio . The complexes were characterized using various techniques including ruthenium metal analysis, elemental analysis, UV–Vis, FT-IR, NMR (1H and 13C), and mass spectrometry. Antibacterial activity of the complexes was evaluated using the agar well diffusion method against ten pathogenic strains. The complexes showed significant inhibition zones and were more active than their corresponding ligands. DNA binding studies indicated intercalative binding mode, with hypochromism and red shift observed. Computational and structural parameters were determined using Frontier Molecular Orbital (FMO) energies and Density Functional Theory (DFT) calculations. The complexes demonstrated favorable molecular geometry, chemical reactivity, and biological activity.

Unveiling the interaction modes of Imiquimod with DNA: Biophysical and computational studies

Herein the manuscript, we report the interaction of an important drug, Imiquimod (IMQ), with Calf Thymus Deoxyribonucleic Acid (ct-DNA). Despite of being used IMQ in multiple medicinal applications such as immune response modifier, antitumor and antiviral drug its interaction with DNA is not studied yet. To understand their interaction and characterize the binding mechanism between groove and intercalation modes, we used various spectroscopic tools. Fluorescence quenching, time-resolved emission, steady state anisotropy technique, ethidium bromide (EtBr), and 4′,6-diamidino-2-phenylindole (DAPI) displacement assays provided us biophysical aspects of IMQ-DNA interactions. All the above studies revealed the binding mode as intercalation mechanism. Circular Dichroism (CD) also well corroborated the intercalation of IMQ into DNA. Thermodynamic parameters of these bindinginteractions were interpreted with the help of temperature dependent spectroscopic studies characterizing the interaction as enthalpy driven. Further, the binding interactions is explored with the help of molecular docking studies. Based on experimental and computational studies it was concluded that the drug binds to DNA via intercalation mode in AT-rich DNA sequences. These biophysical investigations not only improve our comprehension of IMQ's therapeutic effectiveness but also clarifies the sequence dependent binding processes underlying comparable drug-DNA interactions.

Carbon-in-Silicate Nanohybrid Constructed by In Situ Confined Conversion of Organics in Rectorite for Complete Removal of Dye from Water.

The complete removal of low concentration organic pollutants from wastewater to obtain clean water has always been a highly desired but challenging issue. In response to this, we proposed a new strategy to fabricate a carbon-in-silicate nanohybrid composite by recycling dye-loaded layered clay adsorbent and converting them to new heterogeneous carbon-in-silicate nanocomposite through an associated calcination-hydrothermal activation process. It has been confirmed that most of the dye molecules were present in waste rectorite adsorbent using an intercalation mode, which can be in situ converted to carbon in the confined interlayer spacing of rectorite. The further hydrothermal activation process may further improve the pore structure and increase surface active sites. As expected, the optimal composite shows extremely high removal rates of 99.6% and 99.5% for Methylene blue (MB) and Basic Red 14 (BR) at low concentrations (25 mg/L), respectively. In addition, the composite adsorbent also shows high removal capacity for single-component and two-component dyes in deionized water and actual water (i.e., Yellow River water, Yangtze River water, and seawater) with a removal rate higher than 99%. The adsorbent has good reusability, and the adsorption efficiency is still above 93% after five regeneration cycles. The waste clay adsorbent-derived composite adsorbent can be used as an inexpensive material for the decontamination of dyed wastewater.

X-ray structures, density functional theory study, DNA binding ability and micellization behaviour of decavanadates anions containing cationic organic moieties

Reported here synthesis, structure, DNA binding ability of three decavanadates complexes containing cationic organic moieties, 2-methylimidazolium (1), 4-dimethylaminopyridinium (2) and protonated 3-pyridiniumcarboxamide (3). Compounds are stable solids, characterized by elemental analyses, spectroscopic, single-crystal X-ray diffraction and theoretical studies. X-ray diffraction analysis indicates, the molecular structures of the compounds are composed of ion pairs formed by decavanadate ion [H2V10O28]4− and the corresponding cationic organic moieties. Complex 1 composed of decavanadate anion in combination with cationic 2-methylimidazolium and 2 contains decavanadate moiety with counter cation protonated 4-dimethylaminopyridine, two DMSO molecules. The structure of 3 consists of [H2V10O28]4−, protonated 3-pyridinecarboxamide, two co-crystallized neutral organic moieties with two molecules of water. The effective interaction of the ion-pair and hydrogen bonding interaction resulted in the cohesion, stabilization of solid state structure of the complexes. In solid state, compounds present interesting assemblies through the formation of H-bonds analyzed using DFT calculations and quantum theory of “atoms in molecules” (QTAIM). Interaction of the compounds with CT-DNA studied by absorption and fluorescence spectroscopy, show moderately strong intercalative mode of binding. Additionally micellization behaviour of the complexes using surfactant CTAB was studied by conductance measurements and absorption spectroscopy. The complexes show an increased solubility on addition of the surfactant.

Comprehensive investigation of Co(II), Ni(II) and Cu(II) complexes derived from a novel Schiff base: Synthesis, characterization, DNA interactions, ADME profiling, molecular docking, and in-vitro biological evaluation

Here, anisidine-based ligand (HL) and its cobalt (1a), nickel (1b) and copper (1c) complexes were synthesized and characterized by various spectroscopic techniques such as NMR, mass, IR, UV–visible, magnetic moments, ESR and TGA. The synthesized [Ni(L)2] and [Cu(L)2] complexes demonstrated square planar geometry around the metal centers, while the cobalt complex [Co(L)2(H2O)2] adopted six coordinated octahedral geometries. The DNA interaction studies of the complexes revealed an intercalative mode of binding, as evidenced by UV absorption, emission, and viscosity experiments, and the binding constant (Kb) follows the order of 1c > 1a > 1b. When exposed to oxidative and photolytic methods, the complexes demonstrated better efficacy in cleaving double-stranded pBR322 DNA compared to their parent Schiff base. When tested for cytotoxicity against A549 and MCF7 cell lines, complexes showed more activity than their parent ligand. In-vitro studies of the complexes' antimicrobial and antioxidant properties shown that they are far more effective than the parent ligand. Further, the biological efficiency of the ligand (HL) and complexes were verified by computational methods, including molecular docking (against protein data bank PDB ID: 2ADO.pdb) and pharmacokinetic studies, both the ligand (HL) and complexes have demonstrated significant potency. This promising result indicated their potential as therapeutic agents for treating pathogen-induced deformities.

Development of new cobalt, copper, and zinc complexes of Schiff-base ligands as prospective chemotherapeutic agents

Fluorobenzaldehyde was converted into new, bidentate Schiff-base ligands with nitrogen and sulphur donor sites in two steps. The first step proceeds via Knoevenagel condensation; the product obtained was treated with thiosemicarbazide to yield the ligand L1. The Schiff-base ligand, L2, was synthesized by treating L1 with 4-chlorobenzylchloride in a basic medium. Co (II), Cu (II), and Zn (II) complexes were synthesized with the ligands L1 and L2. All these complexes were characterized by FTIR, UV–Vis, NMR spectroscopy, ESI-mass spectral analysis, magnetic moment, molar conductance, thermal, powder XRD, and electrochemical studies. From these studies, the molecular formulae of the complexes were found to be [M(L)2Cl2], where M = Co (II), Cu (II) and Zn (II) and L = L1 or L2 based on the ligand used in the synthesis. The synthesized complexes were observed to have a high spin and distorted octahedral geometry and were non-electrolytic. The UV absorption titrimetric analysis confirmed that these complexes would bind strongly to CT-DNA through the intercalative mode. The electrophorograms supported the statement that Cu (II) complexes could effectively catalyze the hydrolytic cleavage of CT-DNA and can be considered potent metallonuclease agents. The DPPH assay determined the antioxidant properties of these complexes, and the cupric complexes were observed to possess better antioxidant properties than the standard used ascorbic acid. The cell viability analysis of these complexes showed an elevated control of proliferation against a human breast adenocarcinoma (MCF-7) cancer cell line compared to a human cervical carcinoma (HeLa) cell line. The results exhibited by these compounds were compared with the standard drug, cisplatin. The binding affinity of the Cu (II) metal ion complex towards CT-DNA was high when compared to Co (II) and Zn (II) metal ions. These results are in line with the cytotoxicity studies. Molecular docking studies also hold up the experimental data. Cu (II) complexes using ligand L2 show higher efficiency than those with ligand L1 in all biological assays and can be considered a potent DNA-targeting drug.

Multi-spectroscopic, calorimetric and molecular dynamics evaluation on non-classical intercalation of antiviral drug Molnupiravir with DNA

The interaction of an antiviral drug Molnupiravir (MOL) with calf thymus DNA (CT-DNA) was investigated using a series of biophysical techniques. A significant hyperchromism with a blue shift nm in the UV-Vis spectra indicated a high binding affinity of MOL for CT-DNA with binding constants in the order of 105 M−1. Competitive fluorescent dye displacement assays with ethidium bromide (EB) and Hoechst 33258 suggested an intercalative mode of binding of MOL with CT-DNA. Thermodynamic profiles determined using fluorescence titration and isothermal titration calorimetric (ITC) analysis matched well with each other. The negative free energy change revealed that the MOL/CT-DNA complexation is a spontaneous process. The negative values of enthalpy and entropy changes indicated that H-bonding and van der Walls interactions play dominant roles in stabilizing the complex. A decrease in viscosity of CT-DNA solution upon adding MOL indicated a partial intercalation mode of binding which was well supported by circular dichroism (CD) spectral and effect of KI and denaturation studies. Molecular docking and metadynamics simulation studies clearly showed the partial intercalation of the pyrimidine ring of MOL into the base pairs of DNA. Free energy surface (FES) contour indicated that the drug/DNA complex is stabilized by H-bonding and pi-pi/pi-cation interactions. Communicated by Ramaswamy H. Sarma

New insights into self-structure induction in poly (rA) by Quinacrine through non-classical intercalation: Spectroscopic and theoretical perspectives

Self-structure induction in a single stranded polyriboadenylic acid [poly (rA)] is an auspicious physiological phenomenon which switches off protein production in tumor cells. In the present study, the self-structure induction process in poly (rA) moiety was thoroughly investigated using various steady state and time resolved techniques. Optical melting pattern directly evidenced the formation of self-structured assembly in single stranded poly (rA) upon complexation with quinacrine. Further, UV-absorption spectroscopic studies revealed that quinacrine binds to poly (rA) in co-operative fashion and the indication of intercalative mode of binding first came out with the involvement of around two base pairs of poly (rA) in the complexation. Experimental observations established the unconventional or non-classical intercalation of quinacrine molecule inside self-structured duplex poly (rA) moiety. This complexation was accompanied with negative enthalpy change and positive entropy change; suggesting strong van der Waals and the H-bonding interactions as the major governing forces in the complexation. Moreover, ionic strength dependent binding study established that the non-polyelectrolytic forces were the dominating forces. Further, the photo physical behavior of QN was authenticated using time dependent density functional theory (TDDFT) where both the ground and excited states were exploited.

Synthesis, structural characterization of dinuclear copper(II) complexes based on Schiff base derived ligands and their impacts on DNA-binding affinities

Two binuclear copper (II) complexes ([Cu2(L1)2(Py)4] (1) and [Cu2(L2)2(Py)4] (2) where H2L1 (3-((2-hydroxybenzylidene)amino)benzoic acid and H2L2 (3-((2-hydroxy-5-nitrobenzylidene)amino)benzoic acid) have been synthesized and characterized by analytical and different spectroscopic technique. The X-ray diffraction analysis of both 1 and 2 complexes revealed that the geometry around the copper (II) centres are distorted square pyramidal. The crystal lattice in both 1 and 2 are stabilized by several types of intermolecular hydrogen bonds and π…π interactions. The intermolecular interactions on the crystal packing of 1 and 2 have been further studied by Hirshfeld surface analysis and corresponding 2D fingerprint plots. The interaction of 1 and 2 with calf thymus DNA (ct-DNA) have also been evaluated using absorption and fluorescence techniques and the result indicates that both 1 and 2 can bind to ct-DNA via an intercalative mode. The binding constant using absorption spectra between 1 with ct-DNA and 2 with ct-DNA have been found to be (10.3 ± 0.02) × 104 M−1 and (6.91 ± 0.01) × 104 M−1 respectively. Molecular docking studies also support the partial insertion of both 1 and 2 into the DNA backbone. Importantly, in Cu(II) complex 2, the Schiff base ligand possessing a significant electron withdrawing –NO2 group exhibits less interaction with ct-DNA compared to 1, containing less or no electron withdrawing character Schiff base.

Effect of an NGR Peptide on the Efficacy of the Doxorubicin Phospholipid Delivery System.

This study is a continuation of an investigation into the effect of a targeted component, a peptide with an NGR, on the properties of the previously developed doxorubicin phospholipid delivery system. The NGR peptide has an affinity for aminopeptidase N (known as the CD13 marker on the membrane surface of tumor cells) and has been extensively used to target drug delivery systems. This article presents the results of a study investigating the physical properties of the phospholipid composition with and without the peptide chain: particle size, zeta potential, stability in fluids, and dependence of doxorubicin release from nanoparticles at different pH levels (5.0, 6.5, 7.4). The cytotoxic effect of the compositions has also been shown to depend on the dose of the drug used for incubation, the presence of the targeted component in the composition, and the time of incubation time of the substances. There was a significant difference in the cytotoxic effect on HT-1080 (CD13-positive) and MCF-7 (CD13-negative) cells. Cell death pathway analysis has shown that death occurred mainly by apoptosis. We also present data on the effect of doxorubicin embedded in phospholipid nanoparticles with the targeted peptide on DNA assessed by differential pulse voltammetry, the mechanism of action being electrostatic interactions. The interactions of native dsDNA with doxorubicin encapsulated in phospholipid nanoparticles with the targeted peptide were studied electrochemically by differential pulse voltammetry. Here, we have highlighted that the targeted peptide in the doxorubicin composition moved specific interaction of the drug with dsDNA from intercalative mode to electrostatic interactions.

Synthesis, photophysical, electrochemical and morphological properties of a novel cross-linked chitosan-based fluorescent polymer: A fluorescence sensor for single-stranded DNA

This report details the first-time use of the perylene-3,4,9,10-tetracarboxylic dianhydride as a cross-linker to synthesize a novel fluorescent, chitosan-based cross-linked polymer (3). The polymer has single-stranded DNA (ssDNA) binding properties that can be used in sensor production for detecting salmon sperm DNA. Chitosan polymer's solubility is poor and restrictedto only acidic media. In contrast, this new fluorescent chitosan polymer was soluble in various organic solvents and aqueous solutions at different pHs. Its absorption, photophysical, electrochemical and morphological properties were investigated in detail. Gel permeation chromatography determined the weight average molecular mass (Mw) of polymer 3 as 21300 g/mol. Seventeen hydrophobic perylene units were determined in the cross-linked network. The energy levels of the highest occupied molecular orbitals and lowest unoccupied molecular orbitals of the new polymer 3 were calculated as −6.24 and −3.96 eV, corresponding to the band gap of 2.28 eV. Fluorescence and ultraviolet spectroscopy techniques were used to study the interaction between ssDNA and polymer 3. The interaction pointed to the intercalative mode, and the cross-linked chitosan can be used as a stable and sensitive platform for ssDNA detection. These results show a new class of organic biopolymers that could yield promising potential in many biomedical applications.

Synthesis and characterization of nanoscale level mono/bi-ligated metal(II) complexes

A series of nanoscale level metal complexes with bidentate (N2MCl2) and tetradentate (MN) chromophores as cisplatin analogues and intercalating agents of, [M(phen)Cl2] (1- 3), [M(bpy)Cl2] (4-6), [M(phen)2] (7-9) and [M(bpy)2] (10-12) (where respectively M = Cu(II), Ni(II) or Zn(II); phen = 1,10-phenanthroline and bpy = 2,2’-bipyridine) respectively were prepared in the present investigation. These complexes were prepared by sonochemical technique and characterized using elemental, spectral, and electrochemical techniques. Their nanorod or stick morphologies and crystalline nature were evaluated with scanning electron microscopy (SEM). Metal complexes, 1-6 are existing with two labile chlorides similar to the chemotherapeutic inorganic drug cisplatin, which may anticipate binding covalently with herring sperm DNA, While, complexes, 7-12 may undergo an intercalative mode of binding due to their structural differences relative to 1-6.