Have you ever struggled with low-yielding and non-reproducible post-synthetic modification of MOFs? Read our recent paper in MSDE for a possible solution!

Post-synthetic modification (PSM) is a powerful tool for introducing complex functionalities into metal–organic frameworks (MOFs). Aldehyde-tagged MOFs are particularly appealing platforms for covalent PSM due to the high reactivity of aldehyde groups, but the same feature also makes their solvothermal synthesis challenging. In this work, we show that while lowering the temperature during the synthesis of aldehyde-tagged UiO-68 avoids aldehyde group degradation and yields a highly porous and crystalline material, the resulting UiO-68–CHO contains a large fraction of missing linker defects and, as a result, its PSM is both inefficient and non-repeatable. However, we also show that this problem could be solved by 1) using an excess of linker during the synthesis of the MOF and 2) by soaking the crude material in the solution of the linker, which together reduce the density of defects enough to yield an excellent substrate for PSM. Treatment of the ‘healed’ material with model amines gives nearly quantitative conversions of aldehydes into imines, even if no excess of reagents is used. Importantly, the PSM of the ‘healed’ UiO-68–CHO gives repeatable results over many days, unlike the PSM of the highly defective MOF. Owing to these developments, various functionalities, such as new coordination sites, drug cargo, chirality, and hydrophobicity, were successfully introduced into the UiO-68 framework. The deleterious influence of defects on the PSM of MOFs and the solution to this problem proposed herein are likely to be of general nature, and hence might help in developing new and versatile platforms for covalent PSMs.

M. Wiszniewski, M. J. Chmielewski, “Reducing defect density in UiO-68–CHO is key for its efficient and reliable post-synthetic modification” Mol. Syst. Des. Eng., 2023, DOI: 10.1039/D3ME00071K

Congratulations to Krystyna Maslowska-Jarzyna on winning the START fellowship from the Foundation for Polish Science! Krystyna was selected among top 100 young polish scientists as one of only 10 chemists and the only chemist from our Department. The recipients were selected in a multi-stage competition on the basis of the quality of their scientific achievements.

For more, see the Foundation for Polish Science page.

In this paper, we propose a new strategy for the development of synthetic amino acid transporters. Such molecules might be expected to display a wide range of biological activities and also find applications in drug delivery, metabolism regulation, and as next-generation antibiotics.

The transport of amino acids across biological membranes is vital for the proper functioning of every living cell. This is because at physiological pH amino acids are very polar (they have a positively charged N-terminus and a negatively charged C-terminus) and therefore cannot pass through lipid bilayers alone. In nature, amino acid transport is carried out by specialized membrane proteins that play important roles in regulating key physiological functions, such as protein biosynthesis, metabolism, gene expression, redox balance and signaling. The dysfunction of these proteins contributes to the development of serious diseases, such as diabetes, neurodegenerative disorders, obesity and cancer. Synthetic amino acid transporters could help in treating these diseases, and might also find applications in drug delivery, metabolism regulation, and as next-generation antibiotics.

Unfortunately, precisely because amino acids are both cations and anions, the development of such synthetic amino acid transporters has so far been extremely difficult, since it required combining both cation and anion binding sites in one structure. In this paper, however, we show that this is not the only possible strategy and that even very simple anion transporters are able to efficiently transport amino acids across lipid bilayers at physiological pH. To explain this unexpected effectiveness of simple anionophores, we developed a new assay for studying the transport of amino acids, that gave us insight into the mechanism of this phenomenon. As a result, we were able to propose a new strategy to search for synthetic amino acid transporters with improved properties and interesting biological activity. Read on here.

The study reveals two distinct HCO3‾ transport mechanisms by simple di(thio)amidocarbazoles as well as their potent antimicrobial properties. Read more here.

Anions are typically too hydrophilic to freely pass through biological membranes. This also applies to those drugs that are anionic at physiological pH. Synthetic anion transporters, i.e. small, lipophilic molecules that facilitate diffusion of anions across lipophilic barriers, may accelerate the diffusion of anionic drugs by many orders of magnitude and thus could dramatically increase their effectiveness. Moreover, transporters whose activity could be controlled by light, pH or other stimuli could enable the targeted delivery of drugs to the desired place and at the right time. The aim of this project is to develop the first switchable transporters for anionic drugs, and hence to demonstrate a new strategy for targeted drug delivery. As part of it, we will undertake research on the construction of transporters switchable by changes in pH or irradiation with light of a specific wavelength. We hope that this research will lead to the development of a new strategy for smart drug delivery, which may find practical applications in the future, e.g. in the treatment of cancer.

A most warming welcome to our new post-doc: Dr. Debashis Mondal!

Debashis did his M.Sc. in chemistry from IIT Bombay (India) in 2015. He then enrolled at IISER Pune (India) for his doctoral studies in 2016, where he studied in the subfield of supramolecular chemistry under the supervision of Prof. Pinaki Talukdar. After completing his Ph.D. graduation in 2022, he joined the Supramolecular Chemistry group of Prof. Michał J. Chmielewski at the University of Warsaw as a post-doctoral fellow in September 2022.

Social media profile: https://twitter.com/DebashisJMChem

We are looking for 2 postdoctoral researchers for a groundbreaking research project on the border of organic, medicinal, and supramolecular chemistry.

Chloride transporters have been intensely investigated because of their potential medicinal applications. In particular, pH-switchable transporters are highly appealing as potential anticancer agents, because they might be more active in cancer cells than in normal cells. Owing to its increased acidity, our simple 3,6-dinitro substituted carbazole receptor acts as a pH-switchable transporter, with physiologically relevant apparent pK_a of 6.4. Read more in our newest paper in special issue of Frontiers in Chemistry, devoted to anion transport:

Maslowska-Jarzyna, M. L. Korczak, M. J. Chmielewski, “Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents” Front. Chem., 2021, 9:690035.

We invite students interested in collaboration on a ground-breaking research project on the border of organic and material chemistry. Attractive fellowships are available!