Anion recongnition using preorganized thiourea functionalized [3]polynorbornane receptors

A new family of [3]polynorbornane frameworks exhibiting conformationally preorganized aromatic thiourea (cleft-like) receptors have been designed and synthesized for anion recognition. These show excellent affinity for the biologically relevant dihydrogenphosphate (H2PO4-) and dihydrogenpyrophosphate (H2P2O72-) anions (among others), which are bound in 1:1 and 2:1 (host:anion) ratio, respectively. Moreover, visually striking color changes accompany guest binding, enabling this family to act as colorimetric anion sensors.

Anion recognition and anion-mediated self-assembly with thiourea-functionalised fused [3]polynorbornyl frameworks

Three conformationally preorganised host molecules based on the [3]polynorbornyl framework and incorporating di-urea receptors were synthesised and their interaction with a series of anions investigated by 1H NMR spectroscopy. A high affinity of each host molecule for dihydrogenphosphate (H2PO4–) and dihydrogenpyrophosphate (H2P2O72–) was identified. In addition to binding to the urea receptors of the host molecules, evidence for an interaction involving the non-polar C–H groups within the binding cavity of the framework and guest anions was also discovered. Furthermore, an unusual 2 : 1 host-to-anion stoichiometry was indicated when binding H2P2O72–, and a model for the anion-mediated self-assembly of this complex species is proposed.

Size matters—strong binding of the terephthalate dianion by thiourea functionalised fused [n]polynorbornane hosts

Remarkably strong binding of the new [5]polynorbornane based host 2b to the terephthalate dianion is based on size complementarity of the preorganised binding cleft with the rigid dicarboxylate guest.

Bis-thiourea macrocycles incorporating fused [n]polynorbornanes: binding of flexible versus rigid dicarboxylates

Two macrocyclic bis-thiourea hosts 5 and 6 were constructed and their interactions with two dicarboxylates of similar size (pimelate = flexible and terephthalate = rigid) were evaluated using 1H NMR titration techniques. In contrast to previous work with thiourea functionalised [n]polynorbornanes (where a notable increase in H:G affinity was noted for the rigid guest), the new macrocyclic hosts, in particular host 6, bind pimelate more strongly than terephthalate (for 6 binding pimelate log Ka = 4.7, terephthalate log Ka = 3.7). A binding arrangement in which the flexible dicarboxylate is ‘perched’ above the macrocycle is proposed to justify these results.

4-Amino-1,8-naphthalimide-based anion receptors: employing the naphthalimide N-H moiety in the cooperative binding of dihydrogenphosphate

The 4-amino-1,8-naphthalimide-based anion receptor 3 binds dihydrogenphosphate with 1:1 stoichiometry through cooperative hydrogen bonding to a naphthalimide N–H and thiourea N–H groups. This was clearly established from ¹H NMR titration experiments in DMSO-d₆ where a substantial shift in the resonance for the naphthalimide N–H was observed concomitant with the expected thiourea N–H chemical shift migration upon successive additions of H₂PO₄⁻. However, whilst ¹H NMR titration experiments indicate that 3 was capable of binding other anions such as acetate, the naphthalimide N–H does not participate and the N–H resonance was essentially invariant during the titration. The lack of cooperative binding in this instance was justifiable on steric grounds.

Fluorescent anion sensors based on 4-amino-1,8-naphthalimide that employ the 4-amino N-H

The new charge neutral 4-amino-1,8-naphthalimide based anion sensors 2 and 3 bind to both acetate and dihydrogenphosphate with 1:1 stoichiometry through hydrogen bonding to both thiourea N–H atoms and in the case of dihydrogenphosphate, the naphthalimide 4 amino N–H group as well. This was clearly established from ¹H NMR titration experiments with H₂PO₄^- in DMSO-d₆ where a substantial shift in the resonance for the naphthalimide N–H was observed concomitant with the expected migration of the thiourea N–H chemical shifts. The binding constants determined from the titration studies indicate that the new sensors bind H₂PO₄^- more strongly than AcO⁻. Fluorescence titrations with sensor 3 indicate quenching of 59% and 36% upon addition of acetate and dihydrogenphosphate, respectively.

Fluorescent photoinduced electron transfer (PET) sensors for anions; from design to potential application

This mini review highlights the synthesis and photophysical evaluation of anion sensors, for nonaqueous solutions, that have been developed in our laboratories over the last few years. We have focused our research mainly on developing fluorescent photoinduced electron transfer (PET) sensors based on the fluorophore-spacer-anion receptor principle using several anthracene (emitting in the blue) and 1,8-naphthalimide (emitting in the green) fluorophores, with the aim of targeting biologically and industrially relevant anions such as acetates, phosphate and amino acids, as well as halides such as fluoride. The receptors and the fluorophore are separated by a short methyl or ethyl spacer, where the charge neutral anion receptors are either aliphatic or aromatic urea (or thiourea) moieties. For these, the anion recognition is through hydrogen bonding, yielding anion:receptor complexes. Such bonding gives rise to enhanced reduction potential in the receptor moieties which causes enhancement in the rate of PET quenching of the fluorophore excited state from the anion:receptor moiety. This design can be further elaborated on by incorporating either two fluorophores, or urea/thiourea receptors into the sensor structures, using anthracene as a fluorophore. For the latter design, the sensors were designed to achieve sensing of bis-anions, such as di-carboxylates or pyrophosphate, where the anion bridged the anthracene moiety. In the case of the naphthalimide based mono-receptor based PET sensors, it was discovered that in DMSO the sensors were also susceptible to deprotonation by anions such as F− at high concentrations. This led to substantial changes in the absorption spectra of these sensors, where the solution changed colour from yellow/green to deep blue, which was clearly visible to the naked eye. Hence, some of the examples presented can act as dual fluorescent-colorimetric sensors for anions. Further investigations into this phenomenon led to the development of simple colorimetric sensors for fluorides, which upon exposure to air, were shown to fix carbon dioxide as bicarbonate.

Anion recognition and sensing in organic and aqueous media using luminescent and colorimetric sensors

This review article focuses primarily on the work carried in our laboratories over the last few years using luminescent and colorimetric sensors, where the anion recognition occurs through hydrogen bonding in organic or aqueous solvents. This review begins with the story of the discovery of fluorescent photoinduced electron transfer (PET) sensors for anions using charged neutral urea or thiourea receptors where both fluorescent and NMR spectroscopic methods monitored anion recognition. This work led to the development of dual luminescent and colorimetric anion sensors based on the use of the ICT based naphthalimide chromophore, where ions such as fluoride gave rise to changes in both the fluorescence and the absorption spectra of the sensors, but at different concentrations. Here, the former changes were due to hydrogen bonding interactions, whereas the latter was due to the deprotonation of acidic protons, giving rise to the formation of the bifluoride anion (HF2−). Modification of the 4-amino-l,8-naphthalimide moiety has facilitated the formation of colorimetric anion sensors that work both in organic or aqueous solutions. Such charge neutral receptor motifs have also been incorporated into organic scaffolds with norbomyl and calixarene backbones, which have enabled us to produce anion directed self-assembled structures.

Determining binding constants from 1H NMR titration data using global and local methods : a case study using [n]polynorbornane-based anion hosts

From data generated using 1H NMR titrations, different methodologies to calculate binding constants are compared. The ‘local’ analysis method that uses only a single isotherm (only one H-bond donor) is compared against the ‘global’ method (that includes many or all H-bond donors). The results indicate that for simple systems both methods are suitable, however, the global approach consistently provides a K a value with uncertainties up to 30% smaller. For more complex binding, the global analysis method gives much more robust results than the local methods. This study also highlights the need to explore several different modes when data do not fit well to a simple 1:1 complexation model and illustrates the need for better methods to estimate uncertainties in supramolecular binding experiments.

On the use of 'shortcuts' in the method of continuous variation (Job's method)

The use of modified Job plot methodology provides a quick and easy means for evaluating host-guest stoichiometry and requires less material than the original method. In this short paper, the results of a recent anion recognition study using thiourea-functionalised norbornanes and [n]polynorbornanes are presented. A significant difference between the plots constructed using the original and modified method was observed and, as such, caution is advised when the modified Job's method is solely used for the determination of host-guest stoichiometry.

Development of a resin based silica monolithic column encapsulation

As monolithic columns become more extensively used in separation based applications due to their good flow and high surface characteristics, there has arisen the need to establish simple, reliable fabrication methods for fluidic coupling and sealing. In particular, the problem of liquid tracking between a monolith's outer surface and the sealing wall, resulting in poor flow-through performance, needs to be addressed. This paper describes a novel resin-based encapsulation method that penetrates 0.3 mm into the outer surface of a 4 mm diameter monolith, removing the so-called wall-effect. Results based on the peak analysis from 1 μL of 0.4% thiourea injected into a 98:2 water:methanol mobile phase flowing at 1 mL min^-1 indicate excellent flow conservation through the monolith. A comparison of peak shape and height equivalent to a theoretical plate (HETP) data between the reported resin-based method and the previously reported heat shrink tubing encapsulation methodology, for the same batch of monoliths, suggests the resin based method offers far superior flow characteristics. In addition to the improved flow properties, the resin casting method enables standard polyether ether ketone (PEEK) fittings to be moulded and subsequently unscrewed from the device offering simple reliable fluidic coupling to be achieved.

Hg2+ -selective fluorescent probe based on rhodamine 6G and its application in aqueous media

Based on rhodamine 6G, a highly sensitive and selective fluorescent sensor R6G1 for Hg2+ detection had been designed and prepared. It was synthesized through the well-known reaction that thiourea derivatives with amine could easily be transformed into guanidine derivatives with the promotion of Hg2+. By coordination with Hg2+, R6G1 exhibited high sensitivity and selectivity over other metal ions in aqueous systems. Furthermore, fluorescence titration experiments established the well-fitted linearity function of the fluorescent intensity with the concentration of Hg2+ in aqueous solution. The results showed that R6G1 provided high water solubility and high selectivity toward Hg2+ but no significant response toward other competitive cations and anions. It was suggested that the chemosensor would find its application in environmental field requiring rapid and accurate Hg2+ ion analysis.