2000手性氨基酸合成钆(III)卟啉的诱导圆二色活性的络合物INDUCED CIRCULAR DICHROISM

www.elsevier.nl/locate/icaInorganica Chimica Acta300–302(2000)243–249Induced circular dichroism active complexes of syntheticgadolinium(III)porphyrinates with chiral amino acids Hitoshi Tamiaki a,*,Natsushi Matsumoto a,Satomi Unno a,Satoshi Shinoda b,Hiroshi Tsukube ba Department of Bioscience and Biotechnology,Faculty of Science and Engineering,Ritsumeikan Uni6ersity,Kusatsu,Shiga525-8577,Japanb Department of Chemistry,Graduate School of Science,Osaka City Uni6ersity,Sugimoto,Sumiyoshi-ku,Osaka558-8585,JapanReceived2September1999;accepted22October1999AbstractSynthetic gadolinium(III)meso-tetrakis(3,5-di-tert-butylphenyl)porphyrinates extracted zwitterionic L-phenylglycine from an aqueous solution to give a1:1complex in benzene through synergistic binding of both amino and carboxylic groups of the amino acids.The resulting highly coordinated complex afforded intense circular dichroism(CD)bands of reversed S-shape type at the Soret region(400–450nm).In the case of D-phenylglycine,a complete mirror image of the CD spectrum was recorded after extraction.While the intensity of the induced CD peak was affected by the nature of the organic solvent,meso-aryl substituent and C a-residue,its sign was well related to the stereochemistry of the bound amino acid.A combination of biphasic extraction and CD spectrometry provides a promising method for determination of the absolute configuration of unprotected a-amino acids.©2000Elsevier Science S.A.All rights reserved.Keywords:Extraction;Gadolinium complexes;Porphyrinate complexes;Amino acid1.IntroductionRecognition of naturally occurring a-amino acids in unprotected forms is an important subject from the aspects of coordination,analytical,biological,organic and physical chemistry.Because the amino acids are very soluble in water as the zwitterionic species but hardly soluble in less polar organic solvents,their ex-traction with synthetic receptor into the organic solvent is a very difficult task.Several sophisticated receptors are available for this purpose[1]:Aoyama et al.re-ported that a synthetic rhodium(III)porphyrinate pos-sessing2-hydroxy-1-naphthyl groups extracted amino acids from the aqueous solution to give a1:1complex in chloroform[2].We also found that lanthanide(III) tris(fluorinated b-diketonates)bound the unprotected amino acids via formation of highly coordinated com-plexes[3].Chirality sensing of the amino acids is also important but more difficult,usually requiring derivatization with suitable chromophores through covalent bonds.Dillon and Nakanishi reported that praseodymium(III)tris-(dipivalomethanate)was a useful sensor of chiral1,2-di-ols;when mixed with chiral diol in dry organic solvent, the resulting complex gave the induced CD peaks[4]. We recently found that several lanthanide(III) tris(fluorinated b-diketonates)formed stable complexes with chiral unprotected amino alcohols and amino acids and offered intense induced CD signals even in a water-saturated dichloromethane[3,5].Interestingly, the signs of the observed CD peaks were dependent on the configurations of the bound amino acids.Therefore, the lanthanide complexes have potential as effective receptors for unprotected amino acids if they are struc-turally optimized.Here we report that synthetic gadolinium(III)por-phyrinate(Fig.1)[6]binds various zwitterionic amino acids at the interface of a biphasic system of organic solvent–water and extracts them into the organic solu-tion to form CD active1:1complexes.The gadolinium*Corresponding author.Tel.:+81-77-5612765;fax:+81-77-5612659.E-mail address:tamiaki@se.ritsumei.ac.jp(H.Tamiaki)0020-1693/00/$-see front matter©2000Elsevier Science S.A.All rights reserved. PII:S0020-1693(99)00536-8H.Tamiaki et al./Inorganica Chimica Acta300–302(2000)243–249 244Fig.1.5,10,15,20-Tetrakis(3,5-di-tert-butylphenyl)porphyrinates.at room temperature for3h.After removal of CH2Cl2, the residue was washed with ether.The ethereal solu-tion(filtrate)was evaporated and purified withflash silica gel column chromatography(CH2Cl2)to give Ar CHO(\93%).3,5-Dimethylbenzaldehyde:color-less liquid;1H NMR(CDCl3)l9.94(1H,s,CHO),7.48 (2H,s,2,6-H),7.26(1H,s,4-H),2.38(6H,s,3,5-CH3). 3,5-Dibromobenzaldehyde:white crystal;1H NMR (CDCl3)l9.89(1H,s,CHO),7.92(2H,d,J=1.5Hz, 2,6-H),7.89(1H,t,J=1.5Hz,4-H).2.2.Synthesis of tetraarylporphyrinAlthough mesitylporphyrin was afforded according to Lindsey’s procedure[9],other porphyrins were pre-pared by slight modification of Adler’s method[10]as follows.To a refluxing propionoic acid(25ml)solution of commercially available or synthetic Ar CHO(5 mmol),pyrrole(5mmol)was added dropwise with vigorous stirring.The reaction mixture was refluxed for 1h and concentrated in vacuo.The residue was washed with CH3OH to give a crude product.Alumina column chromatography(CH2Cl2and AcOEt)and recrystal-lization(from CH3OH)afforded a pure tetraarylpor-phyrin as dark purple powder;m.p.\300°C.In the case of Ar=C6F5,undesired chlorine could not be separated through the above alumina column. After zinc metallation of the crude product (Zn(OAc)2·2H2O/CH3OH CH2Cl2),zinc chlorinate was first removed by the alumina column(hexane/ toluene=1/1)and then zinc porphyrinate was eluted (toluene/CH2Cl2=1/1).Demetallation(conc.HCl/ CH2Cl2)gave the corresponding chlorine-free porphyrin.2.3.Synthesis of gadolinium tetraarylporphyrinate According to the reported procedure[11],gadolinium porphyrinates were prepared.A1,2,4-trichlorobenzene (10ml;150ml in the case of Ar=ortho-substituted-phenyl)solution of metal-free porphyrin(50m mol)and gadolinium acetylacetonate hydrate(90mg,Strem)was refluxed with stirring under N2.After70–80%disap-pearance of the visible Q y-peaks of metal-free por-phyrin,the solvent was evaporated in vacuo.The residue was purified with alumina column chromatogra-phy(toluene acetone DMSO as eluants).The frac-tions of DMSO/H2O=1/0–8/2gave the desired gadolinium complex.The combined elutions were treated with acid-free CHCl3(CH2Cl2/Et2O=1/1in the case of Ar=C6F5)and washed with H2O several times. After evaporation,the residue was precipitated from H2O to give a pure gadolinium porphyrinate as dark purple powder;m.p.\300°C.porphyrinates gave intense CD signals at the Soret region after extraction of various chiral amino acids. Compared with CD spectra of amino acids themselves in the aqueous solutions,amplification of the CD inten-sity and red-shift of the peak from UV to visible region were observed.The effects of structures of porphyrinate ligands and the natures of solvents on the CD active complexation with amino acids are described below[7].2.ExperimentalAll of the apparatus used was described in our previous report[8].HPLC was performed with a chiral-phase column(SUMICHIRAL OA-6100,4.6 ×250 mm,Sumika Chemical Analysis Service,2mM CuSO4 in H2O/CH3CN=95/5, 1.0ml min−1).Solvents for visible and CD spectra were purchased from Nacalai Tesque(Grade for UV-spectroscopy).2.1.Synthesis of Ar–CH2OH and Ar–CHOTo an ice-chilled THF(5ml)solution of Ar COOH (5mmol,Ar=3,5-(CH3)2 C6H3 or3,5-Br2 C6H3 ) under N2was slowly added a1M THF(20ml) solution of BH3.The reaction mixture was stirred at room temperature for3h and cooled to0°C,aqueous THF(1/1)was added and the mixture was saturated with solid K2CO3.The aqueous phase was extracted with ether and the combined organic phases were con-centrated in vacuo to give Ar CH2OH(\95%).3,5-Dimethylbenzyl alcohol:colorless liquid;1H NMR (CDCl3)l6.98(2H,s,2,6-H),6.95(1H,s,4-H),4.58 (2H,s,1-CH2),2.34(6H,s,3,5-CH3).3,5-Dibromoben-zyl alcohol:white crystal;1H NMR(CDCl3)l7.58 (1H,s,4-H),7.45(2H,s,2,6-H),4.67(2H,s,1-CH2).A CH2Cl2(70ml)solution of Ar CH2OH(1mmol) and pyridinium chlorochromate(1.5mmol)was stirredH.Tamiaki et al./Inorganica Chimica Acta300–302(2000)243–2492452.4.Spectral data of porphyrins and their gadoliniumcomplexes5,10,15,20-Tetrakis(3,5-di-tert-butylphenyl)porphyrin(3):[12]20%yield;Vis(CH2Cl2)u max420(m,626000),516(2300),552(12500),591(6900),647nm(7500);(benzene)u max421(rel.1.000),516(0.040),560(0.023),590(0.013),650nm(0.015);IR(KBr)1593,1475cm−1;1H NMR(CDCl3)l8.90(8H,s,b-H),8.08(8H,d,J=1.5Hz,2,6-H),7.78(4H,t,J=1.5Hz,4-H),1.52(72H,s,3,5-(CH3)3),−2.67(2H,s,NH).MS(FAB)Found:m/z1063.Calc.for C76H95N4:MH+,1063.5,10,15,20-Tetrakis(3,5-dimethylphenyl)porphyrin:22%yield;Vis(CH2Cl2)u max419(rel. 1.000),515(0.036),551(0.015),591(0.010),647nm(0.010);IR(KBr)1601,1473cm−1;1H NMR(CDCl3)l8.86(8H,s,b-H),7.83(8H,s,2,6-H),7.40(4H,s,4-H),2.60(24H,s,3,5-CH3),−2.80(2H,s,NH).MS(FAB)Found:m/z727.Calc.for C52H47N4:MH+,727.5,10,15,20-Tetrakis(3,5-dimethoxyphenyl)porphyrin:17%yield;Vis(CH2Cl2)u max420(rel. 1.000),514(0.041),549(0.0095),589(0.012),645nm(0.0072);IR(KBr)1601,1458,1420cm−1;1H NMR(CDCl3)l8.92(8H,s,b-H),7.39(8H,s,2,6-H),6.89(4H,s,4-H),3.95(24H,s,3,5-OCH3),−2.85(2H,s,NH).MS(FAB)Found:m/z855.Calc.for C52H47N4O8:MH+,855.5,10,15,20-Tetrakis(3,5-difluorophenyl)porphyrin:9%yield;Vis(CH2Cl2)u max415(rel.1.000),511(0.047),544(0.0094),587(0.013),646nm(0.0058);IR(KBr)1622,1589,1429cm−1;1H NMR(CDCl3)l8.90(8H,s,b-H),7.76(8H,dd,1,3J HF=7,1,4J HH=2Hz,2,6-H), 7.31(4H,tt,1,3J HF=9,1,4J HH=2Hz,4-H),−2.97 (2H,s,NH).MS(FAB)Found:m/z759.Calc.forC44H23F8N4:MH+,759.5,10,15,20-Tetrakis(3,5-dichlorophenyl)porphyrin:11%yield;Vis(CH2Cl2)u max418(rel. 1.000),513(0.044),547(0.011),589(0.013),645nm(0.006);IR(KBr)1585,1558,1408cm−1;1H NMR(CDCl3)l8.89(8H,s,b-H),8.11(8H,d,J=2Hz,2,6-H),7.84(4H,t,J=2Hz,4-H),−2.8(2H,s,NH).MS(FAB)Found:m/z890.Calc.for C44H2335Cl637Cl2N4:MH+,890.5,10,15,20-Tetrakis(3,5-dibromophenyl)porphyrin:17%yield;Vis(CH2Cl2)u max419(rel. 1.000),514(0.045),548(0.013),589(0.014),645nm(0.006);IR(KBr)1578,1545,1400cm−1;1H NMR(CDCl3)l8.89(8H,s,b-H),8.31(8H,d,J=1.5Hz,2,6-H),8.15(4H,t,J=1.5Hz,4-H),−2.8(2H,s,NH).5,10,15,20-Tetrakis(3,4,5-trimethoxyphenyl)porphy-rin:13%yield;Vis(CH2Cl2)u max422(rel.1.000),515(0.043),552(0.018),590(0.014),648nm(0.013);IR(KBr)1582,1506,1464,1412cm−1;1H NMR(CDCl3) l8.96(8H,s,b-H),7.46(8H,s,2,6-H),4.18(12H,s, 4-OCH3),3.97(24H,s,3,5-OCH3),−2.78(2H,s,NH).MS(FAB)Found:m/z975.Calc.for C56H55N4O12:MH+,975.5,10,15,20-Tetrakis(2,4,6-trimethoxyphenyl)porphy-rin:6%yield;Vis(CH2Cl2)u max420(rel.1.000),514 (0.051),545(0.015),592(0.017),649nm(0.013);1H NMR(CDCl3)l8.70(8H,s,b-H),6.55(8H,s,3,5-H), 4.08(12H,s,4-OCH3),1.84(24H,s,2,6-OCH3),−2.8 (2H,s,NH).MS(FAB)Found:m/z975.Calc.for C56H55N4O12:MH+,975.5,10,15,20-Tetramesitylporphyrin:23%yield;Vis (CH2Cl2)u max417(rel.1.000),514(0.044),546(0.013), 591(0.013),646nm(0.008);1H NMR(CDCl3)l8.61 (8H,s,b-H),7.26(8H,s,3,5-H),2.61(12H,s,4-CH3), 1.84(24H,s,2,6-CH3),−2.50(2H,s,NH).MS(FAB) Found:m/z782.Calc.for C56H54N4:M+,782.5,10,15,20-Tetrakis(pentafluorophenyl)porphyrin:5% yield;Vis(CH2Cl2)u max411(rel.1.000),505(0.069), 583(0.024),638nm(0.005);1H NMR(CDCl3)l8.92 (8H,s,b-H),−2.93(2H,s,NH).MS(FAB)Found: m/z975.Calc.for C44H11F20N4:MH+,975. Gadolinium5,10,15,20-tetrakis(3,5-di-tert-butylphe-nyl)porphyrinate acetylacetonate(1):32%yield;Vis (CH2Cl2)u max420(rel. 1.000),556(0.045),595nm (0.019);(benzene)u max422(m580000),556(26000),594 nm(9900);IR(KBr)1591,1477cm−1.MS(FAB) Found:m/z1218.Calc.for C76H92N4158Gd:[M–acac]+, 1218.Anal.Found:C;70.89,H;7.40,N;3.90.Calc.for C76H92N4Gd·C5H7O2·(CH3)2SO·CH3OH:C;70.65,H;7.69,N;3.92.Zinc5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)por-phyrinate(2):93%yield;Reddish pink powder(from CH2Cl2-hexane);Vis(CH2Cl2)u max422(rel.1.000),549 (0.040),587nm(0.013);IR(KBr)1593,1475cm−1;1H NMR(CDCl3)l9.00(8H,s,b-H),8.09(8H,d,J=1.5 Hz,2,6-H),7.78(4H,t,J=1.5Hz,4-H),1.52(72H,s, 3,5-(CH3)3).MS(FAB)Found:m/z1124.Calc.for C76H92N464Zn:M+,1124.Gadolinium5,10,15,20-tetrakis(3,5-dimethylphenyl)-porphyrinate acetylacetonate:32%yield;Vis(CH2Cl2) u max418(rel.1.000),553(0.047),590nm(0.013);IR(KBr)1601,1456cm−1.MS(FAB)Found:m/z882. Calc.for C52H44N4158Gd:[M–acac]+,882. Gadolinium5,10,15,20-tetrakis(3,5-dimethoxyphenyl)-porphyrinate acetylacetonate:32%yield;Vis(CH2Cl2) u max420(rel.1.000),553(0.051),591nm(0.009);IR (KBr)1601,1589,1456,1420cm−1.MS(FAB)Found: m/z1010.Calc.for C52H44N4O8158Gd:[M–acac]+, 1010.Gadolinium5,10,15,20-tetrakis(3,5-difluorophenyl)-porphyrinate acetylacetonate:64%yield;Vis(CH2Cl2) u max415(rel.1.000),551(0.047),588nm(0.007);IR (KBr)1618,1589,1429cm−1.MS(FAB)Found:m/z 914.Calc.for C44H20F8N4158Gd:[M–acac]+,914. Gadolinium5,10,15,20-tetrakis(3,5-dichlorophenyl)-porphyrinate acetylacetonate:65%yield;Vis(CH2Cl2) u max418(rel.1.000),553(0.051),590nm(0.007);IR (KBr)1583,1558,1408cm−1.MS(FAB)Found:m/z 1045.Calc.for C44H2035Cl637Cl2N4158Gd:[M–acac]+, 1045.H.Tamiaki et al./Inorganica Chimica Acta300–302(2000)243–249 246Gadolinium5,10,15,20-tetrakis(3,5-dibromophenyl)-porphyrinate acetylacetonate:24%yield;Vis(CH2Cl2) u max419(rel.1.000),553(0.050),590nm(0.009);IR (KBr)1578,1545,1400cm−1.Gadolinium5,10,15,20-tetrakis(3,4,5-trimethoxyphen-yl)porphyrinate acetylacetonate:48%yield;Vis(CH2Cl2)u max424(rel. 1.000),556(0.053),593nm(0.014);IR(KBr)1578,1506,1458,1406cm−1.MS(FAB)Found:m/z1130.Calc.for C56H52N4O12158Gd:[M–acac]+,1130.Gadolinium5,10,15,20-tetrakis(2,4,6-trimethoxyphen-yl)porphyrinate acetylacetonate:50%yield;Vis(CH2Cl2)u max423(rel. 1.000),552(0.052),588nm(0.003);IR(KBr)1607,1583,1456,1412cm−1.MS(FAB)Found:m/z1130.Calc.for C56H52N4O12158Gd:[M–acac]+,1130.Gadolinium5,10,15,20-tetramesitylporphyrinate ace-tylacetonate:37%yield;Vis(CH2Cl2)u max424(rel.1.000),554(0.049),590nm(0.009);IR(KBr)1601,1514cm−1.MS(FAB)Found:m/z938.Calc.forC56H52N4158Gd:[M–acac]+,938.Gadolinium5,10,15,20-tetrakis(pentafluorophenyl)-porphyrinate acetylacetonate:20%yield;Vis(CH2Cl2) u max413(rel.1.000),548(0.058),584nm(0.015);IR (KBr)1518,1499cm−1.MS(FAB)Found:m/z1130. Calc.for C44H8F20N4158Gd:[M–acac]+,1130.3.Results and discussionGadolinium(III)porphyrinate(1)was prepared from 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)porphyrin and gadolinium(III)tris(acetylacetonate)according to the reported procedure[11],and was soluble in benzene to give a clear red solution.To the benzene solution was added an aqueous solution of L-phenylglycine(L-Pgl)and the resulting biphasic solutions were stirred at room temperature for30min in the dark.The upper benzene phase was a red solution after the stirring but its visible absorption spectrum showed slight changes, while the lower aqueous phase was a colorless clear solution because of insolubility of porphyrin complex1. Compared with the benzene phase stirred with water (broken line of Fig.2a),the benzene phase stirred with the aqueous solution of L-Pgl gave slightly red-shifted peaks at the Soret and Q y-bands as well as a new band at438nm(solid line of Fig.2a).These changes are ascribed to a highly coordinated complexation of gadolinium porphyrinate(1)with L-Pgl.Moreover,the resulting complex gave intense CD peaks around430 nm and relatively weak CD peaks at the longer wave-lengths of Q-band(solid line of Fig.2b),while gadolin-ium porphyrinate(1)itself was CD silent.The reversed S-shaped band at the Soret region was induced by chirality of L-Pgl extracted from the aqueous solution to the benzene phase.When D-Pgl was used instead of the L-enantiomer,the same visible spectrum was ob-tained for the benzene phase as that with the L-isomer but the sign of the CD spectrum was completely re-versed(dotted line of Fig.2b):strong S-and weak reversed S-shaped bands at the Soret and Q-band re-gions,respectively.After stirring with an aqueous solu-tion of racemic D,L-Pgl,the benzene solution containing gadolinium porphyrinate(1)gave the same visible spectra but no CD peak as expected.When the benzene phase did not contain gadolinium porphyrinate(1),zwitterionic Pgl was not extracted. Gadolinium porphyrinate(1)complexed with Pgl at the biphasic interface and extracted the zwitterion from the aqueous phase into the benzene.The extracted amounts of amino acid were determined by HPLC analysis of the aqueous phase before and after extraction.Fig.3a shows that the extraction stopped when1equiv.of Pgl was bound to the gadolinium porphyrinate(1).The CD peaks at the Soret region grew with increase of the initial concentration of Pgl in water and the intensity finally reached a maximum value(Fig.3b).As shown in Fig.3,the two curves are similar.Since the visible band at438nm also changed in a similar fashion(data not shown),1:1complexation between gadolinium por-phyrinate(1)and Pgl was confirmed in the benzene phase.Fig. 2.Visible spectra(a)of gadolinium(III)porphyrinate(1)in benzene(40ml,1.5×10−5M)after shaking with an aqueous solu-tion(2.3ml)of L-phenylglycine(—,2.7×10−4M)or water(---). CD spectra(b)of1in benzene(40ml,1.5×10−5M)after shaking with an aqueous solution(2.3ml,2.7×10−4M)of L-phenylglycine (—)or D-phenylglycine(---).H.Tamiaki et al./Inorganica Chimica Acta300–302(2000)243–249247Fig. 3.Dependency(a)of extracted L-phenylglycine(L-Pgl)into benzene solution(40ml)of gadolinium(III)porphyrinate(1)(0.6 m mol)upon the initial amount of L-Pgl in aqueous solution(2.3ml). Dependency(b)of the induced CD intensity(436nm negative peak) of benzene solution(1,0.6m mol/40ml)upon the initial amount of L-Pgl in aqueous solution(2.3ml).The extraction process was affected by environmental factors(Table1).Among the examined solvents,2-methyl-tetrahydrofuran and ethyl acetate completely prevented the formation of the CD active complex 1·L-Pgl(entries10and11),because these solvents offered coordination with the gadolinium center.The aromatic solvents,benzene and toluene(entries1and2)provided about twice as intense CD bands of1·L-Pgl as the aliphatic solvents,cyclohexane,hexane and petroleum ether(entries6–8).When L-leucine(L-Leu)was em-ployed as a guest,the same tendency was observed for a series of solvents.No specific interaction between the phenyl group of L-Pgl and the aromatic solvent was confirmed in the complexation of1·L-Pgl,but the aro-matic solvents stabilized the highly coordinated complex-ation.In chlorinated methanes(entries3–5),bothWhen the benzene solution containing1:1complex between L-Pgl and gadolinium porphyrinate(1)was washed with water repeatedly,the induced CD and visible bands around the Soret region decreased inintensity andfinally disappeared,indicating that Pgl molecule was reversibly bound to1and moved to aqueous phase during the washing.What kinds of interactions were involved in the highly coordinated complexation?We carried out the following experiments to answer this question.After a benzene solution of zinc 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)porphyrinate (2)was agitated with an aqueous solution of L-Pgl,the benzene phase gave no CD peak.In the corresponding metal-free porphyrin3,the CD spectrum was alsoflat in the visible region.HPLC analyses of the aqueous solu-tions showed that neither zinc nor metal-free porphyrins 2and3could extract Pgl from the aqueous solution into the benzene.When(R)-1-phenethylammonium acetate was used as the aqueous solute,gadolinium porphyrinate (1)also gave no CD band at the Soret region.Since methylammonium(S)-2-phenylpropionate induced no CD peak,a bidentate Pgl apparently coordinates the gadolinium(III)center tightly to afford a CD active1:1 complex.Table1Induced CD intensity after extraction of L-phenylglycine(L-Pgl)and L-leucine(L-Leu)by gadolinium porphyrinate(1)aEntry−q(mdeg·cm−1)bSolventL-Pgl L-LeuC6H617370C6H5CH374268CH2Cl26336158594CHCl359CCl455963441cyclohexane3940hexane736petroleum ether847(C2H5)2O937292-CH3-tetrahydrofuran0100CH3COOC2H511a CD spectrum of the organic solution was measured after30min stirring of1in organic solvent(10ml,:1.5×10−5M)with L-amino acid in water(5ml,2.7×10−4M).b Ellipticity of the negative longer wavelength peak at the Soret region.H .Tamiaki et al ./Inorganica Chimica Acta 300–302(2000)243–249248Table 2Induced CD intensity after extraction of L -leucine (L -Leu)by gadolin-ium meso -tetrakis-arylporphyrinates aR 2Entry R 3R 1−D m (M −1cm −1)b1C(CH 3)3H H 95CH 3H H 612H 3OCH 3H 65H 4F H 44Cl H H 685H 6Br H 67OCH 3OCH 3H 327OCH 38H OCH 3:09H CH 3CH 35FF2F10aCD spectrum of the CH 2Cl 2solution was measured after 30min stirring of gadolinium porphyrinate in CH 2Cl 2(10ml,:1.3×10−5M)with L -leucine in water (1.78ml,4.8×10−4M).bMolar ellipticity of the negative longer wavelength peak at the Soret region.Table 3Induced CD intensity after extraction of various amino acids by gadolinium porphyrinate (1)a EntryAmino acidsResidues−Do(M −1cm −1)b H Glycine 01Alanine 2 CH 326 CH(CH 3)2324Valine CH 2CH(CH 3)2Leucine 954Isoleucine 5 CH(CH 3)CH 2CH 322 CH 2C 6H 5631Phenylalanine CH 2(3 indolyl)Tryptophane 317Proline 8 (CH 2)3 7 CH 2OH96Serine CH(OH)CH 3Threonine 1910Tyrosine11 CH 2(C 6H 4-p -OH)3 CH 2COOH 12:0Aspartic acid (CH 2)2COOH Glutamic acid 1813Asparagine 14 CH 2CONH 25 (CH 2)2CONH 2415Glutamine (CH 2)4NH 2Lysine :016 (CH 2)2NHC(NH 2) NH 176Arginine CH 2(2-imidazolyl)Histidine −91819Cysteine CH 2SH110 (CH 2)2SCH 3Methionine8820aCD spectrum of the CH 2Cl 2solution was measured after 30min stirring of 1in CH 2Cl 2(10ml,1.3×10−5M)with L -amino acid in water (1.78ml,2.4×10−4M).bMolar ellipticity of the negative longer wavelength peak at the Soret region.1·L -Pgl and 1·L -Leu afforded intense CD bands similar to those in aromatic solvents (entries 1and 2).The chlorinated methane is located lower in an aqueous biphasic system and is easy to measure the CD spectra,while aromatic liquid is located as an upper phase.The water molecules solubilized in the organic phase would be expected to compete with amino acid guests in the complexation,but gadolinium porphyrinate (1),surpris-ingly,prefers amino acids to the water in these solvents.The aryl substituents at the meso -position of the porphyrin ligand would affect a highly coordinated complexation.Various gadolinium meso -arylporphyri-nates were examined in the extraction of L -Leu (Table 2).Ortho -substitution of the meso -aryl group largely suppressed the formation of the CD active complexes (entries 8–10)because of the steric repulsion of theFig.4.Schematic drawing in extraction of zwitterionic L -amino acid and formation of CD-active 1·L -amino acidH.Tamiaki et al./Inorganica Chimica Acta300–302(2000)243–249249a-substituents with Leu.In contrast,the meta-sub-stituents did not much affect the extraction and CD sensing(entries1–7).Since the tert-butyl groups at the meta-positions gave the largest CD intensity of the ten substituents,they provided a high fence around the porphyrin p-plane to accommodate an amino acid guest nicely.The chirality specific CD bands were observed after extraction of a variety of amino acids.When the bipha-sic system of gadolinium porphyrinate(1)in dichloromethane and L-amino acids in water was shaken,the dichloromethane solution gave the charac-teristic CD bands(Table3).The amino acids having hydrophilic residues gave small or no CD bands(entries 9,11,12,and14–18),probably because of their low extraction efficiencies.Amino acids sterically crowded around the a-carbon are generally hydrophobic,but offered lower CD peaks than amino acids possessing an unbranched residue(entries3and5–7vs.4,19,and 20).Proline(entry8)and N,N-dimethyl-L-phenylala-nine also gave small CD bands(−D m=7and B5) after extraction with gadolinium porphyrinate(1).Al-though they are more hydrophobic than amino acids having a-NH2groups,the steric bulkiness around the nitrogen atoms may disturb the formation of CD active complexes.Except for aspartic acid,lysine and his-tidine,all L-amino acids gave reversed S-shaped CD bands in the visible region(400–450nm)[13].There-fore,this combined extraction/CD method(Fig.4)is useful for determination of the absolute configuration of unprotected a-amino acids possessing less coordina-tive residues.AcknowledgementsWe thank Mr Satoshi Takeo of Ritsumeikan Univer-sity for his experimental assistance.This work was partially supported by Grants-in-Aid for Scientific Re-search(Nos.09874125and10440198)from the Min-istry of Education,Science,Sports and Culture,Japan and the Ritsumeikan University Foundation Memorial Trust Research Fund.References[1]C.Seel,A.Gala´n,J.de Mendoza,Top.Cur.Chem.175(1995)101.[2]Y.Aoyama,M.Asakawa,A.Yamaguchi,H.Toi,H.Ogoshi,J.Am.Chem.Soc.112(1990)3145.[3]H.Tsukube,J.Uenishi,T.Kanatani,H.Itoh,O.Yonemitsu,mun.(1996)477.H.Tsukube,S.Shinoda,J.Uenishi,M.Shiode,O.Yonemitsu,Chem.Lett.(1996)969.H.Tsukube,S.Shinoda,Bol.Sci.Chil.Quim.42(1997)237.H.Tsukube,S.Shinoda,J.Uenishi,T.Kanatani,H.Itoh,M.Shiode,T.Iwachido,O.Yonemitsu,Inorg.Chem.77(1998) 1585.[4]J.Dillon,K.Nakanishi,J.Am.Chem.Soc.97(1975)5417.[5]H.Tsukube,M.Hosokubo,M.Wada,S.Shinoda,H.Tamiaki,J.Chem Soc.,Dalton Trans.(1999)11.H.Tsukube,M.Wada, S.Shinoda,H.Tamiaki,mun.(1999)1007.[6]Radzki et al.first reported complexation of gadolinium(III)porphyrinates with N-and O-ligands.S.Radzki,C.Giannotti, Inorg.Chim.Acta205(1993)213.S.Radzki,P.Krausz, Monatsch.Chem.126(1995)51.S.Radzki,P.Krausz, Monatsch.Chem.127(1996)51.[7]Preliminary report:H.Tamiaki,N.Matsumoto,H.Tsukube,Tetrahedron Lett.38(1997)4239.[8]H.Tamiaki,M.Kouraba,Tetrahedron53(1997)10677.[9]J.S.Lindsey,R.W.Wagner,.Chem.54(1989)828.[10]A.D.Adler, F.R.Longo,J.D.Finarelli,J.Goldmacher,J.Assour,L.Korsakoff,.Chem.32(1962)476.[11]C.-P.Wong,Inorg.Synth.22(1983)156.[12]H.Tamiaki,S.Suzuki,K.Maruyama,Bull.Chem.Soc.Jpn.66(1993)2633.[13]Toome and Wegrzynski reported that Eu(III)tris(b-diketonate)complexed with some L-amino acid esters in homogeneous chlo-roform solutions to give S-shaped CD bands in the UV region around300nm.V.Toome, B.Wegrzynski,Amino Acids3 (1992)195..。