WO2020119864A1

WO2020119864A1 - Calix[n]arene derivatives for complexing alkaline earth metal cations

Info

Publication number: WO2020119864A1
Application number: PCT/DE2019/101088
Authority: WO
Inventors: Constantin MAMAT; David Bauer; Falco REISSIG; Hans-Jürgen Pietzsch; Jörg Steinbach
Original assignee: Helmholtz-Zentrum Dresden-Rossendorf E.V.
Priority date: 2018-12-14
Filing date: 2019-12-13
Publication date: 2020-06-18
Also published as: DE102018132293B4; DE102018132293A1; DE102018132293B8

Abstract

The invention relates to a compound which has a calixarene unit having n phenol units, where n is 4, 5, 6 or 8; an ether unit, which is bound to the calixarene unit, forming a crown ether; and at least one sulfonic acid amide unit of the formula -0-(CH)P-C(0)-NH-S(0)2-R1, wherein the at least one sulfonic acid amide units are each bound to the calixarene unit and R1 is respectively selected from the group which comprises a perfluorinated branched or unbranched C2-C8 alkyl group, a perfluorinated aryl group and a group Ar, p is an integer from 1 to 4 and Ar is a phenyl group which is substituted with one or more perfluorinated branched or unbranched C1-C8 alkyl groups.

Description

description

Calix [n] arene derivatives for complexing alkaline earth metal cations

The invention relates to calix [n] arene derivatives for complexing alkaline earth metal cations. The invention further relates to the use of these calix [n] arene derivatives for complexing alkaline earth metal cations, complexes of the calix [n] arene derivatives with alkaline earth metal cations and a process for the preparation of such complexes.

From WO 99/024081 A, calix [n] arene derivatives are known which are to be used for complexing radium ions. These can be, for example, compounds of the formula P-1:

(Formula P-l)

The calix [n] arene derivatives known from WO 99/024081 A can have two ionizable groups which, in their ionized form, are said to have a negative charge. The ionizable groups can carry a carboxylic acid, hydroxamic acid, phosphonic acid, sulfonic acid or diphosphonic acid group. The calix [n] arene derivatives can be used to selectively extract Ra ²⁺ from samples containing Ra ²⁺ . The calix [n] arene derivatives form complexes with Ra ²⁺ . This complex formation can be used to clean with samples contaminated with radium, so that the disposal of the samples cleaned in this way is simplified. In addition, the calix [n] arene derivatives known from WO 99/024081 should be able to be used to transport radionuclides to specific biological targets. Antibodies can be bound to the calix [n] arene derivatives for this purpose. For this purpose, the phenol units of the calix [n] arene unit have a linker group, for example an amino group, via which the antibody can be bound to the phenol unit.

Compounds of the formula P1 were also used for complexing barium ions (X. Chen, M. Ji, DR Fisher, CM Wai, Ionizable Calixarene-Crown Ethers with High Selectivity for Radium over Light Alkaline Earth Metal Ions. Inorg. Chem 1999, 38, 5449-5452).

However, it has been found that complexation of Ba ²⁺ and Ra ²⁺ with calix [n] arene derivatives of the formula P1 only at pH values above the physiological pH value, which is normally between 7.36 up to 7.44. This is disadvantageous for radiopharmaceutical applications. In addition, the stability of the complexes formed is insufficient. The Ra complex dissociates into Ra ²⁺ and the calix [n] arene derivative, which acts as a ligand. The stability of the complexes against competitor ions, as can also be found in blood plasma, is also not given.

Also known are calix [n] arene derivatives which have a sulfonic acid amide unit as a functional group (H. Zhou, K. Surowiec, DW Purkiss, RA Bart sch, Synthesis and alkaline earth metal cation extraction by proton di- ionizable p-tert-butylcalix [4] arene-crown-5 compounds in cone, partial-cone and 1,3-alternate conformations. Org. Biomol. Chem. 2006, 4, 1104-1114; H. Zhou, D Liu, J. Gega, K. Surowiec, DW Purkiss, and R, A. Bartsch, Effect of para-substituents on alkaline earth metal ion extraction by protondi-ionizable calix [4] arene-crown-6 ligands in cone, partial -cone and 1,3-alternate conformations. Org. Biomol. Chem., 2007, 5, 324-332). These are compounds of the general formula P-2: (Formula P-2) wherein R is methyl, phenyl, 4-NO ₂ -phenyl or CF3. These compounds were used to extract natural Ba ²⁺ in a two-phase system (chloroform-water). However, it has been found that the labeling conditions are insufficient for a radiopharmaceutical application. A radiochemical pharmaceutical application requires labeling in aqueous solvents and at pH values that correspond to the physiological pH value or are lower than the physiological pH value.

The object of the invention is to eliminate the disadvantages of the prior art. In particular, calix [n] arene derivatives are to be specified which form stable complexes with alkaline earth metal cations, in particular with Ba ²⁺ and Ra ²⁺ , the complex formation at pH values which correspond to the physiological pH value or lower than that physiological pH are, should be possible. The compounds are also said to be suitable for radiochemical applications. Furthermore, the use of these compounds, a process for the preparation of complexes from these compounds and alkaline earth metal cations and such complexes are to be specified.

This object is achieved by the features of claims 1, 10, 13 and 15 ge. Expedient embodiments of the inventions result from the features of the subclaims.

[0009] According to the invention, a connection is provided which has: a calixarene unit which has n phenol units, where n is 4, 5, 6 or 8;

an ether unit which is bonded to the calixarene unit to form a crown ether; and

- At least one sulfonic acid amide unit of the formula

-0- (CH) pC (0) -NH-S (0) ₂ -R ¹

wherein the at least one sulfonamide unit is in each case bound to the calixarene unit and R ^{1 is in} each case selected from the group consisting of a perfluorinated branched or unbranched C2-C8-alkyl group, a perfluorinated aryl group and an Ar group, p is an integer from 1 to 4 and Ar is a phenyl group substituted with one or more perfluorinated branched or unbranched C1-C8 alkyl groups.

Preferably, the phenol units of the calixarene unit each carry a substituent R ² , where R ^{2 is} each hydrogen, a branched or unbranched, substituted or unsubstituted C _I -C _O alkyl group or a unit of the formula - (L-) _W X is where w is 0 or 1, L is a linker and X is a reactive functional group. The term "each" means here that the substituent R ² at each occurrence can have one of the meanings given for R ^2, independently of each other occurrence. All phenol units of the calixarene unit can each carry the same substituent R ² . However, the phenol units of the calixarene unit can also carry different substituents R ² , it also being possible for several phenol units of the calixarene unit to have the same substituent R ² .

The reactive functional group X can be, for example, a carboxylic acid, a carboxylic acid halide, a carboxylic anhydride, an active ester, an amine, an azide or a maleimide. The reactive functional group can in particular enable the connection of a pharmacologically active unit to the compound according to the invention. The term “pharmacologically active unit” is understood to mean in particular a biological target molecule which can detect tumors in a highly specific manner. For example, the reactive functional Group the connection of a peptide, a protein, an antibody or another pharmacologically active unit to the inventive compound he possible. The pharmacologically active unit can be an immunologically active unit.

The linker can be a hydrocarbon chain which has z methylene units, at least one of the methylene units carrying the reactive functional group X and z being an integer from 1 to 6.

[0013] The calixarene unit of the compound according to the invention preferably has a cone conformation. In the case of a cone conformation, the phenolic units of the calixarene unit are arranged in a goblet shape. The cup has a first edge and a second edge, the first edge having a smaller diameter than the second edge. In WO 99/24081 the first edge is referred to as the lower edge, the second edge as the upper edge. In the present invention it can be seen that the ether unit and the two sulfonamide units are arranged on the first edge of the calixarene unit, while the radicals R ^{2 are arranged} on the second edge of the calixarene unit. The calixarene unit can have 4, 5, 6 or 8 phenol units. Preferably n is 4. In this case the calixarene unit has four phenol units.

The compound of the invention has an ether unit which is bonded to the calixarene unit to form a crown ether. The crown ether may have m oxygen atoms, where m is an integer from 4 to 8. M is preferably 6. The ether unit is bonded to the calixarene unit via oxygen atoms. The number m includes these two oxygen atoms.

The compound of the invention has at least one, preferably two or more sulfonic acid amide units of the formula -0- (CH) _p -C (0) -NH-S (0) ₂ -R ¹ , the sulfonic acid amide units in each case are bonded to the calixarene unit and R ^{1 is in} each case a perfluorinated C2-C8-alkyl group, a perfluorinated aryl group or an Ar group and p is an integer from 1 to 4. Preferably p is 1. The Term "each" means that a substituent R ¹ can have the meaning given for R ¹ at each occurrence herein, irrespective of any other occurrence. However, it can be provided that R ^{1 has} the same meaning every time it occurs. Exactly two sulfonic acid amide units are preferably provided.

The group Ar is a phenyl group which is substituted by one or more perfluorinated branched or unbranched Ci-Cx-alkyl groups. The Ar group is preferably a phenyl group which is substituted by one or two trifluoromethyl groups. If the Ar is a phenyl group which is substituted by a trifluoromethyl group, the trifluoromethyl group can be in the ortho, meta or para position, i.e. the group Ar can be a 2- (trifluoromethyl) phenyl group, a 3- (trifluoromethyl) phenyl group or a 4- (trifluoromethyl) phenyl group. If the Ar is a phenyl group which is substituted by two trifluoromethyl groups, it can be a 2,3-bis (trifluoromethyl) phenyl group, a 2,4-bis (trifluoromethyl) phenyl group, a 2,5-bis (trifluoromethyl) phenyl group, a 2,6-bis (trifluoromethyl) phenyl group, a 3,4-bis (trifluoromethyl) phenyl group or a 3,5-bis (trifluoromethyl) phenyl group. The group Ar is particularly preferably a 2,4-bis (trifluoromethyl) phenyl group.

[0017] R ¹ is preferably selected from a group consisting of a perfluorinated ethyl group, a perfluorinated “propyl group, a perfluorinated iso-

Propyl group, a perfluorinated // - butyl group, a perfluorinated iso-

Butyl group, a perfluorinated .vcc butyl group, a perfluorinated tert-

Butyl group and a perfluorophenyl group exists. R ¹ is not -CF ₃ .

In a preferred embodiment, the compound according to the invention is a compound of the general formula I: where R ¹ and R ^{2 are} as defined above. In the compound of the general formula I, n is 4 and p 1. R ¹ is preferably selected from a group consisting of a per fluorinated ethyl group, a perfluorinated “propyl group, a perfluorinated isopropyl group, a perfluorinated // butyl group, one perfluorinated isobutyl group, a perfluorinated .sfc-butyl group, a perfluorinated tert-butyl group and a perfluorophenyl group. R ² is preferably hydrogen or a tert-butyl group.

According to the invention, the use of a compound according to the invention is also provided to form a complex with an alkaline earth metal cation. The alkaline earth metal cation is preferably Ba ²⁺ or Ra ²⁺ . It can be provided that the alkaline earth metal cation is a radioactive alkaline earth metal cation. Examples of a radioactive alkaline earth metal ^cation are ¹³¹ Ba ²⁺ , ¹³³ Ba ²⁺ , ^135m Ba ²⁺ , ¹³⁷ Ba ²⁺ , ^137m Ba ²⁺ , ¹⁴⁰ Ba ²⁺ or ²²⁶ Ra ²⁺ , the list being not exhaustive. The alkaline earth metal cation is preferably non-radioactive Ba ²⁺ or the radioactive isotopes ¹³¹ Ba ²⁺ , ²²³ Ra ²⁺ or ²²⁴ Ra ²⁺ .

If the compound according to the invention is a compound of the formula I, the complex shown in the general formula II is obtained: where R ¹ and R ^{2 have} the meanings given in connection with formula I and M ^{2+ is} an alkaline earth metal cation, for example Ba ²⁺ or Ra ²⁺ .

The term "Ci-C _ö alkyl" refers, unless stated otherwise, in particular to a saturated aliphatic hydrocarbon group with a branched or unbranched carbon chain with 1 to 6 carbon atoms. Examples of C _I -C _Ö alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl, .sfc-butyl, tert-butyl, pentyl, // - hexyl and the like. The alkyl group may optionally be substituted with one or more substituents, where each substituent is independently hydroxy, alkyl, alkoxy, halogen, haloalkyl, amino, monoalkylamino or dialkylamino, unless specifically stated otherwise.

Unless otherwise stated, the term “perfluorinated Ci-Cs-alkyl” refers in particular to a saturated aliphatic hydrocarbon group with a branched or unbranched carbon chain with 1 to 8 carbon atoms, in which each hydrogen atom is represented by a Fluorine atom is replaced. Examples of perfluorinated Ci -Cs alkyl groups include, but are not limited to, perfluoromethyl, perfluoroethyl, perfluoropropyl, iso-perfluoropropyl, iso-perfluorobutyl, .svc-perfluorobutyl, / t77-perfluorobutyl 1, perfluoropentyl, // - perfluorohexyl, perfluorooctyl and the same. The term "perfluorinated C2-Cs-alkyl" refers, unless otherwise stated, in particular to a saturated aliphatic hydrocarbon group with a branched or unbranched carbon chain with 2 to 8 carbon atoms, in which each hydrogen atom by a fluorine atom is replaced. Examples of C2-C8 perfluorinated alkyl groups include, but are not limited to, perfluoroethyl, perfluoropropyl, iso-perfluoropropyl, iso-perfluorobutyl, sec-perfluorobutyl, / tvV-perfluorobutyl, perfluoropentyl, // - perfluorohexyl, perfluorooctyl and the like.

Unless otherwise stated, the term “perfluorinated aryl” refers to a cyclic, aromatic hydrocarbon group which consists of a mono-, bi- or tri-cyclic aromatic ring system with 5 to 10 ring atoms, preferably 5 or 6 Ring atoms, where each hydrogen atom of the hydrocarbon group is replaced by a fluorine atom. Examples of aryl groups include, but are not limited to, perfluorophenyl and perfluoronaphthyl, with perfluorophenyl being particularly preferred. Unless otherwise stated, the aryl group can be monovalent.

The terms "perfluoromethyl" and "trifluoromethyl" are used synonymously in the present invention.

[0026] Preferred examples of compounds of the general formula I are shown in Table 1:

Table 1

Further preferred examples of compounds of the general formula I are shown in Table 1A:

Table 1A

According to the invention, a method for producing a complex from a compound according to the invention and an alkaline earth metal cation is also provided. The process includes the steps:

(a) providing a solution containing the alkaline earth metal cation; and

(b) contacting the solution with a compound according to the invention.

The solution provided in step (a) of the method according to the invention can be an organic or an aqueous solution in which the alkaline earth metal cation is present together with a counterion. For example, the alkaline earth metal cation can be present as a perchlorate salt, so that the counterion is a perchlorate ion. If the alkaline earth metal cation is present as the perchlorate salt, the solvent is preferably acetonitrile. In another example, the alkaline earth metal cation is in the form of a chloride salt, so that the counterion is a chlorine. In particular, radioactive alkaline earth metal ions, such as Ba ²⁺ or Ra ²⁺ , can be present as chloride salts or nitrate salts, but they can also be present as salts with other anions. In the case of radioactive alkaline earth metal cations, the solvent is preferably water. If the alkaline earth metal cations are present as chloride salts in aqueous solution, the complexation and thus the production of the complexes can be carried out by shaking out from the aqueous phase with an organic solvent. solvent that is not miscible with water, for example chloroform.

The inventive method can be carried out at pH values which correspond to the physiological pH or are lower than the physiological pH. It is possible to carry out the process according to the invention at pH values less than 7. It is even possible to carry out the process according to the invention at pH values less than 4. The compounds according to the invention are therefore suitable for radiochemical, environmental chemical and in particular radiopharmaceutical applications.

According to the invention, a complex is further provided which consists of a compound according to the invention and an alkaline earth metal cation. The alkaline earth metal cation can be, for example, Ba ²⁺ or Ra ²⁺ . Examples of complexes according to the invention are shown in the general formula B. The complexes according to the invention can be produced by means of the method according to the invention. Preferred complexes according to the invention are complexes of the general formula P.

Table 2 shows preferred examples of complexes of the general formula II, in which M ^{2+ is in} each case Ba ²⁺ . Complexes of the general formula II, in which M ^{2+ is in} each case Ba ²⁺ , are also referred to below as barium complexes or Ba ²⁺ complexes.

Table 2

Table 2A shows preferred examples of complexes of the general formula II, in which M ^{2+ is in} each case Ra ²⁺ . Complexes of the general formula II in which M ^{2+ is in} each case Ra ²⁺ are also referred to below as radium complexes or Ra ²⁺ complexes.

Table 2B shows further preferred examples of complexes of the general formula II in which M ^{2+ is in} each case Ba ²⁺ . Table 2B

Table 2C shows further preferred examples of complexes of the general formula II, in which M ^{2+ is in} each case Ra ²⁺ . Table 2C

[0036] The invention is based on the following considerations. Deprotonatable groups are necessary to complex the ions Ba ²⁺ and Ra ²⁺ . In principle, carboxylic acid groups are deprotonic hereditary. However, the protonation equilibrium is wholly or partly on the acid side. Functional groups are therefore required which are to be deprotonated as completely as possible at neutral pH or below. These groups act as negatively charged counterions for Ba ²⁺ and Ra ²⁺ in the complex formed. The compounds according to the invention have at least two sulfonic acid amide units, each of which has a perfluorinated group. The variation of the sulfonamide function through the more electron-withdrawing and perfluorinated groups such as R ² = C2F5, C3F7, C4F9 or Cr.Fs enables deprotonation to be achieved even at low pH values (pH <4). This leads to complete deprotonation and complexation with the corresponding alkaline earth metal cation. In addition, the large perfluorinated side chains formed by the two substituents R ¹ offer steric protection against dissociation of the complex according to the invention and against an exchange with other cations. The selectivity of the compounds according to the invention over other alkaline earth metal cations is given. The introduction of the perfluorinated substituents R ¹ on the sulfonamide function of the compounds according to the invention allows a better deprotonation of the two sulfonamide nitrogen atoms as donors for the alkaline earth metal cations. In addition, longer and / or branched perfluoroalkyl units require a higher steric Protection against dissociation of the complex according to the invention and an exchange with foreign cations. In particular, the heavy alkaline earth metal cations Ba ²⁺ and Ra ²⁺ are complexed highly efficiently and stably by means of the compounds according to the invention, without dissociation of the complex and / or exchange with competitor cations. These effects are in contrast to the compounds known from the prior art, which only have perfluoromethyl groups. The compounds are particularly unsuitable for the complexation of radium ions. The complexes according to the invention, however, are thermodynamically and kinetically stable.

The compounds according to the invention can be used as complexing agents. They thus represent chelators. The compounds according to the invention enable in particular the stable complexation of Ba ²⁺ ions, including radioactive barium isotopes, and Ra ²⁺ ions on one and the same chelator. The compounds according to the invention enable effective extraction and stable binding both to Ba ²⁺ and to Ra ²⁺ even at low pH values <7. In addition, the compounds according to the invention have a high selectivity of Ba ²⁺ and Ra ² when complexing ⁺ compared to the other alkaline earth metal cations, such as Be ²⁺ , Mg ²⁺ , Ca ²⁺ and Sr ²⁺ .

The compounds according to the invention are particularly suitable for the radiolabeling of pharmacologically active carrier molecules, such as, for example, antibodies or peptides. They can thus be used in the diagnosis, therapy and theranostics of tumor diseases. However, they can also be used in other areas of radiochemistry, for example in the separation of radium isotopes or radioactive barium isotopes from contaminated water or other media.

The invention is explained in more detail below with the aid of exemplary embodiments which are not intended to restrict the invention.

General synthesis instructions S1 for the compounds LI to L8 and L9 and L10 25,27-bis (carboxymethoxy) -26,28-dihydroxycalix [4] arene-crown-6 (1) or 5.1 l, 17.23-tetra- / er / -butyl-25.27- Bis (carboxymethoxy) -26,28-dihydroxycalix [4] arene-crown-6 (2) (1 equiv) was suspended in anhydrous carbon tetrachloride (5 mL). Oxalyl chloride was added and the mixture was stirred at 65 ° C for 5 h. After cooling to room temperature, the solvent and excess oxalyl chloride were removed. The residue was then dissolved in anhydrous dichloromethane (5 mL) and a mixture of perfluorinated sulfonamide (2.2-2.5 equiv.) And NaH (60% in mineral oil, 10 equiv.) Dissolved in 5 mL anhydrous dichloromethane was added. After stirring the reaction mixture overnight, the mixture is filtered off and the filtrate is washed with aqueous HCl (10%, 15 mL). After separating the two phases, the organic phase is dried over sodium sulfate, the solvent is removed and the crude product is purified by column chromatography (mobile phase: dichloromethane to dichloromethane / methanol 5: 1). The products LI to L8 were isolated as colorless solids. To prepare the compounds L9 to L10, bis (trifluoromethyl) benzenesulfonamide is used instead of a perfluorinated sulfonamide.

Scheme 1 illustrates the preparation of the compounds LI to L8 according to the general synthesis instruction S 1.

Scheme 1

R ² in the general formula III has the meanings given above in connection with the general formula I. If R ^{2 is} H, then the compound of the general formula III is 25,27-bis (carboxymethoxy) -26,28-dihydroxycalix [4] arene-crown-6 (1). If R ^{2 is} / er / -butyl, then the compound of the general formula III 5,11, 17,23-tetra- / er / -butyl-25,27-bis (carboxymethoxy) -26,28-dihydroxy-calix [ 4] aren-crown-6

(2). R ¹ in the general formula IV has the meanings given above in connection with the general formula I. In the exemplary compounds LI to L8, R ¹ and R ^{2 have} the meanings given in Table 1. Scheme 1 likewise illustrates the preparation of the compounds L9 and L10 according to the general synthesis instruction S1. In the exemplary compounds L9 and L10, R ¹ and R ^{2 have} the meanings given in Table 1A.

Example 1: Compound LI

According to the general synthesis instructions S1 H-calix [4] -krone-6 (1, 300 mg, 0.40 mmol), oxalyl chloride (1.5 mL), NaH (162 mg, 4.03 mmol) and perfluoroethanesulfonamide (201 mg, 1.00 mmol) reacted and gave 213 mg (47%) of the compound HC ₂ F ₅ -calix [4] -krone-6 (LI).

* H NMR (600 MHz, CDCh): d = 3.45 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 3.75 (br. S, 4H, OCH ₂ ), 3.84-3.95 (m, 12 H, 3 x OCH ₂ ), 4.14 (br.s, 4H, OCH ₂ ), 4.22 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 4.65 (s, 4H, CH ₂ C = 0), 6.82 -6.92 (m, 4H, /? - H _Ar ), 7.09-7.16 (m, 8H, wH _Ar ). ¹³ C NMR (151 MHz, CDCh): d = 29.9 (ArCH ₂ ), 69.4, 69.5, 72.1, 72.2, (4 x OCH ₂ ), 77.2 (CH ₂ C = 0), 78.9 (OCH ₂ ), 126.1, 126.5 (2 x p-C _Ar ), 129.3, 129.7 (2 x m-CA _T ), 134.7, 135.0 (2 x O-CA _T ), 150.9, 154.0 (2 x i-C _Ar ), 176.0 (C = 0). ¹⁹ F NMR (565 MHz, CDCh): d = -117.9 (4F), -78.9 (4F).

Example 2: Connection L2

According to the general synthesis instructions S1 / er / -Butyl-calix [4] - crown-6 (2, 300 mg, 0.31 mmol), oxalyl chloride (1.5 mL), NaH (124 mg, 3.1 mmol) and perfluoroethanesulfonamide ( 154 mg, 0.77 mmol) reacted and gave 207 mg (50%) of the compound ^f Bu-C ₂ F ₅ -calix [4] -krone-6 (L2).

'H NMR (600 MHz, CDCh): d = 1.11 (s, 18H, CH ₃ ), 1.15 (s, 18H, CH ₃ ), 3.38 (d, ² J = 12.2 Hz, 4H, ArCH ₂ ) , 3.73 (br. S, 4H, OCH ₂ ), 3.87 (s, 8H, OCH ₂ ), 3.92 (s, 4H, OCH ₂ ), 4.08-4.19 (m, 8H, OCH ₂ + ArCH ₂ ), 4.63 ( s, 4H, CH ₂ C = 0), 7.08 (s, 4H, m- HA _T ), 7.11 (s, 4H, m- HA _T ). ¹³ C NMR (151 MHz, CDCh): d = 30.1 (ArCH ₂ ), 31.3, 31.5 (2 x CH), 34.2, 34.4 (Cq), 69.3, 69.4, 72.0, 72.1, (4 x OCH ₂ ) , 77.0 (CH ₂ C = 0), 79.3 (OCH ₂ ), 125.8, 126.3 (2 x m- CA _T ), 134.1, 134.4 (2 x O-CA _T ), 147.8, 148.5 (2 x p- CA _T ),

148.4, 151.4 (2 x i-CA _T ), 176.2 (C = 0). ¹⁹ F NMR (565 MHz, CDCh): d = -117.9 (4F), -78.9 (4F).

Example 3: Compound L3

According to the general synthesis instructions S1 H-calix [4] crown-6 (1, 300 mg, 0.40 mmol), oxalyl chloride (1.5 mL), NaH (162 mg, 4.03 mmol) and per fluoroisopropylsulfonamide (252 mg, 1.00 mmol) reacted and gave 195 mg (40%) of the compound HC ₃ F ₇ -calix [4] -krone-6 (L3).

Ή NMR (600 MHz, CDCh): d = 3.45 (d, ² J = 12.4 Hz, 4H, ArCH ₂ ), 3.74 (br. S, 4H, OCH ₂ ), 3.85 (br. S, 4H, OCH ₂ ), 3.88-3.93 (m, 8 H, 2 x OCH ₂ ), 4.14 (br.s, 4H, OCH ₂ ), 4.21 (d, ² J = 12.4 Hz, 4H, ArCH ₂ ), 4.64 (s , 4H, CH ₂ C = 0), 6.83-6.92 (m, 4H, p-HAT), 7.10-7.16 (m, m-HAT). ¹³ C NMR (151 MHz, CDCh): d = 29.8 (ArCH ₂ ), 69.4,

69.4, 72.1, 72.2, (4 x OCH ₂ ), 77.2 (CH ₂ C = 0), 79.3 (OCH ₂ ), 126.1, 126.6 (2 x p-CAT), 129.3, 129.7 (2 x m-CAT), 134.8, 135.0 (2 x O-CAT), 150.9, 154.0 (2 x i-CAT), 176.0 (C = 0). ¹⁹ F NMR (565 MHz, CDCh): d = -169.3 (2F), -71.7 (12F).

Example 4: Compound L4

According to the general synthesis instructions S1 / er / -Butyl-calix [4] - crown-6 (2, 300 mg, 0.31 mmol), oxalyl chloride (1.5 mL), NaH (124 mg, 3.1 mmol) and perfluoroisopropylsulfonamide ( 193 mg, 0.77 mmol) reacted and gave 254 mg (57%) of the compound ^f Bu-C ₃ F ₇ -calix [4] -krone-6 (L4).

'H NMR (600 MHz, CDCh): d = 1.11 (s, 18H, CH ₃ ), 1.15 (s, 18H, CH ₃ ), 3.38 (d, ² J = 12.3 Hz, 4H, ArCH ₂ ) , 3.71-3.74 (m, 4H, OCH ₂ ), 3.82-3.86 (m, 4H, OCH ₂ ), 3.86-3.92 (s, 8H, OCH ₂ ), 4.10-4.18 (m, 8H, OCH ₂ + ArCH ₂ ), 4.63 (s, 4H, CH ₂ C = 0), 7.08 (s, 4H, m-HA _T ), 7.11 (s, 4H, m-HA _T ). ¹³ C NMR (151 MHz, CDCh): d = 30.1 (ArCH ₂ ), 31.3, 31.4 (2 x CH ₃ ), 34.1, 34.3 (C _q ), 69.3, 69.4, 72.1, 72.2, (4 x OCH ₂ ), 77.0 (CH ₂ C = 0), 78.8 (OCH ₂ ), 125.8, 126.3 (2 x m-CA _T ), 134.1, 134.4 (2 x O-CA _T ), 147.8, 148.4 (2 x p-CAT), 148.3, 151.5 (2 x / - CAT), 176.2 (C = 0). ¹⁹ F NMR (565 MHz, CDCh): d = -169.3 (2F), -71.7 (12F).

Example 5: Compound L5

According to the general synthesis instructions S1, H-calix [4] -krone-6 (1, 314 mg, 0.42 mmol), oxalyl chloride (1.5 mL), NaH (169 mg, 4.23 mmol) and perfluorobutylsulfonamide (316 mg , 1.06 mmol) and gave 148 mg (26%) of the compound HC ₄ F ₉ -calix [4] -krone-6 (L5).

Ή NMR (600 MHz, CDCb): d = 3.45 (d, ² J = 12.4 Hz, 4H, ArCH ₂ ), 3.74 (br. S, 4H, OCH ₂ ), 3.83-3.94 (m, 12 H , 3 x OCH ₂ ), 4.14 (br. S, 4H, OCH ₂ ), 4.22 (d, ² J = 12.4 Hz, 4H, ArCH ₂ ), 4.66 (s, 4H, CH ₂ C = 0), 6.83- 6.92 (m, 4H, ^ -H _Ar ), 7.10-7.17 (m, m- H _Ar ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 29.9 (ArCH ₂ ), 69.3, 69.4, 71.8, 71.9, (4 x OCH ₂ ), 77.2 (CH ₂ C = 0), 79.2 (OCH ₂ ), 126.0 , 126.4 (2 x p-CAT), 129.2, 129.6 (2 x m-CAT), 134.8, 135.1 (2 x O-CAT), 151.1, 154.0 (2 x i-CAT), 174.1 (C = 0). ¹⁹ F NMR (565 MHz, CDCb): d = -161.0 (4F), -150.8 (2F), -137.9 (4F).

Example 6: Compound L6

According to the general synthesis instructions S1 / er / -Butyl-calix [4] - crown-6 (2, 317 mg, 0.33 mmol), oxalyl chloride (1.5 mL), NaH (131 mg, 3.3 mmol) and perfluorobutylsulfonamide ( 216 mg, 0.72 mmol) reacted to give 346 mg (69%) of the compound ^f Bu-C ₃ F ₇ -calix [4] -krone-6 (L6).

'H NMR (600 MHz, CDCh): d = 1.10 (s, 18H, CH ₃ ), 1.14 (s, 18H, CH ₃ ), 3.37 (d, ² J = 12.3 Hz, 4H, ArCH ₂ ) , 3.71 (br. S, 4H, OCH ₂ ), 3.85 (br. S, 8H, OCH2), 3.90 (s, 4H, OCH ₂ ), 4.07-4.17 (m, 8H, OCH ₂ + ArCH ₂ ), 4.62 (s, 4H, CH ₂ C = 0), 7.07 (s, 4H, m-HAT), 7.10 (s, 4H, mH _Ar ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 30.0 (ArCH ₂ ), 31.3, 31.4 (2 x CH ₃ ), 34.1, 34.3 (C _q ), 69.3, 69.4, 72.0, 72.1, (4 x OCH ₂ ), 77.0 (CH ₂ C = 0), 78.8 (OCH ₂ ), 125.8, 126.2 (2 x m-CAT), 134.1, 134.3 (2 x O-CAT), 147.8, 148.3 (2 x p-CAT), 148.4, 151.4 (2 x i-CAT), 162.7 (C = 0). ¹⁹ F NMR (565 MHz, CDC1 ₃ ): d = -126.0 (4F), - 121.1 (4F), -113.8 (4F), -80.8 (6F). Example 7: Compound L7

According to the general synthesis instructions S1, H-calix [4] -krone-6 (1, 300 mg, 0.40 mmol), oxalyl chloride (1.5 mL), NaH (162 mg, 4.03 mmol) and perfluorophenylsulfonamide (250 mg, 1.00 mmol) reacted and gave 171 mg (35%) of the compound HC ₆ F ₅ -calix [4] -krone-6 (L7).

³ H NMR (600 MHz, CDCh): d = 3.44 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 3.68 (br. S, 4H, OCH ₂ ), 3.73-3.82 (m, 8 H, 2 x OCH ₂ ), 3.85 (br. S, 4H, OCH ₂ ), 3.90 (br. S, 4H, OCH ₂ ), 4.19 (br. S, 4H, OCH ₂ ), 4.26 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 4.65 (s, 4H, CH ₂ C = 0), 6.82-6.90 (m, 4H, /? - H _Ar ), 7.09-7.16 (m, m- H _Ar ). ¹³ C NMR (151 MHz, CDCh): d = 29.8 (ArCH ₂ ), 69.3, 69.4, 72.0, 72.1 (4 x OCH ₂ ), 77.2 (CH ₂ C = 0), 79.3 (OCH ₂ ), 126.1, 126.6 (2 x p- C _Ar ), 129.3, 129.7 (2 x m- C _Ar ), 134.7, 135.0 (2 x O-CA _T ), 150.9, 154.0 (2 x i- C _Ar ), 176.0 (C = 0 ). ¹⁹ F NMR (565 MHz, CDCh): d = -161.0 (4F), - 150.8 (2F), -137.9 (4F).

Example 8: Compound L8

According to the general synthesis instructions S1 / er / -Butyl-calix [4] - crown-6 (2, 300 mg, 0.31 mmol), oxalyl chloride (1.5 mL), NaH (124 mg, 3.1 mmol) and perfluorophenylsulfonamide ( 168 mg, 0.68 mmol) reacted and gave 146 mg (33%) of the compound ^f Bu-C ₆ F ₅ -calix [4] -krone-6 (L8).

'H NMR (400 MHz, CDCh): d = 1.10 (s, 18H, CH ₃ ), 1.16 (s, 18H, CH ₃ ), 3.37 (d, ² J = 12.3 Hz, 4H, ArCH ₂ ) , 3.63-3.68 (m, 4H, OCH ₂ ), 3.74-3.80 (m, 4H, OCH ₂ ), 3.84-3.91 (m, 4H, OCH ₂ ), 4.10-4.22 (m, 4H, OCH ₂ + ArCH ₂ ), 4.63 (s, 4H, CH ₂ C = 0), 7.07 (s, 4H, m-H _AT ), 7.11 (s, 4H, m-H _AT ). ¹³ C NMR (101 MHz, CDC1 ₃ ): d = 30.1 (ArCH ₂ ), 31.2, 31.5 (2 x CH ₃ ), 34.2, 34.4 (C _q ), 69.3, 69.5, 71.8, 72.2, (4 x OCH ₂ ), 77.0 (CH ₂ C = 0), 78.6 (OCH ₂ ), 125.8, 126.3 (2 x m- C _Ar ), 134.1, 134.4 (2 x O-CA _T ), 147.8, 148.4 (2 x p- C _Ar ), 148.6, 151.3 (2 x i-C _Ar ), 174.9 (C = 0). ¹⁹ F NMR (376 MHz, CDC1 ₃ ): d = -160.7 (4F), -150.3 (2F), -138.1 (4F).

Example 8A: Compound L9 According to the general synthesis instructions S1, H-calix [4] -krone-6 (2, 230 mg, 0.31 mmol), oxalyl chloride (1.5 mL), NaH (124 mg, 3.1 mmol) and 3,5-bis ( trifluoromethyl) benzenesulfonamide (168 mg, 0.68 mmol) reacted and gave 216 mg (54%) of the compound ^f Bu-C ₆ H ₃ (CF ₃ ) ₂ -calix [4] -krone-6 (L9).

³ H NMR (600 MHz, CDC1 ₃ ): d = 3.42 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 3.68-3.73 (m, 8 H, 2 x OCH ₂ ), 3.81 (br . s, 4H, OCH ₂ ), 3.90 (br. s, 4H, OCH ₂ ), 4.16 (br. s, 4H, OCH ₂ ), 4.24 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 4.67 (s, 4H, CH ₂ C = 0), 6.81-6.91 (m, 4H, p- H _Ar ), 7.09-7.15 (m, m- H _Ar ), 7.97 (s, 2H, R _F Ar), 8.52 (s, 4H, R _F Ar). ¹³ C NMR (151 MHz, CDCI3): d = 29.9 (ArCH ₂ ), 69.3, 69.6, 71.9 (3 x OCH ₂ ), 77.2 (CH ₂ C = 0), 79.0 (OCH ₂ ), 126.0, 126.4 (2 x p-CA _T ), 129.2, 129.6 (2 x m-CA _T ), 134.8, 135.0 (2 x O-CA _T ), 151.2, 154.0 (2 X 7-CA _T ), 174.0 (C = 0). ¹⁹ F NMR (565 MHz, CDCI3): d = -62.8 (12F).

Example 9B: Compound L10

According to the general synthesis instructions S1 / c / 7-butyl-calix [4] - crown-6 (2, 200 mg, 0.21 mmol), oxalyl chloride (1.5 mL), NaH (83 mg, 2.07 mmol) and 3 , 5-bis (trifluoromethyl) benzenesulfonamide (112 mg, 0.45 mmol) reacted to give 123 mg (39%) of the compound ^f Bu-C ₆ H ₃ (CF ₃ ) ₂ -calix [4] -krone-6 (L10).

'H NMR (400 MHz, CDCL): d = 1.09 (s, 18H, CH ₃ ), 1.16 (s, 18H, CH ₃ ), 3.34 (d, ² J = 12.3 Hz, 4H, ArCH ₂ ) , 3.65-3.72 (m, 8H, 2 x OCH ₂ ), 3.77-3.82 (m, 4H, OCH ₂ ), 3.83-3.88 (m, 4H, OCH ₂ ), 4.11-4.20 (m, 4H, OCH ₂ + ArCH ₂ ), 4.64 (s, 4H, CH ₂ C = 0), 7.05 (s, 4H, m- H _Ar ), 7.10 (s, 4H, m- H _Ar ), 7.95 (s, 2H, R _F Ar ), 8.50 (s, 4H, R _F Ar). ¹³ C NMR (101 MHz, CDCI3): d = 30.2 (ArCH ₂ ), 31.3, 31.5 (2 x CH), 34.1, 34.3 (Cq), 69.3, 69.6, 71.9, 72.1, (4 x OCH ₂ ), 77.1 (CH ₂ C = 0), 78.6 (OCH ₂ ), 125.8, 126.2 (2 x m- CA _T ), 134.1, 134.4 (2 x O-CA _T ), 147.7, 148.4 (2 x p- CA _T ), 148.7, 151.3 (2 x 7-CA _T ), 174.4 (C = 0). ¹⁹ F NMR (376 MHz, CDCL): d = -62.8 (12F).

General svnthesis regulation S2 for the complexes Kl to K8

Barium complexes which had one of the compounds LI to L8 as ligand were prepared. For the production of the barium complexes Kl to K8 the corresponding calixarene ligand LI to L8 (1 equiv.) dissolved in acetonitrile and Ba (C10 ₄ ) ₂ (10 equiv.) added. The reaction mixture was stirred for 5 min at room temperature in an ultrasonic bath. The solvent was then removed in vacuo and dichloromethane was added. The precipitate was filtered off and washed with a little dichloromethane. The filtrate was washed with deionized water and the phases separated. The dichloromethane was removed and the residue was dried under high vacuum in order then to obtain the complexes K1 to K8 as colorless solids in quantitative yields. The general Synthesevor S2 is also suitable for the preparation of complexes K9 to K10.

Scheme 2 illustrates the preparation of complexes K1 to K8 according to the general synthesis instructions S2.

Scheme 2

The compounds of the general formula II-1 are compounds of the general formula II, where Me is ²⁺ Ba ²⁺ . Scheme 2 also illustrates the preparation of complexes K9 to K10 according to the general synthesis instructions S2.

Example 9: Complex Kl

Complex Kl was prepared in accordance with the general synthesis instructions S2 using compound LI.

Ή NMR (600 MHz, CDCh): d = 3.29 (d, ² J = 13.5 Hz, 4H, ArCH ₂ ), 3.80 (br. S, 4H, OCH ₂ ), 3.86 (br. S, 8H, 2 x OCH ₂ ), 3.93 (br. S, 4H, OCH ₂ ), 3.96-4.00 (m, 4H, OCH ₂ ), 4.56 (d, ² J = 13.5 Hz, 4H, ArCH ₂ ), 5.20 (s, 4H, CH ₂ C = 0), 6.25-6.37 (m, 4H, / -HAr + w-HAr), 6.98 (t, = 7.4 Hz, 2H, / H _Al ), 7.14 (d, V = 7.4 Hz, 4H, m- HA _T ). ¹³ C NMR (151 MHz, CDCh): 5 = 31.7 (ArCH ₂ ), 68.7, 70.0, 70.1, 70.3 (4 x OCH ₂ ), 70.4 (CH ₂ C = 0), 72.8 (OCH ₂ ), 123.2, 123.6 (2 x p- CA _T ), 128.0, 129.3 (2 x m- CA _T ), 132.8,

136.4 (2 x O-CA _T ), 154.4, 154.8 (2 x i-CA _T ), 176.5 (C = 0).

¹⁹ F NMR (565 MHz, CDC1 ₃ ): 5 = -115.1 (4F), -78.9 (6F).

Example 10: Complex K2

Complex K2 was prepared according to the general synthesis instructions S2 using compound L2.

'H NMR (600 MHz, CDCh): d = 0.92 (s, 18H, CH ₃ ), 1.28 (s, 18H, CH ₃ ), 3.32 (d, ² J = 12.6 Hz, 4H, ArCH ₂ ) , 3.78-3.82 (m, 4H, OCH ₂ ), 3.85.3.89 (m, 4H, OCH ₂ ), 4.01-4.05 (m, 4H, OCH ₂ ), 4.13 (s, 4H, OCH ₂ ), 4.31 (d , = Hz, 4H, ArCH ₂ ), 4.33- 4.37 (m, 4H, OCH ₂ ), 4.47 (s, 4H, CH ₂ C = 0), 6.85 (s, 4H, m- HA _T ), 7.21 (s , 4H, m- HA _T ). ¹³ C NMR (151 MHz, CDC1 ₃ ): 5 = 29.8 (ArCH ₂ ), 31.1, 31.6 (2 x CH ₃ ), 34.1, 34.4 (C _q ),

66.5, 68.9, 70.8, 71.4, (4 x OCH ₂ ), 77.0 (CH ₂ C = 0), 78.8 (OCH ₂ ), ..., 126.0, 126.3 (2 x m-CAT), 133.2, 134.8 (2 x O-CAT), 147.7, 148.2 (2 x p-C _Ar ), 148.3, 152.3 (2 x i-CAT), 176.0 (C = 0). ¹⁹ F NMR (565 MHz, CDC1 ₃ ): 5 = -117.8 (4F), -79.0 (6F).

Example 11: Complex K3

Complex K3 was prepared according to the general synthesis instructions S2 using compound L3.

* H NMR (600 MHz, CDC1 ₃ ): 5 = 3.29 (d, ² J = 13.4 Hz, 4H, ArCH ₂ ), 3.80-3.88 (m, 12H, 3 x OCH ₂ ), 3.93 (br. s, 4H, OCH ₂ ), 3.98 (br.s, 4H, OCH ₂ ), 4.60 (d, ² J =

13.4 Hz, 4H, ArCH ₂ ), 5.23 (s, 4H, CH ₂ C = 0), 6.25-6.37 (m, 4H, / H _Ar + / nH _Ar ), 6.97 (t, = 7.2 Hz, 2H, p - HA _T ), 7.12 (d, = 7.2 Hz, 4H, m- HA _T ). ¹³ C NMR (151 MHz, CDC1 ₃ ): 5 = 31.7 (ArCH ₂ ), 68.3, 69.9, 70.1, 70.4 (4 x OCH ₂ ), 70.4 (CH ₂ C = 0), 72.4 (OCH ₂ ), 123.1, 123.5 (2 x p-CA _T ), 128.0, 129.2 (2 x m-CA _T ), 132.8, 136.3 (2 x O-CA _T ),

154.5, 154.8 (2 x i-CA _T ), 176.2 (C = 0). ¹⁹ F NMR (565 MHz, CDC1 ₃ ): 5 = -167.8 (2F), - 72.1 (12F). Example 12: Complex K4

Complex K4 was prepared according to the general synthesis instructions S2 using compound L4.

'H NMR (600 MHz, CDCh): d = 0.93 (s, 18H, CH ₃ ), 1.28 (s, 18H, CH ₃ ), 3.32 (d, ² J = 12.6 Hz, 4H, ArCH ₂ ) , 3.77-3.82 (m, 4H, OCH ₂ ), 3.84-3.89 (m, 4H, OCH ₂ ), 4.00-4.05 (m, 4H, OCH ₂ ), 4.13 (s, 4H, OCH ₂ ), 4.28-4.37 (m, 8H, OCH ₂ + ArCH ₂ ), 4.45 (s, 4H, CH ₂ C = 0), 6.85 (s, 4H, m- H _Ar ), 7.21 (s, 4H, m- HA _T ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 29.7 (ArCH ₂ ), 31.1, 31.7 (2 x CH ₃ ), 34.1, 34.4 (C _q ), 66.5, 69.0, 70.9, 71.5, 77.0 (5 x OCH ₂ ), 77.4 (CH ₂ C = 0), 78.8 (OCH ₂ ), 126.0, 126.3 (2 x m- CA _T ), 133.2, 134.9 (2 x O-CA _T ), 147.7, 148.3 (2 x p- CA _T ), 148.4, 152.2 (2 x i-CA _T ), 175.7 (C = 0). ¹⁹ F NMR (565 MHz, CDC1 ₃ ): d = -171.1 (2F), -71.7 (12F).

Example 13: Complex K5

Complex K5 was prepared according to the general synthesis instructions S2 using compound L5.

Ή NMR (600 MHz, CDC1 ₃ ): d = 3.43 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 3.83-3.90 (m, 8H, 3 x OCH ₂ ), 4.02-4.08 (m , 4H, OCH ₂ ), 4.14 (s, 4H, OCH ₂ ), 4.37-4.47 (m, 12H, 0CH ₂ + ArCH ₂ + CH ₂ C = 0), 6.82 (t, V = 7.7 Hz, 2H, / H _Al ), 6.94 (t, 1 / = 7.6 Hz, 2H, p- HA _T ), 7.05 (d, V = 7.7 Hz, 4H, m- HA _T ), 7.20 (d, V = 7.6 Hz, 4H, m- HA _T ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 29.5 (ArCH ₂ ), 67.0, 69.1, 71.1, 71.5 (4 x OCH ₂ ), 77.3 (CH ₂ C = 0), 79.7 (OCH ₂ ), 126.3, 126.5 (2 x p-CA _T ), 129.4, 129.7 (2 x m-CA _T ), 134.4, 135.4 (2 x O-CA _T ), 152.1, 154.3 (2 x i-CA _T ), 175.6 (C = 0). ¹⁹ F NMR (565 MHz, CDC1 ₃ ): d = -125.9 (4F), -121.1 (4F), 113.8 (4F), -80.8 (6F).

Example 14: Complex K6

Complex K6 was prepared according to the general synthesis instructions S2 using compound L6. 'H NMR (600 MHz, CDCh): d = 0.93 (s, 18H, CH ₃ ), 1.28 (s, 18H, CH ₃ ), 3.32 (d, ² J = 12.6 Hz, 4H, ArCH ₂ ) , 3.77-3.81 (m, 4H, OCH ₂ ), 3.84-3.88 (m, 4H, OCH ₂ ), 4.01-4.05 (m, 4H, OCH ₂ ), 4.12 (s, 4H, OCH ₂ ), 4.28-4.37 (m, 8H, OCH ₂ + ArCH ₂ ), 4.47 (s, 4H, CH ₂ C = 0), 6.85 (s, 4H, mH _Ar ), 7.21 (s, 4H, mH _Ar ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 29.8 (ArCH ₂ ), 31.1, 31.7 (2 x CH ₃ ), 34.1, 34.4 (C _q ), 66.5, 68.9, 70.8, 71.4, 78.8 (5 x OCH ₂ ), 126.0, 126.3 (2 x m- C _Ar ), 133.2, 134.8 (2 x o- C _Ar ), 147.7, 148.3 (2 x p- C _Ar ), 148.4, 152.3 (2 x i- C _Ar ) , 176.1 (C = 0). ¹⁹ F NMR (565 MHz, CDC1 ₃ ): d = -125.9 (4F), -121.1 (4F), -113.7 (4F), -80.8 (6F).

Example 15: Complex K7

Complex K7 was prepared according to the general synthesis instructions S2 using compound L7.

³ H NMR (600 MHz, CDC1 ₃ ): d = 3.21 (d, ² J = 13.5 Hz, 4H, ArCH ₂ ), 3.87 (br. S, 4H, OCH ₂ ), 3.91-4.01 (m, 16 H, 4 x OCH ₂ ), 4.51 (d, ² J = 13.5 Hz, 4H, ArCH ₂ ), 5.12 (s, 4H, CH ₂ C = 0), 6.22 (d, V = 7.5 Hz, 4H, m - H _Ar ), 6.28 (t, V = 7.5 Hz, 2H, o- H _Ar ), 6.86 (t, ³ J = 7.5 Hz, 2H, oH _Ar ), 7.03 (d, V = 7.5 Hz, 4H, m - H _Ar ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 31.6 (ArCH ₂ ), 69.0, 69.9, 70.2, 70.3 (4 x OCH ₂ ), 70.3 (CH ₂ C = 0), 73.0 (OCH ₂ ), 123.0, 123.1 (2 x pC _Ar \ 127.9, 128.8 (2 x m- C _M ), 132.7, 136.8 (2 x o- C _AT ), 154.9 (/ -C _Ar ), 168.9 (C = 0). ¹⁹ F NMR ( 565 MHz, CDC1 ₃ ): d = -158.5 (4F), - 144.9 (2F), -134.8 (4F).

Example 16: Complex K8

Complex K8 was prepared according to general synthesis instructions S2 using compound L8.

'H NMR (600 MHz, CDC1 ₃ ): d = 0.92 (s, 18H, CH ₃ ), 1.27 (s, 18H, CH ₃ ), 3.32 (d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 3.72-3.77 (m, 8H, OCH ₂ ), 3.96-4.00 (m, 4H, OCH ₂ ), 4.03 (s, 4H, OCH ₂ ), 4.17 (br. S, 4H, OCH ₂ ), 4.24 ( d, ² J = 12.5 Hz, 4H, ArCH ₂ ), 4.53 (s, 4H, CH ₂ C = 0), 6.84 (s, 4H, mH _Ar ), 7.19 (s, 4H, mH _Ar ). ¹³ C NMR (151 MHz, CDC1 ₃ ): d = 29.8 (ArCH ₂ ), 31.1, 31.6 (2 x CH ₃ ), 34.1, 34.4 (C _q ), 67.1, 68.6, 70.6, 71.0, 78.6 (5 x OCH ₂ ), 76.6 (CH ₂ C = 0), 126.0, 126.2 (2 x m- C _Ar ), 133.2, 134.7 (2 x o- CA _T ), 147.7, 148.3 (2 x p- CA _T ), 148.9, 152.5 (2 x / - CA _T ), 175.8 (C = 0). ¹⁹ F NMR (565 MHz, CDCh): d = -158.5 (4F), -144.9 (2F), -134.8 (4F).

Example 17: Detection of the formation of radium complexes

To detect the complex formation between the ligands LI to L8 and

Radium ions were carried out in two-phase extraction studies. The desired concentration of ligand LI to L8 was adjusted in 600 pL chloroform. With this solution, 600 pL of an aqueous radium stock solution were extracted for one hour at room temperature in an overhead shaker. An aliquot of 200 pL was then removed from each phase and measured in a sodium iodide detector after a 4-day decay time (especially lead-212, but also other daughter nuclides). The measurements were carried out independently and in triplicate. The statistical uncertainty of the sodium iodide detector was less than 3%. Scheme 3 illustrates the preparation of complexes K1A to K8A.

Scheme 3

The compounds of general formula II-2 are compounds of general formula II, where Me is ²⁺ Ra ²⁺ . Scheme 3 also illustrates the preparation of complexes K9A to K10A.

Example 18: Calculation of the complex stability constant logV of the ¹³³ Ba and ²²⁴ Ra

Complexes The stability constants K or their log / are calculated using the following formulas in accordance with that of S. Haupt, R. Schnorr, M. Poetsch, A. Mansel, M. Handke, B. Kersting in J. Radioanal. Nucl. Chem. 2014, 300, 779-786, described method.

ci concentration of the ligand

cp s ₀ count rate corresponding to the radioactivity after extraction in the organic phase

cp s _w count rate corresponding to the radioactivity after extraction in the aqueous phase

As an example, Table 3 shows the calculation of log / values for compound L5 and [ ²²⁴ Ra] Ra ²⁺ . In Table 4, the complex stability constants log K 1 ³³ ²²⁴ Ba and Ra complexes, each comprising one of the connection LI to L8 as ligands shown.

Table 3: Calculation of values for compound L5 and T ²²⁴ Ra1Ra ²⁺

Table 4: Values of ¹³³ Ba and ²²⁴ Ra complexes

Example 19: Stability of radium complexes

Furthermore, the radium complexes K1A to K8A, which had one of the compounds LI to L8 as ligands, were tested for stability to calcium ions in order to demonstrate their selectivity. For this purpose, 400 pL of the chloroform solution, which contains the calix [4] arene-radium complex, were mixed with an aqueous calcium chloride solution (isotonic, 40-fold excess calcium ions / ligand, 400-fold excess calcium ions / radium ions) for one hour at room temperature extracted in an overhead shaker. An aliquot is then removed from each phase and the radioactivity is measured in a sodium iodide detector after a 4-day decay time (as explained in Example 17, above). The data for the ligand already shown in Table 3, above, are shown as an example in Table 5.

Table 5: Determination of the stability of the L5-Ra ²⁺ complex against Ca ²⁺ ions

Claims

1. Connection, having

a calixarene unit which has n phenol units, where n is 4, 5, 6 or 8;

- An ether unit, which is bound to the Cali xaren unit to form a crown ether; and

- At least one sulfonic acid amide unit of the formula

-0- (CH) pC (0) -NH-S (0) ₂ -R ¹

wherein the at least one sulfonic acid amide unit is in each case bound to the calibrarene unit and R ^{1 is in} each case selected from the group consisting of a perfluorinated branched or unbranched C2-C8 alkyl group, a perfluorinated aryl group, and a group Ar, p is an integer from 1 to 4 and Ar is a phenyl group substituted with one or more perfluorinated branched or unbranched C 1 -C ₈ alkyl groups.

2. Compound according to claim 1, characterized in that the phenol units of the calixarene unit each carry a substituent R ² , where R ² each is hydrogen, a branched or unbranched, substituted or unsubstituted C _I -C _Ö alkyl group or is a unit of the formula - (L-) _W X, where w is 0 or 1, L is a linker and X is a reactive functional group.

3. A compound according to claim 2, characterized in that the reactive functional group X is a carboxylic acid halide, a carboxylic acid anhydride, an active ester or a maleimide.

4. Connection according to one of the preceding claims, characterized in that the calixarene unit has a cone conformation.

5. A compound according to any one of the preceding claims, characterized in that the crown ether has m oxygen atoms, where m is an integer from 4 to 8.

6. Compound according to one of the preceding claims, characterized in that R ^{1 is} selected from the group consisting of a perfluorinated ethyl group, a perfluorinated "propyl group, a perfluorinated isopropyl group, a perfluorinated // - butyl group, a perfluorinated iso - Butyl group, a perfluorinated .sfc-butyl group, a perfluorinated tert-butyl group and a perfluorophenyl group is selected.

7. A compound according to any one of claims 1 to 5, characterized in that R ^{1 is} an Ar group which is substituted by one or two or more trifluorometylene groups.

8 Compound according to one of claims 2 to 6, characterized in that it has the general formula I:

(Formula I), wherein R ^{1 is} as defined in claim 1 and R ^{2 is} as defined in claim 2.

9. A compound according to claim 8, characterized in that R ^{2 is} hydrogen or a tert-butyl group on each occurrence.

10. Use of a compound according to any one of claims 1 to 9 to form a complex with an alkaline earth metal cation.

11. Use according to claim 10, characterized in that the alkaline earth metal cation is Ba ²⁺ or Ra ²⁺ .

12. Use according to claim 10 or claim 11, characterized in that the alkaline earth metal cation is a radioactive alkaline earth metal cation.

13. A method for producing a complex from a compound according to any one of claims 1 to 9 and an alkaline earth metal cation, comprising the steps:

(a) providing a solution containing the alkaline earth metal cation; and

(b) bringing the solution into contact with a compound according to one of claims 1 to 9.

14. The method according to claim 13, characterized in that the solution provided in step (a) is an organic or aqueous solution in which the alkaline earth metal cation is present together with a counterion.

15. Complex consisting of a compound according to any one of claims 1 to 9 and an alkaline earth metal cation.