Organic cage

Abstract

The invention generally relates to organic cages and in particular to alkali and alkline earth metal organic cages. The invention also relates to a method of making an organic cage, a method of lithium separation and use of an organic cage for lithium separation. The organic cage comprises at least one first ligand having at least one electron donating binding moiety, at least one second ligand having at least one electron donating binding moiety, and at least one metal ion selected from an alkali or alkaline earth metal ion, where the at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage. Each of the at least one binding pockets has one electron donating binding moiety of at least one first ligand and one electron donating binding moiety of at least one second ligand, and each of the at least one metal ions is multiply coordinated to the binding moieties in one of the at least one binding pocket.

Description

[0001] ORGANIC CAGE

[0002] Related Application

[0003] The present case claims priority to, and the benefit of, GB 2409805.5 filed on 5 July 2024 (05.07.2024), the contents of which are incorporated by reference in their entirety.

[0004] The project leading to this application and the priority application has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 695009 — FunCapSys).

[0005] Technical Field

[0006] This invention relates to organic cages and in particular to alkali and alkaline earth metal organic cages. The invention also relates to a method of making an organic cage, a method of lithium separation and use of an organic cage for lithium separation.

[0007] Background

[0008] Alkali and alkaline earth metals are relatively abundant elements on Earth, with extensive reserves found in minerals, clays, brines, and seawater. Alkali and alkaline earth metals have many uses ranging from industrial to medical applications. In particular, lithium is currently highly sought after for utilization in lithium-ion batteries and can play a crucial role in pharmaceutical applications as well.

[0009] It is therefore desirable to be able to extract alkali and alkaline earth metals so that they can be exploited. However, the extraction of alkali and alkaline earth metals from natural reserves can be complex. There are many components to separate from the different natural reserves containing alkali and alkaline earth metals.

[0010] Alkali and alkaline earth metals can be used in industrial processes and in products. It is generally desirable to be able to re-isolate alkali or alkaline earth metals after use in such processes or when products are recycled.

[0011] It is desirable to provide methods and materials to separate the alkali and alkaline earth metals from mixtures.

[0012] It is also desirable to isolate one alkali or alkaline earth metal from the mixture of alkali and alkaline earth metals. Alkali and alkaline earth metals share similar chemical and physical properties making separation of these metals difficult.

[0013] For example, known methods for selectively extracting alkali metals from other alkali metals are based on ionic radius considerations, and are focussed on the use of crown ether and cryptands. This approach can effectively discriminate between alkali metals, for example 12-crown-4 displays a preference for binding Li+, 15-crown-5 for Na+, and 18-crown-6 for K+. However, this approach does not effectively discriminate between all alkali and alkaline earth metals. For example, ionic radius-based separation in this way lacks the ability to differentiate between Li+and Mg2+due to their closely matched ionic radii (ru+= 76 pm, rMg2+ = 72 pm). Membrane methods based on the Donnan effect can efficiently reject multiple charged alkaline earth metals such as Mg2+, Ca2+, and other multivalent ions from a mixture whilst allowing alkali metal ions such as Li+to pass through. Such membrane methods cannot effectively separate of Li+or Na+ions (or other monovalent ions).

[0014] A typical industrial separation method used to obtain lithium involves a multi step brine evaporation. In this method, before lithium is precipitated from the water phase, magnesium must first be precipitated by the addition of lime (Ca(OH)2) to the brine. Without isolating magnesium ions first, the magnesium ions will precipitate together with the lithium ions.

[0015] The present invention has been devised in light of the above considerations. There is currently a need for new methods for the isolation of alkali and alkaline earth metals. There is also a need for methods which can effectively separate lithium from a metal mixture.

[0016] Summary of the Invention

[0017] In a general aspect, the present invention relates to an organic cage, as described herein, methods of making the organic cage, and methods of lithium separation using the organic cages of the invention.

[0018] In a first aspect there is provided an organic cage. The organic cage has at least one first ligand having at least one electron donating binding moiety, at least one second ligand having at least one electron donating binding moiety; and at least one metal ion selected from an alkali or alkaline earth metal ion. The at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage. Each of the at least one binding pockets has at least one electron donating binding moiety of one of the at least one first ligands and at least one electron donating binding moiety of one of the at least one second ligands. Each of the at least one metal ions is multiply coordinated to the binding moieties in one of the at least one binding pockets.

[0019] As used herein, the terms “first ligand” and “second ligand” refer to the parts of the organic cage originating from the respective starting components after formation of the polyhedral cage and also to denote the starting components of the organic cage. In the former case, the reactive terminal groups of the starting components have undergone reaction in order to covalently bind the first and second ligands together to form the polyhedral cage. The meaning of the term in each particular case will be clear from context, for example, when discussing the first ligand in the polyhedral cage it is clear that the term refers to the part of the cage formed by the first ligand.

[0020] As used herein the term “ligand” refers to a molecule having a functional group or groups that are capable of ligating to a metal such as an alkali or alkaline earth metal. In the present case, the ligand is capable of binding an alkali or alkaline earth metal via the at least one electron donating binding moiety present.

[0021] As used herein the term “electron donating binding moiety” refers to an atom in the ligand or a group of linked atoms (i.e. a functional group) in the ligand that are capable of donating electrons e.g. because they have high electron density or a lone pair. These ‘donated electrons’ can form non-covalent bonding interactions with electron poor species such as alkali and alkaline earth metal cations. Some examples of suitable electron donating binding moieties include amine, imine, nitrogen containing heterocycles (e.g pyridine or pyrrolidine), cyano, ether, carboxylate and phenolate groups.

[0022] In the case of ether, carboxylate and phenolate groups the electron donation is provided by the oxygen atoms in these groups. In the case of amine, imine, nitrogen containing heterocycles and cyano the electron donation is provided by the nitrogen atoms in these groups.

[0023] As used herein the term “polyhedral cage” refers to a 3-dimensional scaffold or shape formed by the first and second ligand after they have covalently bonded together. Put another way, the term “polyhedral cage” defines an isolated three-dimensional structure and does not encompass extended or polymeric structures such as extended or polymeric helicates. That is, the organic cage of the present invention is not an extended or polymeric helicate. The first and second ligands may form the vertices (e.g. caps), faces or edges of a polyhedral shape to form the polyhedral cage. Preferably, the first ligands form the vertices and the second ligands form the faces of the polyhedral cage. As will be understood, the number of first and second ligands is then determined by the number of vertices or faces of the polyhedral cage respectively. For example, in the case of a tetrahedral cage there will be four first ligands forming the four vertices and four second ligands forming the faces. Use of this type of terminology for the description of metal organic cages and frameworks is well known in the art. For example, it is understood to the skilled person that the polyhedral cage may not be a mathematically ‘perfect’ shape, rather it refers to the arrangement of the components making up the cage in space.

[0024] Transition metals have been widely used to template construction of diverse structures including cage structures. Until now, alkali and alkaline earth metals have not been similarly utilised. It is proposed that the weak and non-directional nature of interactions between alkali or alkaline earth metals and organic ligands make templating difficult to achieve using these metals.

[0025] The first aspect of the present invention provides an organic cage containing alkali or alkaline earth metal ions formed through the self assembly of at least one first ligand and at least one second ligand into a polyhedral cage templated by an alkali or alkaline earth metal ion. The first and second ligands contain at least one electron donating binding moiety each that form a binding pocket inside the polyhedral cage. The provision of multiple coordination sites at a single binding site (i.e., localised) facilitates binding of one of the at least one alkali or alkaline earth metal ions present.

[0026] The binding pockets e.g., the binding pockets in each corner of the polyhedral cage may be represented as spheres. Preferably, the diameter of each binding pocket is 4 to 5 A, such as 4.5 to 5 A.

[0027] The size of the binding pocket may be measured from the crystal structure by estimating the corner of the polyhedral cage as a sphere and measuring the diameter of the sphere that would fit into the corner based on its size from the crystal structure. The size of the binding pocket may preferably be determined by measuring the distance between a coordinated metal ion and each of the electron donating binding moieties it is bound to in the crystal structure and calculating the mean average distance. The mean average distance corresponds to the radius of the sphere and can be multiplied by 2 to give the diameter. It is proposed that the provision of electron donating binding moieties in a localised part of the organic cage allows for coordination of alkali and alkaline earth metals despite the non- directional nature of the interactions between the alkali / alkaline earth metal ions and organic ligands.

[0028] In this way, the organic cage of the invention can effectively bind alkali and alkaline earth metals.

[0029] The localised binding assists both in binding the alkali or alkaline earth metal ions but also allows the structure to be templated during formation by an alkali or alkaline earth metal ion. The organic cages may be effectively utilised in the extraction of alkali and alkaline earth metals from mixtures. The cages can then be separated from the mixture and the metal removed from the cage.

[0030] Further, under various routine conditions the cage environment may be adjusted to bind preferentially to one alkali or alkaline earth metal over the others allowing further separation. For example, kinetic vs thermodynamic conditions may be utilised to shift the favour of binding from one alkali or alkaline earth metal to another. Additionally, the choice of solvent can shift the binding preference of the organic cage between alkali or alkaline earth metals. For example, use of oxygen rich solvent (e.g. alcohols or wet acetonitrile) can prefer more oxophilic metal ions such as lithium.

[0031] In a second aspect there is provided an organic cage. The organic cage has at least one first ligand having at least one electron donating binding moiety and at least one second ligand having at least one electron donating binding moiety. The at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage. Each of the at least one binding pockets has at least one electron donating binding moiety of one of the at least one first ligands and at least one electron donating binding moiety of one of the at least one second ligands. In the organic cages of the second aspect at least one first or second ligand is protonated in the polyhedral cage.

[0032] It is proposed that protonation of the organic cage prevents the entry of divalent metal ions such as Mg2+and Ca2+by increasing electrostatic repulsion, and also decreases the number of available electron donating binding moieties for metal ion coordination. The synergistic impact of these effects facilitates kinetic formation of a protonated lithium organic cage.

[0033] In this way, the protonated organic cage of the invention can effectively bind alkali metals, particularly lithium ions, in preference to alkaline earth metals. The protonated organic cages may be effectively used to extract and separate alkali metals from mixtures including alkaline earth metals. The cages can then be separated from the mixture and the metal removed from the cage.

[0034] In some embodiments of the first and second aspect of the invention, the polyhedral cage formed by the at least one first ligand and the at least one second ligand has one binding pocket in each corner. The term “corner” as used herein refers to the space inside the polyhedral cage at the vertices of the polyhedral structure. In some embodiments of the organic cage of the first or second aspect each binding pocket comprises at least four electron donating binding moieties.

[0035] In this way, the binding pocket has high electron -density and is particularly suitable for chelating alkali and alkaline earth metal ions.

[0036] Preferably, the alkali or alkaline earth metal ion is selected from the group consisting of Li+, Na+, Mg2+and Ca2+.

[0037] Where compatible, preferred features of the first aspect apply equally to the second aspect.

[0038] In a third aspect there is provided a method of making an organic cage according to the first or second aspect. The method comprises the steps of: i) combining one of the first or second ligand with the at least one alkali or alkaline earth metal ion in a solvent; ii) adding the other of the first or second ligand to the mixture obtained in step i); iii) heating the mixture of step ii) to a temperature of 24 to 60 °C; iv) concentrating the mixture of step iii) and adding diethyl ether to obtain a precipitate; and v) washing and collecting the precipitate.

[0039] In this way, self assembly of an alkali or alkaline earth metal organic cage comprising at least one first ligand and at least one second ligand, where the ligands are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage, may be achieved despite the weak, non-directional interactions between organic ligands and alkali and alkaline earth metal ions.

[0040] Preferred features of the first and second aspect equally apply to the third aspect.

[0041] In a fourth aspect there is provided a method of lithium separation, the method comprising the steps of: i) providing an organic cage according to the second aspect, ii) adding the organic cage to a metal ion mixture comprising lithium cations; iii) adding a non-polar organic solvent to the mixture to form a precipitate; and iv) collecting the precipitate and adding a polar solvent to obtain a solution comprising lithium cations.

[0042] Preferred features of the first and second aspect equally apply to the fourth aspect.

[0043] In this way, lithium ions may be separated from mixtures (e.g. from natural deposits) comprising different metal ions, particularly other alkali and alkaline earth metal ions.

[0044] In a fifth aspect there is provided a use of an organic cage for lithium separation, where the organic cage is according to the first or second aspect.

[0045] Preferred features of the first and second aspect equally apply to the fifth aspect. The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0046] Summary of the Figures

[0047] Figure 1 shows the chemical structures of a first (A) and second (B) ligand according to the present invention and the structure of a lithium organic cage (1 ) and a sodium organic cage (2) of the invention after self assembly of the ligands. Figure 1 also depicts the synthesis of a magnesium (3) and calcium (4) organic cage according to the present invention through transmetalation of a sodium organic cage of the invention , and depicts the synthesis of a protonated organic cage (5) according to the present invention through the protonation of a sodium organic cage of the invention.

[0048] Figure 2 shows the crude1H NMR spectra for a magnesium organic cage of the invention obtained by self assembly and by transmetalation.

[0049] Figure 3 shows the crude1H NMR spectra for a calcium organic cage of the invention obtained by self assembly and by transmetalation.

[0050] Figure 4a depicts the synthesis of a protonated lithium organic cage (T4H+) of the present invention through the protonation of a lithium organic cage (1 ) of the invention. Figure 4b shows the comparison of1H NMR spectra of a lithium organic cage and a protonated lithium organic cage of the present invention. Figure 4c shows the comparison of7Li NMR spectra of a lithium organic cage and a protonated lithium organic cage of the present invention. Figure 4d shows the X-ray crystal structure of a lithium organic cage and a protonated lithium organic cage of the present invention. Figure 4e shows the1H NMR and23Na NMR spectra of a sodium organic cage of the present invention. Figure 4f shows the X-ray crystal structure of a sodium organic cage of the present invention.

[0051] Figure 5a schematically represents the comparison of binding preference of a protonated organic cage (5) according to the present invention to lithium ions and its analogues. Figure 5b schematically depicts the method of lithium separation of the present invention.

[0052] Figure 6 shows1H NMR spectra for species formed during the lithium separation process outlined in Figure 5 by a protonated cage of the present invention. Figure 6 shows the1H NMR spectrum of a protonated cage in CD3CN before addition of cations (top plot), the crude1H NMR spectrum taken 5 minutes after addition of the protonated cage to a cation mixture indicating an immediate formation of protonated lithium cage after mixing the protonated cage and cations (middle plot), and a crude1H NMR spectrum indicating decomposition of protonated lithium cage overnight (bottom plot).

[0053] Figure 7 shows the1H NMR spectra for a lithium organic cage of the invention. Detailed Description of the Invention

[0054] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0055] In a general aspect, the present invention relates to an organic cage, as described herein, methods of making the organic cage, and its use in methods of lithium separation.

[0056] The invention is based on the finding that the use of ligands having reactive groups and providing multiple coordination sites allows the self assembly of metal organic cages using alkali and alkaline earth metals. In turn, such cages can be used to extract these types of metals from mixtures. It was also found that protonated forms of these organic cages can show preferential binding between alkali and alkaline earth metals. In some such cases there is a preference for lithium over other alkali and alkaline earth metals. This allows the separation of these useful and hard to separate metals.

[0057] Organic Cage

[0058] Specifically, in a first aspect there is provided an organic cage. The organic cage has at least one first ligand having at least one electron donating binding moiety, at least one second ligand having at least one electron donating binding moiety; and at least one metal ion selected from an alkali or alkaline earth metal ion. The at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage. Each of the at least one binding pockets has at least one electron donating binding moiety of one of the at least one first ligands and at least one electron donating binding moiety of one of the at least one second ligands. Each of the at least one metal ions is multiply coordinated to the binding moieties in one of the at least one binding pockets. That is, there is preferably one metal at most in each binding pocket.

[0059] In a second aspect, there is provided an organic cage. The organic cage has at least one first ligand having at least one electron donating binding moiety and at least one second ligand having at least one electron donating binding moiety. The at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pockets inside the polyhedral cage. Each of the at least one binding pockets has at least one electron donating binding moiety of one of the at least one first ligands and at least one electron donating binding moiety of one of the at least one second ligands. In the organic cages of the second aspect at least one first or second ligand is protonated in the polyhedral cage.

[0060] Preferably, the at least one first or second ligand is protonated after formation of the polyhedron. That is, the at least one first or second ligand used as the starting components of the organic cage are not protonated, but at least one of the parts of the organic cage corresponding to these starting components are protonated after self assembly to form the polyhedral cage. In some embodiments, at least one first ligand in the polyhedral cage is protonated. Preferably, each first ligand in the polyhedral cage is protonated. Preferably, the at least one first ligand or each first ligand is protonated after formation of the polyhedral cage.

[0061] In other embodiments, at least one second ligand in the polyhedral cage is protonated. Preferably, each second ligand in the polyhedral cage is protonated. Preferably, the at least one second ligand or each second ligand is protonated after formation of the polyhedral cage.

[0062] In some embodiments of the first and second aspect of the invention, first ligand is a tridentate or tetradentate ligand. Preferably, the first ligand may be a tridentate Cs-symmetric ligand or a tetradentate Cs-symmetric ligand.

[0063] In some embodiments of the first and second aspect of the invention, the polyhedral cage formed by the at least one first ligand and the at least one second ligand has one binding pocket in each corner. The term “corner” as used herein refers to the space inside the polyhedral cage at the vertices of the polyhedral structure.

[0064] As described above, the binding pockets at the corners of the polyhedral cage provide high electron-density environments suitable for chelating alkali and alkali-metal ions. In addition, it is thought that protonation of the organic cage, particularly protonation occurring in the vicinity of the binding pockets, increases electrostatic repulsion between the binding pocket and any chelating metal ions, therefore hindering the entry of Mg2+and Ca2+’ and also reduces the number of available electron donating binding moieties. Therefore, it is possible adjust the selectivity of organic cage for certain alkali or alkali-metal ions. Such tailoring of the organic cages can be utilised in chemical separation, storage and catalysis.

[0065] The preferences described below equally apply to the organic cage of the first and second aspect.

[0066] Ligands

[0067] The first ligand and the second ligand of the organic cages of the first and second aspects of the invention are organic molecules having reactive terminal groups such that they can self assemble to form a polyhedral cage when combined. The terms first and second ligand are also used to refer to the parts of the polyhedral cage that are derived from the self assembly reaction between the precursor first and second ligand molecules.

[0068] The organic cages of the invention comprise at least one first ligand and at least one second ligand, where the at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage.

[0069] The type of polyhedral cage (tetrahedral, cubic etc.) will be determined by the structure and number of the first and second ligands. The skilled person will understand this based on their knowledge of metal organic cages. For example, the first ligands may form the vertices of the polyhedral cage. The shape (structure) of the first ligand and the arrangement of its electron donating binding moieties will play a role in determining the shape of the vertices (e.g. angles). In some cases, the first ligand may contain a central atom with sp3hybridisation providing a vertex suitable for a tetrahedral polyhedral cage. In such cases, there will be four first ligands. In such cases the second ligand may be selected to be a suitable shape (structure) to form the faces of the polyhedral cage.

[0070] The organic cage may comprise at least two first ligands, such as at least three first ligands, such as at least four first ligands. The organic cage may comprise at most 20 first ligands, such as at most ten first ligands, such as at most six first ligands, such as at most five first ligands. In some embodiments, the organic cage may comprise up to and including 20 first ligands, such as up to and including ten first ligands, such as up to and including six first ligands. Preferably, the organic cage may comprise four first ligands.

[0071] In some embodiments, the organic cage may comprise a number of first ligands selected from a range with the upper and lower amounts selected from the values given above. For example, in some embodiments the organic cage may comprise two to 20 first ligands, such as two to ten first ligands, such as two to six first ligands, such as two to five first ligands. In other embodiments, the organic cage may comprise three to 20 first ligands, such as four to 20 first ligands, such as five to 20 first ligands. Preferably, the organic cage may comprise two to six first ligands, more preferably four to six first ligands.

[0072] The organic cage may comprise at least two second ligands, such as at least three second ligands, such as at least four second ligands. The organic cage may comprise at most 30 second ligands, such as at most 20 ligands, such as at most ten ligands, such as at most six second ligands, such as at most five second ligands, such as at most four second ligands. In some embodiments, the organic cage may comprise up to and including 30 second ligands, such as up to and including 20 second ligands, such as up to and including ten second ligands, such as up to and including six second ligands. Preferably, the organic cage may comprise four second ligands.

[0073] In some embodiments, the organic cage may comprise a number of second ligands selected from a range with the upper and lower amounts selected from the values given above. For example, in some embodiments the organic cage may comprise two to 30 second ligands, such as two to 20 second ligands, such as two to ten second ligands, such as two to six second ligands, such as two to five second ligands. In other embodiments, the organic cage may comprise three to 30 second ligands, such as four to 30 second ligands, such as five to 30 second ligands. Preferably, the organic cage may comprise two to six second ligands, more preferably four to six second ligands.

[0074] In some embodiments, the organic cage may comprise an equal number of first and second ligands. The number of first and second ligands may be selected from the values given above.

[0075] Preferably, the organic cage may comprise four first ligands and four second ligands. In such cases the four first ligand may form the vertices of a tetrahedral cage and the four second ligands may for the faces of the tetrahedral cage.

[0076] Each of the first and second ligands comprises at least one electron donating binding moiety. This electron donating binding moiety is present in the polyhedral cage formed when the ligands are covalently bonded together. The polyhedral cage has at least one binding pocket inside the polyhedral cage. Each of the at least one binding pockets has at least one electron donating binding moiety of one of the at least one first ligands and at least one electron donating binding moiety of one of the at least one second ligands. In this way, each binding pocket of the organic cage provides a polydentate chelating environment suitable for binding alkali and alkaline earth metals.

[0077] In some embodiments of the first and second aspect of the invention, the polyhedral cage formed by the at least one first ligand and the at least one second ligand has one binding pocket in each corner. The term “corner” as used herein refers to the space inside the polyhedral cage at the vertices of the polyhedral structure.

[0078] In some embodiments of the organic cage of the first or second aspect, each binding pocket comprises at least four electron donating binding moieties.

[0079] In this way, the binding pocket has high electron -density and is particularly suitable for chelating alkali and alkali-metal ions. That is, coordination of alkali and alkaline earth metals may be achieved despite the weak, non-directional interactions of such metal ions with organic ligands.

[0080] The binding pockets in each corner of the polyhedral cage may be represented as spheres. In some embodiments, the diameter of each binding pocket may be 3 A or more, such as 3.5 A or more, such as 4 A or more. In some embodiments, the diameter of each binding pocket may be no more than 5.5 A, such as no more than 5 A. In some embodiments, the diameter of each binding pocket may be selected from a range with upper and lower amounts selected from the values given above. For example, in some embodiments, the diameter of each binding pocket may be 3 to 5.5 A, such as 3.5 to 5.5 A such as 4 to 5.5 A. In other embodiments, the diameter of each binding pocket may be 3 to 5 A, such as 3 to 4.5 A. Preferably, the diameter of each binding pocket is 4 to 5 A, such as 4.5 to 5 A.

[0081] The size of the binding pocket may be measured from the crystal structure by estimating the corner of the polyhedral as a sphere and measuring the diameter of the sphere that would fit into the corner based on its size from the crystal structure. Alternatively, when metal ions are coordinated with the organic cage, the metal ion may be seen as the centre of the sphere, with the coordinating electron donating moieties located on the surface of the sphere. The distance between each of the coordinating electron donating moieties and the metal ion in the binding pocket can be measured from the crystal structure and a mean average distance can be calculated. Th mean the average distance can be taken to be the radius of the sphere. The diameter can be calculated by multiplying the radius by two.

[0082] In some embodiments, each binding pocket comprises at least five electron donating binding moieties, such as at least six electron donating binding moieties, such as at least seven electron donating binding moieties, such as at least eight electron donating binding moieties. In some embodiments, each binding pocket comprises eight electron donating binding moieties or less, such as seven electron donating binding moieties or less, such as six electron donating binding moieties or less, such as five electron donating binding moieties or less.

[0083] In some embodiments, each binding pocket comprises a number of electron donating binding moieties selected from a range with the upper and lower amounts selected from the values given above. For example, in some embodiments, each binding pocket may comprise four to eight electron donating binding moieties, such as five to eight electron donating binding moieties, such as six to eight electron donating binding moieties. In other embodiments, each binding pocket may comprise four to seven electron donating binding moieties, such as four to six electron donating binding moieties, such as four to five electron donating binding moieties. When each binding pocket comprises a greater number of electron donating binding moieties, higher-order coordination with alkali or alkaline earth metal ion may be achieved.

[0084] Preferably, each binding pocket comprises six or seven electron donating binding moieties.

[0085] In this way, the electron-density provided by the electron donating binding moieties may be distributed around the binding pocket e.g. at the corners of the polyhedral cage, thereby improving coordination with alkali and alkaline earth metal ions despite the non-directional interactions of such metal ions with organic ligands.

[0086] In some embodiments, each of the at least one first ligand and the at least one second ligand provide the same number of electron donating binding moieties per binding pocket. In other embodiments, the at least one first ligand and the at least one second ligand provide a different number of electron donating binding moieties per binding pocket. Preferably, each of the at least one first ligand and the at least one second ligand provide a different number of electron donating binding moieties per binding pocket.

[0087] The number of binding moieties refers to the number of electron donating binding moieties from one, single, ligand. For example, if there are three second ligands, each ligand may provide the number of electron donating binding moieties discussed resulting in 3 x that number of electron donating binding moieties in a pocket.

[0088] In some embodiments, the same number of first and second ligands provide electron donating binding moieties to each binding pocket. In other embodiments, a different number of first and second ligands provide electron donating binding moieties to each binding pocket. Preferably, a different number of first and second ligands provide electron donating binding moieties to each binding pocket.

[0089] In embodiments where the at least one first ligand and the at least one second ligand each provide the same number of electron donating binding moieties per binding pocket, each of the at least one first ligand and the at least one second ligand may each provide two to four electron donating binding moieties, such as two to three electron donating binding moieties, such as three to four electron donating binding moieties.

[0090] Preferably, in embodiments where the at least one first ligand and the at least one second ligand each provide the same number of electron donating binding moieties, each of the at least one first ligand and the at least one second ligand each provide three electron donating binding moieties per binding pocket.

[0091] In embodiments where the at least one first ligand and the at least one second ligand provide a different number of electron donating binding moieties per binding pocket, each of the at least one first ligand may provide at least one electron donating binding moiety per binding pocket, such as at least two electron donating binding moieties, such as at least three electron donating binding moieties. In some embodiments, each of the at least one first ligand may provide at most six electron donating binding moieties per binding pocket, such as at most five electron donating binding moieties, such as at most four electron donating binding moieties. In some such embodiments, each of the least one second ligands may provide at least one electron donating binding moiety per binding pocket, such as at least two electron donating binding moieties per binding pocket, such as at least three electron donating binding moieties. In some embodiments, each of the at least one second ligand may provide at most six electron donating binding moieties per binding pocket, such as at most five electron donating binding moieties, such as at most four electron donating binding moieties.

[0092] In embodiments where each of the at least one first ligand and each of the at least one second ligand provide a different number of electron donating binding moieties per binding pocket, the number of electron donating binding moieties provided by each ligand may be selected from the values given above. For example, in some embodiments, each of the at least one first ligand may provide one electron donating binding moiety and each of the at least one second ligand may provide six electron donating binding moieties per binding pocket. In other embodiments, each of the at least one first ligand may provide four electron donating binding moieties and each of the at least one second ligand may provide one electron donating binding moieties per binding pocket. Preferably, each of the at least one first ligands may provide four electron donating binding moieties and each of the at least one second ligands may provide one electron donating binding moieties per binding pocket.

[0093] By providing one ligand with multiple electron donating binding moieties, the self assembly of the organic cages of the invention may be particularly facilitated.

[0094] In embodiments where a different number of first and second ligands provide electron donating binding moieties to each binding pocket, the number of first ligands that provide electron donating binding moieties to each binding pocket may be less than the number of second ligands that provide electron donating binding moieties to each binding pocket. In these embodiments, the number of electron donating binding moieties provided by each first and second ligand per binding pocket may be the same or different, as described above. In other embodiments, the number of first ligands that provide electron donating binding moieties to each binding pocket may be more than the number of second ligands that provide electron donating binding moieties to each binding pocket. In these embodiments, the number of electron donating binding moieties provided by each first and second ligand per binding pocket may be the same or different, as described above.

[0095] Preferably, the number of first ligands that provide electron donating binding moieties to each binding pocket is less than the number of second ligands that provide electron donating binding moieties to each binding pocket. For example, the number of first ligands that provide electron donating binding moieties to each binding pocket may be one, and the number of second ligands that provide electron donating binding moieties to each binding pockets may be two or more, such as three, such as four. Preferably, one first ligand and three second ligands may provide electron donating binding moieties to each binding pocket.

[0096] By providing a different number of the different types of ligands, the self assembly of the organic cages of the invention may be facilitated.

[0097] In some preferred embodiment, the number of first ligands that provide electron donating binding moieties to each binding pocket is less than the number of second ligands that provide electron donating binding moieties to each binding pocket and each of the at least one first ligand and each of the at least one second ligand provide a different number of electron donating binding moieties per binding pocket. In some such embodiments each of the at least one first ligands provides three or four electron donating binding moieties and each of the at least one second ligands provides one electron donating binding moieties per binding pocket. Preferably, one first ligand and three second ligands provide electron donating binding moieties to each binding pocket.

[0098] As defined herein, an electron donating binding moiety may be any moiety containing a group or atom capable of donating an electron, such as a nitrogen or oxygen atom.

[0099] In some embodiments, all the electron donating binding moieties per binding pocket are nitrogen atoms.

[0100] In some embodiments, the electron donating binding moieties provided by the first and / or second ligand may be part of the terminal reactive group of the first and / or second ligand prior to reaction of the ligands to form the polyhedral cage. In some embodiments, the electron donating binding moieties provided by the first and / or second ligand may be a part of the first and / or second ligand other than the terminal reactive group.

[0101] In embodiments having at least four electron donating binding moieties in each binding pocket, at least one of the at least four electron donating binding moieties is a nitrogen atom, preferably at least two of the at least four electron donating binding moieties per binding pocket are nitrogen atoms, such as at least three of the electron donating binding moieties, such as at least four of the electron donating binding moieties.

[0102] In some embodiments, the number of first ligands is equal to the number of vertices of the polyhedral cage, and the number of second ligands is equal to the number of faces of the polyhedral cage. For example, when the organic cage comprises four first ligands and four second ligands, the ligands may covalently bond so that they form a polyhedral cage having four vertices and four faces i.e., a tetrahedral cage. In another example, when the organic cage comprises eight first ligands and six second ligands, the ligands may covalently bond so that they form a polyhedral cage having eight vertices and six faces i.e., a cubic cage. Therefore, in some embodiments, the polyhedral cage is a tetrahedral cage. In other embodiments, the polyhedral cage is a cubic cage. In other embodiments, the polyhedral cage is a dodecahedral cage. Other possible polyhedra are known to the skilled person.

[0103] First Ligand

[0104] The organic cage of the present invention comprises at least one first ligand. Preferably, the term “first ligand” refers to the ligand which caps the vertices of the polyhedral cage. By “cap” it is meant that the ligand forms the vertex of the polyhedron.

[0105] In some embodiments, the first ligand may be a tridentate or tetradentate ligand. In some embodiments, the first ligand may be a Cs-symmetric ligand. Preferably, the first ligand may be a tridentate Cs-symmetric ligand or a tetradentate Cs-symmetric ligand. In some embodiments, the first ligand may be a tripodal ligand. Preferably, the first ligand is a tripodal, tridentate ligand or a tripodal, tetradentate ligand.

[0106] In this way, the self assembly maybe be coordinated by binding of a first ligand to an alkali or alkaline earth metal ion and reaction with a second ligand as described herein. In some embodiments, the first ligand may be N(R1X1)3or PY(R1X1)3where -R1- is a linker group, -X1is a terminal group, and Y is S, O or Se. In some embodiments, the first ligand may be N(R1X1)s where -R1- is a linker group and -X1is a terminal group. In other embodiments, the first ligand may be PY(R1X1)3where -R1- is a linker group, -X1is a terminal group and Y is S, O or Se.

[0107] As used herein, PY(R1X1)3is used to denote the following structure:

[0108] The group -R1- is a connection between the central N atom or central P atom and -X1.

[0109] In some embodiments, each -R1- is independently selected from C1-6 alkylene, C2-6 heteroalkylene, C5-10 arylene, or C3-3cycloalkylene. Preferably each -R1- is independently selected from C1-6 alkylene or C2-6 heteroalkylene, and more preferably each -R1- is C1-6 alkylene.

[0110] As used herein, the term “alkylene” refers to a divalent alkyl group.

[0111] As used herein, the term “heteroalkylene” refers to a divalent alkyl group in which one or more carbon atoms is replaced by a heteroatom.

[0112] As used herein the term “C5-10 arylene” refers to a divalent carboarylene or a heteroarylene group having 5 to 10 ring atoms. The carboarylene refers to a group which has a ring system comprising one ring or two or more fused rings, wherein at least one ring of the ring system, such as all rings in the ring system, is an aromatic ring and wherein the atoms in the ring are all carbon atoms. Heteroarylene refers to a group having the same structure as a carboarylene groups where one or more of the ring atoms is a heteroatoms (e.g. N, O, S). The one or more heteroatoms are preferably present as ring atoms in an aromatic ring. Preferably the one or more heteroatoms is a nitrogen atom.

[0113] As used herein the term “C3.3cycloalkylene” refers to a divalent carbocyclic or a heterocyclic group having 3 to 8 ring atoms. The carbocyclic cycloalkylene refers to a group which has a ring system comprising one ring or two or more fused rings, wherein the atoms in the ring are all carbon atoms. The heterocyclic cycloalkylene refers to a group having the same structure as a carbocyclic group where one or more of the ring atoms is a heteroatoms (e.g. N, O, S). Preferably the one or more heteroatoms is a nitrogen atom.

[0114] Where -R1- is C1-6 alkylene, this may be C1-5 alkylene, such as C1-4 alkylene, such as C1-3 alkylene, such as C1-2 alkylene. -R1- may be Ci alkylene, C2, alkylene, C3alkylene, C4 alkylene, C5 alkylene or C& alkylene. Representative examples of C1-6 alkylene include, but are not limited to, methylene, ethylene and n-propylene.

[0115] Preferably, -R1- is a linear C1-6 alkylene. More preferably, -R1- is C2 alkylene. Where -R1- is C2-6 heteroalkylene, this may be C2-5 heteroalkylene, such as C2-4 heteroalkylene, such as C2-3 heteroalkylene or C3-4 heteroalkylene. The subscript indicates the total number of atoms in the group.

[0116] The heteroalkylene contains one or two heteroatoms selected from O, S and (NH), such as one. Where the heteroalkylene contains two heteroatoms, the two heteroatoms are not neighbouring atoms. That is, the heteroatoms are not bonded to one another. Preferably the heteroalkylene is linear. The heteroatoms may act as electron donating binding moieties.

[0117] Where -R1- is C5-10 arylene or C3-8 cycloalkylene, this may be cyclohexylene or phenylene. In some embodiments where -R1- is C5-10 heteroarylene, this may be pyridinylene. In some embodiments, -R1- may be selected from the group cyclohexylene, phenylene or pyridinylene.

[0118] Each -X1group is connected to a -R1- group, and is a group suitable for reaction with a terminal group -X2of the second ligand to form a covalent bond such that the ligands may form a polyhedron.

[0119] In some embodiments, -X1is -NH2, -OH or -CHO. In some embodiments, -X1is -NH2 or -OH.

[0120] In some embodiments, -X1is -CHO. Preferably, -X1is -NH2.

[0121] In this way, in some embodiments, the X1group can react with the second ligand by nucleophilic attack of the nitrogen or oxygen (e.g. by nucleophilic attack on the X2group of the second ligand) to form the covalent bond between the first and second ligand. In other embodiments, the X1group can react with the second ligand as an electrophilic moiety for nucleophilic attack e.g. of the nitrogen or oxygen on the X2group of the second ligand to form the covalent bond between the first and second ligand.

[0122] Preferably, in the polyhedral cage, the X1group provides an electron donating binding moiety.

[0123] In some embodiments, each -X1group of the at least one first ligand, after reacting with a terminal -X2group of a second ligand, may comprise the electron donating binding moieties provided to the binding pockets of the organic cage by the first ligands. For example, if -X1is -NH2before reaction with -X2of the second ligand, the resulting group after reaction will contain a nitrogen atom bound to the second ligand and the nitrogen atom can donate a pair of electrons to act as an electron donating binding moiety in the polyhedral cage.

[0124] In some such cases, the central nitrogen atom of the first ligand is an additional electron donating binding moiety provided to the binding pocket by the at least one first ligand. Therefore, the first ligand may provide four electron donating binding moieties per binding pocket.

[0125] In embodiments where -X1is -NH2, the nitrogen atom may be the electron donating binding moiety after the group has reacted with a terminal -X2group of a second ligand.

[0126] When the first ligand is PY(R1X1)3, Y is S, O, or Se. Preferably, Y may be S.

[0127] Preferably, when the first ligand is N(R1X1)3, -R1- may be a linear C1-6 alkylene and -X1may be -NH2, such as -R1- may be a linear C2-4 alkylene and -X1may be -NH2. More preferably, -R1- may be C2 alkylene and -X1may be -NH2. In some embodiments, the first ligand may be:

[0128] NH2H2N^ / —f

[0129] When the first ligand isNH2, the first ligand may provide four electron donating binding moieties to each binding pocket after the first ligand has undergone reaction with terminal -X2groups of at least one second ligand. In these embodiments, the four electron donating binding moieties are nitrogen atoms.

[0130] When at least one first ligand is protonated in the polyhedral cage and the first ligand is N(R1X1)3, the central nitrogen atom of N(R1X1)3may be protonated, where R1and X1as defined above and where X1has reacted with a terminal group X2of a second ligand. Preferably, each central nitrogen atom of each N(R1X1)3first ligand present is protonated. For example, in a tetrahedral cage having four N(R1X1)3first ligands forming the vertices, each of the central nitrogen atoms forming the cap on the vertices is protonated.

[0131] In this way, the electrostatic repulsion between the organic cage and a chelating metal ion may be increased and the number of available electron donating binding moieties may be decreased. This allows for tailoring of the chemical and physical properties of the organic cages of the present invention. For example, protonation of at least one first ligand can lead to more selective binding of lithium ions. This enables direct kinetic separation of lithium ions from a mixture of cations by the protonated organic cage.

[0132] In other embodiments, when the first ligand is PY(R1X1)3, -R1- may be a C5-10 arylene, -X1may be -CHO, and Y may be S, such as -R1- may be a Ce arylene, -Xi may be -CHO, and Y may be S.

[0133] In some embodiments, the first ligand may be:

[0134] When the first ligand i the first ligand may provide three electron donating binding moieties to each binding pocket after the first ligand has undergone reaction with terminal -X2 groups of at least one second ligand. In these embodiments, the electron donating binding moieties are nitrogen atoms.

[0135] In some embodiments, the first ligand may be

[0136] Second Ligand

[0137] The organic cage of the present invention comprises at least one second ligand. In some preferred embodiments, the second ligand joins the first ligands at each vertices to form a polyhedral cage. Preferably, each second ligand forms a face of the polyhedral cage and joins the first ligands at the corners of said face.

[0138] In some embodiments, the second ligand is a tridentate or tetradentate ligand. In some embodiments, the second ligand may be a Cs-symmetric ligand. In other embodiments, the second ligand may be a C4-symmetric ligand.

[0139] In some embodiments, the second ligand may be A(R2X2)nwhere A is a branching group, -R2- is a linker group, -X2is a terminal group, and n is 2, 3, 4 or 5, such as n is 2, 3 or 4, preferably n is 3 or 4.

[0140] The group A is a branching group, and is connected to each -R2- group. In some embodiments, the group A is a ring or a single atom. The ring or single atom is capable of forming multiple bonds and may therefore act as a branching group.

[0141] In some embodiments, the group A is a ring. In some such embodiments, A is C5-10 arylene, C4-7 heterocyclylene or a porphyrin, such as C5-10 arylene or C4-7 heterocyclylene. Preferably, A is C5-10 arylene, such as C5 arylene or C& arylene and more preferably, A is C& arylene. When the group A is a C& arylene, planarity of the second ligand is maintained.

[0142] In other embodiments, A is C4-7 heterocyclylene, such as C4 heterocyclylene, such as C5 heterocyclylene, such as C& heterocyclylene. In other embodiments, the group A is a porphyrin ring, such as porphine.

[0143] In other embodiments, group A is single atom such as N or C.

[0144] The group -R2- is a connection between A and -X2.

[0145] In some embodiments, -R2- is C5-10 arylene.

[0146] Where the group -R2- is C5-10 arylene, this may be a carboarylene or a heteroarylene group. The carboarylene refers to a group which has a ring system comprising one ring or two or more fused rings, wherein at least one ring of the ring system, such as all rings in the ring system, is an aromatic ring, and which is attached at each connection point to the rest of the molecule by an aromatic ring. The heteroarylene refers to a group which has one or more heteroatoms (e.g. N, O, S) forming part of a ring system, wherein the ring system comprises one ring or two or more fused rings, wherein at least one ring of the ring system, such as all rings in the ring system, is an aromatic ring and which is attached at each connection point to the rest of the molecule by an aromatic ring atom. The one or more heteroatoms are preferably present as ring atoms in an aromatic ring. Preferably the one or more heteroatoms is a nitrogen atom. When -R2- is a C5-10 arylene wherein one or more ring atoms is a nitrogen atom, preferably -R2- is connected to A and / or to -X2via a carbon atom.

[0147] Preferably, when -R2- is arylene, -R2- is pyridinylene.

[0148] In some embodiments, the -R2- group may comprise the electron donating binding moieties provided to the binding pockets of the organic cage by the at least one second ligand. In embodiments where the -R2- group is a heteroarylene group, the one or more heteroatoms forming part of the ring system may be the electron donating binding moieties provided by the second ligand. For example, in some embodiments, the electron donating binding moiety provided by the second ligand may be a nitrogen, oxygen or sulfur heteroatom forming part of the ring system of the heteroarylene group. Therefore, the second ligand may provide at least one electron donating binding moiety per binding pocket.

[0149] When -R2- is pyridinylene, the pyridine nitrogen atom is the electron donating binding moiety.

[0150] Each -X2group is connected to a -R2- group, and is a group suitable for reaction with a terminal group -X1of the first ligand to form a covalent bond such that the ligands may form a polyhedral cage.

[0151] In some embodiments, -X2is an aldehyde, a nitroso group, a benzyl halide or an amine group. In some embodiments, -X2is an aldehyde, a nitroso group, or a benzyl halide. Preferably, -X2is aldehyde. Even more preferably, -R2- and -X2together form an aromatic aldehyde, such as pyridinaldehyde. In other preferred embodiments, -X2is an amine.

[0152] In this way, in some embodiments, the X2group can react with the first ligand as an electrophilic moiety for nucleophilic attack e.g. of the nitrogen or oxygen on the X1group of the first ligand to form the covalent bond between the first and second ligand. In other embodiments, the X2group can react with the first ligand by nucleophilic attack of the nitrogen or oxygen (e.g. by nucleophilic attack on the X1group of the first ligand) to form the covalent bond between the first and second ligand.

[0153] In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. Preferably, n is 3.

[0154] Preferably, A may be a C& aryl, -R2- may be pyridinylene, -X2may be an aldehyde and n may be 3. In other embodiments, A may be N, -R2- may be C& arylene and -X2may be an amine. In some embodiments, the second ligand may be selected from the following:

[0155] When the second ligand is selected from these compounds, the second ligand may provide one electron donating binding moiety to each binding pocket.

[0156] In other embodiments, the second ligand may be selected from the following: In some embodiments, the second ligand may be selected from the following:

[0157] When the second ligand is selected from these compounds, the second ligand may provide one electron donating binding moiety to each binding pocket. In these embodiments, the electron donating binding moieties are pyridine nitrogen atoms.

[0158] Preferably, the second ligand may be:

[0159] Assembly of the First and Second Ligands

[0160] During self assembly of the organic cage, the terminal -X1groups of at least one first ligand react with the terminal -X2groups of at least one second ligand in order to form a polyhedral cage.

[0161] -X1and -X2are as defined above. In some embodiments, one of -X1or -X2is an electrophile and the other of -X1or -X2is a nucleophile, preferably X1is a nucleophile and X2is an electrophile.

[0162] In some embodiments, one of -X1or-X2is -NH2 and the other of -X1or-X2is an aldehyde, preferably in such cases X1is -NH2and X2is an aldehyde.

[0163] In other embodiments, one of -X1or -X2is -NH2and the other of -X1or -X2is a nitroso group preferably in such cases X1is -NH2and X2is a nitroso group.

[0164] In other embodiments, one of -X1or -X2is -OH and the other of -X1or -X2is a benzyl halide, preferably X1is -OH and X2is a benzyl halide. Preferably, -X1is -NH2and -X2is aldehyde. In this case, the amine and the aldehyde groups react to form an imine group. In embodiments where an imine group results from the reaction between the -X1and -X2groups, the imine nitrogen may be the electron donating binding moiety provided to the binding pocket by the first ligand.

[0165] In some embodiments, the covalent bond formed between -X1of a first ligand and -X2of a second ligand may be subject to chemical change following formation of the polyhedron. For example, in some embodiments, a double bond formed between -X1of a first ligand and -X2of a second ligand may be reduced to a single bond. In this way, the stability of the organic cage may be altered. For example, when an imine group results from the reaction between the -X1and -X2groups, the carbon-nitrogen double bond may be reduced to a carbon-nitrogen single bond and the nitrogen atom of the imine group may be protonated.

[0166] The first and second ligands are as defined above. In some embodiments, the at least one first ligand may be N(R1X1)3or PY(R1X1)3and the at least one second ligand may be A(R2X2)n, where -R1-, -X1, Y, A, -R2-, -X2and n are as defined above. In some embodiments, the at least one first ligand may be N(R1X1)3and the at least one second ligand may be A(R2X2)n, where - R1-, -X1, A, -R2-, -X2and n are as defined above.

[0167] Specifically, in some embodiments, the at least one first ligand may be N(R1X1)3where -R1- is C1-6 alkylene and -X1is -NH2, and the at least one second ligand may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3.

[0168] In other embodiments, the at least one first ligand may be N(R1X1)3where -R1- is C2-6 heteroalkylene and -X1is -NH2, and the at least one second ligand may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3.

[0169] In other embodiments, the at least one first ligand may be PY(R1X1)3where -R1- is C5-10 arylene, -X1is -CHO, and Y is S, and the at least one second ligand may be A(R2X2)nwhere A is N, -R2- is a C5-10 arylene, -X2is amine and n is 3.

[0170] Preferably, the at least one first ligand may be N(R1X1)3where -R1- is C2alkylene and -X1is -NH2, and the at least one second ligand may be A(R2X2)nwhere A is a C& aryl, R2- is pyridinylene, -X2is an aldehyde and n is 3. The number of electron donating binding moieties provided by the first and second ligand for each binding pocket may be the same or different, as described above.

[0171] . . .. .

[0172] In preferred embodiments, the first ligand may the second ligand may be

[0173] In this embodiment, the amine -X1groups of the first ligand react with the -X2aldehyde groups of the second ligand to form imine groups. In this embodiment, each first ligand provides four nitrogen atoms as electron donating binding moieties per binding pocket, and each second ligand provides one nitrogen atom as an electron donating binding moiety per binding pocket. Specifically, the first ligand provides three imine nitrogen atoms (resulting from the reaction between the reactive terminal groups of the first and second ligands) and the central nitrogen atom, and the second ligand provides a pyridine nitrogen atom.

[0174] In some embodiments, the organic cage may comprise two to six first ligands, where the first ligands may be N(R1X1)3where -R1- is C1-6 alkylene and -X1is -NH2. In some embodiments, the organic cage may comprise two to six second ligands, where the second ligands may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3. In some embodiments, the organic cage may comprise two to six first ligands and two to six second ligands, where the first ligands may be N(R1X1)3where -R1- is C1-6 alkylene and -X1is -NH2, and the second ligands may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3. In some embodiments, the organic cage may comprise two to six first ligands and two to six second ligands, where the first ligands may be N(R1X1)3where -R1- is C1-6 alkylene and -X1is -NH2, and the second ligands may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3, and both the first and second ligands provide electron donating binding moieties for each binding pocket. The number of electron donating binding moieties provided by the first and second ligands for each binding pocket may be the same or different, as described above.

[0175] In some embodiments, the organic cage may comprise four first ligands, where the first ligands may be N(R1X1)3where -R1- is C1-6 alkylene and -X1is -NH2. Preferably, the organic cage may comprise four first ligands may be N(R1X1)3where -R1- is C2alkylene and -X1is -NH2. In some embodiments, the organic cage may comprise four second ligands, where the second ligands may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3. Preferably, the organic cage may comprise four second ligands, where the second ligands may be A(R2X2)nwhere A is a C& aryl, R2- is pyridinylene, -X2is an aldehyde and n is 3. In some embodiments, the organic cage may comprise four second ligands, where the second ligands may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3. Preferably, the organic cage may comprise four second ligands, where the second ligands may be A(R2X2)nwhere A is a Ce aryl, R2- is pyridinylene, -X2is an aldehyde and n is 3, and both the first and second ligands provide electron donating binding moieties for each binding pocket. The number of electron donating binding moieties provided by the first and second ligands for each binding pocket may be the same or different, as described above.

[0176] In some embodiments, the organic cage may comprise four first ligands and four second ligands, where the first ligands may be N(R1X1)3where -R1- is C1-6 alkylene and -X1is -NH2, and the second ligands may be A(R2X2)nwhere A is a ring, -R2- is C5-10 arylene, -X2is aldehyde and n is 3. Preferably, the organic cage may comprise four first ligands and four second ligands, where the first ligands may be N(R1X1)3where -R1- is C2alkylene and -X1is -NH2, and the second ligands may be A(R2X2)nwhere A is a Ce aryl, R2- is pyridinylene, -X2is an aldehyde and n is 3. More preferably, the organic cage may comprise four first ligands and four second ligands, where the first ligands may be N(R1X1)3where -R1- is C2alkylene and -X1is -NH2, and the second ligands may be A(R2X2)nwhere A is a Ce aryl, R2- is pyridinylene, -X2is an aldehyde and n is 3, and the first ligands provide three electron donating binding moieties per binding pocket and the second ligands provide one electron donating binding moiety per binding pocket.

[0177] In preferred embodiments, the organic cage may be:

[0178] In these embodiments, the organic cage comprises four first ligands and four second ligands, where the first ligands are

[0179] In these embodiments, the four first ligands and the four second ligands are covalently bonded such that they form a tetrahedral cage. In these embodiments the amine groups of the first ligand and the aldehyde groups of the second ligand react to form imine groups during formation of the tetrahedron.

[0180] In these embodiments, each first ligand provides four nitrogen atoms as electron donating binding moieties per binding pocket, and each second ligand provides one nitrogen atom as an electron donating binding moiety per binding pocket. Specifically, the first ligand provides three imine nitrogen atoms (resulting from the reaction between the reactive terminal groups of the first and second ligands) and the central nitrogen atom, and the second ligand provides a pyridine nitrogen atom. In total, each binding pocket receives four nitrogen electron donating binding moieties from a first ligand and three nitrogen electron donating binding moieties from three second ligands.

[0181] In other embodiments, the first ligand may be and the second ligand may

[0182] In these embodiments, the aldehyde -X1groups of the first ligand react with the -X2amine groups of the second ligand to form imine groups. In this embodiment, each first ligand provides three nitrogen atoms as electron donating binding moieties per binding pocket, and each second ligand provides one nitrogen atom as an electron donating binding moiety per binding pocket. Specifically, the first ligand provides three pyridine nitrogen atoms and the central nitrogen atom, and the second ligand provides an imine nitrogen atom.

[0183] In some embodiments, the organic cage may comprise two to six first ligands, where the first ligands may be PY(R1X1)3where -R1- may be a C5-10 arylene, -X1may be -CHO, and Y may be S. In some embodiments, the organic cage may comprise two to six second ligands, where the second ligands may be A(R2X2)nwhere A is N, -R2- is C5-10 arylene, -X2is amine and n is 3. In some embodiments, the organic cage may comprise two to six first ligands and two to six second ligands, where the first ligands may be PY(R1X1)3where -R1- may be a C5-10 arylene, -X1may be -CHO, and Y may be S, and the second ligands may be A(R2X2)nwhere A is N, -R2- is C5-10 arylene, -X2is amine and n is 3. In some embodiments, the organic cage may comprise two to six first ligands and two to six second ligands, where the first ligands may be PY(R1X1)3where -R1- may be a C5-10 arylene, -X1may be -CHO, and Y may be S, and the second ligands may be A(R2X2)nwhere A is N, -R2- is C5-10 arylene, -X2is amine and n is 3, and both the first and second ligands provide electron donating binding moieties for each binding pocket. The number of electron donating binding moieties provided by the first and second ligands for each binding pocket may be the same or different, as described above. In some embodiments, the organic cage may be:

[0184] In these embodiments, the organic cage comprises four first ligands and four second ligands, where the first ligands are the second ligands are

[0185] Alkali and Alkaline earth Metals

[0186] The organic cage of the first aspect comprises at least one metal ion multiply coordinated to a first and second ligand. The metal ion is an alkali or alkaline earth metal ion. In some embodiments, the alkali or alkaline earth metal ion is selected from the group consisting of Li+, Na+, Mg2+and Ca2+. Preferably, the alkali or alkaline earth metal ion is Li+.

[0187] It is proposed that the present invention provides alkali and alkaline earth metal organic cages through the self assembly of at least one first ligand and at least one second ligand to form a polyhedral cage which is suitable for coordination with alkali and alkaline earth metal ions. Particularly, the binding pocket(s) of the polyhedral cage provide high electron-density environments suitable for chelating alkali and alkali-metal ions. It is proposed that the provision of electron donating binding moieties in a localised part of the organic cage allows for coordination of alkali and alkaline earth metals despite the non-directional nature of the interactions between the alkali / alkaline earth metal ions and organic ligands.

[0188] In some embodiments, the organic cage of the second aspect comprises at least one metal ion multiply coordinated to a first and second ligand. The metal ion is an alkali or alkaline earth metal ion, where the alkali or alkaline earth metal ion is Li+.

[0189] Protonation of the organic cage hinders the entry of divalent metal ions such as Mg2+and Ca2+by increasing electrostatic repulsion around the binding pockets, and also decreases the number of available electron donating binding moieties for metal ion coordination. The synergistic impact of these effects facilitates formation of a protonated lithium organic cage, presenting the preferential binding of lithium. These effects can therefore be exploited for the separation of alkali and alkaline earth metals from mixtures by adjusting the selectivity of the organic cage for the metal of interest.

[0190] Encapsulation

[0191] In some embodiments, the organic cage of the invention may be encapsulated in a matrix such as a polymer.

[0192] In this way, the organic cage is immobilised. The encapsulated organic cage may be easier to handle whilst maintaining the selectively for alkali and alkaline earth metals. This may allow the organic cages of the invention to be more readily used in existing separation processes.

[0193] In some embodiments, the matrix is a polymer selected from polystyrene, and a copolymer or styrene and acrylamide. In some embodiments, the polymer may be a commercially available polymer, such as Amberlite™ IR120 Na+form.

[0194] In some embodiments, the polymer may be coupled to the at least one first ligand and / or the at least one second ligand. In some examples, the interactions between the polymer and the organic cage may be electrostatic, hydrophobic or TT-TT interactions, or a combination thereof.

[0195] In some embodiments of encapsulation, the protonated organic cage of the second aspect is encapsulated. Preferably the matrix in such cases is a polymer. In some such embodiments, the polymer is negatively charged or comprises negatively charged functional groups, such as sulfate groups. When the polymer is negatively charged, the interaction between the negatively charged polymer and the protonated organic cage may be electrostatic.

[0196] Preferred Organic Cages

[0197] Preferred organic cages of the invention are shown below.

[0198]

[0199] Lithium organic cage Sodium organic cage

[0200] Protonated lithium organic cage

[0201] Protonated organic cage

[0202] Lithium organic cage II In other preferred embodiments, the organic cage of the invention may be selected from the following cages:

[0203] Protonated lithium organic cage

[0204] Protonated organic cage Methods and Uses

[0205] The present invention provides a method of making an organic cage according to the first and second aspect. The inventors have established a method of self assembly of an alkali and alkaline earth metal ion organic cage despite the weak, non-directional interactions between organic ligands and alkali metal ions. These organic cages may be useful in the extraction of alkali and alkaline earth metals and in their separation. A method of making an organic cage according to the first or second aspect may comprise the steps of: i) combining one of the first or second ligand with the alkali or alkaline earth metal ions in a solvent; ii) adding the other of the first or second ligand to the mixture obtained in step i); iii) heating the mixture of step ii) to a temperature of 24 °C to 60 °C; iv) concentrating the mixture of step iii) and adding a low polarity solvent such as diethyl ether to obtain a precipitate; and v) washing and collecting the precipitate.

[0206] The preferred features relating to the first and second ligand previously described for the organic cage equally apply to the method of making an organic cage.

[0207] The method of making an organic cage may be carried out using purified alkali or alkaline earth metal salts to template the formation. In the case of producing a protonated cage of the second aspect, preferably the alkali or alkaline earth metal ion used in step i) is a sodium ion.

[0208] The resulting cage can then be isolated, optionally protonated, and used to extract or separate alkali and alkaline earth metals from mixtures e.g. from natural sources of these metals. In particular, some protonated cages of the invention show particular selectively for lithium over other metals and over alkaline earth metals.

[0209] Alternatively, the method can be carried out directly with mixtures of components e.g. from natural sources, providing the alkali or alkaline earth metal ions. In this way, extraction can occur as the cage structure is formed.

[0210] In some embodiments, step i) of the method may comprise combining the first ligand with the alkali or alkaline earth metal ion in a solvent and step ii) of the method may comprise adding the second ligand to the mixture obtained in step i). In other embodiments, step i) of the method may comprise combining the second ligand with the alkali or alkaline earth metal ion in a solvent and step ii) of the method may comprise adding the first ligand to the mixture obtained in step ii). Preferably, the step i) of the method comprises combining the second ligand with the alkali or alkaline earth metal ion in a solvent and step ii) of the method comprises adding the first ligand to the mixture obtained in step i). In this way, successful self assembly of the polyhedral cage structure is improved.

[0211] The alkali or alkaline earth metal ions may be provided by non-coordinating metal salts. In some embodiments, the non-coordinating metal salts may be selected from the group comprising M-NTf2, M-BF4, M-PFe or M-OTf where ‘M’ denotes the alkali or alkaline earth metal ion. Preferably, the non-coordinating salt is M-NTf2. In some embodiments, M may be Li or Na. Therefore, in some embodiments, the non-coordinating metal salt may be selected from Li-NTf2, U-BF4, Li-PFe or Li-OTf. In other embodiments, the non-coordinating metal salt may be selected from Na-NTf2, Na-BF4, Na-PF6or Na-OTf. Preferably, the non-coordinating metal salt is Li-NTf2or Na-NTf2.

[0212] Without wishing to be bound by theory, it is proposed that there is a need to balance the level of electrostatic interaction between the electron donating binding moieties of the first and / or second ligands and the metal cations to achieve the reversibility needed for consistent self assembly of polyhedral cages of the invention. For example, in some cases, monovalent cation such as Li+or Na+will be preferred for certain ligand combination to balance the electrostatic interactions and reversibility. In some such cases it is possible that the stronger electrostatic interaction of divalent cations such as Mg2+and Ca2+may lead to inconsistent formation of polyhedral cage structures.

[0213] In some embodiments, in step i) the solvent is selected from acetonitrile, nitromethane, acetone, dichloromethane or dimethylformamide. Preferably, the solvent in step i) is acetonitrile.

[0214] In step iii) of the method, the mixture of step ii) may be heated to a temperature of from 25 °C to 60 °C, such as 30 °C to 60 °C, such as 40 °C to 60 °C, such as 50 °C to 60 °C. In some embodiments, in step iii) of the method, the mixture of step ii) may be heated to a temperature of from 25 °C to 50 °C, such as 25 °C to 40 °C, such as 25 °C to 30 °C. In some embodiments, the mixture may be heated to a temperature up to and including 60 °C, such as 55 °C, such as 50 °C. In some embodiments, the mixture may be heated to a temperature of 30 °C or more, such as 35 °C or more, such as 40 °C or more, such as 45 °C or more. In some embodiments, in step iii) of the method, the mixture of step ii) may be heated to a temperature selected from a range with the upper and lower amounts selected from the values given above. In some embodiments, the mixture is heated to ambient temperature, such as around 25 °C. Preferably, the mixture is heated to 60 °C.

[0215] It is proposed that the application of heat to the mixture of step ii) accelerates formation of the organic cage. However, formation of the cage is still observed in the absence of applied heat.

[0216] In some embodiments, in step iii) of the method, the mixture of step ii) may be heated for 1 hour or more, such as 2 hours or more, such as 3 hours or more. In some embodiments, in step iii) of the method, the mixture of step ii) may be heated for up to 24 hours. Preferably, the mixture is heated for 1 hour. Most preferably, in step iii) of the method, the mixture of step ii) is heated to 60 °C for 1 hour.

[0217] The precipitation in step iv) is promoted the addition of low polarity solvent such as toluene, hexane or ethers such as methyl t-butyl ether or diethyl ether. Preferably diethyl ether is used. Other suitable low polarity solvents are known to the skilled person.

[0218] In some embodiments, washing and collecting the precipitate in step v) of the method comprises collecting the precipitate by centrifugation and washing the precipitate with excess diethyl ether. The washing step removes any excess metal ions that are not bound in the cage. Other solvents that are able to dissolve metal salts but do not dissolve the organic cage may be used.

[0219] In some embodiments, after step v) an alcohol such as n-BuOH may be added to the precipitate in order to extract the metal ions from the organic cage. After addition of the alcohol such as n-BuOH to the precipitate, the metal ions in the alcohol such as n-BuOH may be separated from the organic cage.

[0220] Protonation

[0221] The method of making an organic cage may further comprise a protonation step. In some embodiments, the protonation step may be carried out after step v) of the method. In some embodiments, when the method of making an organic cage comprises a protonation step, the organic cage comprises Na+ions.

[0222] When the method of making an organic cage comprises a protonation step, this allows for an organic cage where at least one of the first or second ligands is protonated. That is, an organic cage of the second aspect of the invention is provided.

[0223] In this way, selectivity of the organic cage for Li+ions may be improved.

[0224] In some embodiments, the protonation step may comprise stirring the collected precipitate of step v) with a Bronsted acid such as HCI, H2SO4, HNO3, and CH3COOH, or HNTf2, preferably HNTf2, in a solvent. Other Bronsted acids known to the skilled person may also be used as the protonating agent. In some embodiments, the protonation step further comprises stirring the mixture of precipitate and a Bronsted acid such as HNTf2for 10 minutes at room temperature.

[0225] Transmetalation

[0226] The method of making an organic cage may further comprise transmetalation after step v). As used herein, “transmetalation” refers to the exchange of coordinated metal ions in the organic cage.

[0227] In this way, an organic cage comprising a selected alkali or alkaline earth metal ion can be formed. For some ligand combinations, it may be that a cage is formed preferentially with an alkali metal compared to an alkaline earth metal. In such case, transmetalation can allow the production of that cage with the less preferred metal by transmetalation. Such metal exchange allows for tailoring of the chemical and physical properties of the organic cages of the present invention, which have potential application in chemical separation, storage and catalysis.

[0228] In some embodiments, transmetalation step may comprise the steps of: a) combining the collected precipitate of step v) with Mg- or Ca(NTf2)2in a solvent; b) heating the mixture of step a) to a temperature of 24 °C to 60 °C; c) concentrating the mixture of step b) and adding diethyl ether to obtain a precipitate; and d) washing and collecting the precipitate.

[0229] In some embodiments, the precipitate used in step a) comprises a metal organic cage where the metal is an alkali metal such as lithium or sodium.

[0230] In step b) of the transmetalation, the mixture of step a) may be heated to a temperature of from 25 °C to 60 °C, such as 30 °C to 60 °C, such as 40 °C to 60 °C, such as 50 °C to 60 °C. In some embodiments, in step b) of the transmetalation, the mixture of step a) may be heated to a temperature of from 25 °C to 50 °C, such as 25 °C to 40 °C, such as 25 °C to 30 °C. In some embodiments, the mixture may be heated to a temperature up to and including 60 °C, such as 55 °C , such as 50 °C. In some embodiments, the mixture may be heated to a temperature of 30 °C or more, such as 35 °C or more, such as 40 °C or more, such as 45 °C or more. In some embodiments, in step b) of the transmetalation, the mixture of step a) may be heated to a temperature selected from a range with the upper and lower amounts selected from the values given above. In some embodiments, the mixture is heated to ambient temperature, such as around 25 °C. Preferably, the mixture is heated to 60 °C.

[0231] In some embodiments, in step b) of the method, the mixture of step a) may be heated for 1 hour or more, such as 2 hours or more, such as 3 hours or more. In some embodiments, in step b) of the method, the mixture of step a) may be heated for up to 24 hours, such as up to 12 hours.

[0232] Preferably, in step b) of the transmetalation, the mixture of step a) is heated to 60 °C for 1 hour or more, more preferably up to 12 hours.

[0233] In some embodiments, washing and collecting the precipitate in step d) of the method comprises collecting the precipitate by centrifugation and washing the precipitate with excess diethyl ether.

[0234] Encapsulation

[0235] The method of making an organic cage according to the first or second aspect may further comprise encapsulating the cage in a matrix such as a polymer.

[0236] In some embodiments where an organic cage of the second aspect is encapsulated, encapsulating the cage in a polymer may be carried out after a protonation step has been carried out. In other such embodiments, encapsulating the cage in a polymer may be carried out before a protonation step.

[0237] When the method of making an organic cage comprises an encapsulation step, this allows for the polyhedron formed by the at least one first ligand and the at least one second ligand to be immobilised. The encapsulated organic cage may be easier to handle whilst maintaining the selectively for alkali and alkaline earth metals. This may allow the organic cages of the invention to be more readily used in existing separation processes.

[0238] In some embodiments, encapsulating the cage in a polymer comprises stirring the organic cage with a polymer in a solvent. In some embodiments, the polymer may be polystyrene or a copolymer or styrene and acrylamide. In some embodiments, the polymer may be a commercially available polymer, such as Amberlite™ IR120 Na+ form. In some embodiments, the solvent may be acetonitrile, nitromethane, acetone, dichloromethane, dimethylformamide or a combination thereof. Preferably, the solvent may be acetonitrile.

[0239] Method of Lithium Separation

[0240] Also provided herein is a method of lithium separation. The method of lithium separation may comprise the steps of: i) providing an organic cage according to the second aspect; ii) adding the organic cage to a metal ion mixture comprising lithium cations; iii) adding a non-polar organic solvent to the mixture to form a precipitate; and iv) collecting the precipitate and adding a polar solvent to obtain a solution comprising lithium cations. In this way it is possible to separate and extract lithium from a cation mixture (for example, a mixture comprising Na+, Mg2+, K+and Ca2+).

[0241] The preferred features discussed in relation to the organic cage of the second aspect equally apply to the organic cage used in the method of lithium separation.

[0242] In some embodiments, step iii) of adding the non-polar organic solvent is carried out at from 10 to 90 minutes after added the organic cage in step ii). In some embodiments the separation (such as at least steps i), ii) and iii) above) are carried out without applying any heating. For example, the separation may be carried out at between a room temperature of 20 and 25 °C.

[0243] Preferably, step iii) of adding the non-polar organic solvent is carried out at from 10 to 90 minutes after added the organic cage in step ii) and the separation (such as at least steps i), ii) and iii) above) are carried out without applying any heating e.g. at between 20 and 25 °C.

[0244] In this way, the amount of protonated lithium organic cage that may be obtained is maximised before any decomposition of the protonated lithium organic cage occurs.

[0245] In some embodiments, the non-polar organic solvent used in step iii) of the method of lithium separation may be diethyl ether, dipropyl ether or tetrahydrofuran. Preferably, the non-polar organic solvent may be diethyl ether.

[0246] In some embodiments, the polar solvent used in step iv) of the method of lithium separation maybe water, butanol, methanol, ethanol or propanol.

[0247] In some embodiments, collecting the precipitate in step iv) of the method comprises collecting the precipitate by centrifugation.

[0248] Also provided herein is a use of an organic cage for lithium separation, where the organic cage is according to the first or second aspect, preferably of the second aspect.

[0249] The preferred features discussed in relation to the organic cage of the first and second aspect equally apply to the organic cage used for lithium separation.

[0250] *****

[0251] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0252] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention. For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.

[0253] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0254] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0255] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%.

[0256] Examples

[0257] A number of example organic cages were prepared and tested.

[0258] Materials

[0259] The materials used in the examples were prepared according to the procedures below.

[0260] All starting materials, solvents and reagents were used as supplied and without further purification (Acros Organics, Alfa Aesar, Fisher Scientific, FluoroChem, Sigma Aldrich and VWR).

[0261] 1) Synthesis of Lithium Organic Cage

[0262] To a mixture of tripicolinaldehyde (15.74 mg, 40.00 pmol, 1.000 equiv.) and LiNTf2 (46.00 mg, 160.0 pmol, 4.000 equiv.) in acetonitrile (10 mL), tris(2-aminoethyl)amine (TREN) (5.85 mg, 40.0 pmol, 1.00 equiv.) was added. The suspension was heated at 60eC for 1 hour until the white suspended solid dissolved completely, rendering the mixture clear. Following this, the solution was concentrated to around 2 mL by a rotary evaporator. Subsequently, Et20 (30 mL) was added to the concentrated solution, leading to the formation of a precipitate. The precipitate was collected by centrifugation and washed with Et20 (30 mL, 2 times), affording a lithium organic cage as a pale-yellow solid (28.44 mg, 92%).

[0263] In this example, LiNTf2was added in excess in order to ensure that the reaction proceeded to completion. In principle, only 1 equiv. LiNTf2 is required. 2) Synthesis of Sodium Organic Cage

[0264] To a mixture of tripicolinaldehyde (15.74 mg, 40.00 pmol, 1.000 equiv.) and excess NaNTf2 (48.50 mg, 160.0 pmol, 4.000 equiv.) in acetonitrile (10 mL), TREN (5.85 mg, 40.0 pmol, 1.00 equiv.) was added. The suspension was heated at 60eC for 1 hour until the white suspended solid dissolved completely, rendering the mixture clear. Following this, the solution was concentrated to around 2 mL by a rotary evaporator. Subsequently, Et20 (30 mL) was added to the concentrated solution, leading to the formation of a precipitate. The precipitate was collected by centrifugation and washed with Et20 (30 mL, 2 times), affording a sodium organic cage as a yellow solid (28.60 mg, 91%).

[0265] In this example, NaNTf2was added in excess in order to ensure that the reaction proceeded to completion. In principle, only 1 equiv. NaNTf2 is required.

[0266] 3) Synthesis of Magnesium Organic Cage

[0267] To a sodium organic cage of Example 2 (6.31 mg, 2.00 pmol, 1.00 equiv.) in acetonitrile (2 mL), Mg(NTf2)2 (4.67 mg, 8.00 pmol, 4.00 equiv.) was added. The reaction mixture was heated at 60eC for 12 hours. The solvent was evaporated to around 0.5 mL by a rotary evaporator, and Et20 (10 mL) was then added. The precipitate was collected by centrifugation and washed with Et20 (10 mL, 2 times), affording a magnesium organic cage as a pale-yellow solid (8.13 mg, 95%).

[0268] In this example, Mg(NTf2)2 was added in excess in order to ensure that the reaction proceeded to completion. In principle, only 1 equiv. Mg(NTf2)2 is required.

[0269] 4) Synthesis of Calcium Organic Cage

[0270] To a sodium organic cage of Example 2 (6.31 mg, 2.00 pmol, 1.00 equiv.) in acetonitrile (2 mL), Ca(NTf2)2 (4.80 mg, 8.00 pmol, 4.00 equiv.) was added. The reaction mixture was heated at 60eC for 12 hours. The solvent was evaporated to around 0.5 mL by a rotary evaporator, and Et20 (10 mL) was then added. The precipitate was collected by centrifugation and washed with Et20 (10 mL, 2 times), affording a calcium organic cage as a pale-yellow solid (8.34 mg, 96%).

[0271] In this example, Ca(NTf2)2 was added in excess in order to ensure that the reaction proceeded to completion. In principle, only 1 equiv. Ca(NTf2)2 is required.

[0272] 5) Synthesis of Protonated Organic Cage

[0273] To a sodium organic cage of Example 2 (31.55 mg, 10.00 pmol, 1.000 equiv.) in acetonitrile (10 mL), HNTf2 (76.61 mM in MeCN, 522.3 pL, 40.00 pmol, 4.000 equiv.) was added dropwise. The reaction mixture was stirred for 10 minutes at room temperature. The solvent was then concentrated to around 2 mL by a rotary evaporator. Et20 (30 mL) was added to the concentrated solution, leading to the formation of a precipitate. The precipitate was collected by centrifugation and washed with Et20 (10 mL, 2 times), affording protonated cage as a paleyellow solid (29 mg, 95%). 6) Synthesis of Protonated Lithium Organic Cage

[0274] HNTf2was prepared as a stock solution in acetonitrile to ensure an accurate amount is added to the reaction.

[0275] To a lithium organic cage of Example 1 (6.18 mg, 2.00 pmol, 1.00 equiv.) in acetonitrile (2 mL), HNTf2(25.20 M in acetonitrile, 317.4 pL, 8.000 pmol, 4.000 equiv.) was added. The reaction mixture was stirred for 10 minutes at room temperature. The solvent was evaporated to around 0.5 mL using a rotary evaporator, and Et2O (10 mL) was then added. The precipitate was collected by centrifugation and washed with Et2O (10 mL, 2 times), affording protonated lithium organic cage as a pale-yellow solid (7.58 mg, 90%).

[0276] Or

[0277] To a protonated cage of Example 5 (6.11 mg, 2.00 pmol, 1.00 equiv.) in acetonitrile (2 mL), LiNTf2(3.45 mg, 12.0 pmol, 6.00 equiv.) was added. The reaction mixture was stirred for 10 minutes at room temperature. The solvent was evaporated to around 0.5 mL by a rotary evaporator, and Et2O (10 mL) was then added. The precipitate was collected by centrifugation and washed with Et2O (10 mL, 2 times), affording protonated lithium organic cage as a paleyellow solid (7.60 mg, 90%).

[0278] In this example, LiNTf2was added in excess in order to ensure that the reaction proceeded to completion. In principle, 4 equiv. LiNTf2is required.

[0279] Methods

[0280] The following methods were used in the examples.

[0281] 1H Nuclear Magnetic Resonance (NMR)

[0282] NMR spectra were recorded on a Broker DRX-400, Broker Avance 500 Cryo, Broker 500 TCI- ATM Cryo and Broker 700 TCI-ATM Cryo.

[0283] Chemical shifts (5) for1H NMR spectra are reported in parts per million (ppm) and are reported relative to the solvent residual peak.

[0284] Diffusion Ordered Spectroscopy (DOSY) NMR

[0285] DOSY NMR experiments were performed on a 400 MHz Avance III HD Smart Probe NMR spectrometer. Maximum gradient strength was 6.57 G / cm A. The standard Broker pulse program, Iedbpgp2s, employing a stimulated echo and longitudinal eddy-current delay (LED) using bipolar gradient pulses for diffusion using 2 spoil gradients was utilised. Rectangular gradients were used with a total duration of 1 .5 ms. Gradient recovery delays were 1250- 1500 ps.

[0286] 7Li NMR

[0287] 7Li NMR was performed on a 400 MHz Avance III HD Smart Probe NMR spectrometer.23Na NMR

[0288] 23Na NMR was performed on a 400 MHz Avance III HD Smart Probe NMR spectrometer.

[0289] Single Crystal X-Ray Diffraction

[0290] Single crystal X-Ray diffraction data were collected at Beamline 119 of Diamond Light Source employing silicon double crystal monochromated synchrotron radiation (0.6889 A) with co and i scans at 100(2) K. Data integration and reduction were undertaken with Xia2. A multi-scan empirical absorption correction using spherical harmonics was applied to the data using DIALS. The structure was solved by intrinsic phasing using SHELXT then refined and extended with SHELXL, using ShelXle as a graphical user interface. Carbon-bound hydrogen atoms were included in idealised positions and refined using a riding model. Disorder was modelled using standard crystallographic methods including constraints and restraints where necessary.

[0291] High-resolution electrospray ionisation (ESI)

[0292] High-resolution ESI mass spectra were obtained on a Waters Synapt G2-Si mass spectrometer (capillary voltage 3.0 kV, cone voltage 10 eV; desolvation temp. 373 K; ionisation temp. 333 K) infused from a Harvard syringe pump at a rate of 4-10 pL min-1 .

[0293] Lithium Organic Cage

[0294] This example investigates a Li- organic cage of the present invention. The Li- organic cage was made using the method described above.

[0295] The1H nuclear magnetic resonance (NMR) spectrum revealed high symmetry within the cage structure. Diffusion ordered spectroscopy (DOSY) NMR spectrum affirmed that all proton signals originated from a single species in solution, exhibiting a diffusion coefficient of 5.91 x1 O’10m2s’1in CD3CN. The7Li NMR spectrum displayed a solitary sharp signal, indicative of the presence of lithium, with all four lithium ions occupying identical chemical environments.

[0296] Vapor diffusion of diethyl ether into an acetonitrile solution of cage-Li in the presence of tetra-n- butylammonium hexafluorophosphate (TBAPF6) produced colourless square crystals suitable for analysis by single-crystal X-ray diffraction (Figure 4d). The four coordinated Li+centers are bridged by four Cs-symmetric ligands, each capping a face of the tetrahedron and creating a T- symmetry configuration. TREN residues cap the vertices of the tetrahedron, forming an extended cryptand-like architecture. All Li+stereocenters within a cage share the same A or A stereochemistry, and both cage enantiomers coexist in the crystal. The Li-Li distances fall within the range of 11 .693 - 11 .904 A (with an average of 11 .8 A). The distance of Nimine— Li , Npyridine— Li and Ncentrai— Li measure 2.16 A, 2.27 A, and 3.02 A, respectively, indicating hexacoordination of each Li+by three imine nitrogen atoms and three pyridine nitrogen atoms, while the central nitrogen of TREN does not coordinate with Li+.

[0297] The NMR spectra show that a highly symmetric assembly is obtained, consistent with the formation of a polyhedral cage, and the X-ray diffraction pattern confirmed coordination of each Li ion by six nitrogen atoms (three imine nitrogen atoms from the (first) TREN ligand and one pyridine nitrogen from each of the three (second) tripicolinaldehyde derived ligand). Therefore, this example confirms the assembly of a Li- organic cage of the invention. Sodium Organic Cage

[0298] This example investigates a Na- organic cage of the present invention. The Na- organic cage was made using the method described above.

[0299] The diffusion coefficient of the Na- organic cage in CD3CN was measured to be 5.88x10-10m2s-1in the DOSY NMR spectrum, indicating a similar size to the Li- organic cage. The binding pattern of the four sodium ions was identical, presenting a single sharp peak in the23Na NMR spectrum. Colourless crystals suitable for examination through single-crystal X-ray diffraction were obtained through the gradual vapor diffusion of diethyl ether into an acetonitrile solution of Na- organic cage, facilitated by the presence of tetra-n-butylammonium tetrafluoroborate (TBABF4) (Figure 4f).

[0300] The single-crystal structure of Na- organic cage with Na+vertices instead, closely resembling that of Li- organic cage, was also obtained. The distances between Nimine---Na, Npyridine---Na, and NCentrai-"Na are 2.42 A, 2.53 A, and 2.83 A, respectively, indicating each Na+is coordinated by seven nitrogen atoms, including the central nitrogen of TREN, in contrast to Li- organic cage.

[0301] The NMR spectra (Figure 4e) show that a similar polyhedral cage to the example Li- organic cage was obtained. However, the X-ray diffraction pattern indicates that the sodium ions are coordinated by seven nitrogen atoms (Figure 4f). In contrast to the Li- organic cage, the central nitrogen atom of TREN is an additional coordination atom for the metal ions in the polyhedral cage. This example confirms the assembly of a Na- organic cage of the invention with similar characteristics to the example Li- organic cage.

[0302] Magnesium and Calcium Organic Cages and Transformations of Alkali Metal Organic Cages

[0303] These examples investigate Mg- and Ca- organic cages of the present invention.

[0304] The self assembly of the first and second ligands and either Mg(NTf2)2 or Ca(NTf2)2 led to the formation of assemblies exhibiting lumpy and disorderly peaks in the1H NMR spectrum (Figures 2 and 3). Such peaks in the1H NMR spectra suggest that, while 3D structures were formed, formation of polyhedral cages as described herein was inconsistent. Nevertheless, the formation of 3D assemblies was observed. Although these assemblies were not thoroughly characterized, their potential low symmetry or increased isomeric diversity may arise from the heightened electrostatic interaction between nitrogen atoms and the divalent cations Mg2+and Ca2+, in contrast to Li+and Na+. This stronger electrostatic interaction may result in a lack of reversibility in subcomponent assembly.

[0305] However, through transmetalation, Mg2+and Ca2+have the capability to displace Na+within a Na- organic cage of the invention, giving rise to a Mg- organic cage and a Ca- organic cage, respectively (see scheme in Figure 1 ). Rather than directly mixing subcomponents and alkaline earth metals, the transmetalation process preserves the high symmetry of a Na- organic cage, resulting in only one set of proton signals on the1H NMR spectra (Figures 2 and 3). 2D NMR, DOSY NMR as well as ESI-MS analyses confirmed the tetrahedral structures of Mg- organic cage and Ca- organic cage resemble the Li- organic cage and Na- organic cage. These examples show that Mg- and Ca- organic cages of the present invention may be obtained. However, their assembly directly from the cage subcomponents is not as consistent as was observed for the example Li- and Na- organic cages of the invention, with the1H NMR spectra suggesting that a mixture of structures was obtained. The use of transmetalation to displace Na+from a Na- organic cage of the invention may be used to preserve the high symmetry of the cage and obtain a Mg- or Ca- organic cage according to the present invention.

[0306] These results, along with the results of the formation of cages containing lithium or sodium ions, show that the cages of the present invention bind effectively to alkali and alkaline earth metals in solution. The cages of the invention can therefore be useful in the extraction, separation and storage of alkali and alkaline earth metals.

[0307] Protonated Organic Cage

[0308] This example investigates organic cages of the present invention where at least one of the first or second ligands is protonated.

[0309] Figure 1 shows the synthesis of a protonated cage through the protonation of a Na- organic cage, as described in the method above. Figure 4a shows the synthesis of a protonated Li- organic cage through the protonation of a Li- organic cage, as described in the methods above.

[0310] The1H NMR and7Li NMR spectra of the protonated Li- organic cage are shown in Figures 4b and 4c, respectively, and the X-ray crystal structure is shown in Figure 4d. The7Li NMR spectrum displayed a solitary sharp signal, indicative of the presence of lithium, with all four lithium ions occupying identical chemical environments.

[0311] The1H NMR spectrum of a protonated Li- organic cage, compared with that of a corresponding Li- organic cage, showed an additional broad proton peak at 9.36 ppm (Figure 4b), assigned to the proton located at the central nitrogen of TREN based on correlation spectroscopy (COSY) NMR and nuclear Overhauser effect spectroscopy (NOESY) NMR. The DOSY NMR spectrum showed that all proton signals originated from a single species in solution, exhibiting a diffusion coefficient of 5.11 x1 O-10m2s'1in CD3CN.

[0312] The7Li NMR spectrum of the protonated Li- organic cage displayed a solitary sharp signal, with a downfield shift compared to that of the corresponding Li- organic cage (Figure 4c), thought to be due to the lower electron density after protonation of the polyhedral cage. HR-ESI-MS spectra confirmed the formation of the protonated lithium organic cage with the peak of [Li4H4(C3oH27N7)4-6NTf2]2+found, along with corresponding fragment peaks.

[0313] Compared to the parent structure of Li- organic cage, the Nimine- • • Li distances average 2.33 A, longer than that in Li-organic cage; the Npyridine- -Li distance shortens to 2.15 A, while the Ncentrai--Li distance increases to 3.31 A. This suggests that upon protonation, Li+at each vertex shifts down towards central cavity. Although the proton of Ncentrai cannot be determined unambiguously, the tetrahedral geometry of Ncentrai suggests the Ncentrai-H bond points inward, and the position of this proton was determined based on structural refinement. The Ncentrai’ " Nimine distance measures 2.92 A, the Nimine” ’ H distance measures 2.23 A, and the Ncentrai- H- - -Nimine angel measures 118.34°, indicating the presence of intramolecular hydrogen bonds between three Nimine atoms and H atom on the Ncentrai at each vertex. Nimine atoms serve dual roles, acting both as hydrogen bonding acceptors and as coordinating atoms for Li+, collectively reducing overall energy of cage and enhancing structural stability.

[0314] This example confirms the formation of a protonated lithium organic cage according to the invention, with similar characteristics to the corresponding non -protonated lithium organic cage.

[0315] Kinetic Separation of Lithium from Cation Mixture

[0316] This example investigates the binding affinities of a protonated cage of the present invention to alkali and alkaline earth metal ions, particularly lithium ions, and how this can be exploited for lithium separation.

[0317] Figure 5a schematically represents the comparison of binding affinities of the protonated cage to lithium and its analogues, and Figure 5b depicts the lithium separation process of the invention.

[0318] Describing Figure 5a, upon the addition of a cation mixture comprising LiNTf2(3.0 pmol, 6.0 equiv.), NaNTf2(3.0 pmol, 6.0 equiv.), KNTf2(3.0 pmol, 6.0 equiv.), Mg(NTf2)2(3.0 pmol, 6.0 equiv.) and Ca(NTf2)2(3.0 pmol, 6.0 equiv.) to a protonated cage of the invention (0.5 pmol, 1 .0 equiv.) in a MeCN solvent, immediate formation of a protonated lithium organic cage was observed. This was confirmed by1H NMR, as shown in Figure 6 (see middle NMR plot).

[0319] Overnight exposure of the protonated lithium organic cage led to its decomposition, yielding free ligands which had formed the polyhedral cage structure. This was also confirmed by1H NMR (Figure 6, bottom plot).

[0320] As shown in Figure 5a, exclusive selectivity for lithium ions over sodium, magnesium and calcium ions was observed for the protonated cage under kinetic conditions. These results therefore demonstrate successful isolation of lithium ions from a mixture of lithium ions and one other alkali or alkaline earth metal ion selected from sodium, magnesium or calcium. More generally, the results demonstrate that the organic cages of the invention may be tailored (in this example, protonated) to alter the selectivity of the cage for a desired metal ion (in this example, lithium).

[0321] However, the spectra of Figure 6 (bottom plot) show that in the presence of other metal ions the protonated lithium organic cage will decompose over time under thermodynamic conditions. This change is indicated by the change in chemical shift pattern of the1H NMR spectrum.

[0322] The stability of the protonated Li- organic cage in the presence of other cations was further investigated. Control experiments comprising the protonated organic cage and cation mixtures of Li+ / Na+, Li+ / Mg2+, and Li+ / Ca2+revealed that Mg2+and Ca2+could induce a slow decomposition of the formed protonated lithium organic cage following a first-order reaction, with rate constants of 1.0 x 10-3min-1and 1.5 x 10-3min-1, respectively, while Na+led to no decomposition of the protonated lithium organic cage.

[0323] The control experiments were carried out as follows: Li+ / Na+Cation Mixture

[0324] To a NMR tube, the protonated cage (0.50 pmol, 1.53 mg), 1 ,3,5-trimethoxybenzene (used as internal standard, 25 mM in CD3CN, 2.0 pmol, 80 pL), and CD3CN (0.5 mL) were added.1H NMR was then measured. A mixture of LiNTf2 (3.0 pmol, 0.86 mg) and NaNTf2 (3.0 pmol, 0.91 mg) in CD3CN (20 pL) was then added to the NMR tube. The NMR tube was shaken thoroughly for 2 min and then1H NMR was measured over 18 h. The first spectrum was recorded approximately 5 min after mixing, the following spectrum was recorded at 46 min, 1 h 46 min, 2h 46 min, 3h 46 min and so on, with the final spectrum recorded at 17h 46 min. For each spectrum, the integral of the peak belonging to the internal standard at 5 = 6.09 ppm was recorded as constant, and the integral of the peaks belonging to the protonated cage and the protonated lithium cage were recorded. Based on the integrals, the concentration of the protonated lithium cage was plotted against time, showing that there was no decomposition of the protonated lithium cage by Na+.

[0325] Li Mg2* Cation Mixture

[0326] To a NMR tube, the protonated cage (0.50 pmol, 1.53 mg), 1 ,3,5-trimethoxybenzene (used as internal standard, 25 mM in CD3CN, 2.0 pmol, 80 pL), and CD3CN (0.5 mL) were added.1H NMR was then measured. A mixture of LiNTf2 (3.0 pmol, 0.86 mg) and Mg(NTf2)2 (3.0 pmol, 1 .75 mg) in CD3CN (20 pL) was then added to the NMR tube. The NMR tube was shaken thoroughly for 2 min and then1H NMR was measured over 18 h. The first spectrum was recorded approximately 5 min after mixing, the following spectrum was recorded at 45 min, 1 h 45 min, 2h 45 min, 3h 45 min and so on, with the final spectrum recorded at 17h 45 min. For each spectrum, the integral of the peak belonging to the internal standard at 5 = 6.09 ppm was recorded as constant, and the integral of the peaks belonging to the protonated cage and the protonated lithium cage were recorded. Based on the integrals, the concentration of the protonated lithium cage was plotted against time, showing that there was a first-order decomposition of the protonated lithium cage by Mg2+, and the rate constants was calculated to be 1 .0 x 10-3min-1.

[0327] Lr Ca2+Cation Mixture

[0328] To a NMR tube, the protonated cage (0.50 pmol, 1.53 mg), 1 ,3,5-trimethoxybenzene (used as internal standard, 25 mM in CD3CN, 2.0 pmol, 80 pL), and CD3CN (0.5 mL) were added.1H NMR was then measured. A mixture of LiNTf2 (3.0 pmol, 0.86 mg) and Ca(NTf2)2 (3.0 pmol, 1 .80 mg) in CD3CN (20 pL) was then added to the NMR tube. The NMR tube was shaken thoroughly for 2 min and then1H NMR was measured over 18 h. The first spectrum was recorded approximately 5 min after mixing, the following spectrum was recorded at 48 min, 1 h 48 min, 2h 48 min, 3h 48 min and so on, with the final spectrum recorded at 17h 48 min. For each spectrum, the integral of the peak belonging to the internal standard at 5 = 6.09 ppm was recorded as constant, and the integral of the peaks belonging to the protonated cage and the protonated lithium cage were recorded. Based on the integrals, the concentration of the protonated lithium cage was plotted against time, showing that there was a first-order decomposition of the protonated lithium cage by Ca2+, and the rate constants was calculated to be 1 .5 x 10-3min-1.

[0329] These control experiments demonstrate the stability of a protonated lithium organic cage of the invention under kinetic condition and when in the presence of other alkali or alkaline earth metal ions. The results show that over time, under thermodynamic conditions Mg2+and Ca2+may induce the slow decomposition of a protonated lithium organic cage. Referring to Figure 5b, the lithium separation process of the invention allows for the isolation of lithium ions from a cation mixture through the selective binding of the lithium ions to a protonated organic cage of the invention. The protonated Li- organic cage may then be precipitated through the addition of diethyl ether. n-BuOH is then added to the precipitate to extract the lithium ions from the cage, which can then be removed along with the n-BuOH to leave behind the protonated organic cage.

[0330] Therefore, this example demonstrates that the protonated organic cage of the invention shows preferential binding with lithium ions in the presence of other alkali and alkaline earth metal ions. This preferential binding can be exploited for lithium separation from a cation mixture.

[0331] In general, the organic cages of the invention can be used to extract alkali and alkaline earth metals from mixtures. Different cage structures and different conditions can be employed to separate other alkali or alkaline earth metals. The examples of the application demonstrate the synthesis of the alkali and alkaline earth metal cages of the invention, indicating their applicability for metal ion isolation and extraction from mixtures in solution.

[0332] Further Example

[0333] A further example organic cage was prepared and tested using the methods described above.

[0334] Materials

[0335] The materials used in the further example were prepared according to the procedures below. The formation of the cage was confirmed using1H NMR, DOSY NMR and HR-ESI mass spectrometry, as shown in Figures 7.

[0336] 7) Synthesis of Lithium Organic Cage II

[0337] A 4 mL vial equipped with a stir bar was charged with tris(2-formylpyridin-6-yl)phosphine sulfide (1.52 mg, 4.00 pmol, 1.00 equiv), LiNTf2(3.44 mg, 12.0 pmol, 3.00 equiv), 4, 4', 4- triaminotriphenylamine (1.16 mg, 4.0 pmol, 1.0 equiv), and MeCN (0.5 mL). To this mixture, HNTf2(0.1 M in CD3CN, 4 pL, 0.4 pmol, 0.1 equiv) was added. The reaction mixture was stirred vigorously at 60 °C for 2 hours. After completion, the mixture was used directly for characterization, confirming the formation of the lithium organic cage.

[0338] In this example, LiNTf2was added in excess in order to ensure that the reaction proceeded to completion. In principle, only 1 equiv. LiNTf2is required. The Li-cage is unstable in the solid state but stable in solution.

Claims

Claims:

1. An organic cage comprising: at least one first ligand having at least one electron donating binding moiety; at least one second ligand having at least one electron donating binding moiety; and at least one metal ion selected from an alkali or alkaline earth metal ion; wherein the at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage, wherein each of the at least one binding pockets has one electron donating binding moiety of at least one first ligand and one electron donating binding moiety of at least one second ligand; and wherein each of the at least one metal ions is multiply coordinated to the binding moieties in one of the at least one binding pocket.

2. The organic cage according to claim 1 wherein the alkali or alkaline earth metal ion is selected from the group consisting of Li+, Na+, Mg2+and Ca2+.

3. An organic cage comprising: at least one first ligand having at least one electron donating binding moiety; at least one second ligand having at least one electron donating binding moiety; and wherein the at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage, wherein each of the at least one binding pockets has one electron donating binding moiety of at least one first ligand and one electron donating binding moiety of at least one second ligand; and wherein at least one first or second ligand is protonated in the polyhedral cage.

4. The organic cage according to claim 3, wherein the organic cage further comprises at least one alkali metal ion, and wherein each alkali metal ion is multiply coordinated to the binding moieties in one binding pocket, wherein the alkali metal ion is Li+.

5. The organic cage according to any one of claims 1 to 4, wherein the polyhedral cage has one binding pocket in each corner, preferably wherein the diameter of each binding pocket is 4 to 5 A, such as 4.5 to 5 A.

6. The organic cage according to any one of claims 1 or 5, wherein each binding pocket comprises at least four electron donating binding moieties.

7. The organic cage according to any one of claims 1 to 6 wherein the number of first ligands that provide electron donating binding moieties to each binding pocket is less than the number of second ligands that provide electron donating binding moieties to each binding pocketpreferably, one first ligand and three second ligands provide electron donating binding moieties to each binding pocket.

8. The organic cage according to any one of claims 1 to 7 wherein each of the at least one first ligands and each of the at least one second ligands provide different numbers of electron donating binding moieties per binding pocket preferably each of the at least one first ligands provides three or four electron donating binding moieties and each of the at least one second ligands provides one electron donating binding moieties per binding pocket.

9. The organic cage according to any one of claims 1 to 8 wherein at least one of the electron donating binding moieties is a nitrogen atom, preferably all of the electron donating binding moieties comprise nitrogen atoms.

10. The organic cage according to any one of claims 1 to 9, wherein the polyhedral cage is a tetrahedral cage or cubic cage.1 1 . The organic cage according to any one of claims 1 to 10, wherein the first ligand is a tridentate or tetradentate ligand such as a tripodal, tridentate ligand or a tripodal, tetradentate ligand; preferably the first ligand is N(R1X1)3or PY(R1X1)3where -R1- is a linker group, -X1is a terminal group, and Y is S, O or Se.

12. The organic cage according to any one of claims 1 to 11 , wherein the second ligand is A(R2X2)nwhere A is a branching group, -R2- is linker group, -X2is a terminal group and n is 2, 3 or 4.The organic cage according to claim 1 1 or 12, wherein the first ligand is:and / or wherein the second ligand is:

14. The organic cage according to any one of claims 1 to 13, wherein the cage further comprises a polymer formed around the organic cage.

15. The organic cage according to claim 14, wherein the polymer is polystyrene or a copolymer of styrene and acrylamide.

16. A method of making an organic cage according to any one of claims 1 to 15, the method comprising the steps of: i) combining one of the first or second ligand with the alkali or alkaline earth metal ions in a solvent; ii) adding the other of the first or second ligand to the mixture obtained in step i); iii) heating the mixture of step ii) to a temperature of 24 to 60 °C; iv) concentrating the mixture of step iii) and adding diethyl ether to obtain a precipitate; and v) washing and collecting the precipitate.

17. The method according to claim 16, wherein the alkali or alkaline earth metal ions are provided by non-coordinating metal salts, optionally wherein the non-coordinating metal salt is selected from the group comprising M-NTf2, M-BF4, M-PFe or M-OTf.

18. The method according to claim 17, wherein the non-coordinating metal salt is M-NTf2.

19. The method according to claim 17 or 18, wherein M is Li or Na.

20. The method according to any one of claims 16 to 19, wherein in step iii) the mixture is heated to 60 °C.21 . The method according to any one of claims 16 to 19, wherein the method further comprises a protonation step, optionally wherein the protonation step comprises stirring the collected precipitate with HNTf2in a solvent.

22. The method according to any one of claims 16 to 21 , wherein the solvent is acetonitrile.

23. A method of lithium separation, the method comprising the steps of: i) providing an organic cage according to any one of claims 4 to 15, ii) adding the organic cage to a metal ion mixture comprising lithium cations; iii) adding a non-polar organic solvent to the mixture to form a precipitate; and iv) collecting the precipitate and adding a polar solvent to obtain a solution comprising lithium cations.

24. The method according to claim 23, wherein the non-polar organic solvent used in step iii) is diethyl ether, dipropyl ether or tetrahydrofuran, and / or wherein the polar solvent used in step iv) is water or C1-4 alcohol.

25. Use of an organic cage for lithium separation, wherein the organic cage is according to any one of claims 1 to 15.

Images