Electrochemical investigations of DNA-Intercalation potency of bisnitrophenoxy compounds with different alkyl chain lengths.

In this study, the binding tendency of bisnitrophenoxy compounds (BN) having different methylene (-CH2-)n spacer groups (n = 8-11) with fish sperm double stranded deoxyribonucleic acid (dsDNA) was explored. Cyclic voltammetry (CV) was used to evaluate various kinetic and binding parameters (Ks,h, Do, K b and binding site sizes). Performed electrochemical studies designated strong contact of these symmetric molecules with dsDNA in threading intercalation mode of binding. The number (n) of methylene spacer group in the molecular structure of bisnitrophenoxy compounds, e.g., BN-8 (1-nitro-4-(8-(4-nitrophenoxy)octyloxy)benzene, was observed to have a strong influence on their binding affinity. Decreased peak current values and positively shifted peak potentials recorded via cyclic voltammetry clearly depicted that bisnitrophenoxy compounds can intercalate with dsDNA. Results demonstrated the following order of binding constants; K b (M-1): BN-8 (2.32 × 104) < BN-9 (5.73 × 104) < BN-10 (8.97 × 104) < BN-11 (17.34 × 104). The order of increasing binding sites from BN-8 (0.13) to BN-11 (1.38), revealed the maximum threading intercalation strength by bisnitrophenoxy compound having the longest methylene spacer (n = 11). Thermodynamic studies augmented the strong binding of BN-11 with dsDNA as compared to BN-8 because of the long-chain, -CH2- spacer in its structure. The spontaneity of dsDNA-binding was revealed by the negative ΔG values for interaction of all the compounds. Moreover, binding parameters from thermodynamic and kinetic studies also corresponded to the threading intercalation mode of interaction, which itself points to the potency of the envisioned drug-like molecules.

Investigating the scavenging of reactive oxygen species by antioxidants via theoretical and experimental methods.

Reactive oxygen (hydroxyl OH, hydroperoxyl OOH) species are highly unstable to be studied experimentally under normal conditions. The present study reports the antioxidant potential of the vitamins namely ascorbic acid, riboflavin and nicotinic acid against these reactive oxygen species (ROS) using the predictive power of Density Functional Theory (DFT) (B3LYP with 6311G basis set) calculations. The order of reactivity of aforementioned vitamins was assessed by determining the bond dissociation enthalpy (BDE) of the OH bond, which is the controlling factor, if hydrogen atom transfer (HAT) mechanism is considered. Transition state calculations were also carried out to determine the reaction barrier for the radical scavenging reaction of vitamins by calculating the forward and the backward activation energies using the same level of theory as mentioned above. The theoretical methodology was first validated by taking a model stable free radical, 2, 2-diphenyl-1, picrylhydrazyl radical (DPPH) and applying the proposed approach followed by the experimental studies using UV-visible spectroscopy and cyclic voltammetry. The close agreement between the theoretical prediction and experimental observations proved the authenticity of theoretical approach.

Interaction of gold nanoparticles with free radicals and their role in enhancing the scavenging activity of ascorbic acid.

The present study investigates the interaction of citrate stabilized gold nanoparticles (12±1.5nm) (GNPs) with free radicals; 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable and electrochemically generated superoxide, O2(-). Different experiments were designed to understand the interaction between GNPs and DPPH by employing cyclic voltammetry, UV-vis spectroscopy and computational chemistry using 6-311G basis set. The increase in heterogeneous rate constant, ksh, of DPPH upon addition of GNPs pointed towards possible complex formation, DPPH-GNPs which were further explained by a model assuming surface adsorption of DPPH on GNPs. Further, the model was validated by studying interaction of GNPs with a biologically important free radical, O2(-). Exciting result in terms of disappearance of anodic peak after GNPs addition confirmed that gold nanoparticles interacted with stable as well as unstable free radicals. Also, the stoichiometry of the most stable complex GNP-DPPH was determined from UV-vis spectroscopy by applying Job's method. The GNP-DPPH complex was found to be active with 46.0% reduction of the IC50 value of standard antioxidant, ascorbic acid (AA), indicating its role in enhancing antioxidant activity. Hence, this study presents a simple and potential approach to enhance the efficiency of natural antioxidants without modifying their structure, or involving the complex functionalization of GNPs with antioxidants.

Natural flavonoids interact with dinitrobenzene system in aprotic media: an electrochemical probing.

Three structurally related natural flavonoids (FlOH), quercetin (Q), rutin (R) and morin (M), were investigated by cyclic voltammetry to probe their interactions with hazardous 1,4-dinitrobenzene (1,4-DNB) using a glassy carbon electrode. Scavenging of 1,4-DNB by FlOH was inferred from a positive shift in reduction potential, decrease in anodic peak current, and irreversible electrochemical behavior of 1,4-DNB on increasing the flavonoid concentration. The homogeneous bi-molecular rate constant (k2) was determined using the Nicholson-Shain equation and found to be higher for the dianion. Morin posed a comparatively higher k2 value for its interaction with the 1,4-DNB electrochemical system owing to its more acidic nature and least intramolecular hydrogen bonding. The cyclic voltammetric (CV) results were further supported by HyperchemPM3 quantum mechanical semi-empirical calculations, which point towards E(r)C(i) interactions between flavonoids and 1,4-DNB. The present investigation is biologically significant in terms of natural flavonoidal scavenging activity toward toxins such as dinitroaromatics.

Flavonoid-DNA binding studies and thermodynamic parameters.

Interactional studies of new flavonoid derivatives (Fl) with chicken blood ds.DNA were investigated spectrophotometrically in DMSO-H2O (9:1 v/v) at various temperatures. Spectral parameters suggest considerable binding between the flavonoid derivatives studied and ds.DNA. The binding constant values lie in the enhanced-binding range. Thermodynamic parameters obtained from UV studies also point to strong spontaneous binding of Fl with ds.DNA. Viscometric studies complimented the UV results where a small linear increase in relative viscosity of the DNA solution was observed with added optimal flavonoid concentration. An overall mixed mode of interaction (intercalative plus groove binding) is proposed between DNA and flavonoids. Conclusively, investigated flavonoid derivatives are found to be strong DNA binders and seem to be promising drug candidates like their natural analogues.

Spectrophotometric analysis of flavonoid-DNA binding interactions at physiological conditions.

Mode of interactions of three flavonoids [morin (M), quercetin (Q), and rutin (R)] with chicken blood ds.DNA (ck.DNA) has been investigated spectrophotometrically at different temperatures including body temperature (310 K) and at two physiological pH values, i.e. 7.4 (human blood pH) and 4.7 (stomach pH). The binding constants, K(f), evaluated using Benesi-Hildebrand equation showed that the flavonoids bind effectively through intercalation at both pH values and body temperature. Quercetin, somehow, showed greater binding capabilities with DNA. The free energies of flavonoid-DNA complexes indicated the spontaneity of their binding. The order of binding constants of three flavonoids at both pH values were found to be K(f(Q)) > K(f(R)) > K(f(M)) and at 310 K.