Dissertation topics for PhD. study programmes for the academic year 2024/2025

Pavol Jozef Šafárik University in Košice, Faculty of Science

Institute of Chemistry

Study programme

Inorganic Chemistry (ACHdAj)

Title

Bioavailable coordination compounds as potential chemotherapeutics

Abstract

The thesis is focused on observation the conditions of coordination compounds preparation predominantly based on transition metal ions with N- and/or O-donor bioligands and to theirself preparation in order to obtain substances with expected antimicrobial activity. Solution studies will be performed by potentiometric and spectroscopic (NMR, UV-Vis, fluorescence) methods and isolated synthetic products will be characterized by available techniques (IR, UV-VIS, NMR, CHN, thermal analysis, X-ray structural analysis). Further biological evaluations will be performed against selected pathological strains of microorganisms and cancer cell lines, and the acquired knowledge about the structure, other physicochemical and biological properties will allow their correlation and subsequent modifications to increase efficiency and selectivity.

Objective

1. Preparation of complexes of selected metal ions with selected bioavailable ligands 2. Characterization of the prepared coordination compounds by physicochemical methods (IR spectroscopy, X-ray analysis, thermal analysis, elemental analysis and mass spectrometry). 3. Study of the stability of the complexes in solution 4. Study of the antimicrobial and anticancer activity of selected prepared complexes against several types of pathogen microorganisms and cancer cell lines. 5. Study of bioavailability of selected complexes . 6. Publication of the achieved results in the form of papers, and lectures or posters on conferences 7. Writing and submission of the dissertation thesis

References

Current overview of scientific articles on the given issue registered in the WOS and Scopus databases

Tutor

prof. RNDr. Zuzana Vargová, Ph.D.

Consultant

Mgr. Michaela Rendošová, PhD.


Study programme

Physical Chemistry (FYCHd)

Title

Biodegradable Metallic Scaffolds for Orthopedic Tissue Regeneration

Abstract

Investigation of biodegradable metallic scaffolds as a novel approach to tissue regeneration. Addressing the need for temporary implants in orthopedics, the study delves into the design, fabrication, physical-chemical, biological and mechanical properties of these innovative scaffolds. By combining materials science, biomechanics, and regenerative medicine focuse on the study and evaluation of biodegradable metallic scaffolds properties in promoting tissue regeneration within orthopedic contexts.

Objective

This dissertation investigates the biodegradable metallic scaffolds as a novel approach to tissue regeneration. Addressing the need for temporary implants in orthopedics, the study delves into the design, fabrication, physical-chemical, biological and mechanical properties of these innovative scaffolds. By combining materials science, biomechanics, and regenerative medicine, the research is focused on the study and evaluation of biodegradable metallic scaffolds properties in promoting tissue regeneration within orthopedic contexts. This work should contribute to the growing body of knowledge in physical chemistry and biomedical engineering and provide a foundation for future developments in the field of biodegradable orthopedic implants.

References

Scientific papers

Tutor

prof. RNDr. Renáta Oriňaková, DrSc.

Consultant

RNDr. Radka Gorejová, PhD.


Study programme

Inorganic Chemistry (ACHd)

Title

Bioavailable coordination compounds as potential chemotherapeutics

Abstract

The thesis is focused on observation the conditions of coordination compounds preparation predominantly based on transition metal ions with N- and/or O-donor bioligands and to theirself preparation in order to obtain substances with expected antimicrobial activity. Solution studies will be performed by potentiometric and spectroscopic (NMR, UV-Vis, fluorescence) methods and isolated synthetic products will be characterized by available techniques (IR, UV-VIS, NMR, CHN, thermal analysis, X-ray structural analysis). Further biological evaluations will be performed against selected pathological strains of microorganisms and cancer cell lines, and the acquired knowledge about the structure, other physicochemical and biological properties will allow their correlation and subsequent modifications to increase efficiency and selectivity.

Objective

1. Preparation of complexes of selected metal ions with selected bioavailable ligands 2. Characterization of the prepared coordination compounds by physicochemical methods (IR spectroscopy, X-ray analysis, thermal analysis, elemental analysis and mass spectrometry). 3. Study of the stability of the complexes in solution 4. Study of the antimicrobial and anticancer activity of selected prepared complexes against several types of pathogen microorganisms and cancer cell lines. 5. Study of bioavailability of selected complexes . 6. Publication of the achieved results in the form of papers, and lectures or posters on conferences 7. Writing and submission of the dissertation thesis

References

Current overview of scientific articles on the given issue registered in the WOS and Scopus databases

Tutor

prof. RNDr. Zuzana Vargová, Ph.D.

Consultant

Mgr. Michaela Rendošová, PhD.


Study programme

Inorganic Chemistry (ACHdAj)

Title

Coordination compounds of 3d metals with ligands of Schiff base’s type with potential biological activity

Abstract

The dissertation thesis follow up research focused on the preparation and characterization of new coordination compounds based on 3d metals with Schiff base ligands. The work will focus on the bases of this type with 4-amino-1,2,4-triazole and its derivatives as central part, as it is known that not only Schiff base compounds of this type, but also coordination compounds with these organic molecules as ligands exhibit a wide spectrum of activity as chemotherapeutics, including antibacterial, antifungal, antitubercular, analgesic, anti-inflammatory, anticonvulsant, antiviral, insecticidal and antidepressant activities [1-4]. Motivation is to design, prepare and characterize ligands of the aforementioned type and then use them in the preparation of new coordination compounds with the aim of studying the influence of the change of substituents on the amino group bound to nitrogen in position 4 on the biological activity of ligands and coordination compounds with 3d metals. For these purposes, the work will also focus on the design and preparation of new ligands based on 4-amino-1,2,4-triazole. The study will be carried out in cooperation with the Institute of Biology of the P. J. Šafárik University in Košice, with the active involvement of the doctoral student in the study of biological activity within this cooperation, and with other partner workplaces abroad.

Objective

1. Describe the current state of the coordination chemistry of 3d metal complexes with Schiff base ligands with special focus on biologically active compounds. 2. Study methods of Schiff bases' preparation based on 4-amino-1,2,4-triazole. 3. Targeted synthesis of the above-mentioned ligands with 1,2,4-triazole and its derivatives. 4. Targeted synthesis leading to coordination compounds of 3d metals with prepared ligands. 5. Chemical, spectroscopic and structural characterization of the prepared complexes. 6. Study of biological properties of selected complexes. 7. Publication of results in the form of conference proceedings and scientific journal publications.

References

1. N. U. Güzeldemirci, Ö. Küçükbasmacı, Eur. J. Med. Chem. 2010, 45, 63. 2. H. Bayrak, A. Demirbas, S. A. Karaoglu, N. Demirbas, Eur. J. Med. Chem. 2009, 44, 1057. 3. S. Eswaran, A. V. Adhikari, N. S. Shetty, Eur. J. Med. Chem. 2009, 44, 4637. 4. A. T. Mavrova, D. Wesselinova, Y. A. Tsenov, P. Denkova, Eur. J. Med. Chem. 2009, 44, 63.

Tutor

doc. RNDr. Juraj Kuchár, PhD.


Study programme

Inorganic Chemistry (ACHdAj)

Title

Coordination compounds with potential use in magnetic cooling

Abstract

The thesis is a follow-up to several years of research focused on the development of novel low-dimensional compounds of Cu(II) with Mn(II) and macrocyclic ligands for potential use in the field of magnetic cooling [1,2]. The motivation is to design, prepare and test new ways of binding the aforementioned metals leading to alternating chains that in the basic state will show a ferrimagnetic state with a potential transition to a ferromagnetic arrangement due to an external stimulus. For these purposes, the work will also focus on the design and preparation of new macrocyclic ligands based on 1,4,8,11-tetraazacyclotetradecane (cyclam) and 1,4,7-triazacyclononane (cyclen). The study will be carried out in cooperation with the Institute of Physics of UPJŠ in Košice and other partners abroad.

Objective

1. Describe the current state of the coordination chemistry of Cu(II)/Mn(II) complexes and methods of preparation of cyclam ligand derivatives. 2. Targeted synthesis of cyclam ligand derivatives. 2. Targeted synthesis leading to low dimensional Cu(II)/Mn(II) compounds with cyclam ligand derivatives. 3. Chemical, spectroscopic and structural characterization of the prepared complexes. 4. Study of magnetic properties of selected complexes. 5. Publication of results in the form of conference proceedings and scientific journal publications.

References

1. Samoľová E., Kuchár J., Čižmár E., Dušek M.: New heterobimetallic Cu(II)/Mn(II) complexes with trans-1,8-cyclam derivatives: Synthesis, characterization, magnetic properties and crystal structures of (µ2-Chloro)-(dpc)-copper(II)-trichloro-manganese(II) and two polymorphs of (µ2-Chloro)-(dac)-copper(II)-trichloro-manganese(II). (2021) Journal of Molecular Structure, 1241, art. no. 130592. DOI: 10.1016/j.molstruc.2021.130592 2. Samoľová E., Kuchár J., Grzimek V., Kliuikov A., Čižmár E.: Synthesis, crystal structure and magnetic properties of the new Cu(II)/Mn(II) coordination polymer [{Cu(cyclam)MnCl3(H2O)2}Cl]n. (2019) Polyhedron, 170, pp. 51 - 59. DOI: 10.1016/j.poly.2019.05.024

Tutor

doc. RNDr. Juraj Kuchár, PhD.


Study programme

Biochemistry (BICHd)

Title

Designing stable chaperone platforms: from evolution to innovation

Abstract

The research group is developing new molecular platforms for detection and therapy, leveraging the potential of chaperone domains. This doctoral project focuses on molecular innovation aimed at stabilizing chaperone platforms for library construction and application. The thesis utilizes a wide range of advanced techniques, including comparative evolutionary analysis, protein crystallization, and structural characterization, in collaboration with the SOLEIL synchrotron science teams. The goal is to develop new molecular platforms with potential applications in detection, thereby bridging the gap between basic molecular biology and applied interdisciplinary research. Doctoral students will play a key role in experiment design, data collection and analysis, as well as interpretation of results. There is an opportunity to work with the latest technologies and contribute significantly to the rapidly evolving field. The thesis objectives include the investigation of natural hyperstable chaperone domains, identification of specific stabilization sites through targeted mutagenesis, comparison of sequences from thermophilic, mesophilic, and psychrophilic variants of chaperone domains, preparation of new variants, and conducting functional analysis and crystallization of new chaperone domains and variants.

Tutor

doc. RNDr. Gabriel Žoldák, DrSc.

Consultant

doc. RNDr. Rastislav Varhač, PhD.

RNDr. Michal Nemergut, PhD.


Study programme

Biochemistry (BICHd)

Title

DNA/BSA binding characteristic and photophysico-chemical properties of newly synthesized low-molecular ligands

Abstract

Uv-Vis and fluorescence spectrophotometric methods were used to determination of calf thymus DNA and albumin binding with newly synthesized low-molecular ligands. The Stern-Volmer and binding constants were calculated. CD spectra were measured to specify the mode of binding (intrecalation /or groove binding) of investigated compounds. The nuclease activity test with plasmid DNA and topoisomerase I/II inhibitory assay were performed using electrophoretic methods.

Tutor

RNDr. Danica Sabolová, PhD., univerzitná docentka


Study programme

Physical Chemistry (FYCHd)

Title

Innovative Coating Strategies for Enhancing Biodegradable Metal Implant Performance in Biomedical Applications

Abstract

This dissertation deals with the optimization of biodegradable metal implant performance through innovative coating strategies with the aim to enhance the functionality of orthopedic implants by tailoring corrosion and enhancing their compatibility with the physiological environment. The goal of thesis is to systematically explores advanced techniques such as electrospinning to apply tailored coatings to biodegradable metal surfaces. Emphasizing aspects of corrosion behavior and biocompatibility, the research employs rigorous materials analysis to assess the effectiveness of these coating methodologies.

Objective

This dissertation deals with the optimization of biodegradable metal implant performance through innovative coating strategies. The aim of thesis is to systematically explore advanced techniques such as electrospinning to apply tailored coatings to biodegradable metal surfaces. Emphasizing aspects of corrosion behavior and biocompatibility, the research employs rigorous materials analysis to assess the effectiveness of these coating methodologies. The investigation aims to enhance the functionality of orthopedic implants by tailoring corrosion and enhancing their compatibility with the physiological environment. The findings should contribute valuable insights to the scientific discourse, advancing the understanding of coating strategies and performance of biodegradable metal implants within biomedical applications.

References

Scientific papers

Tutor

prof. RNDr. Renáta Oriňaková, DrSc.

Consultant

RNDr. Radka Gorejová, PhD.


Study programme

Physical Chemistry (FYCHd)

Title

High-entropy alloy based catalysts for electrochemical water splitting

Abstract

The aim of the dissertation is the preparation of high-entropy alloys based catalysts in the form of nanoparticles, their structural characterization and the study of their properties. We will focus on the study of electrocatalytic activity in the hydrogen evolution reaction and oxygen evolution reaction. Another goal of the work is to find the optimal composition of high-entropy alloys based catalysts for highly efficient electrochemical water splitting.

Objective

The aim of the dissertation is the preparation of high-entropy alloys based catalysts in the form of nanoparticles, their structural characterization and the study of their properties. We will focus on the study of electrocatalytic activity in the hydrogen evolution reaction and oxygen evolution reaction. Another goal of the work is to find the optimal composition of high-entropy alloys based catalysts for highly efficient electrochemical water splitting.

References

Scientific papers

Tutor

prof. RNDr. Renáta Oriňaková, DrSc.


Study programme

Inorganic Chemistry (ACHd)

Title

Coordination compounds with potential use in magnetic cooling

Abstract

The thesis is a follow-up to several years of research focused on the development of novel low-dimensional compounds of Cu(II) with Mn(II) and macrocyclic ligands for potential use in the field of magnetic cooling [1,2]. The motivation is to design, prepare and test new ways of binding the aforementioned metals leading to alternating chains that in the basic state will show a ferrimagnetic state with a potential transition to a ferromagnetic arrangement due to an external stimulus. For these purposes, the work will also focus on the design and preparation of new macrocyclic ligands based on 1,4,8,11-tetraazacyclotetradecane (cyclam) and 1,4,7-triazacyclononane (cyclen). The study will be carried out in cooperation with the Institute of Physics of UPJŠ in Košice and other partners abroad.

Objective

1. Describe the current state of the coordination chemistry of Cu(II)/Mn(II) complexes and methods of preparation of cyclam ligand derivatives. 2. Targeted synthesis of cyclam ligand derivatives. 2. Targeted synthesis leading to low dimensional Cu(II)/Mn(II) compounds with cyclam ligand derivatives. 3. Chemical, spectroscopic and structural characterization of the prepared complexes. 4. Study of magnetic properties of selected complexes. 5. Publication of results in the form of conference proceedings and scientific journal publications.

References

1. Samoľová E., Kuchár J., Čižmár E., Dušek M.: New heterobimetallic Cu(II)/Mn(II) complexes with trans-1,8-cyclam derivatives: Synthesis, characterization, magnetic properties and crystal structures of (µ2-Chloro)-(dpc)-copper(II)-trichloro-manganese(II) and two polymorphs of (µ2-Chloro)-(dac)-copper(II)-trichloro-manganese(II). (2021) Journal of Molecular Structure, 1241, art. no. 130592. DOI: 10.1016/j.molstruc.2021.130592 2. Samoľová E., Kuchár J., Grzimek V., Kliuikov A., Čižmár E.: Synthesis, crystal structure and magnetic properties of the new Cu(II)/Mn(II) coordination polymer [{Cu(cyclam)MnCl3(H2O)2}Cl]n. (2019) Polyhedron, 170, pp. 51 - 59. DOI: 10.1016/j.poly.2019.05.024

Tutor

doc. RNDr. Juraj Kuchár, PhD.


Study programme

Inorganic Chemistry (ACHd)

Title

Coordination compounds of 3d metals with ligands of Schiff base’s type with potential biological activity

Abstract

The dissertation thesis follow up research focused on the preparation and characterization of new coordination compounds based on 3d metals with Schiff base ligands. The work will focus on the bases of this type with 4-amino-1,2,4-triazole and its derivatives as central part, as it is known that not only Schiff base compounds of this type, but also coordination compounds with these organic molecules as ligands exhibit a wide spectrum of activity as chemotherapeutics, including antibacterial, antifungal, antitubercular, analgesic, anti-inflammatory, anticonvulsant, antiviral, insecticidal and antidepressant activities [1-4]. Motivation is to design, prepare and characterize ligands of the aforementioned type and then use them in the preparation of new coordination compounds with the aim of studying the influence of the change of substituents on the amino group bound to nitrogen in position 4 on the biological activity of ligands and coordination compounds with 3d metals. For these purposes, the work will also focus on the design and preparation of new ligands based on 4-amino-1,2,4-triazole. The study will be carried out in cooperation with the Institute of Biology of the P. J. Šafárik University in Košice, with the active involvement of the doctoral student in the study of biological activity within this cooperation, and with other partner workplaces abroad.

Objective

1. Describe the current state of the coordination chemistry of 3d metal complexes with Schiff base ligands with special focus on biologically active compounds. 2. Study methods of Schiff bases' preparation based on 4-amino-1,2,4-triazole. 3. Targeted synthesis of the above-mentioned ligands with 1,2,4-triazole and its derivatives. 4. Targeted synthesis leading to coordination compounds of 3d metals with prepared ligands. 5. Chemical, spectroscopic and structural characterization of the prepared complexes. 6. Study of biological properties of selected complexes. 7. Publication of results in the form of conference proceedings and scientific journal publications.

References

1. N. U. Güzeldemirci, Ö. Küçükbasmacı, Eur. J. Med. Chem. 2010, 45, 63. 2. H. Bayrak, A. Demirbas, S. A. Karaoglu, N. Demirbas, Eur. J. Med. Chem. 2009, 44, 1057. 3. S. Eswaran, A. V. Adhikari, N. S. Shetty, Eur. J. Med. Chem. 2009, 44, 4637. 4. A. T. Mavrova, D. Wesselinova, Y. A. Tsenov, P. Denkova, Eur. J. Med. Chem. 2009, 44, 63.

Tutor

doc. RNDr. Juraj Kuchár, PhD.


Study programme

Inorganic Chemistry (ACHdAj)

Title

Magnetically active complex compounds of Co(II)

Abstract

Within this thesis, new magnetically active complex compounds of Co(II) with a heteroleptic coordination sphere will be studied. It is known that high values of D-parameter and possible slow magnetic relaxation can be expected in the case of pentacoordinated Co(II) complexes [1,2]. For this reason, pentacoordinated Co(II) complexes will be prepared preferentially. The strategy of their synthesis will be based on the use of a combination of sterically demanding 2- and 3-donor ligands. To stabilize the 2+ oxidation state, suitable O- and N-donor ligands will be used, while in addition to commercially available ligands, Schiff base-type ligands synthesized in this work will also be used [3]. Emphasis will be done on the preparation of compounds in the form of single crystals. The prepared complex compounds will be characterized by standard chemical and spectroscopic methods and their crystal structures will be solved. The results of the experimental study of the magnetic properties will be correlated with the results of the structural analyses.

Objective

1. Literature review on Co(II) complexes with emphasis on pentacoordinate ones. 2. Elaboration of small thesis based on literature review and accomplish dissertation examination. 3. Preparation and characterization of new, mainly pentacoordinate Co(II) complexes. 4. Elucidation of the crystal structures of complexes prepared in the single crystal form and study of spectroscopic properties of the prepared complexes. 5. Study of the magnetic properties of selected compounds. 6. Writing the dissertation thesis.

References

1. C. Rajnák, J. Titiš, I. Šalitroš, R. Boča, O. Fuhr, M. Ruben: Polyhedron 65 (2013) 122-128. 2. J. Titiš, C. Rajnák, R. Boča: Inorganics, 11 (2023) 452. 3. M. Kumar, A. Kumar Singh, A. Kumar Singh, R. K. Yadav, S. Singh, A. P. Singh, A. Chauhann: Coord. Chem. Rev., 488 (2023) 215176.

Tutor

prof. RNDr. Juraj Černák, DrSc.

Consultant

doc. RNDr. Juraj Kuchár, PhD.


Study programme

Inorganic Chemistry (ACHd)

Title

Magnetically active complex compounds of Co(II)

Abstract

Within this thesis, new magnetically active complex compounds of Co(II) with a heteroleptic coordination sphere will be studied. It is known that high values of D-parameter and possible slow magnetic relaxation can be expected in the case of pentacoordinated Co(II) complexes [1,2]. For this reason, pentacoordinated Co(II) complexes will be prepared preferentially. The strategy of their synthesis will be based on the use of a combination of sterically demanding 2- and 3-donor ligands. To stabilize the 2+ oxidation state, suitable O- and N-donor ligands will be used, while in addition to commercially available ligands, Schiff base-type ligands synthesized in this work will also be used [3]. Emphasis will be done on the preparation of compounds in the form of single crystals. The prepared complex compounds will be characterized by standard chemical and spectroscopic methods and their crystal structures will be solved. The results of the experimental study of the magnetic properties will be correlated with the results of the structural analyses.

Objective

1. Literature review on Co(II) complexes with emphasis on pentacoordinate ones. 2. Elaboration of small thesis based on literature review and accomplish dissertation examination. 3. Preparation and characterization of new, mainly pentacoordinate Co(II) complexes. 4. Elucidation of the crystal structures of complexes prepared in the single crystal form and study of spectroscopic properties of the prepared complexes. 5. Study of the magnetic properties of selected compounds. 6. Writing the dissertation thesis.

References

1. C. Rajnák, J. Titiš, I. Šalitroš, R. Boča, O. Fuhr, M. Ruben: Polyhedron 65 (2013) 122-128. 2. J. Titiš, C. Rajnák, R. Boča: Inorganics, 11 (2023) 452. 3. M. Kumar, A. Kumar Singh, A. Kumar Singh, R. K. Yadav, S. Singh, A. P. Singh, A. Chauhann: Coord. Chem. Rev., 488 (2023) 215176.

Tutor

prof. RNDr. Juraj Černák, DrSc.

Consultant

doc. RNDr. Juraj Kuchár, PhD.


Study programme

Biochemistry (BICHd)

Title

Deciphering the mechanisms of pathological IgG aggregation in oncohematological diseases

Abstract

This thesis presents a unique opportunity to explore the molecular foundations of pathological IgG aggregation present in oncohematological diseases such as multiple myeloma and light chain amyloidosis. These conditions, characterized by the aggregation of pathological light chains of immunoglobulin G (IgG), lead to serious health complications and are currently classified as incurable. A wide range of innovative techniques will be employed to study these processes ex vivo, thereby gaining a deeper understanding of these molecularly complex mechanisms. The work will contribute to a deeper understanding of the mechanisms of pathological IgG aggregation, which could potentially lead to new therapeutic strategies. As a doctoral candidate, involvement in the design of experiments, data collection, and analysis will be crucial. Additionally, the role of chaperone domains as potential neutralizing and therapeutic molecules will be explored. This thesis represents a significant opportunity to contribute to a field of high medical importance. Thesis objectives include investigating the biological and biochemical factors contributing to the aggregation of pathological IgG light chains, studying the interactions between serum proteins, lipid vesicles, and cell surface properties that catalyze or drive this aggregation process, and exploring the potential of chaperone domains as potential neutralizing drugs.

Tutor

doc. RNDr. Gabriel Žoldák, DrSc.

Consultant

doc. RNDr. Rastislav Varhač, PhD.

RNDr. Michal Nemergut, PhD.


Study programme

Inorganic Chemistry (ACHdAj); Inorganic Chemistry (ACHdAj)

Title

Nanoporous silica particles for targeted drug delivery

Objective

The thesis is a follow-up to several years of research focused on the development of new intelligent drug delivery systems releasing bioactive substances in a targeted way by the influence of physical or chemical stimulus. The aim of the PhD thesis will be the synthesis and investigation of silica-based nanomaterials, which will be studied for two purposes. The first purpose is the synthesis and testing of materials that can be used for targeted, vectored transport and the subsequent release of antithrombotic drugs. The problem with antithrombotic drugs is their short half-life, thus frequent dosing is required. Such administration of antithrombotics via silica can lead to a prolongation of their half-life, uniform administration and reduction of therapeutic doses. As a carriers, mesoporous silica nanoparticles (MSNs) and core@shell systems based on MSNs containing gold or SPION nanoparticles, will be studied. Such systems will enable the targeted administration and release of antithrombotic drugs in response to an external stimulus. Magnetic field can be used to deliver such a system with drug directly into the thrombotic site.

References

1. M. Vallet-Regí, F. Schüth, D. Lozano, M. Colilla, M. Manzano, Engineering mesoporous silica nanoparticles for drug delivery: where are we after two decades?, Chem. Soc. Rev., 51 (2022) 5365-5451, DOI: http://dx.doi.org/10.1039/D1CS00659B. 2. M. Isroni, F. Sagita, N.T.U. Culsum, G.T.M. Kadja, Molecule gated mesoporous silica for on-command drug delivery: A review, Results in Chemistry, 6 (2023) 101053, DOI: https://doi.org/10.1016/j.rechem.2023.101053.

Tutor

prof. RNDr. Vladimír Zeleňák, DrSc.


Study programme

Inorganic Chemistry (ACHd)

Title

Silica-based nanoporous particles for controlled drug delivery

Abstract

Nanoporous silica-based drug delivery systems (MSNs) have enhanced efficacy in drug delivery and reduced side effects, due to the properties brought on by nanoscale. The MSNs show superlative properties like excellent biocompatibility, high drug loading capacity, well-defined pore structure, easily controllable morphology, and tunable surface chemistry. One of the major advantages of MSNs is the possibility to design zero-premature cargo release nanosystems using various gatekeepers and release the loaded drugs using different physical or chemical stimuli. The aim of the PhD thesis will be design and synthesis of advanced MSNs for anticancer or antithrombic drug delivery, which will release the drug in a targeted manner using a variety of external stimuli, e.g. IR light-controlled release.

Objective

The thesis is a follow-up to several years of research focused on the development of new intelligent drug delivery systems releasing bioactive substances in a targeted way by the influence of physical or chemical stimulus. The aim of the PhD thesis will be the synthesis and investigation of silica-based nanomaterials, which will be studied for two purposes. The first purpose is the synthesis and testing of materials that can be used for targeted, vectored transport and the subsequent release of antithrombotic drugs. The problem with antithrombotic drugs is their short half-life, thus frequent dosing is required. Such administration of antithrombotics via silica can lead to a prolongation of their half-life, uniform administration and reduction of therapeutic doses. As a carriers, mesoporous silica nanoparticles (MSNs) and core@shell systems based on MSNs containing gold or SPION nanoparticles, will be studied. Such systems will enable the targeted administration and release of antithrombotic drugs in response to an external stimulus. Magnetic field can be used to deliver such a system with drug directly into the thrombotic site.

References

1. M. Vallet-Regí, F. Schüth, D. Lozano, M. Colilla, M. Manzano, Engineering mesoporous silica nanoparticles for drug delivery: where are we after two decades?, Chem. Soc. Rev., 51 (2022) 5365-5451, DOI: http://dx.doi.org/10.1039/D1CS00659B. 2. M. Isroni, F. Sagita, N.T.U. Culsum, G.T.M. Kadja, Molecule gated mesoporous silica for on-command drug delivery: A review, Results in Chemistry, 6 (2023) 101053, DOI: https://doi.org/10.1016/j.rechem.2023.101053.

Tutor

prof. RNDr. Vladimír Zeleňák, DrSc.


Study programme

Inorganic Chemistry (ACHd)

Title

Nanoporous silica particles for targeted drug delivery

Abstract

The thesis is a follow-up to several years of research focused on the development of new intelligent drug delivery systems releasing bioactive substances in a targeted way by the influence of physical or chemical stimulus. The aim of the PhD thesis will be the synthesis and investigation of silica-based nanomaterials, which will be studied for two purposes. The first purpose is the synthesis and testing of materials that can be used for targeted, vectored transport and the subsequent release of antithrombotic drugs. The problem with antithrombotic rugs is their short half-life, thus frequent dosing is required. Such administration of antithrombotics via silica can lead to a prolongation of their half-life, uniform administration and reduction of therapeutic doses. As a carriers, mesoporous silica nanoparticles (MSNs) and core@shell systems based on MSNs containing gold or SPION nanoparticles, will be studied. Such systems will enable the targeted administration and release of antithrombotic drugs in response to an external stimulus. Magnetic field can be used to deliver such a system with drug directly into the thrombotic site.

Tutor

prof. RNDr. Vladimír Zeleňák, DrSc.


Study programme

Biochemistry (BICHd)

Title

Non-canonical structural motifs of nucleic acids

Abstract

The occurrence and localization of non-canonical structural motifs in nucleic acids, such as DNA hairpins, triplexes and G-quadruplexes, is not random. These motifs, and not the mutations in genes themselves, that are considered the key control points of many biological processes and are also responsible for the very expression of regulatory proteins in cells. The result is, for example, uncontrolled proliferation, induction of neoplasm formation, increased malfunctions in DNA repair and recombination mechanisms, uncontrolled differentiation, but also senecsence of cells. The main task will be to define the conditions for the formation of non-canonical structures, their stabilization using specific ligands and possible impacts on cell viability.

Objective

The main goal will be to define the conditions for the formation of non-canonical structures, their stabilization using specific ligands and possible impacts on cell viability.

Tutor

doc. RNDr. Viktor Víglaský, PhD.


Study programme

Analytical Chemistry (AnCHd)

Title

On-line and off-line sample-preparation microextraction techniques for the determination of components from selected matrices.

Abstract

Sample preparation is an important stage in separation and determination of analytes from complex matrices. Sample preparation strongly influences the precision, accuracy and reproducibility of the analysis. Recent trends in sample preparation include miniaturization, automation, highthroughput performance, on-line coupling with analytical instruments and low-cost operation using little or no solvent consumption. In the past decade, also microextraction by packed sorbent was introduced as a simple, fast, on-line sample-preparation technique. This kind of microextraction requires less sample and less solvent.

Tutor

doc. Ing. Viera Vojteková, PhD.

Consultant

prof. Mgr. Vasiľ Andruch, DSc.


Study programme

Inorganic Chemistry (ACHd)

Title

Porous coordination polymers for environmental applications

Abstract

The dissertation thesis builds on many years of research in developing and applying porous coordination polymers (MOF). The aim of the dissertation will be the preparation and post-synthetic modification of MOF materials for environmental applications in the form of removing pollutants from the aqueous environment. In the first step, the design and synthesis of the adsorbent will be proposed, the surface of which will be post-synthetically modified with various functional groups (amines, Schiff bases) that will increase the sorption capacity of the material for selected pollutants. The studied pollutants will be metal ions originating from electronic waste (Cu2+, Ni2+ and Co2+), toxic metal ions (Hg2+, Cd2+ and Pb2+) and organic molecules (azo dyes and drugs). Pollutant adsorption experiments will take place at different pH and temperature values. Based on the measured adsorption isotherms, various kinetic models will be calculated to describe the adsorption mechanism and the thermodynamics of adsorption processes.

Tutor

doc. RNDr. Miroslav Almáši, PhD.


Study programme

Inorganic Chemistry (ACHdAj); Inorganic Chemistry (ACHdAj)

Title

Silica-based nanoporous particles for controlled drug delivery

Abstract

Nanoporous silica-based drug delivery systems (MSNs) have enhanced efficacy in drug delivery and reduced side effects, due to the properties brought on by nanoscale. The MSNs show superlative properties like excellent biocompatibility, high drug loading capacity, well-defined pore structure, easily controllable morphology, and tunable surface chemistry. One of the major advantages of MSNs is the possibility to design zero-premature cargo release nanosystems using various gatekeepers and release the loaded drugs using different physical or chemical stimuli. The aim of the PhD thesis will be design and synthesis of advanced MSNs for anticancer or antithrombic drug delivery, which will release the drug in a targeted manner using a variety of external stimuli, e.g. IR light-controlled release.

Objective

The thesis is a follow-up to several years of research focused on the development of new intelligent drug delivery systems releasing bioactive substances in a targeted way by the influence of physical or chemical stimulus. The aim of the PhD thesis will be the synthesis and investigation of silica-based nanomaterials, which will be studied for two purposes. The first purpose is the synthesis and testing of materials that can be used for targeted, vectored transport and the subsequent release of antithrombotic drugs. The problem with antithrombotic drugs is their short half-life, thus frequent dosing is required. Such administration of antithrombotics via silica can lead to a prolongation of their half-life, uniform administration and reduction of therapeutic doses. As a carriers, mesoporous silica nanoparticles (MSNs) and core@shell systems based on MSNs containing gold or SPION nanoparticles, will be studied. Such systems will enable the targeted administration and release of antithrombotic drugs in response to an external stimulus. Magnetic field can be used to deliver such a system with drug directly into the thrombotic site.

References

1. M. Vallet-Regí, F. Schüth, D. Lozano, M. Colilla, M. Manzano, Engineering mesoporous silica nanoparticles for drug delivery: where are we after two decades?, Chem. Soc. Rev., 51 (2022) 5365-5451, DOI: http://dx.doi.org/10.1039/D1CS00659B. 2. M. Isroni, F. Sagita, N.T.U. Culsum, G.T.M. Kadja, Molecule gated mesoporous silica for on-command drug delivery: A review, Results in Chemistry, 6 (2023) 101053, DOI: https://doi.org/10.1016/j.rechem.2023.101053.

Tutor

prof. RNDr. Vladimír Zeleňák, DrSc.


Study programme

Organic Chemistry (OCHd)

Title

Stereoselective synthesis piperidine-containing sphingomimetics from saccharide synthons.

Abstract

Stereoselective synthesis of a small library of natural piperidine-containing sphingomimetics and their unnatural analogues, sometimes referred to as alkaloid lipids, from available chiral synthons, such as dimethyl-L- and D-tartarate, L- and D-arabinose. The above mentioned alkaloids possess a wide range of biological activities, including anticancer and the ability to inhibit glycosidases. The developed strategy relies on: (i) HWE olefination for elongation of the carbon backbone, (ii) sigmatropic rearrangements to implement a novel stereocentre with an amino group, (iii) intramolecular nucleophilic substitution to form the piperidine unit, and (iv) Grubbs’ cross-metathesis chemistry to introduce the alkyl side chain at a later stage of the synthesis, which provides high flexibility for analogue synthesis. In the case of deoxocassine and its enantiomer, the Garegg’s protocol followed by a reductive dehalogenation is applied. It should be mentioned that this approach is accompanied by the selective execution of suitable protection-deprotection protocols. The target compounds will be subjected to evaluation of their antiproliferative activity on a panel of human cancer cell lines. To allow comparison, the cytotoxicity against non-malignant cells will also be evaluated.

Objective

The aim of this work is the stereoselective total synthesis of piperidine-containing sphingomimetics, sometimes also referred to as alkaloid lipids, with their ability to inhibit the proliferation of cancer cells.

References

1. Online chemical databases. 2. The available journal literature.

Tutor

doc. RNDr. Miroslava Martinková, PhD., univerzitná profesorka


Study programme

Biochemistry (BICHd)

Title

Affinity study of biotechnologically important proteins

Abstract

The functioning of living matter is dependent on mutual interactions between the macromolecules (proteins, nucleic acids, lipids) that make it up. Without them, processes in organisms as we know them would not exist. In doing so, it is necessary that the interacting molecules show a certain degree of affinity towards each other. In this dissertation, the mode of interaction and degree of affinity between selected proteins and their partners (e.g. staphylokinase with plasmin) will be studied. To monitor the formation of intermolecular association complexes, techniques that use phenomena such as surface plasmon resonance, fluorescence, or light scattering will be employed. The acquired results will be able to be used in the procedures applied in the method of controlled evolution (ribosome display), in the isolation of proteins, as well as in the basic research related to biomacromolecules.

Tutor

doc. RNDr. Rastislav Varhač, PhD.

Consultant

prof. RNDr. Erik Sedlák, DrSc.


Study programme

Biochemistry (BICHd)

Title

Study of topoisomerase I and II activity with new acridine/acridone derivatives

Abstract

In the thesis, the interaction of a series novel derivatives of acridines/acridones with nucleic acids will be investigated. The effect of these new drugs on the target DNA and RNA molecules, which are potential inhibitors of topoisomerases I and II and telomerases, will be analysed by monitoring the changes in the DNA/RNA-ligand complexes using UV-Vis, fluorescence spectroscopy, linear and circular dichroism. The mode of interaction of ligands with DNA/RNA will be determined, and the cytostatic/cytotoxic effect on selected tumor and non-tumor cell lines will also be tested. The effect of the substances on cells will be studied using flow cytometry analysis and the mode of cell death will be determined. Lastly, the localization of derivatives within the cells will be investigated using confocal microscopy.

Tutor

prof. RNDr. Mária Kožurková, CSc.

Consultant

doc. RNDr. Ladislav Janovec, PhD.


Study programme

Biochemistry (BICHd)

Title

Study of topoisomerase activity of new 3,6 disubstituted derivatives of acridines

Abstract

In the thesis, we will deal with an interaction of novel derivatives of 3,6 disubstituted derivatives of acridines with nucleic acids. The spectroscopic characteristics, hydrophibicity, stability in water solution and reactivity of the newly synthesized compounds will be studied. We will determine the mode of interaction; calculate binding constants and neighbor exclusion parameters. Inhibition effects of these compounds on topoisomerase I and II will be examined. The potential antitumor effects of these compounds will be tested against both human and mice leukemia cell lines and HeLa cell. The effect of substances on cells will be studied using flow cytometry analysis and the mode of cellular death will be determined. The localization of derivatives in cells will also be analyzed using confocal microscopy.

Objective

To study the interactions of selected 3,6-disubstituted acridine derivatives with DNA using spectroscopic methods: UV-Vis spectrometry and CD spectroscopy. To determine the activity of these substances against type I and II topoisomerase using electrophoretic methods. Based on the measured values, determine the binding properties of the given derivatives and the way they bind to DNA. To study the biological properties of these substances.

Tutor

prof. RNDr. Mária Kožurková, CSc.


Study programme

Physical Chemistry (FYCHd)

Title

Study of the influence of the polymer membrane on sensing properties

Objective

The aim of the dissertation is to study application of various types of polymers in development of electrochemical sensors for bioanalytes determination. Study of the effect of pH, temperature, storage conditions e.g. for sensing properties of various modified electrochemical sensors.

Tutor

RNDr. Ivana Šišoláková, PhD., univerzitná docentka

Consultant

RNDr. Jana Shepa, PhD.


Study programme

Physical Chemistry (FYCHd)

Title

Study of the influence of polysulfides and additives on the lifetime and stability of Li-S batteries

Abstract

The aim of this work is the preparation and characterization of sulfur-based cathode materials and the study of the influence of polysulfide migration on the degradation processes inf Li-S batteries. Another goal will be to propose a strategy for the treatment of cathode materials and separators in order to reduce the mobility of the resulting lower polysulfides. Reducing the mobility of lower polysulfides can significantly improve the stability, cyclability, and overall lifetime of Li-S batteries.

Tutor

doc. RNDr. Andrea Straková Fedorková, PhD.


Study programme

Analytical Chemistry (AnCHd)

Title

Use of ionic associates of fluorescein dyes in pharmaceutical analysis

Abstract

A large number of pharmaceutical substances contain a basic nitrogen atom. Such substances can form ionic associates with anionic fluorescein dyes. The result of this interaction is the appearance of new bands in the absorption spectra, quenching of the dye luminescence and resonant scattering of light. All these phenomena are still little used in pharmaceutical analysis, and only one procedure has been automated so far. The reactions used are very simple, fast, and the resulting sensitivity is one of the best for these pharmaceutical substances.

Objective

Determination of active ingredients of pharmaceutical formulations or their mixtures by batch spectrophotometric and sequential injection analysis

References

M. Florea, M. Ilie, Ion-pair spectrophotometry in pharmaceutical and biomedical analysis: challenges and perspectives, in: E. Sharmin, F. Zafar (Eds.), Spectroscopic Analyses – Developments and Applications, IntechOpen, London, 2017, pp. 173–191, https://doi.org/10.5772/intechopen.69778.

Tutor

prof. Dr. Andrii Vyshnikin, PhD.


Study programme

Analytical Chemistry (AnCHd)

Title

Use of innovative approaches for the analysis of samples of biological origin

Objective

The topic is focused on the development of new innovative approaches to the analysis of samples of biological and environmental origin. The goal is to use chemicals and procedures in accordance with the requirements of green analytical chemistry.

Tutor

prof. Mgr. Vasiľ Andruch, DSc.

Consultant

RNDr. Alina Diuzheva, PhD.


Study programme

Biochemistry (BICHd)

Title

Targeted contrast nanoconjugates based on DNA aptamers

Abstract

Nanoparticles are often used in bioimaging and transport of drugs, e.g. in cancer diagnosis and treatment. Their properties are continuously improved thanks to the modification of their surfaces with DNA aptamers, engineered ligands that specifically recognize target molecular structures. DNA aptamers conjugated to nanoparticles are responsible for their accumulation near the site of their subsequent biological action. The aim of the PhD student's research work will be to develop targeted nanoparticle bioconjugates with aptamers and to establish a universal procedure for the efficient production of receptor bio-nano-conjugates that will be suitable for use in the diagnosis of a wide range of molecular targets.

Objective

The goal of the research work will be the development of targeted bioconjugates of nanoparticles with aptamers and the creation of a universal procedure for the effective production of receptor bio-nano-conjugates, which will be suitable for diagnosic of a wide range of molecular targets.

Tutor

doc. RNDr. Viktor Víglaský, PhD.


Study programme

Biochemistry (BICHd)

Title

Development of efficient genetically encoded photosensitizers based on selected flavoproteins

Abstract

Genetically encoded photosensitizers (GKFs) have a critical advantage over traditional small molecule photosensitizers used in photodynamic therapy in the ability to selectively distribute to diseased tissue. However, a significant functional limit of GKF compared to small photosensitizers is a significant reduction in the efficiency of singlet oxygen production of the protein-bound photosensitizer. In this project, we will use our recently developed GKF singlet oxygen production enhancement design in combination with a high-throughput method for analyzing efficient singlet oxygen producers at the clone level to develop efficient GKFs. We will test our approach on selected flavoproteins. This project assumes the mastery of several biophysical, biochemical and molecular biological methods.

Tutor

prof. RNDr. Erik Sedlák, DrSc.

Consultant

RNDr. Nataša Tomášková, PhD.

Mgr. Ľuboš Ambro, PhD.


Study programme

Biochemistry (BICHd)

Title

Establishment of advanced techniques for insect cell-based production of proteins

Tutor

prof. RNDr. Erik Sedlák, DrSc.

Consultant

Mgr. Ľuboš Ambro, PhD.


Study programme

Physical Chemistry (FYCHd)

Title

Fabrication and evaluation of redox-flow batteries with different types of water-based electrolytes

Abstract

The aim of this work is fabrication and characterization of different types of redox flow batteries using novel inorganic and organic water-based electrolytes with improved properties. The next step will be the electrochemical characterization of individual battery components and their compatibility, and then testing of the overall efficiency, performance and cycling of new types of redox flow batteries.

Tutor

doc. RNDr. Andrea Straková Fedorková, PhD.