Background of the project

There is number of drugs showing promising biological effects in (pre)clinical studies, but their practical applications are limited because of their low bioavailability and stability, or deleterious side-effects. These drawbacks can be reduced or eliminated by application of biocompatible carrier systems. Porous hybrid materials (nanoparticles of metal-organic frameworks - MOFs) are currently a new promising approach in development of efficient drug carriers. Key advantages of MOFs lie in their tunable composition, large loading capacities of drugs and their controlled release, and the possibility for particle surface modification (targeting). Nevertheless, the amount of available non-toxic linkers is limited. Unique idea described in our project is to utilize natural bile acids (BAs) in preparing organic linkers for biocompatible MOFs (BA-MOFs). BAs’ low toxicity, ability to activate transport mechanisms through biological membranes, amphiphilic character and structural rigidity foreordain them to be successful candidates in preparing efficient biocompatible drug carrier materials.

Initial design and optimization of bile-acid-based linkers, of their coordination to metal cations, and possible molecular organization will be done by using computer simulations. Selected linkers will be synthesized and used in preparation of defined nanoparticles of BA-MOFs, which will be characterized by combination of analytical methods. Their affinity to various guests will be screened in silico and in vitro. Drug loaded materials will be studied for their biological activity.

The MOPHARM project brings a new concept of medicinal material research to South Moravian region. Dr. Jurček brings the expertise in design and development of nanosized supramolecular coordination systems, their solid-state and solution studies, expertise in steroid chemistry and prodrug design, together with worldwide contact network gained over 11 years of research in prominent scientific groups around Europe.

Main aim of the project:

The goal of the MOPHARM project is to design, synthesize, and characterize BA-based linkers; and subsequently use these likers for coordination with metal ions and preparation of porous metal-organic frameworks (BA-MOFs), carry out their characterization, and finally to study their loading capacities and biological activities.

Figure. Flower-like concave Pd3L6 supramolecular complex derived from ursodeoxycholic bile acid (for more see literature 3).

Selected publications:

1.  Jurček O., Valkenier H., Puttreddy R., Novák M., Sparkes H.A., Marek R., Rissanen K., Davis A.P.: Anion Recognition by a Bioactive Diureidodecalin Anionophore: Solid-State, Solutionm, and Computational Study, Chem. Eur. J. 2018, 32, 8178. 
2. Li H., Valkenier H., Judd L., Brotherhood P., Hussain S., Cooper J., Jurček O., Sparkes H., Sheppard D., Davis A. P.: Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia, Nat. Chem. 2016, 8, 24-32.
3. Jurček O., Bonakdarzadeh P., Kalenius E., Linnanto J. M., Groessl M., Knochenmuss R., Ihalainen J., Rissanen K.: Superchiral Pd3L6 Coordination Complex and Its Reversible Structural Conversion into Pd3L3Cl6 Metallocycles, Angew. Chem. Int. Ed. 2015, 54, 15462-15467.
4. Bonakdarzadeh P., Pan F., Kalenius E., Jurček O., Rissanen K.: Spontaneous Resolution of an Electron-Deficient Tetrahedral Fe4L4 cage, Angew. Chem. Int. Ed. 2015, 54, 14890-14893.
5. Jurček O., Cammetti M., Pontini M., Kolehmainen E., Rissanen K.: A zinc–salophen/bile-acid conjugate receptor solubilized by CTABr micelles binds phosphate in water, Org. Biomol. Chem. 2013, 11, 4585-4590.
6. Jurček O., Ikonen S., Buřičová L., Wimmerová M., Wimmer Z., Drašar P., Horníček J., Galandáková A., Ulrichová J., Kolehmainen E.: Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability, Molecules 2011, 11, 9404-9420.
7. Jurček O., Wimmer Z., Svobodová H., Bennettová B., Kolehmainen E., Drašar P.: Preparation and preliminary biological screening of cholic acid–juvenoid conjugates, Steroids 2009, 74, 779-785. 

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie and it is co-financed by the South Moravian Region under grant agreement No. 665860. This material reflects only the author’s view and the EU is not responsible for any use that may be made of the information it contains.​