Rakiba Rohman

Methanol–water composition modulates solvation structure and dynamics around calix[4]tyrosols, with enhanced structuring in water-rich media and faster dynamics in methanol-rich mixtures, while conformational stability remains unchanged.

Loss-of-function mutations in copper-ATPase ATP7B underlie Wilson disease (WD), a disorder characterized by hepatic copper accumulation and severe hepato-neuropathology. Existing chelation therapeutics remove excess copper but lack intrinsic antioxidant capacity and frequently cause systemic toxicity. Here we evaluate melatonin, an FDA-approved indoleamine with antioxidant and putative metal-chelating activity, as a candidate therapeutic for WD. In ATP7B⁻ ^/ ⁻ hepatocytes, melatonin restored copper-induced reactive oxygen species (ROS) to basal levels, reduced apoptosis twofold, and attenuated Nrf2 nuclear translocation leading to reduction of Hemoxygenase-1 abundance. Live-cell ratiometric analysis of GSSG/GSH using GRX1-roGFP2 expressed in melatonin-treated ATP7B⁻ ^/ ⁻ hepatocytes revealed a significant reduction in intensity-ratio, indicating an effective mitigation of copper-induced glutathione oxidation. Isothermal calorimetric titration revealed moderate Cu ²⁺ affinity (K ^ITC =4.54 × 10³ M⁻¹), rationalized by MD-simulations showing an interaction energy of 18.5 × 10⁻³ kcal·mol⁻¹ via amide–Cu²⁺ coordination. In-cellulo studies also revealed that copper-induced vesicularized ATP7B reinstates to Golgi in melatonin-treated hepatocytes. In vivo , melatonin treatment reduced copper-induced oxidative stress in zebrafish embryos and lowered copper burden in Caenorhabditis elegans WD model. Our studies revealed that encapsulation of melatonin within an engineered polymeric nanocapsules having dithiol linkers, susceptible to cleavage by GSH, extended melatonin’s circulatory half-life ten-fold and enhanced its ROS-scavenging efficacy three-fold relative to free melatonin. This work introduces a unique dual-function therapeutic strategy that integrates antioxidant activity with copper chelation, simultaneously addressing copper overload and redox imbalance. Repurposing melatonin, with its established clinical safety, offers rapid and cost-effective translational pathway toward WD-therapy while providing a generalizable platform for redox- and metal-associated disorders.

Due to the disruption of homeostasis, the amount of free radicals produced may increase during metabolic processes leading to oxidative stress and may cause numerous diseases. Antioxidant prevents oxidative stress. Here, we have designed twenty hybrid antioxidant molecules which are also potential drugs. These molecules are mainly hybrids of hydroxybenzoic acids and hydroxycinnamic acids. At first, we have carried out a conformational analysis to find out the most stable structure of the molecules. Conformational studies are performed with the MP2 method. Thereafter, the physicochemical parameters are calculated, showing that these molecules are probable antioxidants. Further, we have investigated the free radical scavenging capacity of these molecules for inactivating eight prototype oxyradicals. The scavenging capacity was estimated by considering Gibbs free energy for the three mechanisms, viz. HAT, SPLET, and SET‐PT. Our study on mechanisms shows that for these molecules HAT and SPLET are favorable in the gas phase, while in solvent medium HAT and SET‐PT are competitive. An empirical rule for combining such hydroxycinnamic and hydroxybenzoic acids is proposed. In addition, the druglikeness of the molecules is calculated using Lipinski's rule of five. The advantage of our set of designed hybrid molecules is that they show antioxidant behavior with pharmacophoric characteristics. Thus, the set of promising antioxidants with drug‐like properties could create new prospects in drug discovery.

Polyphenolic antioxidants are an integral component of the present-day lifestyle due to growing environmental and pollution-related issues. Gallic acid (GA), a popular polyphenolic antioxidant, is widely distributed in different fruits and vegetables. It scavenges free radicals mostly through the hydrogen atom transfer (HAT) mechanism. The present work reports a fundamental understanding of the atom transfer involved in the antioxidant activity of GA in the presence of prototype oxyradicals. In this article, the behavior of GA in the presence of three prototype oxyradicals, based on the availability in biological systems, viz. hydroxyl (•OH), hydroperoxyl (•OOH), and methyl peroxyl (•OOMe) is studied. On radical scavenging, a sharp change in the structural, electronic, and thermodynamic properties of GA is observed. Finally, a new descriptor based on chemical hardness, which describes the stability of the antioxidant molecule during a HAT reaction, is also proposed. The present work reports a fundamental understanding of the atom transfer involved in antioxidant activity of gallic acid in presence of prototype oxyradicals

The effect of external electric field on the antioxidant properties of gallic and caffeic acids is studied. The performance of range-separated functionals in reproducing the O–H BDE is tested in the presence of an external electric field.