Simon J. Brooks

1,3-Diindolylureas: high affinity dihydrogen phosphate receptors

Neutral 1,3-di(1H-indol-7-yl)ureas are selective dihydrogen phosphate receptors in polar solvent mixtures (DMSO-d(6)-25% water).

Carboxylate complexation by a family of easy-to-make ortho- phenylenediamine based bis-ureas : studies in solution and the solid state

Simple bis-urea compounds based on ortho-phenylenediamine function as excellent receptors for carboxylate anions in DMSO-d6–0.5% water solution. By varying the functional groups in these compounds, the binding affinity of carboxylate anions can be modulated. Solid-state studies illustrate the cleft-like arrangement of the DDDD hydrogen bond array in the carboxylate complexes of these compounds.

Chloride, carboxylate and carbonate transport by ortho-phenylenediamine-based bisureas

Highly potent but structurally simple transmembrane anion transporters are reported that function at receptor to lipid ratios as low as 1:1000000. The compounds, based on the simple ortho-phenylenediamine-based bisurea scaffold, have been studied for their ability to facilitate chloride/nitrate and chloride/bicarbonate antiport, and HCl symport processes using a combination of ion selective electrode and fluorescence techniques. In addition, the transmembrane transport of dicarboxylate anions (maleate and fumarate) by the compounds was examined. Molecular dynamics simulations showed that these compounds permeate the membrane more easily than other promising receptors corroborating the experimental efflux data. Moreover, cell based assays revealed that the majority of the compounds showed cytotoxicity in cancer cells, which may be linked to their ability to function as ion transporters.

Fluorescent Anthracene-based Anion Receptors

A variety of amide-substituted anthracene derivates have been synthesised and their anion complexation properties studied using 1H-NMR titration techniques. Additionally, bis-urea functionalised anthracene derivatives have been shown to serve as excellent receptors for oxo-anions and to function as sensors via fluorescence quenching in DMSO-d 6 /0.5% water and MeCN/DMSO (96.5:3.5 v/v).

Towards the Discrimination of Carboxylates by Hydrogen-Bond Donor Anion Receptors

The binding constants (log Kass ) of small synthetic receptor molecules based on indolocarbazole, carbazole, indole, urea and some others, as well as their combinations were measured for small carboxylate anions of different basicity, hydrophilicity and steric demands, that is, trimethylacetate, acetate, benzoate and lactate, in 0.5 % H2 O/[D6 ]DMSO by using the relative NMR-based measurement method. As a result, four separate binding affinity scales (ladders) including thirty-eight receptors were obtained with the scales anchored to indolocarbazole. The results indicate that the binding strength is largely, but not fully, determined by the strength of the primary hydrogen-bonding interaction. The latter in turn is largely determined by the basicity of the anion. The higher is the basicity of the anion the stronger in general is the binding, leading to the approximate order of increasing binding strength, lactate<benzoate<acetate≤trimethylacetate, which holds with all investigated receptors. Nevertheless, there are a number of occasions when the binding order changes with changing of the carboxylate anion, sometimes quite substantially. Principal component analysis (PCA) reveals that this is primarily connected to preferential binding of trimethylacetate, supposedly caused by an additional hydrophobic/solvophobic interaction. These findings enable making better predictions, which receptor framework or cavity is best suited for carboxylate anions in receptor design.

Extending the Hydrogen-bonding Array in ortho-Phenylenediamine Based Bis-ureas

Two new ortho-phenylenediamine based bis-urea compounds have been synthesized with pendant amide groups. The stability constants of the new compounds with a variety of anionic guests have been measured by 1H NMR titration techniques and compared to the parent bis-urea. The X-ray crystal structure of the acetate and benzoate complexes of a bis-amide functionalized system have been solved and reveal the receptor forming a dimer with two anions bound at the termini of the hydrogen bonded assembly.

Network formation by a pyrrole functionalized isophthalamide

N1,N3-Bis(2,4-diphenyl-1H-pyrrol-3-yl)benzene-1,3-dicarbamide forms a network containing clusters of water molecules when crystallized from wet methanol.

Cyclic and acyclic amidopyrrole containing anion receptors

Intense recent interest in anion complexation has resulted in significant advances in the design of potent anion binding agents. The development and implementation of the amidopyrrole motif for the complexation of anions is a relatively new and exciting area of anion coordination chemistry. The motif is of particular interest due to the convergent hydrogen bond donor characteristics that distinguish it from other dual hydrogen bond donor systems such as urea (Figure 1). The advances in this area are outlined in this short review.