CHIRALITY (2014)
Lanthanide Tris(β-diketonates) as Useful Probes for Chirality Determination of Biological Amino Alcohols in Vibrational Circular Dichroism: Ligand to Ligand Chirality Transfer in Lanthanide Coordination Sphere 1
HIROYUKI MIYAKE,1* KEIKO TERADA,1 AND HIROSHI TSUKUBE1,2 Department of Chemistry, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka, Japan 2 JST, CREST, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka, Japan
ABSTRACT A series of lanthanide tris(β-diketonates) functioned as useful chirality probes in the vibrational circular dichroism (VCD) characterization of biological amino alcohols. Various chiral amino alcohols induced intense VCD signals upon ternary complexation with racemic lanthanide tris(β-diketonates). The VCD signals observed around 1500 cm 1 (β-diketonate IR absorption region) correlated well with the stereochemistry and enantiomeric purity of the targeted amino alcohol, while the corresponding monoalcohol, monoamine, and diol substrates induced very weak VCD signals. The high-coordination number and dynamic property of the lanthanide complex offer an effective chirality VCD probing of biological substrates. Chirality 00:000–000, 2014. © 2014 Wiley Periodicals, Inc. KEY WORDS: chiral amino alcohol; absolute configuration; VCD; ternary complex; sensing INTRODUCTION
Chiral molecules play a fundamental role in biology, chemistry, and medicine. Thus, sensitive and noninvasive chirality determination methods have received much attention in the structure elucidation of biologically significant molecules as well as in the practical syntheses and manufacturing of chiral drugs and functional materials. X-ray crystallographic and nuclear magnetic resonance (NMR) spectroscopic methods are widely used for these purposes.1,2 While they have successfully been used to deduce three-dimensional information of chiral molecules and their assemblies, they often require laborious, time-consuming, and expensive procedures before measurement. Electronic circular dichroism (ECD) is a complementary method by virtue of its applicability to the targeted molecules in both solution and solid states.3,4 In addition to the normal direct measurements, a variety of achiral and chromophoric probes enable versatile chirality determinations of nonchromophoric substrates.5–7 Berova et al. developed dimeric metalloporphyrin host systems which incorporate chiral substrates between two porphyrin rings to show characteristic ECD signals as exciton-coupled ECD in the porphyrin spectral region.3,5 Di Bari, Anslyn, and colleagues reported enantiomeric purity determination of chiral primary amines by in situ formation of Fe(II) complexes.6 Canary, Anslyn, and colleagues used a Cu(II) complex with tripodal ligand to detect the enantiomeric purity of chiral carboxylic acids.7 Vibrational circular dichroism (VCD) is another chiroptical spectroscopic method for chirality determination,8–12 which offers vibrational difference spectra with respect to the left and right circularly polarized radiation. The VCD spectroscopy is widely applicable to a variety of chiral molecules and supramolecules and has become an increasingly popular method, because most organic molecules absorb IR radiation. Taniguchi and Monde recently developed an exciton chirality method via interaction of two IR chromophores to show strong VCD signals.13 Another advantage of the VCD method © 2014 Wiley Periodicals, Inc.
is that the observed VCD spectral information can be successfully combined with theoretical calculations for practical analyses of organic molecules,13–17 and VCD was recently applied in the characterization of chiral metal complexes.18–25 Although the chirality determination of a chiral molecule with IR-inactivity or small activity requires complexation with IR-active probe in the VCD method, this kind of example has rarely been reported. Lanthanide complexes have recently been identified as useful probes in chirality sensing methods such as ECD, NMR,26,27 circularly polarized luminescence,28–32 and Raman optical activity33 measurements based on their unique physical and chemical properties. Since their central lanthanide ions have larger ionic radii (0.99–1.13 Å)34 and higher coordination numbers (7–12) than those of transition metal cations, the lanthanide tris(β-diketonates) usually include one or more solvent molecules in addition to three β-diketonate ligands in solution and its labile nature promotes rapid interconversion between two ideal structures of the dodecahedron and the square antiprism including propeller-like arrangement of three β-diketonates. These solvent molecules are easily replaced by donating substrates such as halide ions, dimethylformamide, and pyridine as monodentate substrates, dimethoxyethane, 2,2’-bipyridine, and 1,10-phenanthroline as bidentate substrates, and 2,2’:6’2”-terpyridine and 2,6-bis(2oxazolinyl)pyridine as tridentate substrates to form ternary complexes.27,35–47 Since these ternary complexations often induce different spectroscopic characters from the original complexes, these supramolecular assemblies are useful methods to detect external molecules. We report here that
*Correspondence to: H. Miyake, Department of Chemistry, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan. E-mail: [email protected] Received for publication 7 December 2013; Accepted 11 February 2014 DOI: 10.1002/chir.22319 Published online in Wiley Online Library (wileyonlinelibrary.com).
MIYAKE ET AL.
racemic lanthanide tris(β-diketonates) serves as effective chirality probes of amino alcohols in the VCD method. In addition to the observations in ECD and luminescence probing experiments,40–44 chirality information can be transferred from external chiral substrates via noncovalent ligand-to-ligand interactions to offer characteristic induced VCD signals at IR absorption regions of β-diketonate, depending on the absolute configuration and enantiomeric purity of the small IR active substrates. MATERIALS AND METHODS Measurements VCD and IR spectra were measured on an FT/IR-4100 spectrometer with VFT-4000 attachment (JASCO, Japan) using a BaF2 cuvette (0.05 mm). The ternary metal complexes with chiral substrates for VCD and IR studies were generated in situ by mixing each metal complex and substrate under conditions shown in each figure caption. The signal 3 3 was obtained by 16,000 (for the sample of 5 × 10 mol dm ) or 2000 (for other samples) accumulations. The correction was performed by baseline subtraction with the spectrum of the cuvette filled with same concentration of racemic sample solution; a chiral sample (2000 accumulations) – racemic sample (2000 accumulations) methodology.
Materials The lanthanide tris(β-diketonates) 1a–1g, 2, 3a–3d, and 4 and copper bis(β-diketonates) 5 illustrated in Figure 2 were obtained from Aldrich Chemical (Milwaukee, WI) (1a–1g and 5), Strem Chemicals (Newburyport, MA) (3a, 3b, 3c), Apollo Chemical (Burlington, NC) (3d), Alfa Aesar (Ward Hill, MA) (4) and Gelest (Morrisville, PA) (5). Chiral substrates were received as enantiomerically pure forms from Aldrich Chemical {(R)-6a, (S)-6c, (S)- and (R)-6d, (S)- and (R)-6f, (R)-7a, (R)-7e, (R)-7f}, Nacalai Tesque (Kyoto, Japan) {(S)-7a}, Lancaster Synthesis (Ward Hill, MA) {(S)-7d, (S)-7e}, Wako Pure Chemical Industries (Osaka, Japan) {(S)-6a, (R)-6b}, Tokyo Chemical Industries (Tokyo, Japan) {(S)-6b, (R)-6c, (S)- and (R)-6e, (S)- and (R)-7b, (R)-7d, (S)-7f, (S)- and (R)-7g} and Kanto Chemical (Japan) {(S)- and (R)-7c}. These were used without further purification.
chiral building blocks in organic synthesis as well as biological substrates.48–51 We chose a series of lanthanide tris(fluorinated β-diketonates) 1a–1g including Yb3+, Er3+, Ho3+, Dy3+, Gd3+, Eu3+, and Pr3+ centers (Fig. 2). These complexes have been employed as NMR shift reagents, luminescence emitters, anion-selective electrodes, and other functional devices, as well as ECD chirality probes,13,14 because fluorinated ligand increases the formation constant of ternary complex more than alkyl chain ligand due to its strong Lewis acidity. They exhibit intense IR signals which can be divided into five regions: Region I (1600–1650 cm 1), Region II (1420–1550 cm 1), Region III (~1350 cm 1), Region IV (1250–1300 cm 1), and Region V (1200–1250 cm 1) due to their coordinating diketonates (Supporting Fig. S1).18,51–53 These are assignable to 1) the inphase and out-of phase C–O stretches for Region I; 2) C–H and CH3 bending, and C–C–C and C–O stretches for Region II; 3) CH3 bending for Region III; 4) C–CF3 stretches and C–C–C bending for Region IV; and 5) CF stretches for Region V. These lanthanide complexes are achiral and VCD-inactive. We found that addition of a chiral amino alcohol having small IR activity to the lanthanide tris(β-diketonate) solution produced enhanced VCD signals at the coordinating β-diketonate absorption regions (Region II, 1420–1550 cm 1), although the amino alcohol itself did not exhibit detectable VCD signals in solution (Figs. 1 and 3). The sign and intensity of the observed VCD signals correlated well with the absolute configuration and enantiomeric purity of the targeted amino alcohol, indicating that the present lanthanide tris(β-diketonates) worked as effective VCD chirality probes. Chirality Probing of Amino Alcohols Detected by VCD Measurements
Figure 3 shows that amino alcohol (S)- or (R)-6c having a chiral element exhibited no detectable VCD signal in CD3CN
RESULTS AND DISCUSSION Concept of VCD Chirality Probe via Ternary Complexation
As schematically illustrated in Figure 1, the lanthanide tris (β-diketonates) were demonstrated to form ternary complexes with external substrates.40–47 Furthermore, these lanthanide tris(β-diketonates) have 1) coordinating diketonate chromophores to offer intense IR absorptions suitable for induction of VCD signals; 2) high thermodynamic stability to work in various media, besides 3) two or more coordination sites on the lanthanide center available for an external chiral substrate; and 4) lanthanide-centered chirality via chiral ternary complexation. Amino alcohols were selected as chiral external substrates because they are useful
Fig. 1. Spectroscopic characteristics of lanthanide tris(β-diketonates), amino alcohols, and their ternary complex. Chirality DOI 10.1002/chir
Fig. 2. Structures of lanthanide tris(β-diketonates) 1–5, amino alcohols 6a–6f, and related substrates 7a–7g.
VCD CHIRALITY PROBING METHOD
Fig. 4. VCD (top) and IR (bottom) spectral changes of Yb–tris (β-diketonates) 1a upon addition of (S)-valinol (S)-6c in CD3CN. (Inset) titra1 3 3 tion profiles of the VCD intensities at 1467 cm . [1a] = 80 × 10 mol dm , 0.05 mm BaF2 cuvette.
ESI-MS spectra of the 1:1 solution of 1a and (S)- 6c in CD3CN mainly showed the ion clusters of 1:1 complex of 1a and 6c in addition to those of 1:2 complex {[1a•6c•H]+ (37%), [1a•6c•Na]+ (100%), [1a•6c•Na•CD3CN]+ (18%), and
Fig. 3. VCD (upper) and FT-IR (middle and lower) spectra of (a) valinol 6c, (b) Yb–tris(β-diketonate) 1a : 6c = 1:1 and 1a only (blue), (c) Yb–tris (β-diketonate) 3a : 6c = 1:1 and 3a only (blue) in CD3CN, 0.05 mm BaF2 3 cuvette with 2000 accumulations. [Yb–tris(β-diketonate)], [6c] = 80×10 mol 3 dm . Black and red lines indicate the spectra obtained with (S)- and (R)-6c, respectively.
solution at 80×10 3 mol dm 3. However, addition of racemic lanthanide tris(β-diketonate) 1a produced intense VCD signals at Region II, around 1480 cm 1: [1a] = [6c] = 80×10 3 mol dm 3 for 2 h of measurement (2000 accumulations), although Regions III and IV rarely exhibited VCD signals (Fig. S1). The sign and shape of the observed VCD signals at Region II were indicative of the stereochemistry of the targeted amino alcohol: positive (Region IIa) and negative (Region IIb) signs for the 1:1 solution of 1a and (S)-6c, and vice versa for the solution of 1a and (R)-6c (Fig. 3b). Thus, the present Yb–tris(β-diketonate) 1a functions as an effective VCD probe and has the advantage of a convenient procedure to amplify chirality information of biological amino alcohols. During the titration experiments of (S)-6c to 1a in CD3CN (Fig. 4), the VCD intensity at 1467 cm 1 changed to the negative direction and reached a plateau at one equivalent of (S)-6c. This observation indicates that one equivalent of the chiral amino alcohol is sufficient to offer intense VCD spectra and that 1:1 complexation between 1a and 6c must be involved in the enhancement of VCD signals, as illustrated in Figure 1.
Fig. 5. VCD (top) and IR (bottom) spectra of the 1:1 solution of Yb–tris (β-diketonates) 1a and valinol 6c in different concentration in CD3CN. (a) 3 3 3 3 [1a] = [6c] = 5 × 10 mol dm , (b) [1a] = [6c] = 10 × 10 mol dm and 3 3 (c) [1a] = [6c] = 80 × 10 mol dm , 0.05 mm BaF2 cuvette. Black and red lines indicate the spectra obtained with (S)- and (R)-6c, respectively. Chirality DOI 10.1002/chir
MIYAKE ET AL.
[1a•(6c)2•H]+ (58%)}. Thus, the 1:1 complex is stable enough for VCD measurement in CD3CN (logK = 4.67 for (S)-6c/1a complex in CH3OH/CH2Cl2 = 1/9940). The VCD measurements normally require a highly concentrated solution with a short pathlength cuvette to make the IR signals of the employed solvent small. We examined minimum concentrations for the VCD probing ability of lanthanide tris(β-diketonates) toward amino alcohols. When both concentrations of 1a and 6c are 5 × 10 3 mol dm 3, which is same order of concentration for 1H NMR measurements, the induced VCD signals included large noise signals (16,000 scans), but the sign of the signal clearly had a characteristic pattern enough for an indication of stereochemistry of the employed amino alcohols (Fig. 5). Since 50 μl of the solution was sufficient for this VCD measurement with a 0.05 mm cuvette, the requisite mol of the complex is similar to that required for normal UV–vis and ECD measurements. Table 1 summarizes the VCD probing profiles of 1a for several amino alcohols 6a–6f, monoalcohol 7a, diols 7b, 7c, monoamines 7d, 7e, and diamines 7f, 7g. Among them,
amino alcohols having –NH2 and –OH moieties and diamines having two –NH2 moieties were well sensed by 1a, while the chiral monoalcohol, diol, and monoamine were not efficiently detected (Fig. S1). All the examined (S)-amino alcohols and diamines except for prolinol 6d exhibited positive signal at Region IIa ~1500 cm 1 and negative signal at Region IIb ~1470 cm 1, while the corresponding (R)-amino alcohols exhibited signals with the opposite signs (Fig. 6). (S)-prolinol (S)-6d provided a positive VCD signal at Region IIa and no significant signal at Region IIb, probably due to induced chirality at the coordinating nitrogen atom. Various combinations of β-diketonate ligands and central lanthanide centers were compared. When the amino alcohol 6c was fixed as the chiral substrate, both the structure of the β-diketonate ligand and the nature of the central lanthanide cation had large influences on the intensity of the VCD signals. Although the IR signals of lanthanide tris(βdiketonates) 3a–3d appeared at higher energy field, the signs of the observed VCD signals were not changed by such structural perturbation, and signal intensities at Region IIa
TABLE 1. VCD probing profiles of lanthanide tris(β-diketonates) for various substrates in CD3CN Run
Ln-tris(β-diketonate)
VCD Intensity (× 105)
Substrate at 1496 cm
1 2 3 4 5 6 b 7 8 b 9 b 10 b 11 12 13 14 15 16 b 17 b 18 19
(S)-6a (S)-6b (S)-6c (S)-6d (S)-6e (S)-6f (S)-7a (S)-7b (S,S)-7c (S)-7d (S)-7e (S)-7f (S,S)-7 g (S)-6c (S)-6c (S)-6c (S)-6c (S)-6c (S)-6c
1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1b 1c 1d 1e 1f 1g
1
4.31 5.74 6.43 2.84 7.35 6.13 1.17 2.69 3.73 1.17 0.62 3.10 4.92 6.81 8.95 6.38 3.76 6.33 2.31
20
(S)-6c (S)-6c (S)-6c (S)-6c
3a 3b 3c 3d
1
0.86 6.26 0.06 0.02
(S)-6c
5 3
3
[Ln-tris(β-diketonate)] = [substrate] = 80 × 10 mol dm , 0.05 mm BaF2 cuvette with 2000 accumulations. 5 a With an error of 0.6 ×10 or less. b Slightly precipitated. 3 3 c [2] = [6c] = 10×10 mol dm in THF/CD3CN = 1/9. Chirality DOI 10.1002/chir
1
1
0.88 at 1496 cm
26
at 1492 cm
at 1405 cm
(S)-6c
4
1
5.76 4.36 0.08 0.25
– 25
1
0.18 at 1530 cm
21 22 23 24
at 1414 cm
(S)-6c
2
at 1468 cm 3.56 5.21 6.94 0.01 6.72 5.08 1.74 0.12 2.26 0.11 0.24 2.46 2.95 7.89 6.15 1.16 5.20 1.69 0.15
– c
a
0.14
1
at 1468 cm 0.31
1
VCD CHIRALITY PROBING METHOD
Fig. 6. VCD signs observed in lanthanide tris(β-diketonates) and amino alcohols.
were relatively small (Fig. 3c; Supporting Figs. S2 and S3). The order of influence of various ligands was 1 > 3 > > 2, 4. Interestingly, the order for various lanthanide centers was Yb(III) ~ Er(III) ~ Ho(III) > Dy(III) ~ Gd(III) ~ Eu(III) >> Pr(III), which has no correlation with the order of the lanthanide-induced VCD enhancement reported by the group of Di Bari (Tm3+ >> Yb3+ ~ Tb3+ > Nd3+ ~ Pr3+ for chiral cyclen and Tm3+ > Tb3+ > Yb3+ > Dy3+ > Ho3+ ~ Er3+ for lasalocid)22 and is similar to that observed in induced ECD intensity of probe 1a–1g with 6c.40 Since their ionic radii increased on the order Yb3+ (0.99 Å) < Er3+ (1.00 Å) < Ho3+ (1.02 Å) < Dy3+ (1.03 Å) < Gd3+ (1.05 Å) < Eu3+ (1.07 Å) < Pr3+ (1.13 Å) for octadentate coordination,34 it is likely that steric proximity between the coordinating β-diketonates and the chiral center of the amino alcohol 6c regulates the chirality transfer in the lanthanide coordination sphere. Table 1 and Supporting Figures S1 and S2 also show that the Yb–tris(β-diketonates) 1a and 3a exhibited higher VCD probing sensitivity for chiral amino alcohols 6a–6f than related substrates 7a–7g. Among the examined amino alcohols, valinol 6c and 2–phenylglycinol 6e exhibited the most intense VCD signals, although these amino alcohols were bound quantitatively with the lanthanide complex (Fig. 4). The origin of the induced VCD signal is most likely from the vibration of coordinated β-diketonates,25,53 because the VCD signals were observed at Region II of the parent lanthanide complexes which can be shifted depending on the employed β-diketonate (see IR spectra of 1a and 3a at Fig. 3). Since the IR intensity of the amino alcohol in the employed condition is very small and negligible, as shown in Figure 3a, induced VCD signals of amino alcohol is considered small. Because the small stretching vibration of coordinated amino alcohol around 1500 cm 1 is overlapped with Region II of the parent lanthanide complex, a detailed theoretical study or more VCD study using different ternary systems having independent vibrations should be required to clear this point. Some lanthanide tris(β-diketonates) also exhibited VCD signals at Region I (C–O stretches) and Region V (CF stretches) in the presence of chiral amino alcohols; the combination of 1a–6c, 1f–6c, and 3a–6 were typical examples (Figs. S1–S3). Symmetrically-substituted β-diketonate 3 is probably well arranged in a helical manner to exhibit VCD signals at Region I and V by ternary complexation with chiral alcohol. On the other hand, the complexes with unsymmetrical β-diketonate having bulky substituent 1 exhibited large VCD signal at Region II, but small signals at Regions I and V.
▪
Fig. 7. Plots of VCD signals of Yb–tris(β-diketonate) 1a ( ◯) and 3a ( ) systems at 1468 nm and 1494 nm, respectively, against enantiomer excess values of the added amino alcohol 6c. [Yb–tris(β-diketonate)] = [6c] = 80 × 10 3 mol dm 3 in CD3CN, 0.05 mm BaF2 cuvette with 2000 accumulations.
Enantiomeric Purity Determination of Amino Alcohols by VCD Detection
Lanthanide tris(β-diketonates) are applicable as VCD probes not only in the chirality sensing of amino alcohols but also in the quantitative determination of their enantiomeric purity. When the lanthanide probe was added to a mixture of (S)and (R)-amino alcohol, the sign and amplitudes of the observed VCD signals exhibited quantitative indication of enantiomer excess percentages (ee %) of amino alcohol. Figure 7 illustrates the relationship between ee % of the chiral amino alcohol 6c and the intensities of the induced VCD signal with 1a at 1468 cm 1 or 3a at 1494 cm 1. The concentration of probe 1a and 3a and total concentration of amino alcohol were fixed as 80 × 10 3 mol dm 3. The amino alcohol 6c itself did not exhibit detectable IR or VCD signals (Fig. 3a), but the induced VCD signals upon ternary complexation linearly correlated with the ee % of the employed amino alcohol with R value of more than 0.998, indicating that these kinds of lanthanide complexes work as practical VCD probes to determine the optical purity of specific substrates. CONCLUSIONS
A series of lanthanide tris(β-diketonates) served as useful chirality probes in the VCD characterization of biological amino alcohols. The racemic lanthanide complex assumed to be eight–coordinate existing in equilibrium in some structures incorporates a chiral amino alcohol in its coordination sphere. Then the chirality was effectively transferred from the external chiral substrate to the coordinating β-diketonate via ternary complexation to offer intense VCD signals, which correlated well with their stereochemistry and enantiomeric purities. Therefore, lanthanide coordination chemistry leads to the effective chirality VCD probing of biological amino alcohols. Combination with theoretical simulation would provide precise information of solution structures of the labile lanthanide complexes and further design of ligand architecture offers the potential for more practical probes in VCD methods. ACKNOWLEDGMENTS
This research was supported by Grants-in-Aid for Scientific Research (Nos. 23350029, 23111718 and 24655053) from the Japan Society for the Promotion of Science, and the Core Research for Evolutional Science and Technology (CREST) program of the Japan Science and Technology Agency (JST). Chirality DOI 10.1002/chir
MIYAKE ET AL.
SUPPORTING INFORMATION
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22. Lo Piano S, Di Pietro S, Di Bari L. Shape-conserving enhancement of vibrational circular dichroism in lanthanide complexes. Chem Commun 2012;48:11996–11998. 23. He Y, Cao X, Nafie LA, Freedman TB. Ab initio VCD calculation of a transition-metal containing molecule and a new intensity enhancement mechanism for VCD. J Am Chem Soc 2001;123:11320–11321. 24. Szilvágyi G, Brém B, Báti G, Tölgyesi L, Hollósia M, Vass E. Dirhodium complexes: determination of absolute configuration by the exciton chirality method using VCD spectroscopy. Dalton Trans 2013;42:13137–13144. 25. Kaizaki S, Shirotani D, Sato H. A novel correlation of vibrational circular dichroism spectra with the electronic ground state for Δ-SAPR-8-cesiumtetrakis((+)-heptafluorobutyrylcamphorato) lanthanide(III) complexes. Phys Chem Chem Phys 2013;15:9513–9515. 26. Tsukube H, Shinoda S. Lanthanide complexes in molecular recognition and chirality sensing of biological substrates. Chem Rev 2002;102:2389–2403. 27. Shinoda S, Miyake H, Tsukube H. Molecular recognition and sensing via rare earth complexes. In: Gschneidner Jr KA, Bünzli J-CG, Pecharsky VK, editors. Handbook on the physics and chemistry of rare earths. Amsterdam: Elsevier; 2005;35:273–335. 28. Muller G. Luminescent chiral lanthanide(III) complexes as potential molecular probes. Dalton Trans 2009;9692–9707. 29. Tang Y, Cohen AE. Enhanced enantioselectivity in excitation of chiral molecules by superchiral light. Science 2011;332:333–336. 30. Carr R, Evans NH, Parker D. Lanthanide complexes as chiral probes exploiting circularly polarized luminescence. Chem Soc Rev 2012;41:7673–7686. 31. Iwamura M, Kimura Y, Miyamoto R, Nozaki K. Chiral sensing using an achiral europium(III) complex by induced circularly polarized luminescence. Inorg Chem 2012;51:4094–4098. 32. Carr R, Di Bari L, Lo Piano S, Parker D, Peacock RD, Sanderson JM. A chiral probe for the acute phase proteins alpha-1-acid glycoprotein and alpha-1-antitrypsin based on europium luminescence. Dalton Trans 2012;41:13154–13158. 33. Yamamoto S, Bouř P. Detection of molecular chirality by induced resonance Raman optical activity in europium complexes. Angew Chem Int Ed 2012;51:11058–11061. 34. The ionic radii reported for coordination number 8 are shown: Shannon RD. Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides. Acta Crystallogr Sect A 1976; A32:751–767. 35. Cunningham JA, Sievers RE. Structures of europium complexes and implications in lanthanide nuclear magnetic resonance shift reagent chemistry. Inorg Chem 1980;19:595–604. 36. Laplanche LA, Vanderkooi G. Calculation of steric interactions between a lanthanide shift reagent and substituted pyridines. J Chem Soc Perkin Trans 2 1983;1585–1589. 37. Baxter I, Drake SR, Hursthouse MB, Malik KMA, McAleese J, Otway J, Plakatouras JC. Effect of polyether ligands on stabilities and mass transport properties of a series of gadolinium(III) β-diketonate complexes. Inorg Chem 1995;34:1384–1394. 38. Batista HJ, de Andrade AVM, Longo RL, Simas AM, de Sa GF, Ito NK, Thompson LC. Synthesis, X-ray structure, spectroscopic characterization, and theoretical prediction of the structure and electronic spectrum of Eu (btfa)3•bipy and an assessment of the effect of fluorine as a β-diketone substituent on the ligand-metal energy transfer process. Inorg Chem 1998;37:3542–3547. 39. Melby LR, Rose NJ, Abramson E, Caris JC. Synthesis and fluorescence of some trivalent lanthanide complexes. J Am Chem Soc 1964;86:5117–5125. 40. Tsukube H, Hosokubo M, Wada M, Shinoda S, Tamiaki H. Specific recognition of chiral amino alcohols via lanthanide coordination chemistry: structural optimization of lanthanide tris(β-diketonates) toward effective circular dichroism/fluorescence probing. Inorg Chem 2001;40:740–745. 41. Mahajan RK, Kaur I, Kaur R, Onimaru A, Shinoda S, Tsukube H. Lipophilic lanthanide tris(β-diketonate) complexes as an ionophore for Cl anion-selective electrodes. Anal Chem 2004;76:7354–7359. 42. Tsukube H, Yano K, Shinoda S. Near-infrared luminescence sensing of glutamic acid, aspartic acid, and their dipeptides with tris(β-diketonato) lanthanide probes. Helv Chim Acta 2009;92:2488–2496. 43. Yano M, Matsuhira K, Tatsumi M, Kashiwagi Y, Nakamoto M, Oyama M, Ohkubo K, Fukuzumi S, Misaki H, Tsukube H. “ON–OFF” switching of
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48. Lippard SJ, Berg JM. Principles of bioinorganic chemistry. Mill Valley, CA: University Science Books; 1994. 49. Graves SW, Fox JA, Babior BM. Deamination of 2-aminopropanol by ethanolamine ammonia-lyase, an AdoCbl-requiring enzyme. Kinetics and isotope effects for the R and S enantiomers of the substrate. Biochemistry 1980;19:3630–3633. 50. Shibata T, Takahashi T, Konishi T, Soai K. Asymmetric self-replication of chiral 1,2-amino alcohols by highly enantioselective autoinductive reduction. Angew Chem Int Ed 1997;36:2458–2460. 51. Schrader T. Toward synthetic adrenaline receptors: strong, selective, and biomimetic recognition of biologically active amino alcohols by bisphosphonate receptor molecules. J Org Chem 1998;63:264–272. 52. Misumi S, Iwasaki N. The infrared spectra and some properties of tris(acetylacetonato) lanthanide(III) complexes. Bull Chem Soc Jpn 1967;40:550–554. 53. Binnemans K. Rare-earth beta-diketonates. In: Gschneidner Jr KA, Bünzli J-CG, Pecharsky VK, editors. Handbook on the physics and chemistry of rare earths. Amsterdam: Elsevier; 2005;35:107–272.
Chirality DOI 10.1002/chir
Lanthanide Tris(β-diketonates) as Useful Probes for Chirality Determination of Biological Amino Alcohols in Vibrational Circular Dichroism: Ligand to Ligand Chirality Transfer in Lanthanide Coordination Sphere 1
HIROYUKI MIYAKE,1* KEIKO TERADA,1 AND HIROSHI TSUKUBE1,2 Department of Chemistry, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka, Japan 2 JST, CREST, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka, Japan
ABSTRACT A series of lanthanide tris(β-diketonates) functioned as useful chirality probes in the vibrational circular dichroism (VCD) characterization of biological amino alcohols. Various chiral amino alcohols induced intense VCD signals upon ternary complexation with racemic lanthanide tris(β-diketonates). The VCD signals observed around 1500 cm 1 (β-diketonate IR absorption region) correlated well with the stereochemistry and enantiomeric purity of the targeted amino alcohol, while the corresponding monoalcohol, monoamine, and diol substrates induced very weak VCD signals. The high-coordination number and dynamic property of the lanthanide complex offer an effective chirality VCD probing of biological substrates. Chirality 00:000–000, 2014. © 2014 Wiley Periodicals, Inc. KEY WORDS: chiral amino alcohol; absolute configuration; VCD; ternary complex; sensing INTRODUCTION
Chiral molecules play a fundamental role in biology, chemistry, and medicine. Thus, sensitive and noninvasive chirality determination methods have received much attention in the structure elucidation of biologically significant molecules as well as in the practical syntheses and manufacturing of chiral drugs and functional materials. X-ray crystallographic and nuclear magnetic resonance (NMR) spectroscopic methods are widely used for these purposes.1,2 While they have successfully been used to deduce three-dimensional information of chiral molecules and their assemblies, they often require laborious, time-consuming, and expensive procedures before measurement. Electronic circular dichroism (ECD) is a complementary method by virtue of its applicability to the targeted molecules in both solution and solid states.3,4 In addition to the normal direct measurements, a variety of achiral and chromophoric probes enable versatile chirality determinations of nonchromophoric substrates.5–7 Berova et al. developed dimeric metalloporphyrin host systems which incorporate chiral substrates between two porphyrin rings to show characteristic ECD signals as exciton-coupled ECD in the porphyrin spectral region.3,5 Di Bari, Anslyn, and colleagues reported enantiomeric purity determination of chiral primary amines by in situ formation of Fe(II) complexes.6 Canary, Anslyn, and colleagues used a Cu(II) complex with tripodal ligand to detect the enantiomeric purity of chiral carboxylic acids.7 Vibrational circular dichroism (VCD) is another chiroptical spectroscopic method for chirality determination,8–12 which offers vibrational difference spectra with respect to the left and right circularly polarized radiation. The VCD spectroscopy is widely applicable to a variety of chiral molecules and supramolecules and has become an increasingly popular method, because most organic molecules absorb IR radiation. Taniguchi and Monde recently developed an exciton chirality method via interaction of two IR chromophores to show strong VCD signals.13 Another advantage of the VCD method © 2014 Wiley Periodicals, Inc.
is that the observed VCD spectral information can be successfully combined with theoretical calculations for practical analyses of organic molecules,13–17 and VCD was recently applied in the characterization of chiral metal complexes.18–25 Although the chirality determination of a chiral molecule with IR-inactivity or small activity requires complexation with IR-active probe in the VCD method, this kind of example has rarely been reported. Lanthanide complexes have recently been identified as useful probes in chirality sensing methods such as ECD, NMR,26,27 circularly polarized luminescence,28–32 and Raman optical activity33 measurements based on their unique physical and chemical properties. Since their central lanthanide ions have larger ionic radii (0.99–1.13 Å)34 and higher coordination numbers (7–12) than those of transition metal cations, the lanthanide tris(β-diketonates) usually include one or more solvent molecules in addition to three β-diketonate ligands in solution and its labile nature promotes rapid interconversion between two ideal structures of the dodecahedron and the square antiprism including propeller-like arrangement of three β-diketonates. These solvent molecules are easily replaced by donating substrates such as halide ions, dimethylformamide, and pyridine as monodentate substrates, dimethoxyethane, 2,2’-bipyridine, and 1,10-phenanthroline as bidentate substrates, and 2,2’:6’2”-terpyridine and 2,6-bis(2oxazolinyl)pyridine as tridentate substrates to form ternary complexes.27,35–47 Since these ternary complexations often induce different spectroscopic characters from the original complexes, these supramolecular assemblies are useful methods to detect external molecules. We report here that
*Correspondence to: H. Miyake, Department of Chemistry, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan. E-mail: [email protected] Received for publication 7 December 2013; Accepted 11 February 2014 DOI: 10.1002/chir.22319 Published online in Wiley Online Library (wileyonlinelibrary.com).
MIYAKE ET AL.
racemic lanthanide tris(β-diketonates) serves as effective chirality probes of amino alcohols in the VCD method. In addition to the observations in ECD and luminescence probing experiments,40–44 chirality information can be transferred from external chiral substrates via noncovalent ligand-to-ligand interactions to offer characteristic induced VCD signals at IR absorption regions of β-diketonate, depending on the absolute configuration and enantiomeric purity of the small IR active substrates. MATERIALS AND METHODS Measurements VCD and IR spectra were measured on an FT/IR-4100 spectrometer with VFT-4000 attachment (JASCO, Japan) using a BaF2 cuvette (0.05 mm). The ternary metal complexes with chiral substrates for VCD and IR studies were generated in situ by mixing each metal complex and substrate under conditions shown in each figure caption. The signal 3 3 was obtained by 16,000 (for the sample of 5 × 10 mol dm ) or 2000 (for other samples) accumulations. The correction was performed by baseline subtraction with the spectrum of the cuvette filled with same concentration of racemic sample solution; a chiral sample (2000 accumulations) – racemic sample (2000 accumulations) methodology.
Materials The lanthanide tris(β-diketonates) 1a–1g, 2, 3a–3d, and 4 and copper bis(β-diketonates) 5 illustrated in Figure 2 were obtained from Aldrich Chemical (Milwaukee, WI) (1a–1g and 5), Strem Chemicals (Newburyport, MA) (3a, 3b, 3c), Apollo Chemical (Burlington, NC) (3d), Alfa Aesar (Ward Hill, MA) (4) and Gelest (Morrisville, PA) (5). Chiral substrates were received as enantiomerically pure forms from Aldrich Chemical {(R)-6a, (S)-6c, (S)- and (R)-6d, (S)- and (R)-6f, (R)-7a, (R)-7e, (R)-7f}, Nacalai Tesque (Kyoto, Japan) {(S)-7a}, Lancaster Synthesis (Ward Hill, MA) {(S)-7d, (S)-7e}, Wako Pure Chemical Industries (Osaka, Japan) {(S)-6a, (R)-6b}, Tokyo Chemical Industries (Tokyo, Japan) {(S)-6b, (R)-6c, (S)- and (R)-6e, (S)- and (R)-7b, (R)-7d, (S)-7f, (S)- and (R)-7g} and Kanto Chemical (Japan) {(S)- and (R)-7c}. These were used without further purification.
chiral building blocks in organic synthesis as well as biological substrates.48–51 We chose a series of lanthanide tris(fluorinated β-diketonates) 1a–1g including Yb3+, Er3+, Ho3+, Dy3+, Gd3+, Eu3+, and Pr3+ centers (Fig. 2). These complexes have been employed as NMR shift reagents, luminescence emitters, anion-selective electrodes, and other functional devices, as well as ECD chirality probes,13,14 because fluorinated ligand increases the formation constant of ternary complex more than alkyl chain ligand due to its strong Lewis acidity. They exhibit intense IR signals which can be divided into five regions: Region I (1600–1650 cm 1), Region II (1420–1550 cm 1), Region III (~1350 cm 1), Region IV (1250–1300 cm 1), and Region V (1200–1250 cm 1) due to their coordinating diketonates (Supporting Fig. S1).18,51–53 These are assignable to 1) the inphase and out-of phase C–O stretches for Region I; 2) C–H and CH3 bending, and C–C–C and C–O stretches for Region II; 3) CH3 bending for Region III; 4) C–CF3 stretches and C–C–C bending for Region IV; and 5) CF stretches for Region V. These lanthanide complexes are achiral and VCD-inactive. We found that addition of a chiral amino alcohol having small IR activity to the lanthanide tris(β-diketonate) solution produced enhanced VCD signals at the coordinating β-diketonate absorption regions (Region II, 1420–1550 cm 1), although the amino alcohol itself did not exhibit detectable VCD signals in solution (Figs. 1 and 3). The sign and intensity of the observed VCD signals correlated well with the absolute configuration and enantiomeric purity of the targeted amino alcohol, indicating that the present lanthanide tris(β-diketonates) worked as effective VCD chirality probes. Chirality Probing of Amino Alcohols Detected by VCD Measurements
Figure 3 shows that amino alcohol (S)- or (R)-6c having a chiral element exhibited no detectable VCD signal in CD3CN
RESULTS AND DISCUSSION Concept of VCD Chirality Probe via Ternary Complexation
As schematically illustrated in Figure 1, the lanthanide tris (β-diketonates) were demonstrated to form ternary complexes with external substrates.40–47 Furthermore, these lanthanide tris(β-diketonates) have 1) coordinating diketonate chromophores to offer intense IR absorptions suitable for induction of VCD signals; 2) high thermodynamic stability to work in various media, besides 3) two or more coordination sites on the lanthanide center available for an external chiral substrate; and 4) lanthanide-centered chirality via chiral ternary complexation. Amino alcohols were selected as chiral external substrates because they are useful
Fig. 1. Spectroscopic characteristics of lanthanide tris(β-diketonates), amino alcohols, and their ternary complex. Chirality DOI 10.1002/chir
Fig. 2. Structures of lanthanide tris(β-diketonates) 1–5, amino alcohols 6a–6f, and related substrates 7a–7g.
VCD CHIRALITY PROBING METHOD
Fig. 4. VCD (top) and IR (bottom) spectral changes of Yb–tris (β-diketonates) 1a upon addition of (S)-valinol (S)-6c in CD3CN. (Inset) titra1 3 3 tion profiles of the VCD intensities at 1467 cm . [1a] = 80 × 10 mol dm , 0.05 mm BaF2 cuvette.
ESI-MS spectra of the 1:1 solution of 1a and (S)- 6c in CD3CN mainly showed the ion clusters of 1:1 complex of 1a and 6c in addition to those of 1:2 complex {[1a•6c•H]+ (37%), [1a•6c•Na]+ (100%), [1a•6c•Na•CD3CN]+ (18%), and
Fig. 3. VCD (upper) and FT-IR (middle and lower) spectra of (a) valinol 6c, (b) Yb–tris(β-diketonate) 1a : 6c = 1:1 and 1a only (blue), (c) Yb–tris (β-diketonate) 3a : 6c = 1:1 and 3a only (blue) in CD3CN, 0.05 mm BaF2 3 cuvette with 2000 accumulations. [Yb–tris(β-diketonate)], [6c] = 80×10 mol 3 dm . Black and red lines indicate the spectra obtained with (S)- and (R)-6c, respectively.
solution at 80×10 3 mol dm 3. However, addition of racemic lanthanide tris(β-diketonate) 1a produced intense VCD signals at Region II, around 1480 cm 1: [1a] = [6c] = 80×10 3 mol dm 3 for 2 h of measurement (2000 accumulations), although Regions III and IV rarely exhibited VCD signals (Fig. S1). The sign and shape of the observed VCD signals at Region II were indicative of the stereochemistry of the targeted amino alcohol: positive (Region IIa) and negative (Region IIb) signs for the 1:1 solution of 1a and (S)-6c, and vice versa for the solution of 1a and (R)-6c (Fig. 3b). Thus, the present Yb–tris(β-diketonate) 1a functions as an effective VCD probe and has the advantage of a convenient procedure to amplify chirality information of biological amino alcohols. During the titration experiments of (S)-6c to 1a in CD3CN (Fig. 4), the VCD intensity at 1467 cm 1 changed to the negative direction and reached a plateau at one equivalent of (S)-6c. This observation indicates that one equivalent of the chiral amino alcohol is sufficient to offer intense VCD spectra and that 1:1 complexation between 1a and 6c must be involved in the enhancement of VCD signals, as illustrated in Figure 1.
Fig. 5. VCD (top) and IR (bottom) spectra of the 1:1 solution of Yb–tris (β-diketonates) 1a and valinol 6c in different concentration in CD3CN. (a) 3 3 3 3 [1a] = [6c] = 5 × 10 mol dm , (b) [1a] = [6c] = 10 × 10 mol dm and 3 3 (c) [1a] = [6c] = 80 × 10 mol dm , 0.05 mm BaF2 cuvette. Black and red lines indicate the spectra obtained with (S)- and (R)-6c, respectively. Chirality DOI 10.1002/chir
MIYAKE ET AL.
[1a•(6c)2•H]+ (58%)}. Thus, the 1:1 complex is stable enough for VCD measurement in CD3CN (logK = 4.67 for (S)-6c/1a complex in CH3OH/CH2Cl2 = 1/9940). The VCD measurements normally require a highly concentrated solution with a short pathlength cuvette to make the IR signals of the employed solvent small. We examined minimum concentrations for the VCD probing ability of lanthanide tris(β-diketonates) toward amino alcohols. When both concentrations of 1a and 6c are 5 × 10 3 mol dm 3, which is same order of concentration for 1H NMR measurements, the induced VCD signals included large noise signals (16,000 scans), but the sign of the signal clearly had a characteristic pattern enough for an indication of stereochemistry of the employed amino alcohols (Fig. 5). Since 50 μl of the solution was sufficient for this VCD measurement with a 0.05 mm cuvette, the requisite mol of the complex is similar to that required for normal UV–vis and ECD measurements. Table 1 summarizes the VCD probing profiles of 1a for several amino alcohols 6a–6f, monoalcohol 7a, diols 7b, 7c, monoamines 7d, 7e, and diamines 7f, 7g. Among them,
amino alcohols having –NH2 and –OH moieties and diamines having two –NH2 moieties were well sensed by 1a, while the chiral monoalcohol, diol, and monoamine were not efficiently detected (Fig. S1). All the examined (S)-amino alcohols and diamines except for prolinol 6d exhibited positive signal at Region IIa ~1500 cm 1 and negative signal at Region IIb ~1470 cm 1, while the corresponding (R)-amino alcohols exhibited signals with the opposite signs (Fig. 6). (S)-prolinol (S)-6d provided a positive VCD signal at Region IIa and no significant signal at Region IIb, probably due to induced chirality at the coordinating nitrogen atom. Various combinations of β-diketonate ligands and central lanthanide centers were compared. When the amino alcohol 6c was fixed as the chiral substrate, both the structure of the β-diketonate ligand and the nature of the central lanthanide cation had large influences on the intensity of the VCD signals. Although the IR signals of lanthanide tris(βdiketonates) 3a–3d appeared at higher energy field, the signs of the observed VCD signals were not changed by such structural perturbation, and signal intensities at Region IIa
TABLE 1. VCD probing profiles of lanthanide tris(β-diketonates) for various substrates in CD3CN Run
Ln-tris(β-diketonate)
VCD Intensity (× 105)
Substrate at 1496 cm
1 2 3 4 5 6 b 7 8 b 9 b 10 b 11 12 13 14 15 16 b 17 b 18 19
(S)-6a (S)-6b (S)-6c (S)-6d (S)-6e (S)-6f (S)-7a (S)-7b (S,S)-7c (S)-7d (S)-7e (S)-7f (S,S)-7 g (S)-6c (S)-6c (S)-6c (S)-6c (S)-6c (S)-6c
1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1b 1c 1d 1e 1f 1g
1
4.31 5.74 6.43 2.84 7.35 6.13 1.17 2.69 3.73 1.17 0.62 3.10 4.92 6.81 8.95 6.38 3.76 6.33 2.31
20
(S)-6c (S)-6c (S)-6c (S)-6c
3a 3b 3c 3d
1
0.86 6.26 0.06 0.02
(S)-6c
5 3
3
[Ln-tris(β-diketonate)] = [substrate] = 80 × 10 mol dm , 0.05 mm BaF2 cuvette with 2000 accumulations. 5 a With an error of 0.6 ×10 or less. b Slightly precipitated. 3 3 c [2] = [6c] = 10×10 mol dm in THF/CD3CN = 1/9. Chirality DOI 10.1002/chir
1
1
0.88 at 1496 cm
26
at 1492 cm
at 1405 cm
(S)-6c
4
1
5.76 4.36 0.08 0.25
– 25
1
0.18 at 1530 cm
21 22 23 24
at 1414 cm
(S)-6c
2
at 1468 cm 3.56 5.21 6.94 0.01 6.72 5.08 1.74 0.12 2.26 0.11 0.24 2.46 2.95 7.89 6.15 1.16 5.20 1.69 0.15
– c
a
0.14
1
at 1468 cm 0.31
1
VCD CHIRALITY PROBING METHOD
Fig. 6. VCD signs observed in lanthanide tris(β-diketonates) and amino alcohols.
were relatively small (Fig. 3c; Supporting Figs. S2 and S3). The order of influence of various ligands was 1 > 3 > > 2, 4. Interestingly, the order for various lanthanide centers was Yb(III) ~ Er(III) ~ Ho(III) > Dy(III) ~ Gd(III) ~ Eu(III) >> Pr(III), which has no correlation with the order of the lanthanide-induced VCD enhancement reported by the group of Di Bari (Tm3+ >> Yb3+ ~ Tb3+ > Nd3+ ~ Pr3+ for chiral cyclen and Tm3+ > Tb3+ > Yb3+ > Dy3+ > Ho3+ ~ Er3+ for lasalocid)22 and is similar to that observed in induced ECD intensity of probe 1a–1g with 6c.40 Since their ionic radii increased on the order Yb3+ (0.99 Å) < Er3+ (1.00 Å) < Ho3+ (1.02 Å) < Dy3+ (1.03 Å) < Gd3+ (1.05 Å) < Eu3+ (1.07 Å) < Pr3+ (1.13 Å) for octadentate coordination,34 it is likely that steric proximity between the coordinating β-diketonates and the chiral center of the amino alcohol 6c regulates the chirality transfer in the lanthanide coordination sphere. Table 1 and Supporting Figures S1 and S2 also show that the Yb–tris(β-diketonates) 1a and 3a exhibited higher VCD probing sensitivity for chiral amino alcohols 6a–6f than related substrates 7a–7g. Among the examined amino alcohols, valinol 6c and 2–phenylglycinol 6e exhibited the most intense VCD signals, although these amino alcohols were bound quantitatively with the lanthanide complex (Fig. 4). The origin of the induced VCD signal is most likely from the vibration of coordinated β-diketonates,25,53 because the VCD signals were observed at Region II of the parent lanthanide complexes which can be shifted depending on the employed β-diketonate (see IR spectra of 1a and 3a at Fig. 3). Since the IR intensity of the amino alcohol in the employed condition is very small and negligible, as shown in Figure 3a, induced VCD signals of amino alcohol is considered small. Because the small stretching vibration of coordinated amino alcohol around 1500 cm 1 is overlapped with Region II of the parent lanthanide complex, a detailed theoretical study or more VCD study using different ternary systems having independent vibrations should be required to clear this point. Some lanthanide tris(β-diketonates) also exhibited VCD signals at Region I (C–O stretches) and Region V (CF stretches) in the presence of chiral amino alcohols; the combination of 1a–6c, 1f–6c, and 3a–6 were typical examples (Figs. S1–S3). Symmetrically-substituted β-diketonate 3 is probably well arranged in a helical manner to exhibit VCD signals at Region I and V by ternary complexation with chiral alcohol. On the other hand, the complexes with unsymmetrical β-diketonate having bulky substituent 1 exhibited large VCD signal at Region II, but small signals at Regions I and V.
▪
Fig. 7. Plots of VCD signals of Yb–tris(β-diketonate) 1a ( ◯) and 3a ( ) systems at 1468 nm and 1494 nm, respectively, against enantiomer excess values of the added amino alcohol 6c. [Yb–tris(β-diketonate)] = [6c] = 80 × 10 3 mol dm 3 in CD3CN, 0.05 mm BaF2 cuvette with 2000 accumulations.
Enantiomeric Purity Determination of Amino Alcohols by VCD Detection
Lanthanide tris(β-diketonates) are applicable as VCD probes not only in the chirality sensing of amino alcohols but also in the quantitative determination of their enantiomeric purity. When the lanthanide probe was added to a mixture of (S)and (R)-amino alcohol, the sign and amplitudes of the observed VCD signals exhibited quantitative indication of enantiomer excess percentages (ee %) of amino alcohol. Figure 7 illustrates the relationship between ee % of the chiral amino alcohol 6c and the intensities of the induced VCD signal with 1a at 1468 cm 1 or 3a at 1494 cm 1. The concentration of probe 1a and 3a and total concentration of amino alcohol were fixed as 80 × 10 3 mol dm 3. The amino alcohol 6c itself did not exhibit detectable IR or VCD signals (Fig. 3a), but the induced VCD signals upon ternary complexation linearly correlated with the ee % of the employed amino alcohol with R value of more than 0.998, indicating that these kinds of lanthanide complexes work as practical VCD probes to determine the optical purity of specific substrates. CONCLUSIONS
A series of lanthanide tris(β-diketonates) served as useful chirality probes in the VCD characterization of biological amino alcohols. The racemic lanthanide complex assumed to be eight–coordinate existing in equilibrium in some structures incorporates a chiral amino alcohol in its coordination sphere. Then the chirality was effectively transferred from the external chiral substrate to the coordinating β-diketonate via ternary complexation to offer intense VCD signals, which correlated well with their stereochemistry and enantiomeric purities. Therefore, lanthanide coordination chemistry leads to the effective chirality VCD probing of biological amino alcohols. Combination with theoretical simulation would provide precise information of solution structures of the labile lanthanide complexes and further design of ligand architecture offers the potential for more practical probes in VCD methods. ACKNOWLEDGMENTS
This research was supported by Grants-in-Aid for Scientific Research (Nos. 23350029, 23111718 and 24655053) from the Japan Society for the Promotion of Science, and the Core Research for Evolutional Science and Technology (CREST) program of the Japan Science and Technology Agency (JST). Chirality DOI 10.1002/chir
MIYAKE ET AL.
SUPPORTING INFORMATION
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