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.

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.

Norbornenes and [n]polynorbornanes as molecular scaffolds for anion recognition

In total, 18 novel norbornene and [n]polynorbornane based anion receptors were synthesised and evaluated. The host:guest complexes examined were influenced by the position and number of available recognition sites within each binding cleft. It was concluded that [n]polynorbornane scaffolds are ideal for studying the fundamental concepts of supramolecular chemistry.

Examples of regioselective anion recognition among a family of two-, three-, and four-"armed" bis-, tris-, and tetrakis(thioureido) [n]polynorbornane hosts

A family of conformationally preorganized, [n]polynorbornane-based anion hosts 1a,b–6a,b have been synthesized. The series includes receptors with 4, 8, and 12 H-bond donors. Using ¹H NMR titration techniques, evaluation of the new hosts against a series of alkyl and aryl dicarboxylates as well as a range of phosphoanionic species has revealed that the tris(thioureido) hosts (in particular 3a) are capable of regioselectively binding dicarboxylates and pyrophosphate (H₂PPi^2–).

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.

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.

Factors influencing anion binding stoichiometry : the subtle influence of electronic effects

Six new, charge-neutral norbornene-based receptors 1a,1b– 3a,3b were prepared, and their ability to interact with simple anions in DMSO was investigated using 1H NMR and UV/ Vis spectroscopy. Binding of dihydrogenphosphate by the six receptors appeared to be based solely on steric constraints. In contrast, the binding stoichiometry of 3a and 3b to acetate was controlled by subtle electronic factors.

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.

Using steric bulk for selective recognition; blocking the binding site to differentiate guests

Selectivity is demonstrated in a supramolecular host:guest system using a receptor with a non-linear binding site. For the "open" receptor 1 strong binding for both flexible and rigid guests was observed. Receptor 2, with a "blocked" binding site, also bound flexible guests effectively but its affinity for rigid guests was 50 fold lower.

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.

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.

Modular synthesis of linear Bis- and Tris-monodentate fused [6]Polynorbornane-Based Ligands and their assembly into coordination cages

A modular approach has been developed for the synthesis of rigid linear di- and tritopic ligands based on a fused [6]polynorbornane scaffold. The design provides up to three sites for installing functionality, including both "ends" and a "central" position with the advantage that each region can be independently addressed during synthesis. To illustrate the utility of the approach, both pyridyl and picolyl units were incorporated to provide six new ligands, with centers and ends either matched or mismatched. Indeed, both [M2 L4 ] cages with endohedral functionality and [M3 L4 ] complexes were cleanly produced from these ligands with assembled structures confirmed by using (1) H NMR spectroscopy, HRMS, and molecular modelling.

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.

Desymmetrization of an octahedral coordination complex Inside a self-assembled exoskeleton

The synthesis of a centrally functionalized, ribbon-shaped [6]polynorbornane ligand L that self-assembles with PdII cations into a (Pd2L4) coordination cage is reported. The shape-persistent (Pd2L4) cage contains two axial cationic centers and an array of four equatorial H-bond donors pointing directly towards the center of the cavity. This precisely defined supramolecular environment is complementary to the geometry of classic octahedral complexes [M(XY)6] with six diatomic ligands. Very strong binding of [Pt(CN)6]2- to the cage was observed, with the structure of the host-guest complex ([Pt(CN)6]@Pd2L4) supported by NMR spectroscopy, MS, and X-ray data. The self-assembled shell imprints its geometry on the encapsulated guest, and desymmetrization of the octahedral platinum species by the influence of the D4h-symmetric second coordination sphere was evidenced by IR spectroscopy. [Fe(CN)6]3- and square-planar [Pt(CN)4]2- were strongly bound. Smaller octahedral anions such as [SiF6]2-, neutral carbonyl complexes ([M(CO)6]; M=Cr, Mo, W) and the linear [Ag(CN)2]- anion were only weakly bound, showing that both size and charge match are key factors for high-affinity binding.