Influence of acid-base equilibrium on interactions of some monofunctional coumarin Pd(II) complexes with biologically relevant nucleophiles-comprehensive kinetic study.

This aimed to develop a comprehensive theoretical protocol for examining substitution reaction processes. The researchers used a theoretical quantum-mechanical protocol based on the QM-ORSA approach, which estimates the kinetic parameters of thermodynamically favourable reaction pathways. This theoretical protocol was validated by experimentally investigating substitution mechanisms in two previously synthesised Pd(II) complexes: chlorido-[(3-(1-(2-hydroxypropylamino)ethylidene)chroman-2,4-dione)]palladium(II) (C1) and chlorido-[(3-(1-(2-mercaptoethylamino)-ethylidene)-chroman-2,4dione)]palladium(II) (C2), along with biologically relevant nucleophiles, namely L-cysteine (l-Cys), L-methionine (l-Met), and guanosine-5'-monophosphate (5'-GMP). Reactions were investigated under pseudo-first-order conditions, monitoring nucleophile concentration and temperature changes using stopped-flow UV-vis spectrophotometry. All reactions were conducted under physiological conditions (pH = 7.2) at 37 °C. The reactivity of the studied nucleophiles follows the order: l-Cys > l-Met > 5'-GMP, and the reaction mechanism is associative based on the activation parameters. The experimental and theoretical data showed that C2 is more reactive than C1, confirming that the complexes' structural and electronic properties greatly affect their reactivity with selected nucleophiles. The study's findings have confirmed that the primary interaction occurs with the acid-base species L-Cys, mostly through the involvement of the partially negative sulfur atom (87.2%). On the other hand, C2 has a higher propensity for reacting with L-Cys-, primarily through the partially negative oxygen atom (92.6%). The implementation of this theoretical framework will significantly restrict the utilization of chemical substances, hence facilitating cost reduction and environmental protection.

Biosynthesis and characterization of silver nanoparticles synthesized using extracts of Agrimonia eupatoria L. and in vitro and in vivo studies of potential medicinal applications.

This research explores the synthesis, characterization, and biological activities of silver nanoparticles (AgNPs) derived from acetone (AgNPs-acetone) and aqueous (AgNPs-H2O) extracts of Agrimonia eupatoria. The nanoparticles exhibit isometric morphology and uniform size distribution, as elucidated through Transmission Electron Microscopy (TEM) and high-resolution TEM (HRTEM) analyses. The utilization of Scanning Transmission Microscopy (STEM) with High-Angle Annular Dark-Field (HAADF) imaging and energy dispersive spectrometry (EDS) confirms the crystalline nature of AgNPs. Fourier Transform Infrared (FTIR) analysis reveals identical functional groups in the plant extracts and their corresponding AgNPs, suggesting the involvement of phytochemicals in the reduction of silver ions. Spectrophotometric monitoring of the synthesis process, influenced by various parameters, provides insights into the kinetics and optimal conditions for AgNP formation. The antioxidant activities of the plant extracts and synthesized AgNPs are evaluated through DPPH and ABTS methods, highlighting AgNPs-acetone as a potent antioxidant. Third-instar larvae exposed to the extracts have differential effects on DNA damage, with the acetone extract demonstrating antigenotoxic properties. Similarly, biosynthesized AgNPs-acetone displays antigenotoxic effects against EMS-induced DNA damage. The genotoxic effect of water extract and AgNPs-acetone was dose-dependent. Hemolytic potential is assessed on rat erythrocytes, revealing that low concentrations of AgNPs-acetone and AgNPs-H2O had a nontoxic effect on erythrocytes. Cytotoxicity assays demonstrate time-dependent and dose-dependent effects, with AgNPs-acetone exhibiting superior cytotoxicity. Proapoptotic activity is confirmed through apoptosis induction, emphasizing the potential therapeutic applications of AgNPs. The antimicrobial activity of AgNPs reveals concentration-dependent effects. AgNPs-H2O display better antibacterial activity, while antifungal activities are comparable between the two nanoparticle types.

Gold(III) Complexes with Phenanthroline-derivatives Ligands Induce Apoptosis in Human Colorectal and Breast Cancer Cell Lines.

Due to their promising effects, gold(III) complexes recently drew increasing attention in the design of new metal-based anticancer therapeutics. Two gold(III) complexes, square-planar [Au(DPP)Cl2]+ - Complex 1 and distorted square-pyramidal [Au(DMP)Cl3] - Complex 2 (where DPP=4,7-diphenyl-1,10-phenanthroline and DMP=2,9-dimethyl-1,10-phenanthroline) were previously synthetized, described and approved as complexes with pronounced cytotoxic effects on colorectal HCT-116 and breast MDA-MB-231 cancer cells. This study investigated the type of cell death by AO/EB double staining, and identification of possible targets responsible for their cytotoxicity, monitored by immunofluorescence and qPCR methods. Both complexes induced apoptosis in all applied concentrations. In the HCT-116 cells apoptosis was activated by external apoptotic pathway, via increase of Fas receptor protein expression and Caspase 8 gene expression. Also, the mitochondrial pathway was triggered by affecting the Bcl-2 members of regulatory proteins and increased caspase 9 protein expression. In MDA-MB-231 cells, apoptosis was initiated from the mitochondria, due to disbalance between expressions of pro- and anti-apoptotic Bcl-2 family members and caspase 9 activation. Complex 1 shows better activity compared to Complex 2, which is in accordance with its structural characteristics. The results deal weighty data about proapoptotic activity of gold(III) complexes and highlighted potential targets for cancer therapy.