Synthetic Macrocyclic Anion-Selective Anion Receptors
Synthetic macrocyclic anion-selective anion receptors
Template of the doctoral project
The text highlighted in yellow (see below) should be substituted by input from PhD candidate.
Anion-selective receptor molecules (RM) have numerous applications (sensors and sensor arrays, sample pre-concentration, etc), as many important analytes are anionic (e.g. a myriad of carboxylates).
The main binding mode for the anion-receptor interaction is hydrogen bond (HB) between the HB donor groups of the receptor and the anionic centre(s) of the anion. However, HB alone does not usually enable satisfactory selectivity.
Improved selectivity, especially in the case of larger anions, can be achieved by following the principles of complementarity of geometries, preorganization of the receptor and taking into account the reorientation of solvent molecules. In addition, all evidence suggests that the most promising candidates for high-affinity and selective receptors are macrocyclic and/or cage-like molecules, because they provide possibilities for interacting with all parts of the anion and in aqueous medium they enable displacement of the so-called high-energy water from the binding cavity, which greatly enhances binding.
The main goal and innovativeness: In spite of very substantial effort in creating anion receptors, only a limited number of macrocyclic or cage-like structures are in use. Thus, the main goal of this dissertation is to create a novel family of macrocyclic anion receptor molecules, mainly targeting carboxylates, on the basis ofbis-carbazolyl-urea moiety (1)[1] and on the basis of suitable candidate build a potentiometric sensor prototype.
(1)
Here X can stand for almost any bivalent residue, such as –(CH2)n–, –(CH2CH2O)n–,
–(CH2NHCO)n–, –(O-C6H4-O)n–, etc. The system of closely positioned NH fragments binds the carboxylate group of the anion Y-COO– while X can be tailored to accommodate carboxylates of different size and chemistry of Y.
Possible synthetic pathways:Here the candidate is expected to propose concrete and realistic synthetic pathways for the synthesis of derivatives of (1), involving assembling the bis-carbazolyl-urea fragment and attaching the linker. The candidate is welcome to choose different types of X, but it has to be justified, why the specific X are proposed.
Concrete work plan:
Problem/task/question / Expected outcome1. The synthetic approach is needed for assembling the simplest representatives of (1) with X = –(CH2)n–. Preliminary experiments have been carried out in our group using diacids as reagents with reasonable success, but work is needed form the candidate for large n values (n > 10). Here the candidate is expected to outline a concrete plan, how to assemble such challengingly large macrocycles with n > 10. / Robust synthetic approach for (1) with n > 10. A set of molecules with different n is available.
Article submission in 2019.
2. How does the cavity size of (1) with
–(CH2)n– influence binding of aliphatic and aromatic Y-COO– with different size of Y? Is there any dependence on whether Y is saturated or unsaturated (e.g. aromatic)? / A set of around 10 carboxylate anions with different size and chemistry (formate, acetate, benzoate, lactate, pivalate, sorbate, glucuronate, etc) will be studied for binding with receptors prepared in step 1, using a consistent methodology. The results enable several key conclusions about relations between receptor design and anion binding.
Article submission in 2020.
3. The synthetic approach developed above in step 1 will be generalised for different linkers, so that besides size, also the different chemistries of the Y fragment of Y-COO–can be differentiated. Here the candidate has to explain why he/she thinks that her synthetic approach presented above is generalizable and what types of linkers can be utilized. / Generalised synthetic approach is available, a number of different receptors (ca 20) are available and their binding will be studied against the set of around 10 carboxylates. This will lead to a data pool for choosing promising candidates for building real sensor.
Article submission: 2021.
4. Sensor prototype will be built for some carboxylate ion and characterised. / The most promising representatives synthesized in steps 1-3 will be used for building potentiometric sensor prototypes for sensing certain carboxylate anions. Our group now has experience in building potentiometric anion sensors in cooperation with ÅboAkademi university.
Article submission: 2022.
PhD defence: 2022
[1] The eventual synthetic work can divert from this family of compounds, but in order to rank the candidates on a comparable basis, all candidates are required to present their synthesis strategy for this compound family. However, specific molecules can differ by the chemistry of X.