Partha Sarathi Guin

Electrochemical Reduction of Quinones in Different Media: A Review

The electron transfer reactions involving quinones, hydroquinones, and catechols are very important in many areas of chemistry, especially in biological systems. The therapeutic efficiency as well as toxicity of anthracycline anticancer drugs, a class of anthraquinones, is governed by their electrochemical properties. Other quinones serve as important functional moiety in various biological systems like electron-proton carriers in the respiratory chain and their involvement in photosynthetic electron flow systems. The present paper summarizes literatures on the reduction of quinones in different solvents under various conditions using different electrochemical methods. The influence of different reaction conditions including pH of the media, nature of supporting electrolytes, nature of other additives, intramolecular or intermolecular hydrogen bonding, ion pair formation, polarity of the solvents, stabilization of the semiquinone and quinone dianion, catalytic property, and adsorption at the electrode surface, are discussed and relationships between reaction conditions and products formed have been presented.

Studies on the formation of a complex of Cu(II) with sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate – An analogue of the core unit of anthracycline anticancer drugs and its interaction with calf thymus DNA

Copper(II) forms a complex with sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (sodium quinizarin-2-sulphonate, NaQSH(2)), an analogue of the core unit of anthracycline antibiotics used in the treatment of cancer. The 1:2 metal-ligand complex is formed in aqueous solution at neutral and acidic pH while in alkaline pH both 1:1 and 1:2 species are formed. The effective stability constant of the 1:2 metal-ligand complex is 9.64x10(16) while that of the 1:1 metal-ligand complex is 9.4x10(9). The 1:2 complex Cu(NaQSH)(2)(H(2)O)(2) was synthesized and characterized by different techniques in solid state and in solution. The complex Cu(NaQSH)(2)(H(2)O)(2) interacts with calf thymus DNA which was studied by fluorescence spectroscopy. The binding constant and site size for the interaction with DNA were determined.

X-ray crystal structure of a Cu(II) complex with the antiparasitic drug tinidazole, interaction with calf thymus DNA and evidence for antibacterial activity

Interaction of metal ions with biologically active molecules like 5-nitroimidazoles modulates their electronic environment and therefore influences their biological function. In the present work, an antiparasitic drug tinidazole (tnz) was selected and a Cu(II) complex of tnz [Cu2(OAc)4(tnz)2] was prepared. A dinuclear paddle-wheel [Cu2(OAc)4(tnz)2] was obtained by single-crystal XRD and further characterized by spectroscopic techniques and cyclic voltammetry. To understand the biological implications of complex formation, interaction of tnz and its complex was studied with calf thymus DNA, bacterial and fungal cell lines. Results of calf thymus DNA interaction using cyclic voltammetry indicate the overall binding constant (K*) of Cu2(OAc)4(tnz)2 [(59 ± 6) × 104 M−1] is ~17 times greater than that of tnz [(3.3 ± 0.4) × 104 M−1]. Minimum inhibitory concentration values suggest that [Cu2(OAc)4(tnz)2] possesses better antibacterial activity than tnz on both bacterial strains, while the activity on a fungal strain was comparable. Tinidazole, a 5-nitroimidazole is active on protozoan and bacterial infections. This study made an attempt to see if a Cu(II) complex of tinidazole had comparable efficacy on chosen bacteria and fungi. The prepared complex was characterized by XRD, spectroscopy, elemental analysis cyclic voltammetry. DNA interaction was studied using cyclic voltammetry and fitted by non-linear analysis.

A comparative study on the interaction with calf thymus DNA of a Ni(II) complex of the anticancer drug adriamycin and a Ni(II) complex of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate

The anthracycline drug adriamycin and its metal complexes are efficient in treating several forms of human cancers with recognized antineoplastic activity attributed to strong interactions with DNA within the target cells. The hydroxy-9,10-anthraquinone unit present in the molecule controls and regulates drug action. Metal ions when linked to adriamycin help to reduce the generation of radicals responsible for toxic side effects. A complex of adriamycin with Ni(II) was prepared and its physicochemical characteristics and DNA-binding ability were compared to a Ni(II) complex of sodium-1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (NaLH2), an analog of adriamycin. Interactions with calf thymus DNA of both complexes were studied by UV-Vis and fluorescence spectroscopy. Binding parameters determined for both complexes agree with each other. Binding of the Ni(II)-adriamycin complex to DNA was five to eight times stronger than for the Ni(II) complex of the hydroxy-9,10-anthraquinone analog, Na2[Ni(NaLH)2Cl2] · 2H2O, i.e., Ni(NaLH)2. The difference in binding was attributed to the presence of sugar units in adriamycin and to its absence in NaLH2. Although the Ni(II) complex of the hydroxy-9,10-anthraquinone analog of adriamycin [Ni(NaLH)2] was slightly weaker in binding DNA than the drug and its Ni(II) complex, a much lower cost of the former justifies its consideration as a substitute for the anthracycline drugs that are now in use.

A complex of Co(II) with 2-hydroxyphenyl-azo-2'-naphthol (HPAN) is far less cytotoxic than the parent compound on A549-lung carcinoma and peripheral blood mononuclear cells: Reasons for reduction in cytotoxicity.

Cytotoxic studies using an azo compound HPAN and its Co(II) complex were carried out on non-small lung epithelium carcinoma (A549) cells and peripheral blood mononuclear (PBM) cells. The results obtained suggest that the Co(II) complex is much less toxic toward both cell lines and the decreased toxicity due to the complex was more pronounced with carcinoma A549 cells. An attempt was made to correlate the findings related to cytotoxicity with the interaction of the compounds with DNA using calf thymus DNA as the target. The study was able to conclude that the complex was a relatively weak binder to calf thymus DNA. This information was used to explain the interaction of azo compounds with DNA in peripheral blood mononuclear cells and A549 lung carcinoma cells. It was concluded that the Co(II) complex interacts with DNA to a much lesser extent than HPAN alone. Cyclic voltammetry experiments carried out with HPAN and the Co(II) complex further showed that the presence of the metal ion in the complex prevents reduction of the azo group to such species that are responsible for inducing cytotoxicity. The overall finding was that complex formation with azo compounds might serve as a possible route to curb their toxicities.

Interaction of Calf Thymus DNA with the Ni(II) Complex of Sodium 1,4-Dihydroxy-9,10-Anthraquinone-2-Sulphonate: A Novel Method of Analysis Using Cyclic Voltammetry

Hydroxy-9,10-anthraquinones are cheaper alternatives to anthracycline drugs. They closely resemble anthracycline drugs both from a structural and functional viewpoint. Electrochemical behavior of the Ni(II) complex (Na2[Ni(NaLH)2Cl2]⋅2H2O) of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (NaLH2), analogue of the core unit of anthracycline anticancer drugs, was studied at physiological pH using cyclic voltammetry. The Ni(II) complex of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate undergoes diffusion-controlled one-electron reduction that enables performing an electrochemical study on the interaction of the complex with calf thymus DNA. The complex was titrated with increasing concentrations of DNA, and the reduction peak for the unbound complex helped in evaluating binding parameters. Analysis of binding data using nonlinear curve fit in a cyclic voltammetry experiment is the first such attempt. The paper evaluates site size of interaction that also serves as a means to determine stoichiometry of complex formation, between a metal ion and ligand from a DNA interaction study, probably a first of its kind.

Studies on the interaction of 2-amino-3-hydroxy-anthraquinone with surfactant micelles reveal its nucleation in human MDA-MB-231 breast adinocarcinoma cells

Structural and spectroscopic studies on 2-amino-3-hydroxy-anthraquinone (AQ), an analogue of anthracycline drugs, were carried out using computational methods. The interactions of AQ with anionic surfactant sodium dodecyl sulphate (SDS) and cationic surfactant cetyltrimethylammonium bromide (CTAB) were investigated in aqueous solution at physiological pH (7.4) by UV-Vis spectroscopy, and compared with the well-known anthracycline drugs. The affinity of such molecule to surfactant micelles may mean it can act as a model system for a biological membrane–drug interaction, which is important in determining the biological action of this molecule. The binding constant, partition coefficient and Gibbs free energy for the binding and distribution of AQ between the bulk aqueous solution and surfactant micelles were determined for AQ–surfactant interactions. It was observed that hydrophobic interaction plays a crucial role in the binding of AQ to SDS micelles, while the hydrophilic interaction plays an important role in its interaction with CTAB micelles. These interactions also have a vital role in the distribution of AQ between surfactant micelle–water phases. This study gives an idea that the present molecule may successfully permeate biological membranes, so AQ was allowed to interact with human breast adinocarcinoma cell MDA-MB-231. Experimental findings established that AQ induces apoptosis by means of nucleation into these cells.

1-Amino-4-hydroxy-9,10-anthraquinone – An analogue of anthracycline anticancer drugs, interacts with DNA and induces apoptosis in human MDA-MB-231 breast adinocarcinoma cells: Evaluation of structure–activity relationship using computational, spectroscopic and biochemical studies

The X-ray diffraction and spectroscopic properties of 1-amino-4-hydroxy-9,10-anthraquinone (1-AHAQ), a simple analogue of anthracycline chemotherapeutic drugs were studied by adopting experimental and computational methods. The optimized geometrical parameters obtained from computational methods were compared with the results of X-ray diffraction analysis and the two were found to be in reasonably good agreement. X-ray diffraction study, Density Functional Theory (DFT) and natural bond orbital (NBO) analysis indicated two types of hydrogen bonds in the molecule. The IR spectra of 1-AHAQ were studied by Vibrational Energy Distribution Analysis (VEDA) using potential energy distribution (PED) analysis. The electronic spectra were studied by TDDFT computation and compared with the experimental results. Experimental and theoretical results corroborated each other to a fair extent. To understand the biological efficacy of 1-AHAQ, it was allowed to interact with calf thymus DNA and human breast adino-carcinoma cell MDA-MB-231. It was found that the molecule induces apoptosis in this adinocarcinoma cell, with little, if any, cytotoxic effect in HBL-100 normal breast epithelial cell.

Exploration of Electrochemical Intermediates of the Anticancer Drug Doxorubicin Hydrochloride Using Cyclic Voltammetry and Simulation Studies with an Evaluation for Its Interaction with DNA

Electrochemical behavior of the anticancer drug doxorubicin hydrochloride was studied using cyclic voltammetry in aqueous medium using Hepes buffer (pH~7.4). At this pH, doxorubicin hydrochloride undergoes a reversible two-electron reduction with value −  mV (versus Ag/AgCl, saturated KCl). Depending on scan rates, processes were either quasireversible (at low scan rates) or near perfect reversible (at high scan rates). This difference in behavior of doxorubicin hydrochloride with scan rate studied over the same potential range speaks of differences in electron transfer processes in doxorubicin hydrochloride. Attempt was made to identify and understand the species involved using simulation. The information obtained was used to study the interaction of doxorubicin hydrochloride with calf thymus DNA. Cathodic peak current gradually decreased as more calf thymus DNA was added. The decrease in cathodic peak current was used to estimate the interaction of the drug with calf thymus DNA. Nonlinear curve fit analysis was applied to evaluate the intrinsic binding constant and site size of interaction that was compared with previous results on doxorubicin hydrochloride-DNA interaction monitored by cyclic voltammetry or spectroscopic techniques.

A Co(II) complex of a vitamer of vitamin B6 acts as a sensor for Hg2+ and pH in aqueous media

A Co(II) complex of molecular formula C48H96.8N12O22.4Co2Cl2, 1, was synthesized from the Schiff base [H2pydmdp]Cl by a template reaction of pyridoxal (pyd), a vitamer of vitamin B6, N-methyl-1,3-diaminopropane (mdp) and cobalt(II) acetate. It was characterized by elemental analysis, 1H NMR, IR and UV-Vis spectroscopy, thermal analysis, electrochemistry and single crystal X-ray diffraction. The experimental results suggested that in complex 1, the central Co(II) is bonded to two phenolato-oxygens, two imine nitrogens and two amine nitrogens in an octahedral geometry. In aqueous media complex 1 exhibits an intense fluorescence emission peak at 506 nm when it was excited at 425 nm. The fluorescence behavior of complex 1 in aqueous media was employed to determine whether it acts as a chemosensor for some selective toxic metal ions. The studies showed that the present complex behaves as a promising sensor for Hg2+ even at the sub-micromolar level. In addition in aqueous solution, complex 1 acts as a sensor for the pH of the medium. A detailed study on the mechanism of sensing behavior established that Hg2+ interacts with complex 1 via weak non-covalent interaction with the N-atom of the pyridine moiety of the molecule. The pyridine nitrogen also plays a vital role in sensing the pH of the medium.