Abstract:
An ion sensitive compound has the formula ##STR1## wherein R 1 , R 2 , R 3  and R 4  are each independently hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, an alkylamido group, an arylamido group, an alkylsulfonamido group, an arylsulfonamido group or a nitro group; 
     R 5  and R 6  are each independently a substituted or unsubstituted alkylene group; 
     X is Fe or Co +  ; 
     Y is a counter anion; and, 
     n is 0 or 1. 
     Such compounds can be used for sensing anions.

Description:
FIELD OF THE INVENTION 
     The invention relates to ion-sensitive compounds. More particularly, the invention relates to ion-sensitive compounds comprising a receptor designed to bind anionic species by the formation of a receptor-substrate complex. The compounds can be used to detect anions in solution by sensing the electrochemical change which results from the formation of the complex. 
     BACKGROUND OF THE INVENTION 
     A calix[4] arene ditopic anion receptor molecule containing two cobalticinium moieties capable of coordinating and electrochemically recognising anions has been reported, P. D. Beer, M. G. B. Drew, C. Hazlewood, D. Hesek, J. Hodacova and S. E. Stokes, J. Chem. Soc., Chem. Commun., 1993, 229. Anions recognised include the dicarboxylate anion adipate. 
     PROBLEM TO BE SOLVED BY THE INVENTION 
     There is a continuing need to provide new receptor compounds for a variety of applications. For example, there is a need for compounds which can be incorporated in electrochemical sensors for anion determination. There is also a need for compounds which can be used in removal devices where levels of a given anion need to be kept low. 
     It is also desirable to provide receptor compounds which can be readily synthesised. 
     SUMMARY OF THE INVENTION 
     The ion-sensitive compounds of the invention have the formula ##STR2## wherein R 1 , R 2 , R 3  and R 4  are each independently hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, an alkylamido group, an arylamido group, an alkylsulfonamido group, an arylsulfonamido group or a nitro group; 
     R 5  and R 6  are each independently a substituted or unsubstituted alkylene group; 
     X is Fe or Co +  ; 
     Y is a counter anion; and, 
     n is 0 or 1. 
     The invention also provides a method of sensing an anion in solution by contacting the anion with a receptor for the anion to form a receptor-substrate complex and sensing a detectable change which results from the formation of the complex characterised in that the receptor is a compound of the invention. 
     ADVANTAGEOUS EFFECT OF THE INVENTION 
     The compounds of the invention are capable of capturing and electrochemically recognising anions. The compounds can show selectivity for a particular anion in a mixture of anions. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Preferably, R 1 , R 2 , R 3  and R 4  are each independently H, a substituted or unsubstituted alkyl group having from 1 to 20 carbon atoms e.g. methyl, ethyl, propyl, butyl, pentyl, hexyl and eicosyl. Tertiary alkyl groups are particularly preferred e.g. t-butyl. Suitable substituents include alkylamido, arylamido, alkoxycarbonyl, aryloxycarbonyl, alkylsulfonamido, arylsulfonamido, alkylcarbonyl, alkoxy, cyano and nitro. 
     Preferably, R 1 , R 2 , R 3  and R 4  are each independently a substituted or unsubstituted phenyl group. Suitable substituents include alkyloxy, aryloxy, alkylamido, arylamido, alkylsulfonamido, arylsulfonamido, alkyloxycarbonyl, aryloxycarbonyl and nitro. 
     Preferably, R 5  and R 6  are each independently an alkylene group having from 1 to 6 carbon atoms e.g. --(CH 2 ) 2  --. 
     Y represents any suitable anion which together with the cobalticinium moiety is capable of forming a stable compound. Examples of such anions include sulphate, nitrate, phosphate, borate and halide e.g. iodide. Preferably, Y represents weakly coordinating anions such as hexafluorophosphate and tetrafluoroborate. 
     The synthesis of unsubstituted and substituted calixarenes is well documented. By way of example, reference is made to Calixarenes by C. David Gutsche, Royal Society of Chemistry, 1989. 
     Compounds of the invention can be prepared according to the following method. An unsubstituted or substituted calix(4)arene is reacted with two equivalents of haloalkylnitrile to produce the 1,3-biscyano derivative. Subsequent reduction of the cyano groups using, for example, lithium aluminium hydride produces the corresponding 1,3-bisamine derivative. Condensation of the 1,3-bisamine derivative with one equivalent of either 1,1&#39;-bis (chlorocarbonyl) ferrocene or a 1,1&#39;-bis (chlorocarbonyl) cobalticinium salt e.g. chloride, yields a compound of the invention. The counter anion of the cobalticinium salt can be exchanged for a more weakly coordinating anion e.g. hexafluorophosphate, tetrafluoroborate. 
     The compounds of the invention can be used in a method of sensing anions as indicated above. The detectable change resulting from formation of the complex can be measured by any suitable means such as NMR measurement or electrochemical measurement e.g. cyclic voltammetry. 
     The invention is further illustrated by way of example as follows. 
     EXAMPLE 1 
     5,11,17,23-Tetra-Tert-Butyl-25,27-Bis (Cyanomethoxy)26,28-Dihydroxy-Calix [4]Arene 
     Para-tertiarybutylcalix [4]arene was recrystalised from hot toluene/ethanol and dried under high vacuum. 
     A slurry of paratertiarybutylcalix [4] arene (3.0 g, 4.05 mmol) and anhydrous potassium carbonate (1.12 g, 8.1 mmol) was stirred in predried acetone (100 ml ) at room temperature for 10 mins. Bromoacetonitrile (0.77 ml, 8.1 mmol) was added and the reactants stirred for 48 hours at room temperature. The salt precipitated was removed by filtration and the acetone removed under reduced pressure to leave the crude product. This was taken up in dichloromethane and washed with 1×100 ml HC1.sub.(aq) the solvent again removed under reduced pressure to leave the product as a white crystalline solid. Yield 95%. 
     M.S. (F.A.B) m/z MH +  727, MK +  766 
     I.R. 3500 cm -1  broad O-H stretch, 2330 cm -1  CN absorption. 
       1  H N.M.R. (CDC1 3 ,300 MHz) δ:0.69(18H,s, t  Bu), 1.33(18H,s, t  Bu), 3.46(4H,d(J=12 Hz), ArCH 2  Ar:H eq ), 4.24(4H,d(J=12 Hz), ArCH 2  Ar:H ax ), 4.62(4H,s,OCH 2  CN), 5.58(2H,s,O-H), 6.74(4H,s,Ar-H), 7.13(4H,s,Ar-H). 
       13  C N.M.R. (CDC1 3 ,75.42 MHz) δ:30.89(CH 3 ), 31.47(C-CH 3 ), 31.53(C-CH 3 ), 31.73(CH 3 ), 34.00 (ArCH 2  Ar), 60.47(CH 2  O), 115.26(CN), 125.51(Ar-C), 126.36(Ar-C), 128.02(Ar-C), 132.03(Ar-C), 142.75(Ar-C), 148.77(Ar-C), 148.93(Ar-C), 150.17(Ar-C) 
       13  C N.M.R.D.E.P.T. (CDC1 3 ,75.42 MHz) δ:30.89(CH 3 ), 31.73(CH 3 ), 34.00(ArCH 2  Ar), 60.47(CH 2  O), 125.51(ArC-H), 126.36(ArC-H) 
     5,11,17,23-Tetra-Tert-Butyl-25,27-Bis [Aminoethoxy]-26,28-Dihydroxy-Calix [4 ]Arene 
     A slurry of the biscyanocalix[4]arene (1.5 g, 2.2 mmol) and lithium aluminium hydride (0.66 g, 17.6 mmol) was refluxed in dry diethylether (75 ml) for 4 hours under a nitrogen atmosphere. The reaction flask was then placed in an ice bath and the excess lithium aluminium hydride destroyed using water (dropwise, vigorous stirring). The alumina precipated was filtered and washed with chloroform and the solvents removed under reduced pressure to leave the product as a white crystalline solid. Yield 75%. 
     M.S. (NH 3  D.C.I.) m/z MH +  735 
     I.R. 3600-3300 cm -1  broad O-H, N-H stretch. 
       1  H N.M.R. (CDC1 3 ,300 MHz) δ:1.15(18H,s, t  Bu), 1.28(18H,s, t  Bu), 3.35(4H,quin,CH 2  -NH 2 ) 3.41(4H,d(J=12 Hz), ArCH 2  Ar:H eq ), 4.08(4H,t,CH 2  -O), 4.35(4H,d(J=12 Hz), ArCH 2  Ar:H ax ), 4.77(2H,s,O-H), 7.02(4H,s,Ar-H), 7.08(4H,s,Ar-H), 8.46(4H,br,NH) 
     5,11,17,23-Tetra-Tert-Butyl-25,27-Bis(1,1&#39;-Bis[Ferrocenecarbomylethoxy])-26,28-Dihydroxy-calixy [4]arene 
     A slurry of 1,3 bisaminecalix[4]arene (0.330 g, 0.45 mmol), dry triethylamine (0.07 ml, 0.495 mmol), a microspatulae of dimethylaminopyridine in dry dichloromethane (75 ml) was stirred under an atmosphere of nitrogen. To this slurry 1,1&#39;-bis (chlorocarbonyl)ferrocene in dry dichloromethane (25 ml) was added dropwise. On completion of the addition the reactants were stirred overnight at room temperature. The solvent was removed under reduced pressure to leave a crude orange solid that was purified using column chromatography. Silica (mesh 230-400); Eluent, Petroleum ether: Ethylacetate (4:1), Rf0.60, Yield 20% of an orange crystalline solid. 
     M.S. (F.A.B) m/z MH +  974 
     I.R. 1640 cm -1  Amide I carbonyl absorption, 1546 cm -1  Amide II N-H bend. 
       1  H N.M.R. (CDC1 3 ,300 MHz) δ:1.02(18H,s, t  Bu), 1.27(18H,s, t  Bu), 3.37 (4H,d(J=12 Hz),ArCH 2  Ar:H eq ), 4.06(4H,q,CH 2  NH), 4.21(4H,t,CH 2  O), 4.24(4H,d(J=12 Hz), ArCH 2  Ar:H ax ), 4.41(4H,t(J=1.7 Hz),Cp-H), 4.78(4H,t(1.7 Hz),Cp-H), 6.69(4H,s,Ar-H), 7.05(4H,s,Ar-H), 7.62(2H,t(5.4 Hz),CH 2  NH), 7.63(2H,s,O-H) 
       13  C N.M.R.(CDC1 3 ,75.42 Hz) δ:31.00(CH 3 ), 31.95(CH 3 ) 32.30(ArCH 2  Ar), 34.10(C-CH 3 ), 34.20(C-CH 3 ), 40.07(CH 2  -N), 70.05(Cp-C), 71.90(Cp-C), 76.00(CH 2  O), 78.00(Cp-C), 125.50(Ar-C), 126.00(Ar-C), 128.00(Ar-C), 132.70(Ar-C), 142.50(Ar-C), 147.50(Ar-C), 149.50(Ar-C), 149.90(Ar-C), 171.00(R&#39;COR&#34;) 
       13  C N.M.R.D.E.P.T. (CDC1 3 ,75.42 Hz) δ:31.95(CH 3 ), 32.30(ArCH 2  Ar), 40.07(CH 2  -N), 70.05(CpC-H), 71.90(CpC-H), 76.00(CH 2  O), 125.50(ArC-H), 126.00(ArC-H) 
     Example 2 
     Anion recognition by the compound of Example 1 has been demonstrated by  1  H NMR and cyclic voltammetry. Addition of tetrabutyl ammonium halides, hydrogen sulphate and dihydrogen phosphate to solutions of the compound in Cl 2  C 12  solution resulted in perturbations of the receptor&#39;s protons. With chloride, the amide proton of the compound of Example 1 is shifted downfield by .increment.δ 0.3 ppm. Using cyclic voltammetry to compare the redox couple of the free ligand with the anionic complex provides further evidence for anion recognition. 
     Electrochemical competition experiments with the compound show that when an equimolar mixture of H 2  PO 4   -- , HSO 4   --  and C1 --  was added to an acetonitrile electrochemical solution of the compound the ferrocene/ferrocinium redox couple shifted cathodically by an amount approximately the same as that induced by the H 2  PO 4   --  anion alone. The same result was even obtained when HSO 4   --   and C1 --  anions were in tenfold excess concentrations over H 2  PO 4   -- . These results indicate that the receptor would be useful for electrochemically based anion sensors, particularly targeted towards dihydrogen phosphate. 
     
                       TABLE 1______________________________________Electrochemical data forcompound of Example 1.sup.a______________________________________Epa (free, mV).sup.b             450Epc (free, mV).sup.b             380ΔE (H.sub.2 PO.sub.4.sup.-, mV).sup.c,d             110ΔE (HSO.sub.4.sup.-, mV).sup.c,d             &lt;5ΔE (C1.sup.-, mV).sup.c,d             40______________________________________ .sup.a Obtained in CH.sub.3 CN solution containing 0.1M[NBu.sub.4 ] as supporting electrolyte. Solutions were ca. 1 × 10.sup.-3 M in compound and potentials were determined with reference to a Ag.sup.+ /Ag electrode at 21 ± 1° C., 50 m Vs.sup.-1 scan rate. .sup.b Epa and Epc represent the anodic and cathodic current peak potentials of the ferrocene/ferricinium redox couple of the free ligand. .sup.c Cathodic shifts in the ferrocene redox couples produced by presenc of anion (5 equiv.) added as their tetrabutylammonium salts. .sup.d As the concentration of anion increased the cathodic current peak potential of the ferrocene/ferricinium redox couple began to exhibit the features of an EC mechanism.