Projects / Programmes
Organic Chemistry: Synthesis, Structure, and Application
January 1, 2022
- December 31, 2027
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| Code |
Science |
Field |
| 1.04 |
Natural Sciences |
Chemical sciences |
Organic chemistry; synthesis; structure; catalysis, mechanism; green chemistry; ligand; organometallic chemistry; coordinate chemistry; hydrogen trioxide; functional group conversion; oxidation, reduction, cross-coupling reaction; molecular probe, fluorescence, neurodegenerative diseases.
Data for the last 5 years (citations for the last 10 years) on
April 25, 2024;
A3 for period
2018-2022
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
467 |
11,168 |
8,839 |
18.93 |
| Scopus |
437 |
11,721 |
9,561 |
21.88 |
Researchers (26)
Organisations (1)
Abstract
Presented research program lies at the intersection of organic, inorganic, coordinative, pharmaceutical and medicinal chemistry. It focuses on the discovery and application of new, more efficient and sustainable reactions and synthetic methods for new catalysts, bioactive compounds and organic materials. Another important focus of our program is the study of mechanisms of chemical reactions. Understanding reaction mechanisms is a cornerstone in chemical science, enabling rational design of reaction conditions, improving the scope and yields of products, lowering the cost of starting materials, and reducing problematic wastes. There are three major research themes within the program, i.e. mechanistic insight, synthesis and catalysis, and practical application. Mechanistic insight will address fundamental mechanistic questions about fully catalytic cross-coupling reactions by studying stoichiometric transmetallation reactions. New insights will help improve existing methods and lead to new approaches. We also aim to extend our recent discovery of the catalytic palladium-palladium system to other metal-metal compounds. The knowledge gained will support the pursuit of our other research interests, including the isolation of highly reactive and unstable intermediate species, such as hydrogen trioxide (HOOOH) and its derivatives. Here we will seek to identify the solid-state structures of hydrotrioxides to reveal the properties of -OOOH functionality. In the context of synthetic chemistry, we will continue developing synthetic methods by replacing harmful reagents and solvents with environmentally friendly substances to meet safety, waste minimization, reaction design and cost efficiency. We intend to develop green and selective methods for a range of organic reactions, including oxidation, halogenation, and chalcogenation. Green chemistry is often enabled by catalysis; therefore, one of our main goals is to develop homogeneous catalytic systems based on organometallic catalysts that are more efficient than those used in industry today. Based on our recent discovery of the PyMIC ligand (PyMIC = pyridine appended triazole-based N-heterocyclic carbene of a mesoionic (MIC) structure), we will design novel ligands to build advanced catalysts suitable to address the most difficult challenges in catalysis. The combined knowledge from the above topics will help us to tackle several applied projects. One of these involves the design, synthesis and evaluation of novel fluorescent molecular probes that bind specifically to various Alzheimer's biomarkers with high affinity and may be able to translate subtle changes in their environment to their optical properties. This will potentially help in the development of ex vivo prognostic and diagnostic tools for the early detection of Alzheimer's disease.
Significance for science
Chemical synthesis and the resulting availability of synthetic compounds has brought untold benefits to society in every aspect of our existence. The challenge of synthesis today, however, is not whether a molecule can be made, but whether it can be made in a practical way, and which molecules deserve synthesis. Our research programme is driven by this challenge. It lies at the interface of organic, inorganic, coordination, pharmaceutical and medicinal chemistry. It focuses on the discovery and application of new, more efficient and sustainable reactions and synthetic methods, both for the synthesis of catalysts, bioactive compounds and organic materials. This includes the study of chemical reaction mechanisms, as understanding reaction mechanisms is a cornerstone of chemical science, enabling the rational design of reaction conditions, improving the scope and yields of products, reducing the cost of starting materials and reducing problematic wastes. There are three major research themes within the programme, i.e., mechanistic insight, synthesis and catalysis, and practical application. Mechanistic insights are crucial to the fundamental understanding of chemical processes and thus elementary to their discovery, rational design, and optimization. Recently, we have addressed critical mechanistic questions of various reactions, including classical, (organo)catalytic, redox-triggered, and cross-coupling reactions. We have elucidated the mechanism of the copper-free Sonogashira reaction, which had been unsolved for nearly five decades. Our research also addresses the challenge of isolating highly reactive and unstable intermediate species, such as hydrogen trioxide (HOOOH) and its derivatives. These are ubiquitous in oxidation reactions and are gaining interest in the scientific community as key intermediates in many chemical, biochemical, atmospheric, and environmental processes. Many fundamental mechanistic questions about these compounds remain unanswered and are addressed here. In the field of cross-coupling reactions, our goal is to extend the chemistry to other metal-metal manifolds, possibly leading to the discovery of new reactions, similar to our recent discovery of the palladium-palladium catalytic system. Steadily advancing experimental techniques (spectroscopy, electrochemistry, X-ray analysis) and a growing arsenal of modern theoretical methods (e.g. DFT) will provide us with unprecedented tools to explore short-lived, sensitive, and highly reactive intermediates and to solve the mechanistic puzzles associated with them. Mechanistic insights will bring advances in synthesis and catalysis. Green chemistry, as one of the most important directions to make chemistry healthier and more environmentally friendly, with the goal of nature-based and sustainable development, will be a focus here. The major challenges are replacing volatile organic solvents and harmful reagents with friendlier alternatives. Our recent contributions in this area include conversion of thiols to sulfonyl halides using atmospheric oxygen as a terminal oxidant, oxidations of neat sulfides to sulfones using hydrogen peroxide solution under solvent- and catalyst-free conditions, and reduction of neat sulfoxides to sulfides without organic solvent. In this research program, we will continue to replace harmful reagents and hazardous, flammable and explosive volatile organic solvents, with more sustainable substances to meet safety, waste minimization, reaction design and cost efficiency. Similarly, cost efficiency can be achieved through catalysis. It is not surprising that catalysis is now involved in the production of over 80% of the chemicals we encounter in our daily lives and is associated with about 30% of the total GDP of European economies. For homogeneous catalysis, we have recently developed advanced N-heterocyclic carbenes (NHCs) based on pyridine-appended triazoles with mesoionic (MIC) structure (PyMIC), which possess metal-stabilising properties superior to those of other ligands. PyMICs, which belong to a new class of SMART (Switchable, Multifunctional, Adaptable, oR Tuneable) ligands, have allowed us to develop highly active transition metal catalysts. These include Ru-, Os-, and Ir-based catalysts for selective oxidations and reductions, as well as Pd complexes for Suzuki-Miyaura and Sonogashira cross-couplings that functions in pure water as a solvent and in the presence of air. The Pd-PyMIC complex exhibits enzyme-like behaviour in the catalytic hydroamination of alkynes. The unique properties of the metal-PyMIC have potential for other catalytic reactions and will be the focus of this part of the project. It will pave the way to even more advanced architectures suitable to overcome the most difficult challenges in catalysis. One of our advanced research topics connected to practical applications addresses development of molecular probes for the early detection of Alzheimer disease. Alzheimer disease, as one of the leading problems of modern medicine, affects the lives of patients and their families and strains national health budgets worldwide. We have contributed to this field by developing the radiotracer [18F]FDDNP for in vivo positron emission tomography (PET) imaging of pathological protein aggregates. However, routine screening of at-risk populations using PET and similar techniques is severely limited due to the extremely expensive specialized infrastructure required and the health risks to patients, including radiation exposure. We intend to use the latest insights into the disease mechanism to develop smart molecular probes for blood-based prediction of Alzheimer's disease based on the detection of specific biomarkers in blood or cerebrospinal fluid. This will provide an alternative to in vivo imaging techniques and promote early diagnosis and potentially aid the discovery of new treatments.
Significance for the country
Chemistry is of extremely high socio-economic importance in the Slovenian chemical and especially pharmaceutical industry. The development of new knowledge, including new techniques, methods, catalysts, intermediates and useful compounds, is central to the sustainable development of the research-based chemical industry and thus modern society. In this context, the contribution of our program group, whose achievement of scientific excellence is one of the main objectives, can be seen in many areas. These include the development of new knowledge, the establishment of a broad network of collaborations with domestic and foreign institutions, the transfer of knowledge from academia to industry and vice versa, and the generation of highly qualified young scientists. We achieve the development of new knowledge through our own creative work and in fruitful formal and informal collaboration with experts, scientists, research groups and institutions from at least 14 countries around the world (Austria, Belgium, Czech Republic, Chile, Croatia, Italy, Japan, Latvia, Germany, Romania, Vietnam, Spain, USA, UK), as well as with researchers from several domestic academic and research institutions (UL, Faculty of Pharmacy; UL, Faculty of Medicine; UL, Faculty of Computer and Information Sciences; Jožef Stefan Institute; National Institute of Chemistry; National Forensic Laboratory, Slovenian National Building and Civil Engineering Institute) and industrial institutions and companies (Krka, Belinka Perkemija, Helios, Lek, Sandoz Slovenia, Sandoz Austria, Novartis, Eustone, Cinkarna, Isomerlab). A broad network of cooperation, which is an important feature of the proposed program in the future, will contribute to the promotion and consolidation of Slovenian national identity in the world. A wide network of connections with scientific and industrial partners at home and abroad provides a positive and highly stimulating environment for the scientific growth of our students, young researchers and young doctors. Through various mechanisms, we promote and facilitate international exchange of students and researchers from Slovenia to the international space and vice versa. These mechanisms include bilateral projects, Erasmus exchanges, etc. After graduation, our students are usually employed in the Slovenian chemical and pharmaceutical industry, where they are highly appreciated. Among others, the recognition of our students in the Slovenian pharmaceutical industry is reflected in the exceptional number of awards for diploma, master and doctoral theses. Recently, our students have received 19 different Krka awards. We also promote Slovenia, as an important socio-economic element, through membership in editorial boards of journals, organization and active participation in domestic and international scientific conferences in the form of lectures and posters, and most importantly, publication of scientific research results in patent applications, patents and domestic and international scientific journals. Open access and promotion of publications on the front pages of journals are important for dissemination of results. Recently, our articles have been highlighted by journal editors with images on journal covers 13 times. Several articles were among the most read after publication. Contributing to the popularization of science is the communication of results through interviews on radio and television programs, as well as via the Internet and digitally related technologies, including the group's website (https://www.kosmrlj-group.com/) and social media profiles (https: //twitter.com/KosmrljGroup, https://www.facebook.com/kosmrljgroup). Through our work, we make an important contribution to the protection and preservation of human health and nature. Recently, we have actively participated in an European project led by National Forensic Laboratory (NFL), Republic of Slovenia, Ministry of the Interior, by identifying illicit psychoactive substances using nuclear magnetic resonance (NMR) and other chemical and spectroscopic techniques. We have also signed collaborative agreements with the NFL for the future. In cooperation with the Jožef Stefan Institute, we contributed our knowledge to the analysis and removal of chemical pollutants in the Slovenian aquatic environment. The results of our research represent a contribution to the fight against cancer and bacteria. We participate in the development of industrially important reactions (green catalysis, peroxide chemistry, etc.) and products (e.g. rosuvastatin, developed in collaboration with Lek/Sandoz, analytical standards, etc.). We are intensively involved in the discovery of tools for early detection and diagnosis of Alzheimer disease. In the past, we have developed radioactively labelled tracers for in vivo detection by positron emission tomography (PET), and in the future we will focus on the development of fluorescent probes for ex vivo diagnostics based on the detection of Alzheimer disease-specific biomarkers in body fluids, such as blood or cerebrospinal fluid. Alzheimer disease is emerging as one of the leading problems in modern medicine and, through increasing life span and medical attention costs, represents one of the biggest pending socio-economic problem in healthcare for the world.
