Department of Organic Chemistry

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in Czech language )
Supervisor:	prof. Ing. Pavel Lhoták, CSc.

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The aim of this work is focused on the design and synthesis of higher calixarene analogues (with five or more phenolic subunits) that could be applied as receptors for fullerene recognition. The aim of this work is to achieve selective complexation of C60 or C70 using suitably chemically modified calixarene skeletons and concave/convex principle of the interactions. Novel compounds will be used as receptors for the complexation of fullerenes and as the building blocks for construction of supramolecular self-assembly systems.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in Czech language )
Supervisor:	prof. Ing. Michal Kohout, Ph.D.

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High performance liquid chromatography (HPLC) is the world’s leading method for separation of chemical mixtures. Despite undoubtful progress in numerous areas of this field in recent years, resolution of polar ionised and ionisable analytes still represents a very challenging task to solve. Moreover, most advancements achieved are of purely academic nature and are not transferred into any actual technology used in practice. The present Ph.D. project covers the full scope of research and development of a new portfolio of brush-type stationary phases bearing ion-exchange selectors intended for both chiral and achiral separations of ionised and ionisable compounds. The candidate is expected to synthesise a new library of cation exchangers (CX), anion exchangers (AX) and zwitterion ion exchangers (ZW) derived from natural precursors (e.g., cinchona alkaloids, amino acids, etc.). The prepared selectors will be immobilised to silica gel solid support and tested as separation media for various sets of analytes (e.g., amino acids, organic acids, basic drugs, short peptides, etc.). In collaboration with our laboratory spinoff - Galochrom s.r.o., the synthesis of the stationary phases with the best separation performance will be scaled-up and marketed as a part of the new generation of Galochrom’s product portfolio. Therefore, a direct industrial impact of the Ph.D. project is expected.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Drugs and Biomaterials ( in Czech language )
Supervisor:	prof. Ing. Michal Kohout, Ph.D.

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High performance liquid chromatography (HPLC) is the world’s leading method for final purification of most active pharmaceutical substances. Despite undoubtful progress in numerous areas of this field in recent years, resolution of polar ionised and ionisable analytes still represents a very challenging task to solve. Moreover, most advancements achieved are of purely academic nature and are not transferred into any actual technology used in practice. The present Ph.D. project covers the full scope of research and development of a new portfolio of brush-type stationary phases bearing ion-exchange selectors intended for both chiral and achiral separations of ionised and ionisable compounds. The candidate is expected to synthesise a new library of cation exchangers (CX), anion exchangers (AX) and zwitterion ion exchangers (ZW) derived from natural precursors (e.g., cinchona alkaloids, amino acids, etc.). The prepared selectors will be immobilised to silica gel solid support and tested as separation media for various sets of analytes (e.g., amino acids, organic acids, basic drugs, short peptides, etc.). In collaboration with our laboratory spinoff - Galochrom s.r.o., the synthesis of the stationary phases with the best separation performance will be scaled-up and marketed as a part of the new generation of Galochrom’s product portfolio. Therefore, a direct industrial impact, particularly on pharmaceutical industry, of the Ph.D. project is expected.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in Czech language )
Supervisor:	prof. Ing. Radek Cibulka, Ph.D.

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The use of excited organic anions as photoredox catalysts offers several advantages as compared to commonly used neutral molecules, particularly in reductive chemistry. This project aims to explore the photophysical and chemical properties of anionic forms of flavin derivatives. Based on the results, new photocatalytic systems using excited flavin anions will be designed with a focus on photoreductions beyond the current scope of photoredox catalysis.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Ing. Markéta Rybáčková, Ph.D.

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Planar chiral [2.2]paracyclophanes featuring rigid structure and chemical stability have been widely applied e.g. in asymmetric synthesis. Aza[2.2]paracyclophanes, also known as pyridinophanes, are quite rare but intriguing compounds with interesting chiroptical properties. They have been employed as enantioselective catalysts. The aim of the work will be the synthesis of novel nucleophilic fluorination reagents bearing a chiral aza[2.2]paracyclophane unit and their application in enantioselective synthesis.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Ing. Markéta Rybáčková, Ph.D.

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Triptycenes are intriguing organic molecules that have found applications in several scientific fields, including supramolecular and materials chemistry, due to their unique properties and rigid framework. Yet, their potential in asymmetric synthesis and catalysis remains to be unveiled. Heterotriptycenes, which contain a heteroarene ring as a part of the bicyclo[2.2.2]octane core, are quite novel class of compounds. The aim of the work will be synthesis of fluorination reagents based on chiral azatriptycene unit and their application in enantioselective synthesis.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	doc. Ing. Tomáš Tobrman, Ph.D.

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: Currently, most multicomponent reactions make use of three or four components. In both cases, the reactions can be catalyzed by transition metal complexes. However, transition-metal-catalyzed multicomponent reactions that use five or more components are rare. Therefore, the aim of this project is to develop new five- and six-component reactions catalyzed by transition metal complexes. The core components will be disubstituted, trisubstituted, and tetrasubstituted alkenes.

Granting Departments:	Department of Organic Chemistry
Study Programme/Specialization:	Chemistry ( in Czech language )
Supervisor:	prof. Ing. Pavel Lhoták, CSc.

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Pillar[n]arenes can be considered relatively new members of the family of phenolic macrocycles. Due to their unique cylindrical shape and electron-rich cavity with adjustable size, pillar[n]arenes have already found many applications in contemporary supramolecular chemistry. To name at least a few such applications, the sensing of various analytes, supramolecular self-assemblies, stimuli-responsive supramolecular polymers and model systems to study various noncovalent interactions can be mentioned. It is well known from the chemistry of calixarenes that the introduction of sulfur instead of common methylene bridges leads to dramatic changes in chemical and supramolecular behaviour of such systems. The aim of this project is the construction of pillararenes and their analogues bearing sulfur as the bridging units and the investigation of these new macrocycles including their characterization, derivatization and the study of supramolecular applications.

Institute of Chemical Process Fundamentals of the CAS, v.v.i.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Chemistry and Chemical Technologies ( in English language )
Supervisor:	Dr. Ing. Vladimír Církva

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Proposal is based on the connection of two scientific disciplines: traditional photochemistry and recently developed microwave chemistry, when the effect of UV/Vis and microwave radiation on the chemical and physical properties of molecules is studied. The required radiation is generated completely atypically directly by the microwave field using so-called electrodeless discharge lamps (EDLs). The aim of the project is basic research in the preparation of EDLs (mercury, sulfur, other metal) and optimization of the effect of microwave and UV/vis radiation on the photocyclization of stilbene derivatives, which can lead to polyaromatics. Required education and skills: • master degree in organic technology or organic chemistry, • experimental skill and practical knowledge of reaction optimization, • team work ability, • employment contract at ICPF.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Dr. Ing. Vladimír Církva

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Proposal is based on the connection of two scientific disciplines: traditional photochemistry and recently developed microwave chemistry, when the effect of UV/Vis and microwave radiation on the chemical and physical properties of molecules is studied. The required radiation is generated completely atypically directly by the microwave field using so-called electrodeless discharge lamps. The aim of the project is basic research and optimization into the influence of microwave radiation on the course of cis-trans photoisomerization and photocyclization of stilbene and o-terphenyl derivatives, leading to phenanthrene, triphenylene, phenacene, helicene analogues or their N- and S-hetero derivatives, which may find application in molecular electronics. Required education and skills: • master degree in organic technology, • experimental skill and practical knowledge of reaction optimization, • team work ability.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Drugs and Biomaterials ( in English language )
Supervisor:	Ing. Tomáš Strašák, Ph.D.

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The project is focused on the application of modular synthesis principles to a preparation of novel dendritic materials with properties tailored for medicinal applications, especially in the field of regenerative medicine. The first stage comprises the synthesis of a library of carbosilane building blocks (dendrons) using silicon atom as a branching point and bearing suitable peripheral functional groups (saccharide ligands, cationic groups, PEGyl chains etc.). These components will then be used for the construction of multifunctional macromolecular compounds with precisely defined dendritic structure. The application of prepared materials to the encapsulation of small molecule drugs, complexation of therapeutically active proteins and growth factors, and physically-chemical characterization of these systems will be an inherent part of the work, with emphasis on suitable pharmacokinetic and cytotoxic behavior. The work is a part of the research project supported from OP JAK fund; within this project the student will closely collaborate with external partners on the application of the prepared materials. Required education and skills • Master degree in organic chemistry, organic technology; • enthusiasm for experimental work and learning of new things; • team work ability.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Ing. Jan Storch, Ph.D.

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The transition to a low-carbon economy requires renewable energy sources and increased energy storage capacity in stationary applications. Lithium-ion batteries, despite their recent advancements, are constrained by short-term storage capacity and energy loss over multiple cycles, diminishing their lifespan. They also present safety and reliability concerns. Organic radical flow batteries (ORFBs), using organic redox-active molecules instead of traditional metal compounds, offer an alternative. This project aims to develop phosphorus heterocycles for ORFBs, ensuring stability over a broad temperature range, and providing high energy density and cyclability. The goal is to surpass the limitations of existing quinone and phenazine-based electrolytes, matching the performance of commercially used vanadium-based ORFBs. Required education: • Master's degree in Organic/Inorganic Chemistry or Organic Technology and related fields.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Ing. Jan Storch, Ph.D.

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π-Conjugated organophosphorus systems have become the subject of intensive research in recent years, primarily due to their applications in materials chemistry. The presence of the phosphorus atom in these molecules facilitates further derivatization, effectively altering some key characteristics of the target molecules and their intended applications. A special place in this class of substances is occupied by six-membered phosphacycles. Although considerable progress has been made recently in synthesizing these substances, polyaromatic compounds incorporating a phosphinine ring remain rare. This study will investigate synthetic routes for introducing the phosphinine core into nanographene structures. The properties of these novel compounds will also be extensively studied. Required education: • Master's degree in Organic/Inorganic Chemistry or Organic Technology and related fields.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Mgr. Jindřich Karban, Ph.D.

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Galectins are a class of lectins (carbohydrate-binding proteins other than enzymes and antibodies) characterized by affinity to some galactosides and sequence homology. Non-covalent interactions of galectins with oligosaccharides are involved in many fundamental biological events. Inhibition of these interactions by synthetic analogs of saccharides (glycomimetics) is of principal significance in their study as well as in drug development. The main goal of this PhD project is the synthesis and evaluation of hybrid glycomimetic galectin inhibitors based on the combination of carbohydrate and organometallic structural motifs. Installation of an organometallic moiety into the structure of a glycomimetic inhibitor can not only result in higher affinity or selectivity of inhibition, but also enable to study the interactions with galectins by means of electrochemical methods. Required education and skills • Master degree in chemistry. • The willingness to acquire and apply advanced methods of organic synthesis.

Granting Departments:	Department of Organic Chemistry Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Mgr. Jindřich Karban, Ph.D.

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Galectins are a class of lectins (carbohydrate-binding proteins other than enzymes and antibodies) characterized by affinity to galactosides and sequence homology. The so-called tandem galectins comprise two related but non-identical carbohydrate-binding domains (CRD) with a partially different substrate specificity. The inhibition of tandem galectins by synthetic analogs of saccharides (glycomimetics) is of principal significance in fundamental research as well as in drug development. Attachment of monovalent domain-specific inhibitors to suitable carriers will give rise to multivalent inhibitors that can inhibit both domains within the tandem galectin simultaneously and very effectively if the right topology is achieved. The main goal of this PhD project is the synthesis and evaluation of glycomimetic inhibitors of individual domains and verification of the hypothesis that an appropriate spatial arrangement of domain-specific inhibitors on a multivalent carrier can lead to high affinity inhibitors of tandem galectins due to a multivalent effect. Required education and skills • Master degree in chemistry. • The willingness to learn and apply advanced methods of organic synthesis.

Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Dr. Paulo Paioti

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Atropisomers are conformational isomers arising from restricted rotation around a single bond. Our main goal is inducing conformational restriction to create pharmaceutical leads by developing catalytic stereoselective synthesis toward difficult-to-access drug-like atropisomers. Atropisomers are chiral, giving rise to two or more isomers that have different pharmacological properties. These attributes relate to a poorly understood fundamental question of how conformational changes, from achiral and flexible to chiral and more rigid impact a molecule’s ability to interact with biological receptors. But to study such concepts, one must first of all create and then synthesize this challenging class of compounds. The main challenge is that atropisomers are intrinsically sterically hindered and potentially configurationally unstable. Accordingly, we will develop new catalytic synthesis methods and strategies, hoping to deliver more efficient, practical and (atropo)selective methods.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Bioinformatics ( in English language )
Supervisor:	Mgr. Tomáš Pluskal, Ph.D.

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Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants. The successful candidate for this position will be developing machine learning models for the prediction of enzymatic activities of enzymes in specialized biosynthetic pathways.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Mgr. Radim Nencka, Ph.D.

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The thesis will focus on the research of new inhibitors of methyltransferases. These enzymes play an important role in the pathogenesis of many diseases and are essential for the life cycle of many infectious pathogens. In this thesis, the student will investigate the rational design and synthesis of novel methyltransferase inhibitors that use S-adenosylmethionine (SAM) as the methyl group donor. Both SAM derivatives and compounds obtained by screening will be studied. The student will use computational methods to design and optimize new derivatives.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	prof. Ing. Michal Hocek, DSc.

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We will design and synthesize modified nucleoside triphosphates bearing diverse functional groups for enzymatic synthesis of modified oligonucleotides which will be applied in selection and construction of new functional nucleic acids, e.g. aptamers or aptazymes and for the construction of fluorescent or redox probes for applications in chemical biology. References: 1. Hocek, M.: "Enzymatic Synthesis of Base-Functionalized Nucleic Acids for Sensing, Cross-linking, and Modulation of Protein–DNA Binding and Transcription" Acc. Chem. Res. 2019, 52, 1730-1737. 2. Micura, R.; Höbartner, C. Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes. Chem. Soc. Rev. 2020, 49, 7331–7353.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Mgr. Jiří Kaleta, Ph.D.

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The multiphotochromic systems are made by interconnection of two or more photoswitches (molecules, whose geometry can be reversibly switched using light). Individual parts (photoswitches and unidirectional molecular motors) of these molecules will be selectively activated/switched by action of a light of defined wavelength. The goal of this Ph.D. project is design, synthesis and study of these unique molecules and their possible utilization for construction of first prototypes of molecular machines of this kind. Special attention will be dedicated to various combinations of individual photoswithes as well as the type of their mutual interconnection (orthogonal vs. non-orthogonal).

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	prof. Ing. Michal Hocek, DSc.

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We will design and synthesize new modified nucleosides and nucleotides as potential cytostatic agents with new mechanisms of action which includes modulation of receptors or activation of cytostatic proteins. Selected active compounds will be further optimized in order to identify preclinical drug candidates. References: 1. Jordheim, L. P.; Durantel, D.; Zoulim, F.; Dumontet, C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov. 2013, 12, 447–464. 2. Perlíková, P.; Hocek, M. Pyrrolo[2,3-d]pyrimidine (7-deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides. Med. Res. Rev. 2017, 37, 1429–1460.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Ing. Zlatko Janeba, Ph.D.

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The project aims to design and synthesize novel inhibitors of nucleotide salvage pathway enzymes (phosphoribosyltransferase, phosphorylases) and evaluate their biological properties (in collaboration with biochemistry groups). Such inhibitors have the potential to treat various types of cancer.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	RNDr. Tomáš Slanina, Ph.D.

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Stable radical cations and anions are unique molecules that have found numerous applications in photovoltaics, organic electronics, batteries, and catalysis. While electrochemical and redox preparation of radical ions has been studied in detail, little is known about their photochemistry. The candidate will synthesize radical ions based on triarylamines, hexaarylethanes, perylene diimides, quinones, and other motives, and will study their photochemical stability and reactivity in perspective of the application in photoredox and hydrogen atom transfer catalysis. The candidate will use steady state and time-resolved spectroscopy of stable radical ions to elucidate the mechanisms of photochemical redox reactions.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Ing. Milan Vrábel, Ph.D.

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Our group recently described the development and first applications of N1-alkyl-1,2,4-triazinium salts in bioorthogonal reactions (Angew. Chem. Int. Ed., 2023, e202306828). In this project, we want to explore the chemistry of these charged heterodienes in more detail. In addition, we want to apply the developed reagents in applications ranging from selective modification of biomolecules to cellular applications (e.g. bioimaging). The project combines synthetic organic chemistry, reaction kinetics and stability studies with biological experiments that will be performed mainly in collaboration with biologists in the group.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	prof. Ing. Michal Hocek, DSc.

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We will design and synthesize modified ribonucleoside triphosphates bearing diverse functional groups at nucleobase. These nucleotides will be used for sequence-specific enzymatic synthesis of oligoribonucleotides (RNA) bearing labels or modifications at specific positions using engineered DNA polymerases. The applications will include tRNA, mRNA, sgRNA etc. References: 1. Micura, R.; Höbartner, C. Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes. Chem. Soc. Rev. 2020, 49, 7331–7353. 2. Milisavljevic, N.; Perlíková, P.; Pohl, R.; Hocek, M. Enzymatic synthesis of base-modified RNA by T7 RNA polymerase. A systematic study and comparison of 5-substituted pyrimidine and 7-substituted 7-deazapurine nucleoside triphosphates as substrates. Org. Biomol. Chem. 2018, 16, 5800-5807.

Granting Departments:	Department of Organic Chemistry Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Study Programme/Specialization:	Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

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With the project, synthetic approaches to complex indoloterpene and their analogs displaying wide-ranging biological activity will be developed.