Macedonian Journal of Chemistry and Chemical Engineering

Impressum 2025/44-2

Zoran Zdravkovski — 2026-01-02

LC-HRMS and NMR study of the esterification products of ibuprofen with solketal: Formation, isolation and identification

Viktorija Jakimovska Pokupec — 2025-12-24

Ibuprofen is a widely used non-steroidal anti-inflammatory drug dispensed in tablets, capsules, suspensions, oral solutions, creams, and gels. Ibuprofen's poor water solubility and gastrointestinal side-effects present ongoing formulation challenges. Alcoholic excipients are often employed to enhance solubility and minimise adverse effects. Solketal (1,2-isopropylidene glycerol), a ketal produced by the condensation of glycerol with acetone, offers further versatility as an excipient due to its free hydroxyl group, which enables esterification reactions with acidic active pharmaceutical ingredients like ibuprofen. Introducing any excipient, especially in direct contact with the active pharmaceutical ingredient, necessitates careful evaluation of potential drug–excipient interactions, as these can alter the drug's physicochemical properties and impact clinical performance. Chromatographic techniques coupled with mass spectrometry and nuclear magnetic resonance spectroscopy remain essential for identifying and characterising related and degradation products in pre-formulation studies. In this study, we investigated the esterification of ibuprofen with solketal to identify possible interaction products. Two major compounds were isolated and thoroughly characterised by MS and NMR, confirming their chemical structures: 1-mono-glycerol ester of ibuprofen and ibuprofen-solketal-ester, which contained a 1,3-dioxolane ring. This finding highlights the importance of comprehensive analytical evaluation of drug–excipient interactions during formulation development, as these can affect drug stability and performance.

Multi-class analysis of antimicrobial substances in poultry feed at cross-contamination levels by UHPLC-MS/MS – Method establishment, validation, and application

Elizabeta Dimitrieska Stojkovikj — 2025-12-24

ABSTRACT

The Commission Delegated Regulation (EU) 2024/1229 establishes maximum limits (MLs) for the cross-contamination of antimicrobial substances in feed intended for food-producing animals. This study presents the development and in-house validation of two multi-class analytical methods for detecting antimicrobial substances in poultry feed at cross-contamination levels, using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Methods with and without solid-phase extraction (SPE) purification were developed for 26 antimicrobial substances across eight classes, covering a concentration range of 5–300 µg kg^–1. The established methods were validated for parameters including selectivity, limit of quantification, within- and between-day precision, accuracy, decision limit, matrix effect, and short-term analyte stability in the corresponding extracts. Both methods met the required performance criteria for detecting antimicrobial substances at cross-contamination levels, except for reduced sensitivity to lincomycin in the SPE method. The between-day precision was below 18 % and 19 %, with recoveries ranging from 95 to 103 %, for the method without SPE, and from 88 % to 101 % for the method with SPE, respectively. The analytes remained stable after two days of storage in the dark under two temperature regimes. These methods were applied to 39 poultry feed samples, revealing that approximately 41 % contained one or more antimicrobial substances, some of which exceeded the cross-contamination MLs. This study underscores the importance of simple, rapid, sensitive, and reliable analytical methods for controlling the presence of antimicrobials at cross-contamination levels. Such methods enable stringent control to prevent uncontrolled antimicrobial use in poultry production systems, thereby mitigating the development of antimicrobial resistance.

16th Students’ Congress of the Society of Chemists and Technologists of Macedonia

Marija Prosheva — 2025-12-31

On October 27–28, 2025, the 16^th Students' Congress of the Society of Chemists and Technologists of Macedonia (SCTM) was successfully held at the Faculty of Technology and Metallurgy in Skopje.

Another outstanding achievement of the Macedonian chemistry team at the International Chemistry Olympiad

Miha Bukleski — 2025-12-31

Each year, the Macedonian chemistry team continues to reach new heights at the International Chemistry Olympiads.^1-8 This year marks a historic milestone: for the first time since Macedonia began participating at the International Mendeleev Chemistry Olympiad (IMChO), the team won two bronze medals. At the same time, the team achieved its best-ever results at the International Chemistry Olympiad (IChO), securing one silver medal, one bronze medal, and one honorable mention.

Even more remarkable was the performance of Mario Vančoski in the practical part of the IChO exam. His outstanding result placed him third overall in this segment, highlighting his exceptional experimental skills and placing Macedonia among the respected participants.

„Ноември – Месец на науката 2025“ – Институт за хемија

Пеце Шеровски — 2025-12-31

Ова година, по шести пат, успешно беше реализирана манифестацијата „Ноември – месец на науката“, во организација на Сојузот на хемичарите и технолозите на Македонија како координатор, со поддршка од Македонското биолошко друштво, Сојузот на математичарите на Македонија, Македонското географско друштво, Македонското еколошко друштво, Македонското и Скопското астрономско друштво, како и Природно-математичкиот факултет.
Настанот се одржа на Институтот за хемија при Природно-математичкиот факултет во Скопје и понуди богата програма составена од научно-популарни предавања, демонстрации од страна на учениците, „Хемиски спектакл“, работилници од областа на природните науки и математиката, како и презентации на наставници посветени на размена на искуства и идеи за унапредување на наставата.

Jean-Jacques Aaron

Zoran Zdravkovski — 2025-12-31

Jean-Jacques Aaron

Fontainebleau, 1939 – Skopje, 2025

Fabrication and characterization of electrospun PLA/tuff composite membranes as potential eco-friendly metal adsorbents

Aleksandra Ivanoska-Dacikj — 2025-12-24

In this study, electrospinning was successfully employed to fabricate membranes based on polylactic acid (PLA), a polymer known for its biodegradability, containing varying amounts of opalized tuff (0, 2, 5, and 10 wt%). The addition of tuff introduced active mineral sites within the fibrous network, while the PLA matrix ensured mechanical stability, environmental sustainability, and prevention of secondary pollution. The electrospun membranes exhibited a uniform fibrous morphology with well-developed surface porosity, as confirmed by scanning electron microscopy. X-ray powder diffraction and Fourier-transform infrared spectroscopy verified the preservation of the characteristic structural features of both PLA and tuff, indicating successful incorporation of the filler without chemical alteration of the polymer matrix. Scanning electron microscopy combined with energy dispersive X-ray spectroscopy analysis demonstrated effective adsorption of nickel (Ni²⁺) and lead (Pb²⁺) ions from aqueous solutions, attributed to the high surface activity of the silicate mineral phase. These findings highlight the synergistic combination of a renewable, environmentally friendly polymer and a naturally occurring mineral filler to produce efficient and eco-friendly adsorptive membranes for heavy metal removal from aqueous solution.

Open circuit potentials in biofilms: Biotransformation kinetics governs the dynamics under anaerobic conditions

Ljupcho Pejov — 2025-12-24

This study proposes a generalized model describing the temporal changes in open-circuit potentials in microbial biofilm systems. Using an Nernstian equilibrium approach combined with a series of different kinetic models for each experimental stage, it examines nutrient oxidation by microbes under anaerobic conditions with a continuous supply. New functions are derived to fit the experimental data and to provide in-depth understanding of the complex bioelectrochemical transformations occurring during the oxidation of nutrients by a biofilm.

Biochemical insights into cannabidiol–endocannabinoid system interactions in the regulation of metabolic pathways

Elona Xhemaili — 2026-03-27

Cannabidiol (CBD), a non-psychoactive phytocannabinoid from Cannabis sativa, has emerged as an important compound of interest in biochemical and pharmaceutical research. Its molecular activity is closely linked to the endocannabinoid system (ECS), which plays a central role in the regulation of metabolic homeostasis. Dysregulation of the ECS has been associated with insulin resistance, lipid imbalance, obesity, and increased cardiovascular risk. This review summarizes the current biochemical evidence on the mechanisms by which CBD modulates metabolic pathways through interactions with cannabinoid receptors and related molecular targets. Special emphasis is placed on the antioxidant and anti-inflammatory properties of CBD, its capacity to influence mitochondrial function, and its impact on glucose and lipid metabolism. Furthermore, this review discusses the influence of physicochemical factors, such as bioavailability and route of administration, on the pharmacokinetic and pharmacodynamic behavior of CBD. Potential interactions with other biomolecules and therapeutic agents are also considered, highlighting the need for systematic biochemical and pharmacological evaluation. Overall, the synthesis of the available literature indicates that CBD is a promising candidate for further biochemical and preclinical studies aimed at elucidating its regulatory role in metabolic processes and its potential for the development of novel therapeutic strategies.

Design, synthesis, and biological evaluation of novel water-soluble quinoline-based conjugates with antioxidant, antimicrobial, and DNA-binding activities

Ayşegül Gümüş — 2025-12-24

Considering the extremely valuable biological and pharmaceutical properties of quinolines, novel water-soluble quinoline-based conjugates were designed and synthesized. In vitro antioxidant activities, such as free radical scavenging, metal chelating, and reducing-power activities, of the newly synthesized compounds (WQ-1, WQ-2, WQ-3, WQ-4, and WQ-5) were determined. Although the highest scavenging activity (41.21 ± 1.18%) and chelating activity (23.53 ± 0.97%) at a concentration of 500.0 µg/ml were observed in WQ-4, it was determined that WQ-5 had the highest reducing-power ability (0.417 ± 0.0116). The synthesized compounds were also tested for their antimicrobial activities against two Gram-positive and two Gram-negative bacteria, and it was determined that only WQ-3 showed low activity against Enterococcus hirae and Staphylococcus aureus. DNA-binding activities of the compounds were also studied using calf thymus DNA (CT-DNA). Additionally, the three-dimensional geometries and some electronic properties of the synthesized compounds were investigated with the density functional theory approach at B3LYP/6-31++G(d,p) level of theory.

Preparation, characterization, adsorption, and antibacterial assessments of silane-functionalized zeolites

Jelena Dimitrijević — 2025-12-24

In this study, the preparation and comparative analysis of two adsorbents based on silane-modified natural and synthetic zeolites for binding silver ions from aqueous solutions and evaluating their potential application as antibacterial agents against two strains of bacteria were conducted. (3-aminopropyl)triethoxysilane (APTES) was used for modification, and its presence in the resulting samples was confirmed by thermal analysis, BET surface area measurements, and infrared spectroscopy. Kinetic analysis showed that the silver adsorption process followed the Lagergren pseudo-second-order model, while the data were best described by the Freundlich isotherm, indicating multilayer adsorption on a heterogeneous surface. The maximum adsorption capacities for silver ions were 89.49 mg/g for natural zeolite and 61.19 mg/g for synthetic Beta zeolite. Natural zeolite exhibited a higher silver-binding capacity, leading to the conclusion that exchangeable cations in the structure of the starting material played a key role in silver binding and that ion exchange was the dominant mechanism. Both materials demonstrated good antibacterial properties against gram-negative Escherichia coli and the gram-positive Staphylococcus aureus. These findings highlighted the potential of APTES-modified zeolites as efficient adsorbents for silver ion removal and as antibacterial agents, paving the way for applications in water purification and antimicrobial technologies.

Dual role of lignin in waterborne polymer composites: Reinforcement and stimuli-triggered degradation

Marija Proševa — 2025-12-24

Improving the sustainability of polymer composites is a pressing priority, particularly in reducing reliance on fossil-derived components and minimizing environmental impact during synthesis. Lignin, an abundant and renewable natural polymer, offers significant potential as a bio-based additive due to its aromatic structure and intrinsic functionality. Conventional methods for incorporating lignin into polymer matrices often rely on non-sustainable, solvent-based routes, leading to poor dispersion and aggregate formation due to lignin’s incompatibility with polymers. This study presents a more sustainable approach using waterborne, in-situ semicontinuous miniemulsion polymerization to integrate lignin (0.5–1 wt%) into (meth)acrylic matrices. The resulting composite films, formed via water evaporation, exhibited enhanced UV and visible light absorption, improved mechanical strength, particularly at 1 wt% lignin and increased thermal stability even at low loadings. Despite lignin’s hydrophilicity, the composites demonstrated reduced water permeability. UV degradation studies showed that lignin’s chromophoric groups generate free radicals under UV exposure, triggering controlled photodegradation of both lignin and polymer phases. This controlled breakdown combined with the composite’s enhanced structural integrity highlights lignin’s dual function: reinforcing the material under standard conditions while enabling degradation under specific environmental stimuli.

Electrochemical and structural evaluation of CoFeNiOx-based catalysts for water splitting applications

Yasir Hashmi — 2025-12-24

We report trimetallic cobalt-iron-nickel oxide (CoFeNiO_x) electrocatalysts prepared by a hydrothermal route followed by thermal annealing and post-synthesis alkaline activation (sodium hydroxide [NaOH]/potassium hydroxide [KOH]/urea). By tuning the Co:Fe:Ni molar ratio (1:1:1, 1:3:1, and 3:1:1), we correlate phase composition and morphology with electrocatalytic water splitting performance. X-ray powder detraction indicates the coexistence of layered double hydroxide–derived motifs with spinel-type oxides, while scanning and transmission electron microscopy reveal increased roughness and porosity in Co-rich samples after KOH/urea treatment. In 1 M KOH, the CoFeNiO_x (1:1:1) electrocatalyst exhibits the most favorable oxygen evolution reaction activity (η10 = 264 mV; Tafel slope = 84.4 mV dec⁻¹), stable chronopotentiometry at 10 mA cm⁻² for 24 h with a ~40 mV increase in overpotential, and low charge transfer resistance based on electrochemical impedance spectroscopy. The CoFeNiOx (3:1:1) electrocatalyst delivers the best hydrogen evolution reaction response among the tested electrocatalysts. X-ray photoelectron spectroscopy confirms mixed valence states with enrichment of trivalent species (Co³⁺/Co²⁺, Ni³⁺/Ni²⁺, Fe³⁺/Fe²⁺) on the surface, consistent with the formation of catalytically active oxyhydroxide layers under alkaline conditions. Overall, controlled composition coupled with urea‑assisted alkaline activation enhances the exposure of active sites exposure and charge transport, enabling the production of bifunctional CoFeNiO_x electrocatalysts that are suitable for integrated water‑splitting systems.

Simulation-based strategy to distinguish between EC (reversible) and EC (dimerization) mechanisms in square-wave voltammetry

Pavlinka Kokoskarova — 2025-12-24

Square-wave voltammetry (SWV) is a highly sensitive and widely utilized electrochemical technique suitable of probing the kinetics of various electrochemical electrode processes coupled with different chemical reactions. However, its application to electrode mechanisms involving subsequent chemical steps is somewhat limited, particularly in scenarios such as those discussed in recent work [1]. Among the electrochemical mechanisms coupled with chemical reactions, the EC-type pathways, where an electron transfer step is followed by a reversible chemical transformation, remains fundamental for elucidating interfacial reaction dynamics. A significant variant of this mechanism is the EC(dimerization) model. This mechanism features a reversible bimolecular chemical step in which two oxidized species (2Ox ⇌ Ox–Ox) get in reversible dimerization, while introducing second-order kinetics into the entire electrode reaction. Although mechanistically distinct, these two pathways often yield similar voltammetric signatures, making them difficult to distinguish under certain experimental conditions. This challenge is further complicated by the fact that frequency modulation, a commonly used diagnostic tool in SWV, simultaneously influences both the electron transfer kinetics and the chemical reaction rate, thus diminishing its discriminatory power. In this work, we examine the key voltammetric features of both mechanisms under SWV conditions and propose theoretical strategies to differentiate them. Emphasis is placed on the use of numerical simulations as a robust and reliable approach for resolving mechanistic ambiguity.

From theory to simulation: Open interactive MATHCAD simulation protocols for exploring common electrode mechanisms in cyclic voltammetry

Rubin Gulaboski — 2025-12-24

Cyclic voltammetry is considered as one of the most important techniques in electrochemistry, widely applied to investigate mainly mechanistic aspects, but also kinetics and thermodynamics of various redox processes. Many biochemical transformations in living systems involve electron transfer steps coupled with preceding, follow-up or regenerative chemical reactions, commonly assigned in electrochemistry as CE, EC, and EC′ mechanisms, respectively. Accurately simulating such processes is essential for understanding their behavior and for interpreting experimental voltammetric data. Despite extensive theoretical works available in the literature, freely accessible computational tools for simulating these mechanisms are scarce, thus limiting their use in both teaching and research contexts. This work introduces a set of ready-to-use simulation files developed in software package MATHCAD, designed to model cyclic staircase voltammograms for diffusional CE, EC, and EC′ mechanisms under the Butler-Volmer kinetic formalism. The protocols provided define and explain all relevant physical constants, potential waveform parameters, and dimensionless kinetic and thermodynamic variables required to define recurrent formulas for currents calculation. The approach also highlights the diagnostic value of analyzing relevant features of cyclic voltammograms to recognize particular mechanism from simulated voltammetric patterns. By making these simulation files freely available, the platform offers students and all electrochemists an interactive and intuitive learning tool, while providing experienced scientists with a useful theoretical platform for their experiments. This mainly educational work brings theoretical electrochemistry closer to all electrochemists, while enabling better mechanistic understanding of some of the most important electrode processes.

Quality-based design and stability assessment of sodium 18F-fluoride radiopharmaceutical for PET imaging

Marija Atanasova Lazareva — 2025-12-24

This study presents the results of the stability assessment conducted on three production batches of sodium ¹⁸F-fluoride radiopharmaceutical intended for intravenous injection. The objective was to evaluate the physicochemical and microbiological stability, establish an appropriate shelf life, and confirm the overall quality of this radiopharmaceutical over a defined period under controlled storage conditions.

The stability study was designed to assess the quality of in-house produced sodium ¹⁸F-fluoride radiopharmaceutical, with quality control tests performed at two-hour intervals. All pre-release and post-release tests established in the [¹⁸F]NaF specification were examined, including appearance, identification, pH, chemical, radiochemical, radionuclide purity, bacterial endotoxins, and sterility. The results of pH, chemical, radiochemical, and radionuclide purity met the acceptance criteria for all tested points across the three batches, demonstrating the physicochemical stability of the preparation. Microbiological stability was also proved through compliance with bacterial endotoxins and sterility requirements.

Overall, the obtained results confirmed that sodium ¹⁸F-fluoride is stable for up to 10 hours after the end of synthesis, ensuring its suitability for clinical use.

Green extraction of methylxanthine derivatives from food and beverages using deep eutectic solvents and in silico studies of neuroprotective potential

Nevena Grujić-Letić — 2025-12-24

In the food and pharmaceutical industries, green technologies refer to the use of methods and materials that do not negatively impact the environment and offer safety advantages. The aim of this paper is to extract methylxanthine derivatives from food and beverage samples using ultrasound-assisted deep eutectic solvent extraction (UAE-DES), ultrasound (UAE), and microwave-assisted extraction (MAE), and traditional extraction with chloroform. A chemometric tool was applied for data analysis and molecular docking was used to predict neuroprotective potential. The high-performance liquid chromatography (HPLC) method was employed for methylxanthines determination. The results showed that green approaches effectively extracted theobromine (1,3-dimethylxanthine) and caffeine (1,3,7-trimethylxanthine) from food and beverages, with UAE-DES emerging as the most effective technique. Caffeine's high binding energy (–6.7 kcal/mol) against the adenosine receptor (A2A) observed by molecular docking suggested that it may have neuroprotective effects and could be used in multiple fields with promising future development possibilities. According to the results, the application of DESs as high dissolving, low cost, and environmental-friendly solvents has significant potential in the pharmaceutical and food industry.