Solvation of 1-Amino-4-Hydroxy-9,10-Anthraquinone Governs Its Electrochemical Behavior in Non-Aqueous and Aqueous Media: A Cyclic Voltammetry Study

The electrochemical behavior of 1-amino-4-hydroxy-9,10-anthraquinone (1-AHAQ) was studied in acetonitrile, dimethyl formamide and dimethyl sulfoxide. In such solvents 1-AHAQ undergoes successive two one-electron reduction forming semiquinone and quinone dianion respectively in which the first step is completely reversible and the second step is quasi-reversible. The reduction and oxidation potentials are dependent on the polarity of the media. The electrochemical parameters are evaluated and correlated with the polarity index of the media. During such reductions a comproportionation reaction operates between the quinone (1-AHAQ) and its dianion (1-AHAQ 2-) to form a semiquinone radical (1-AHAQ • -). The apparent comproportionation constants are calculated to find a comparative account on the stability of the radical intermediate in such solvents. In the presence of benzoic acid the electrochemical behavior of 1-AHAQ is altered significantly which is determined in this study. Role of the polarity of the solvents, intra or intermolecular hydrogen bonding and acidic additives on the stability of the radical species is evaluated. In aqueous buffer the reduction of 1-AHAQ follows a one step two-electron process where a kinetic study was carried out to determine the apparent charge transfer rate constants at various scan rates. The results show that electrochemical behavior of 1-AHAQ in non-aqueous and aqueous media mimics the action of anthracycline anticancer drugs which may find a similarity in their biological activities at the cellular level. Anthracycline drugs such as doxorubicin, daunorubicin, carminomycin, aclacinomycin, nogalamycin, etc., are some of the important chemotherapeutic agents used in the treatment of various forms of human cancers. 1-4 Since their discovery, studies on anthracycline antibiotics have been actively pursued for their anticancer activity and mechanism of drug action. Most of these studies on anthracyclines and its metal complexes concentrate on the interaction with DNA. 5-8 Some studies showed that the sugar moiety present in these drugs help in the recognition of cancer cells. 9,10 At the same time, the presence of the sugar moiety on the aliphatic side chain attached to the hydroxy-9,10-anthraquinone in these molecules makes them so costly that it is not always possible for many to continue treatment using this category of drugs. This is particularly true for the people affected with cancer residing in the developing countries. Though there is very wide application of anthracyclines in cancer chemotherapy the above mentioned aspects are very unfortunate and needs serious consideration. Efforts are therefore on to find out new but cheaper analogues and derivatives of anthracycline drugs. In several studies 18 It is used for the treatment of breast cancer, prostate cancer, leukemia and lymphoma. Mitoxantrone induces compaction of isolated chromatin, 19 protein associated DNA cleavage 20 and inhibits DNA and RNA synthesis. Although several studies on hydroxy-9, 10-anthraquinones 18-22 were extensively carried out the other amino hydroxy-9,10-anthraquinones have not been seriously investigated as a possible substitute of anthracycline anticancer drugs. However, the major limitation of the use of anthracycline drugs includes their acute and chronic toxicities, of which cardiotoxicity is an aspect that requires most attention. • -and then Q 2− . The formal potentials for these reduction steps depend upon the polarity of the solvent, 32-35 the nature of the cation of the supporting electrolyte How the hydrogen bonding affects the stability of electrogenerated quinone radicals and hence mechanism of the electrochemical reaction were extensively investigated by I. González, F. González, N. MaciasRuvalcaba and their groups in several studies. 51 The focus of our study is to find out whether 1-amino-4-hydroxy-9, 10-anthraquinone which is much less costly, mimics the electrochemical behavior and hence the mechanism of drug action of the anthracyclines. The present study concentrates on the detailed electrochemical behavior of 1-amino-4-hydroxy-9, 10-anthraquinone (1-AHAQ), an analogue of the core unit of anthracycline drugs, using cyclic voltammetry in non-aqueous and aqueous solvents. Th

Solubility and transfer Gibbs free energetics of glycine, DL-alanine, DL-nor-valine and DL-serine in aqueous sodium fluoride and potassium fluoride solutions at 298.15 K

The experimental saturated solubilities of glycine, DL-alanine, DL-nor-valine and DL-serine in aqueous mixtures of NaF and KF solutions at 298.15 K are measured by using an analytical ‘formol titrimetry’ method. Subsequently, the standard transfer Gibbs free energy, enthalpy for cavity formation, Gibbs free energy for cavity formation and Gibbs free energy for dipole-dipole interaction have been computed. The chemical contribution for the standard transfer Gibbs free energies for the experimental amino acids have been obtained by subtracting the cavity effects and dipole-dipole interaction effects from the total standard transfer Gibbs free energy (∆ (i)). The stability of the studied amino acids in aqueous NaF and KF in terms of thermodynamic parameters are discussed and compared

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 E1/2 value −665±5 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

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

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

Solubility and Thermodynamics of Solute–Solvent Interactions of Some Amino Acids in Aqueous Sodium Bromide and Potassium Bromide Solutions

The study presents the saturated solubilities of four amino acids such as glycine, dl-alanine, dl-valine, and dl-serine in water media containing sodium bromide and potassium bromide electrolytes at standard temperature (298.15 K) which were evaluated by applying the “gravimetric method”. Various physicochemical and thermodynamical parameters such as enthalpy of solvation, free energy change, density, molar volume, solvent diameter, cosolvent diameter, apparent dipole moment of aqueous electrolyte systems, mole fraction of salt and solvent, mean molecular weight of electrolyte solvent and isothermal expansibility constant of aqueous electrolytes were estimated at standard temperature (298.15 K). The characteristics and degree of solubilities of the experimental molecules in water media in the presence of NaBr and KBr were examined by means of the salting-in effect which was further justified by relative solubility and salting-in constants. Various reasonings influencing the solubility were introduced and interrelated with appropriate thermodynamical issues. Ultimately the chemical transfer Gibbs free energies were measured and used to justify the stability of the experimental molecules in water media in the presence of electrolytes

Model studies on the interactions of a Cu(II)-quinone complex with surfactant micelles and DNA explore its induction of apoptosis in human MDA-MB-231 breast adenocarcinoma cells

<p>The interactions of copper complex (CuQ₂) of 1-amino-4-hydroxy-9,10-anthraquinone (QH) with calf thymus DNA, anionic surfactant sodium dodecyl sulfate (SDS), and cationic surfactant cetyltrimethylammonium bromide (CTAB) were investigated in an aqueous solution at physiological pH (7.4). Affinities of such molecule to DNA and surfactant micelles, a model for a biological membrane, are important in determining its biological action. Using different models, various binding parameters were evaluated in both of molecule–DNA interaction and molecule–surfactant interaction. The study showed that hydrophobic interaction plays a major role in the binding of CuQ₂ to surfactant micelles. In addition, the hydrophobic interaction has an important role in the distribution of CuQ₂ between micelle-water phases. Gibbs free energy for the binding and distribution of CuQ₂ between the bulk aqueous medium and surfactant micelles were calculated. In order to correlate the physicochemical properties deciphered from the aforementioned studies with the biological property of the molecule, CuQ₂ was treated with MDA-MB-231 breast adenocarcinoma cells where it was found that the molecule affects the viability of the cancer cells. Fluorescent staining of the treated cells with AO/EB and Hoechst indicated that the CuQ₂ induces apoptosis, suggesting its use in the treatment of breast cancer.</p