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. Design, syntheses, and in vitro evaluation of new fluorine-18 radiolabeled Tau-labeling molecular probes [J. Med. Chem. 2017, 60, 8741] is a step forward from FDDNP [Proc. Natl. Acad. Sci. USA 2012, 109, 16492]. Combining [arene-Ru] with azocarboxamids generates complexes with cytotoxic properties [Chem. – Eur. J. 2014, 20, 17296]. 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].
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].