This project is focused to the synthesis of multideprotonable, hybrid and ambiphilic ligands
suitable for complexation of metal centres in generally low oxidation states. Suggested ligands
are: amidinato/guanidinato ligands combined with N-heterocyclic carbenes, hybrid neutral
ligands (betaines), non-innocent imido-amides, oligodeprotonable amidinates/guanidinates,
bis-trisamido/bis-trisimido-phosphonates/phosphinates and various amidinate, guanidinate and
carbene ligands decorated by R2B group. The use of such ligands in synthesis of coordination
compounds of main group, environmentally acceptable and catalytically applicable metals will be
the major target of the project along with its use in catalytically driven organic chemistry
transformations, and in a part in material science.

In terms of this project our pilot study of ring opening of lactides by using a mixtures of alcohols, organic solvent and a catalytic amount of volatile mineral or organic acid to appropriate esters usable in various kinds of food, cosmetic or pharma industry will be evaluated.

This project deals with the preparation of hybrid ligands suitable to stabilize d- and f-block as well as the main group metal centers in generally low oxidation states. The ligands are proposed to be the hybrid aminocarbenes, amidinates and guanidinates with adjacent coordinating group, thiaamidinates, boraamidinates, amido-amidinates or guanidinates and other derivatives of macrocyclic ligands. The metals of interest are the environmentally friendly Ca, Zn, Al, Fe, Zr, Bi and Cu, and metals with a high potential in homogenous catalysis and material applications as for example Ge, Sn, Sc, Y, La, Au, Pt, Pd, Rh, Ru, Ce, Sm, Yb and others. The stabilization of respective organometallic compounds or complexes in unusual, and often obscure, low oxidation states will be evaluated and the activity in important chemical processes tested. A quest for compounds with metals in lower oxidation state (also radical and biradicalloid species) than is
usual as for example Ca(I), Zn(I), Au(0), Bi(I and II), Al(I and II) Si(I, II and III; also for Ge, Sn and Pb) etc. will be performed.

The main goal of this project is the development of overall methodology for comprehensive quantitative characterization of lipidome and metabolome in human plasma and urine samples of healthy volunteers considering age and sex groups. All analytical methods will be validated for high-throughput quantitation of lipids and metabolites. This comprehensive approach covers all steps including the selection of objects, sample collection, sample preparation, mass spectrometry based analysis and quantitation, data processing, statistical evaluation, and biological interpretation. The developed methodology will be applied to a case study of renal cell carcinoma (RCC) patients with the goal to identify the most dysregulated lipids and metabolites using advanced multivariate data analysis methods and biological interpretation of observed changes for both groups together. Extracellular vesicles will be tested as perspective biomarker source in cancer diagnostics. The database of over 1000 lipids and metabolites will be built and used for other human healthcare and biomarker discovery projects.

Reason for the research

Of all cancers, pancreatic cancer is the most difficult to detect early, as there are no specific symptoms. And since early detection offers the best hope of successful treatment, it means that this cancer has the worst prognosis for survival. In addition, current cancer detection methods are limited in that they cannot be applied for large-scale screening, or they have limited sensitivity at early stages or for small tumours.

Using chemistry as possible solution

Using the existing knowledge that there are changes in the lipid metabolism of tumour cells, prof. Michal Holčapek from the Department of Analytical Chemistry at the Faculty of Chemical Technology set out to determine if chemistry could offer an effective alternative to existing screening methods. They performed several comprehensive analyses of a wide range of serum lipids by ultra-high performance supercritical fluid chromatography-mass spectrometry, which goes further than testing only one biomarker, and monitors the whole lipidome (all the lipids in given biological system).

The results

This method could not only detect pancreatic cancer, but had a throughput of over 1000 samples per month with samples being analysed within a week, and had a much greater sensitivity than current methods in use, regardless of the cancer stage. The lipid profiling could also distinguish between chronic inflammation of the pancreas (pancreatitis) and pancreatic cancer.

The way forward

Based on these results and the clear possible contribution of this method, prof Holčapek and his colleagues will be taking their research even further, determining whether it can be extended to other cancer types besides pancreatic cancer, or perhaps whether it can be used to monitor the effectiveness of cancer treatment. Their goal is to save lives: for this screening to be available in clinics and hospitals throughout the world, accessible and affordable to regular patients.

Challenges

Despite the success of their study, prof. Holčapek notes that there are still challenges before they can achieve this dream. They need funding for the very advanced and very costly equipment.  They would also require the acceptance of this alternative by the medical community and the public, who could prefer to rely on traditional methods.

Persons who are interested in this study, or prospective students who could like to work on this project, are welcome to contact prof. Holčapek at Michal.Holcapek@upce.cz.

Nowadays, kinetic analysis of complex processes is of major interest for scientists dealing with solid-state kinetics. Complex processes can be characterized as those during which at least two different mechanisms proceed simultaneously ? most solid-state processes are in fact complex. However, routine application of complex kinetic analysis is restrained by the lack of concrete methodologies and procedural standards. The only developed approach involves extremely time-consuming random testing of extensive number of different models combinations, which makes the routine virtually impossible to apply in practice. Main objective of the introduced grant project is a systematic study of complex kinetic processes and their mutual dependences (both theoretically and experimentally) and a development, optimization and verification of a general algorithm for quick and effective determination of the most probable complex kinetic mechanism. Extensive testing of the algorithm for various real-life complex solid-state processes will be performed.

The project is concerned with the integrations of, and conflicts and passages between biomedicine and complementary and alternative
medicine (CAM). Drawing upon medical anthropology, science and technology studies and the sociology of medicine, we propose to carry out
a multi-sited ethnographic research in the Czech Republic which will, first, contribute to these three fields of study with original theoretical
insights and methodological strategies regarding disease, health and body, and second, enhance the understanding of the specificities of
CAM treatments and their interfaces with biomedicine in the contemporary Czech society. Distinctive features of the project include the focus
on 1) interfaces between biomedicine and CAM but also between different CAM approaches and practices; 2) heterogeneous materialities
and technologies as agents in the therapeutic practices; 3) technologies of the self, emerging socialities, and biosocial differentiation and
transformation taking place also beyond the medical/therapeutic settings in a strict sense.