The Centre of New Technologies invites to a seminar by
Prof. Michał Chmielewski
CNBCh and Faculty of Chemistry, University of Warsaw, Poland
Title: From simple building blocks to anion transporting nanomachines: the development of supramolecular transporters for biologically active anions
Date: 21st of April 2023, Friday
Time: 1:00 pm (Central European Time)
Host: Prof. Bartosz Trzaskowski
The seminar will be in the CeNT aula hall (01.130) on the first floor
Abstract: The transport of various oxyanions across biological membranes is of paramount importance for every living cell, as exemplified by cellular respiration – a process that involves the transport of numerous carboxylates, phosphates and bicarbonate. Also, many drugs are negatively charged under physiological conditions and need to be transported across lipophilic barriers to reach their targets quickly. Despite this, the development of synthetic transporters for carboxylates and other oxyanions remains largely underdeveloped.
In this lecture, we present a family of simple, multispecific anion transporters based on the 1,8-diaminocarbazole moiety and show that they are not only extremely active carriers for chloride, but also for a rich variety of biologically active carboxylates, such as deprotonated amino acids, drugs, and bicarbonate. We also present the first in vivo studies that show synergy between negatively charged carboxylate antibiotic and various small-molecule anion carriers, despite the latter were used in very small, catalytic amounts.
In the second part of this talk, we show how the simple 1,8-diaminocarbazole building block can be used to construct prototype nanomachines for anion transport. First, in a strategic effort to develop more selective anion transporters, we incorporated two such building blocks into an interlocked structure, and obtained the first anion carrier with the catenane structure. Owing to the unique properties of mechanical bond, this new class of anion transporters is expected to combine preorganization and flexibility – i.e. two seemingly contradictory features that are both considered desirable for fast and selective transmembrane transport. Next, as a step towards smart, multifunctional transporters for particularly problematic cargo, we assembled multiple carbazole and (thio)urea moieties on a gold nanoparticle core. Preliminary chloride transport studies revealed that the activity of the resulting NPs is either comparable, or even higher than that of the monovalent ligands. We believe that such multivalent ligands might allow for synergistic binding and thus transport of large, multiply charged anions.