Sankaralingam Arunachalam

DNA binding and antimicrobial studies of polymer-copper(II) complexes containing 1,10-phenanthroline and L-phenylalanine ligands

Some water-soluble polymer-copper(II) complexes, [Cu(phen)(l-phe)(BPEI)]ClO(4).4H(2)O (phen=1,10-phenanthroline, l-phe=l-phenylalanine, and BPEI=branched polyethyleneimine), with various amounts of copper(II) chelates in the polymer chain, were prepared by ligand substitution method in water-ethanol medium and characterized by infra-red, UV-visible, EPR spectral and elemental analysis methods. Binding of these complexes with calf thymus DNA (CT DNA) has been investigated by absorption spectroscopy, emission spectroscopy and gel electrophoresis techniques. The experimental results indicate that the amount of copper(II) chelate content in the polymer backbone have marked effect on the binding affinity to CT DNA. Interactions like electrostatic interaction, van der Waals interaction, hydrogen bonding and/or partial intercalation binding modes exist in this system. A sample of polymer-copper(II) complex was tested for its antibacterial and antifungal activity against certain human pathogenic organisms and it was found to have good antibacterial and antifungal activities.

Synthesis, nucleic acid binding and cytotoxicity of polyethyleneimine-copper(II) complexes containing 1,10-phenanthroline and l-valine.

The polymer-copper(II) complex samples, [Cu(phen)(l-Val) BPEI]Cl·H(2)O, with varying degrees of coordination in the polymer chain, were prepared and characterized by elemental analysis and spectroscopic methods. The binding of these complex samples with both DNA and RNA has been investigated. The experimental results indicate that the polyethyleneimine-copper(II) complex samples bind with DNA and RNA mostly through surface binding; but hydrogen bonding and van der Waals interactions are also present. Evaluation of cytotoxic activity of a sample of polymer-copper(II) complex with higher degree of coordination against different cancer cell lines proved that the complex exhibited cytotoxic specificity and significant cancer cell inhibition rate.

DNA/RNA binding and anticancer/antimicrobial activities of polymer-copper(II) complexes.

Water soluble polymer-copper(II) complexes with various degrees of coordination in the polymer chain were synthesized and characterized by elemental analysis, IR, UV-visible and EPR spectra. The DNA/RNA binding behavior of these polymer-copper(II) complexes was examined by UV-visible absorption, emission and circular dichroism spectroscopic methods, and cyclic voltammetry techniques. The binding of the polymer-copper(II) complexes with DNA/RNA was mainly through intercalation but some amount of electrostatic interaction was also observed. This binding capacity increased with the degree of coordination of the complexes. The polymer-copper(II) complex having the highest degree of coordination was subjected to analysis of cytotoxic and antimicrobial properties. The cytotoxicity study indicated that the polymer-copper(II) complexes affected the viability of MCF-7 mammary carcinoma cells, and the cells responded to the treatment with mostly through apoptosis although a few cells succumbed to necrosis. The antimicrobial screening showed activity against some human pathogens.

A comparative study on the binding of single and double chain surfactant-cobalt(III) complexes with bovine serum albumin.

The comparative binding effect of single and double aliphatic chain containing surfactant-cobalt(III) complexes cis-[Co(bpy)2(DA)2](ClO4)3·2H2O (1), cis-[Co(bpy)2(DA)Cl](ClO4)2·2H2O (2), cis-[Co(phen)2(CA)2](ClO4)3·2H2O (3), and cis-[Co(phen)2(CA)Cl](ClO4)2·2H2O (4) with bovine serum albumin (BSA) under physiological condition was analyzed by steady state, time resolved fluorescence, synchronous, three-dimensional fluorescence, UV-Visible absorption and circular dichroism spectroscopic techniques. The results show that these complexes cause the fluorescence quenching of BSA through a static mechanism. The binding constants (Kb) and the number of binding sites were calculated and binding constant values are found in the range of 10(4)-10(5) M(-1). The results indicate that compared to single chain complex, double chain surfactant-cobalt(III) complex interacts strongly with BSA. Also the sign of thermodynamic parameters (ΔG°, ΔH°, and ΔS°) indicate that all the complexes interact with BSA through hydrophobic force. The binding distance (r) between complexes and BSA was calculated using Förster non-radiation energy transfer theory and found to be less than 7 nm. The results of synchronous, three dimensional fluorescence and circular dichroism spectroscopic methods indicate that the double chain surfactant-cobalt(III) complexes changed the conformation of the protein considerably than the respective single chain surfactant-cobalt(III) complexes. Antimicrobial studies of the complexes showed good activities against pathogenic microorganisms.

Human serum albumin binding and cytotoxicity studies of surfactant–cobalt(III) complex containing 1,10-phenanthroline ligand

The characteristics of the binding reaction of surfactant-cobalt(III) complex, cis-[Co(phen)₂(C₁₄H₂₉NH₂)]Cl₂·3H₂O (phen=1,10-phenanthroline, C₁₄H₂₉NH₂=tetradecylamine) with human serum albumin (HSA) were studied by fluorescence and UV-vis absorption spectroscopy. In addition, the effect of the surfactant-cobalt(III) complex on the conformation of HSA was analysed using synchronous fluorescence spectroscopy. The experimental results showed that surfactant-cobalt(III) complex caused the fluorescence quenching of HSA through a combination of static and dynamic quenching. The number of binding sites (n) and apparent binding constant (K(a)) of surfactant-cobalt(III) complex (above and below the critical micelle concentration (cmc) were determined at various temperatures. According to the thermodynamic parameters, it is likely that hydrophobic interactions are involved in the binding process. The cancer chemotherapeutic potential of surfactant-cobalt(III) complex on ME-180 cervical cancer cell was determined using MTT assay and specific staining techniques. The complex affected the viability of the cells significantly and the cells succumbed through an apoptosis process as seen in the nuclear morphology and cytoplasmic features. In addition, single-cell electrophoresis indicated DNA damage.

Synthesis, nucleic acid binding, anticancer and antimicrobial activities of polymer–copper(II) complexes containing intercalative phenanthroline ligand(DPQ)

Polymer complexes [Cu(dpq)2BPEI](ClO4)2·2H2O (dpq-dipyrido[3,2-d;2′,3′-f]quinoxaline; BPEI-branched polyethyleneimine] with different degrees of copper complex content in the polymer chain (x) were synthesized and characterized by UV-Vis, IR, EPR and elemental analysis methods. Absorption spectroscopy, emission spectroscopy, cyclic voltammetry and circular dichroism techniques were used to investigate the binding nature of these polymer–copper(II) complexes with both CT-DNA and yeast tRNA. These experiments revealed that these the polymer–copper(II) complexes bind to both DNA and RNA by an intercalation mode via ligand dpq into the base pairs of DNA/RNA. The binding constant of the polymer–copper(II) complex increases with the degree of coordination. Furthermore, the anti-microbial effects and in vitro cytotoxicity of one of the polymer copper(II) complexes (x = 0.326) were investigated using the disk diffusion method and MTT assay and AO/EB staining. These results suggests that the polymer–copper(II) complex can be used as an effective therapeutic agent.

Surfactant–copper(II) Schiff base complexes: synthesis, structural investigation, DNA interaction, docking studies, and cytotoxic activity

A series of surfactant–copper(II) Schiff base complexes (1–6) of the general formula, [Cu(sal-R2)2] and [Cu(5-OMe-sal-R2)2], {where, sal = salicylaldehyde, 5-OMe-sal = 5-methoxy- salicylaldehyde, and R2 = dodecylamine (DA), tetradecylamine (TA), or cetylamine (CA)} have been synthesized and characterized by spectroscopic, ESI-MS, and elemental analysis methods. For a special reason, the structure of one of the complexes (2) was resolved by single crystal X-ray diffraction analysis and it indicates the presence of a distorted square-planar geometry in the complex. Analysis of the binding of these complexes with DNA has been carried out adapting UV-visible-, fluorescence-, as well as circular dichroism spectroscopic methods and viscosity experiments. The results indicate that the complexes bind via minor groove mode involving the hydrophobic surfactant chain. Increase in the length of the aliphatic chain of the ligands facilitates the binding. Further, molecular docking calculations have been performed to understand the nature as well as order of binding of these complexes with DNA. This docking analysis also suggested that the complexes interact with DNA through the alkyl chain present in the Schiff base ligands via the minor groove. In addition, the cytotoxic property of the surfactant–copper(II) Schiff base complexes have been studied against a breast cancer cell line. All six complexes reduced the visibility of the cells but complexes 2, 3, 5, and 6 brought about this effect at fairly low concentrations. Analyzed further, but a small percentage of cells succumbed to necrosis. Of these complexes (6) proved to be the most efficient aptotoxic agent.

Polyethyleneimine anchored copper(II) complexes: Synthesis, characterization, in vitro DNA binding studies and cytotoxicity studies

The water soluble polyethyleneimine-copper(II) complexes, [Cu(phen)(L-tyr)BPEI]ClO4 (where phen=1,10-phenanthroline, L-tyr=L-tyrosine and BPEI=branched polyethyleneimine) with various degree of copper(II) complex units in the polymer chain were synthesized and characterized by elemental analysis and electronic, FT-IR, EPR spectroscopic techniques. The binding of these complexes with CT-DNA was studied using UV-visible absorption titration, thermal denaturation, emission, circular dichroism spectroscopy and cyclic voltammetric methods. The changes observed in the physicochemcial properties indicated that the binding between the polymer-copper complexes and DNA was mostly through electrostatic mode of binding. Among these complexes, the polymer-copper(II) complex with the highest degrees of copper(II) complex units (higher degrees of coordination) showed higher binding constant than those with lower copper(II) complex units (lower degrees of coordination) complexes. The complex with the highest number of metal centre bound strongly due to the cooperative binding effect. Therefore, anticancer study was carried out using this complex. The cytotoxic activity for this complex on MCF-7 breast cancer cell line was determined adopting MTT assay, acridine orange/ethidium bromide (AO/EB) staining and comet assay techniques, which revealed that the cells were committed to specific mode of cell death either apoptosis or necrosis.

Study of single and double chain surfactant–cobalt(III) complexes and their hydrophobicity, micelle formation, interaction with serum albumins and antibacterial activities

To develop surfactant based metallodrugs, it is important to know the role of the tail part of the surfactant–metal complexes in their hydrophobicity, micellization behaviour, interaction with biomacromolecules and cell penetration. Here, we have taken a new series of single and double chain surfactant–cobalt(III) complexes with alkylamine ligands of different chain length, [Co(dien)(DA)Cl2]ClO4 (1), [Co(dien)(HA)Cl2]ClO4 (2), [Co(dien)(DA)2Cl](ClO4)2 (3) and [Co(dien)(HA)2Cl](ClO4)2 (4), where dien = diethylenetriamine, DA = dodecylamine and HA = hexadecylamine. The complexes were characterised by elemental analysis, NMR, ESI-MS, UV-visible and FTIR techniques. In addition, the average size distribution and morphology of self-assembled surfactant–cobalt(III) complexes were examined by DLS and SEM, respectively. The hydrophobicity, critical micelle concentration (CMC) values, thermodynamics of micellization (ΔG°m, ΔH°m and ΔS°m) and the nature of the interaction of these complexes with bovine and human serum albumins (BSA/HSA) were evaluated. The obtained CMC values were in the order 1 > 2 > 3 > 4, indicating that double chain systems have lower CMC values compared to single chain systems due to the increase in the hydrophobicity of the alkyl amine ligands. The thermodynamics of micellization indicated that the process is spontaneous, exothermic and entropy driven. The interaction of complexes 1–4 with serum albumins indicated that the quenching process follows a static mechanism, and the extent of quenching and binding parameters were in the order 1 < 2 < 3 < 4. Interestingly, on increasing the temperature, the protein–complex stability decreased for the single chain systems, and increased for the double chain systems, probably due to the involvement of electrostatic and hydrophobic interactions. This was further supported by the thermodynamics of protein interaction and synchronous fluorescence studies. Moreover, the results from UV-vis, synchronous and circular dichroism (CD) showed the occurrence of conformational and micro environmental changes in BSA/HSA. It is also noted that BSA has more binding affinity with surfactant–metal complexes compared to HSA. Furthermore, the antimicrobial effects of these complexes were investigated by disk diffusion method; complex 4 has a better antimicrobial activity due to the ease of bacterial cell penetration due to its more hydrophobic nature.

Synthesis, DNA binding and docking studies of copper(II) complexes containing modified phenanthroline ligands

Copper(II) complexes, [Cu(Hsal)(L)(ClO4)] (where Hsal = salicylaldehyde, 1: L = dpqC = dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro)phenazine and 2: L = dppz = dipyrido[3,2-a:2′,3′-c]phenazine), were synthesized and characterized using elemental analysis and spectroscopic methods. Single-crystal XRD on 1 confirms the presence of square pyramidal geometry around Cu(II). DNA interaction studies were performed for both the complexes using UV–visible, fluorescence and circular dichroism spectroscopic techniques, and viscosity. These complexes bind with DNA through partial intercalation. Molecular docking studies confirm our experimental findings of mode of binding of our complexes with DNA. Graphical Abstract