Unraveling the Mysteries of Science
Research in the Košmrlj's group lies at the interface of organic, inorganic, coordination and medicinal chemistry. It is focused on the discovery and application of new reactions and synthetic methodologies, both towards the synthesis of bioactive compounds and organic materials, and includes the study of organic reactions.
Understanding Reaction Mechanisms
Understanding reaction mechanisms is a cornerstone in chemical science. It allows the rational design of reaction conditions, improving the scope and the yields of the products, cutting down on starting materials cost, and reducing problematic wastes.
We have discovered a novel reaction mechanism for the palladium-catalysed alkynylation of aryl halides, known as the copper-free Sonogashira reaction [Nature Communications 2018, 9, 4814].
Higher Homologues of Water
Hydrogen polyoxides (HOnH, n=3,4) may be regarded as higher homologues of water, hydrogen peroxide (HOOH), alkyl hydroperoxides (ROOH), and dialkyl peroxides (ROOR). These species are believed to be key intermediates in low-temperature oxidations, atmospheric and environmental chemistry, and in normal and pathological processes in the living organisms [Polyoxides; Acta. Chim. Slov. 2005, 52, 1]. Dihydrogen trioxide (HOOOH), the simplest of polyoxides, was unambiguously identified only recently (17O NMR, IR, Raman, and MW spectroscopy) [Chem. Rev. 2013, 113, 7930], and a simple and an efficient method for the preparation of pure solutions of HOOOH was developed [Angew. Chem. Int. Ed. 2015, 54, 9917], to be more accessible to a wider audience of researchers.
Ligands and Beyond
Ligands of click triazole [Inorg. Chem. 2010, 49, 4820] and azocarboxamide [Synlett 2009, 2217] structures have been developed. An efficient synthesis of pyridine tagged triazolium salts [Org. Lett. 2013, 15, 5084] enabled development of Pd–NHC (N-heterocyclic carbene) from an iPEPPSI (internal-pyridine-enhanced precatalyst preparation, stabilization, and initiation) series with remarkable catalytic activities in copper free Sonogashira reaction in water [Chem. Commun. 2016, 52, 1571]. Versatile coordination of azocarboxamides enables redox-triggered change of the binding chelate in ruthenium complexes [Chem. Eur. J. 2018, 24, 18020].
Chemistry for Health
We are strongly focused at developing new molecules of biological relevance. Combining [arene-Ru] with azocarboxamids generates complexes with cytotoxic properties [Chem. – Eur. J. 2014, 20, 17296]. Iridium and osmium complexes of pyridyl-mesoionic carbenes exhibited high toxicity against tumor cell lines and preferentially killed cancer over normal cells [Organometallics 2019, 38, 4082–4092]. Diaryltriazenes possess antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA), Mycobacterium smegmatis [Eur. J. Med. Chem. 2017, 127, 223], and Mycobacterium tuberculosis [Chem. Biol. Drug Des. 2018, 91, 631]. Additionally, we are involved in the development and modification of new organic molecules and synthetic chemistry procedures that comply with requirements of radiochemical laboratory set-up, which would in turn expand the possibilities for the synthesis of radiotracers used in disease diagnostics [Curr. Med. Chem. 2020, 27, 501–522; Chem. Commun. 2018, 54, 4398].
Let’s not forget Alzheimer
Rising problem of Alzheimer's disease urged us to dedicate a part of our research to finding new ingenious ways of early detection of the disease and to ameliorate the disease progression, using small organic molecules [J. Alzheimers Dis. 2020, 77, 99–112]. Decades of research have borne fruits in the fields of fluorescent and azo dye synthesis [Tet. Lett. 2014, 55, 1218–1221; Molecules 2016, 21, 267; Dyes and Pigments 2021,184, 108726] that could be used in ex vivo detection of disease-specific protein aggregates by fluorescence microscopy or undergo radiolabeling with positron-emitting fluorine-18 isotope for the use in in vivo Positron Emission Tomography Imaging [Proc. Natl. Acad. Sci. USA 2012, 109, 16492; J. Med. Chem. 2017, 60, 8741].
Connecting with Industry
As one of the ultimate goals of our research endeavour is a transfer of knowledge from academia to industry, as well as the other way around, long-standing partnerships with a broad range of chemical companies have been developed. Many applicative-research projects have been successfully executed including development of a completely stereocontrolled aldol reaction of β-amino acid derivatives [Org. Lett. 2015, 17, 512], the first synthesis of efavirenz cyclobutenylindole analogue USP impuity [J. Org. Chem. 2018, 83, 2486], and development of a novel and sustainable approach for the preparation of Rosuvastatin [J. Org. Chem. 2010, 75, 6681; WO2010086438A1; US20120022091A1; JP5558492B2].