Thermodynamic elucidation and prediction of chemical synergism in complex chemical processes

Summary of the activity and results obtained in 2024

The goal of this project is to investigate synergism in complex chemical processes through a rigorous thermodynamic approach, with applications in chemistry, biochemistry, and the pharmaceutical, medical, and chemical industries. The research focuses on elucidating synergistic interactions, identifying conditions that favor or inhibit this phenomenon, and promoting synergistic mixtures as sustainable alternatives to costly individual reactants. By deepening the understanding of synergism and antagonism phenomena, the project aims to develop efficient chemical processes with a reduced environmental impact.

A comprehensive methodology has been developed, based on standard thermodynamic data, mass balance equations, and experimental observations, to evaluate the conditions under which synergism and antagonism manifest during extraction processes. Theoretical and experimental studies targeted well-documented systems, such as Zn²⁺-thenoyltrifluoroacetone-TBP, providing detailed insights into the distribution of chemical species between the aqueous and organic (benzene) phases as a function of pH, temperature, and chemical composition. The analysis of these systems allowed for the definition of a synergism index (SI) to quantify the phenomenon and identify the conditions triggering the transition from synergism to antagonism.

Advanced thermodynamic calculations and theoretical simulations provided an in-depth understanding of the behavior of selected systems, validating the proposed methodology through the correlation of results with experimental data from the literature. The findings offer a robust foundation for predicting synergism and antagonism phenomena under various experimental conditions, such as the chemical composition and pH of heterogeneous liquid-liquid systems.

The applicability of the results spans multiple fields:

1. Optimization of industrial processes – The use of synergistic mixtures can significantly reduce production costs and increase the efficiency of chemical processes.
2. Development of new reagents and products – Chemical synergism offers a viable alternative to expensive reactants, fostering innovation in the pharmaceutical and chemical industries.
3. Sustainability – Reducing resource consumption and environmental impact through the use of synergistic mixtures instead of less efficient conventional processes.

The project also included dissemination of the results at three international conferences: MARBLUE 2024 (Constanța, Romania), IasiCHEM 2024 (Iași, Romania), and SIMI 2024 (Constanța, Romania) and one national conference with international participation (Tiraspol 2024). Participation in these events facilitated the exchange of ideas and collaborations with experts in the field, advancing research in chemical synergism.

By applying this methodology, the project findings provide an innovative framework for the design and implementation of sustainable chemical processes with significant implications in analytical chemistry, pharmaceuticals, biochemistry, and synthetic organic chemistry. These contributions support the development of a sustainable model for resource utilization and environmental impact reduction, addressing current challenges in chemical and industrial research.

Summary of the activity and results obtained in 2025

The aim of the project was to investigate chemical synergism in complex chemical processes through a rigorous thermodynamic approach, with applications in chemistry, biochemistry, environmental science, and the pharmaceutical and medical fields. The research focused on elucidating the mechanisms of synergistic and antagonistic interactions, identifying the conditions that promote or inhibit these effects, and promoting synergistic mixtures as sustainable alternatives to costly individual reagents. By developing predictive models, the project sought to optimize chemical processes while reducing environmental impact.

The central element of the methodology was the introduction of the synergistic coefficient (SC), a quantitative thermodynamic parameter that enables the clear identification, comparison, and direct quantification of synergistic and antagonistic effects. The coefficient describes changes in system stability upon the addition of an auxiliary ligand in the presence of a primary ligand and provides a numerical evaluation of how pH, chemical composition, concentrations, and complex stability influence solubility and phase equilibria. The definition of SC represents an original conceptual contribution, as synergism had previously been described mainly in qualitative or indirect terms.

The methodology was successfully validated in three major application areas. In liquid–liquid metal extraction, thermodynamic modeling enabled prediction of the pH and composition domains where synergism or antagonism occurs and supported rational optimization of extractant combinations, demonstrated on model systems such as Zn²⁺–chelating ligand–TBP. In iron-containing mineral systems, it was shown that siderophores combined with auxiliary ligands (oxalate, phenanthrolines, and sulfonated derivatives) induce strong synergistic dissolution of minerals such as goethite, hematite, and ferrihydrite, with important implications for metal mobility, soil fertility, and environmental remediation. In the pharmaceutical field, studies of “drug–cyclodextrin–auxiliary ligand” systems demonstrated that ternary complex formation significantly enhances the solubility of poorly soluble drugs, enabling rational formulation design and reducing experimental development costs.

Overall, the project outcomes provided a unified, predictive, and transferable theoretical framework with interdisciplinary applicability, contributing to the development of more efficient, sustainable, and competitive chemical technologies.