Achiral Solvent Research Articles

Effects of Complex Formation on Vibrational Circular Dichroism Spectra

The determination of absolute configurations of chiral compounds using VCD is performed by comparing measured vibrational circular dichroism (VCD) spectra with calculated spectra. The process is based on two facts: the two enantiomers have rotational strengths of opposite sign, and the absolute configuration of the molecule used in the calculation is known. However, calculations on isolated molecules very often predict VCD intensities of very different magnitude or even different signs compared to the spectra measured in solution. Therefore, we have carefully analyzed what type of changes are induced by complexation of a solvent molecule to a solute. In the theoretical example of benzoyl-benzoic acid (in a particular chiral conformation) hydrogen bonded to the achiral NH3, we distinguish six cases, ranging from no or very small changes in the rotational strengths of solute modes (case A) to changes of sign of rotational strengths (case B), changes in magnitude (case C), nonzero rotational strengths for modes of the achiral solvent ("transfer of chirality", case D), large frequency shifts accompanied by giant enhancements of the IR and VCD intensities of modes involved in hydrogen bonding (case E), and emergence of new peaks (case F). In this work, all of these situations will be discussed and their origin will be elucidated. On the basis of our analysis, we advocate that codes for VCD rotational strength calculation should output for each mode i the angle xi(i) between the electric and magnetic transition dipole moments because only "robust modes" with xi far from 90 degrees should be used for the determination of the absolute configuration.

Apparent and true enantioselectivity of single- and binary-selector chiral stationary phases in gas chromatography

Almost all gas-chromatographic chiral stationary phases (CSPs) are complex systems containing one or more chiral selector(s) dissolved in, or bonded to, an achiral solvent such as squalane or poly(dimethylsiloxane). The presence of different components in the total CSP, interacting independently with the analyte enantiomers, impairs the elucidation of enantiorecognition mechanisms and complicates the optimization of enantioseparations. In the present work a quantitative analysis of the influence of different factors on the observed enantioselectivity is performed. The parameters varied in this study were the composition of the CSP, the concentration and the enantiomeric excess of the chiral selector(s) and the presence of achiral selectors (including racemic compositions). Special attention is given to the determination of distribution and association constants, as well as apparent and true enantioseparation factors.

Modelling neurotransmitter functions: a laser spectroscopic study of (1S,2S)-N-methyl pseudoephedrine and its complexes with achiral and chiral molecules

Wavelength and mass resolved resonance-enhanced two photon ionization (R2PI) excitation spectra of (1S,2S)-N-methyl pseudoephedrine (MPE) and its complexes with several achiral and chiral solvent molecules, including water (W), methyl (R)-lactate (L(R)), methyl (S)-lactate (L(S)), (R)-2-butanol (B(R)), and (S)-2-butanol (B(S)), have been recorded after a supersonic molecular beam expansion and examined in the light of ab initio calculations. The spectral patterns of the selected complexes have been interpreted in terms of the specific hydrogen-bond interactions operating in the diastereomeric complexes, whose nature in turn depends on the structure and the configuration of the solvent molecule. The obtained results confirm the view that a representative neurotransmitter molecule, like MPE, "communicates" with the enantiomers of a chiral substrate through different, specific interactions. These findings can be regarded as a further contribution to modelling neurotransmitter functions in biological systems.

Assignment of the relative and absolute configurations of acyclic secondary 1,2-diols

The NMR profiles ( 13C- δ, 1H- δ, 1H(OH)- δ, and 3 J H,H) of syn- and anti-diols— 3a, b in achiral solvents were found to be very similar to each other. Contrarily, their Δ δ (Δ δ= δ ( R, R)- 2 − δ ( S, S)- 2 ) behaviors in chiral bidentate NMR solvent ( R, R)- and ( S, S)-BMBA- p-Me ( 2 ) were found to be significantly different. On the basis of this NMR characteristic, a method has been developed to predict both the relative and absolute configurations of acyclic secondary 1,2-diols.

The Critical Phase Changes of a Forward-scattered Light in a Nonpolar Binary Liquid Mixture

In a previous paper 1 the author and his coworkers have obtained analytic results for the phase changes of the forward-scattered light in a nonpolar chiral fluid, when the incident light is completely linearly polarized above (or below) the horizontal at 45 o , using the formalism given by Barron 2 and the theory for the dielectric tensor developed by Lee and Kim. 3 The method is so effective that it enables us to calculate phase changes of the forward-scattered light in the critical region with the aid of Ornstein-Zernike theory of the correlation function of density fluctuations. Then, the method was extended to a binary liquid mixture composed of a chiral solute and an achiral solvent. 4 The mixture is more suitable for experimental verification than the pure fluid. The basic difference with the latter is that there is one more extra variable in the mixture, i.e., the concentration fluctuations. The results for the azimuth and ellipticity changes were extended in the critical region that the Fisher theory holds. 5 The purpose of the present paper is to discuss the phase changes in the critical region of a nonpolar binary liquid mixture, using the Fisher form for the correlation function of concentration fluctuations. 6,7 The explicit results are given without the detailed procedures, which were derived in the previous papers. 1,4

Complete Stereochemistry of Tetrafibricin.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Complete stereochemistry of tetrafibricin.

With use of the NMR databases in achiral and chiral solvents, the complete stereochemistry of tetrafibricin (1) has been elucidated without degradation of the carbon framework. [structure--see text]

Molecular Chirality Recognized by Achiral Compounds

Three cases are described where chirality is recognized by achiral molecules, where chirality is induced into achiral compounds through interactions with chiral compounds, and lastly where induced chirality in the solid-state is utilized for an enantio-selective photoreaction. In the first instance, the thermodynamically and kinetically preferred diastereoisomer of an optically labile chromium complex depended on the nature of the achiral solvent. In the second case, for the first time 1,2-chloroethane was trapped and observed in a chiral near-eclipsed form and 1-chloropropane in the truly eclipsed form at room temperature in a 1:1 inclusion complex with an optically active host molecule. Finally, induced chirality in a prochiral compound in the solid-state was successfully employed in an enantio-selective photoreaction. In the two cases, solid-state CD provided valuable information.

Theory of chiral imprinting

We present a continuum model for a nematic elastomer network formed in a chiral environment, for instance, in the presence of a chiral solvent. When this environment is removed, the network can retain some memory of its chiral genesis. We predict the residual chiral order for a number of possible scenarios, and examine the robustness (stability) of the imprinted chirality. We show that a twist-untwist transition can take place, which determines whether the imprinting has been successful. A transition is via a coarsening of the helical director pattern and a lengthening of its pitch. Finally, the effect due to a subsequent swelling by an achiral solvent, or by a solvent of differing chirality, is considered.

Expression of Chirality by Achiral Coadsorbed Molecules in Chiral Monolayers Observed by STM.

The supramolecular packing mode of physisorbed monolayers built up by chiral isophthalic acid derivatives and coadsorbed achiral solvent molecules was imaged at the liquid/graphite interface with scanning tunneling microscopy (STM). The picture on the right shows the submolecularly resolved STM image of an enantiomorphous domain composed of the R enantiomer of the isophthalic acid derivative studied and 1-heptanol molecules; the latter express the chirality of the monolayer. Upon adsorption a racemic mixture is separated into enantiomorphous domains.

Ferroelectric liquid crystals derived from isoleucine I. Synthesis and characterization

A series of ferroelectric liquid crystals (FLCs), 4 (3-methyl-2-halopentanoyloxy)- 4-hexyloxybiphenyls (3M2XPHOB, X=F for fluorine, C for chlorine, B for bromine) and their racemates (3M2XPHOB-R), were synthesized and characterized. The FLCs contain a chiral tail comprised of alpha -halo acids which are derived from L-isoleucine (DL-isoleucine for the racemates). The mesogens were characterized by high-resolution 1H and 13C NMR and their phase behaviour was studied by optical microscopy and differential scanning calorimetry. The chloro and bromo derivatives show both chiral smectic C (SmC*) phases and smectic A (SmA) phases, while the fluoro derivatives exhibit only a SmA phase. The spontaneous polarization of 3M2CPHOB and 3M2BPHOB were measured in the respective SmC* phases; that of the fluoro derivative was inferred by extrapolating its concentration dependent polarization in an achiral SmC solvent, a racemic mixture of 3M2BPHOB.

On the scattering phenomena for various kinds of polarized light in a nonpolar binary liquid mixture

The explicit result for the Mueller matrix for the sum of single and double scatterings is obtained in a nonpolar binary liquid mixture composed of a chiral solute and an achiral solvent are obtained with the aid of the Ornstein–Zernike form for the correlation function of concentration fluctuations. The explicit result of the matrix shows that the law of reciprocity does not hold in the mixture. The scattering phenomena for six kinds of completely polarized light in a nonpolar binary liquid mixture are different from those in a pure chiral fluid because of the failure of the law and the large effect of concentration fluctuations. The scattering phenomena are in detail discussed in the region far from and near the critical point.

Conformational studies by dynamic NMR. Part 56. Enantiotopomerization and conformational analysis of hindered aryl alkyl ketones investigated by dynamic and solid state NMR

The barriers (ΔG ∗) for the degenerate interconversion (enantiotopomerization) of a number of mesityl alkyl ketones have been measured by dynamic NMR in a chiral environment. These barriers were compared with those of more hindered ketones having the three methyl groups of the mesityl moiety replaced by three isopropyl groups. These prochiral probes allowed the barriers to be determinated in achiral solvents. The conformations were also assessed by high resolution solid state 13C NMR and Molecular Mechanics calculations.

Chiral discrimination in electronic energy-transfer processes in solution. Effects of temperature and solution properties on chirality-dependent rate parameters

Abstract Time-resolved chiroptical luminescence (TR-CL) measurements are used to study the kinetics of chilality-dependent excited-state quenching processes in solution. Solution samples contain a racemic mixture of chiral luminophore molecules (L) and a small, optically-resolved concentration of chiral quencher molecules (Q) in an achiral solvent (H 2 O, D 2 O, or an H 2 O-ethylene glycol mixture). The luminophores are excited with a pulse of unpolarized light to create an initially racemic excited-state population of ΔL ∗ and ΛL ∗ enantiomers, and TR-CL measurements are then used to monitor the differential decay kinetics of the ΔL ∗ and ΛL ∗ subpopulations. Observed differences between the ΔL ∗ and ΛL ∗ decay kinetics differential rate processes and efficiencies for ΔL ∗ -Q versus ΛL ∗ -Q quenching actions, and they are diagnostic of chiral discriminatory interactions between the luminophore and quencher molecules. In each of the systems examined here, quenching occurs via electronic energy-transfer processes in transient (ΔL ∗ -Q) and (ΛL ∗ -Q) encounter complexes, and the chiral discriminatory rate parameters reflect the relative stabilities and lifetimes of these complexes as well as their structures and internal (electronic and nuclear) dynamics. Both quenching rates and enantioselectivity are observed to increase with increasing temperature over the temperature ranges represented in this study (253–353 K for H 2 O-ethylene glycol solutions and 273–353 K for H 2 O and D 2 O solutions), and differences between the free-energies of activation for ΔL ∗ -Q versus ΛL ∗ -Q quenching processes increase from ≈ 2.5 to 4.8 kJ/mol over the 273–353 K temperature range. Both the luminophore and quencher molecules examined in this study have three-bladed propeller-like structures with very similar shapes and sizes, and differential steric constraints in (ΔL ∗ -Q) versus (ΛL ∗ -Q) contact pairs are small. However, at room temperature and above, the relative efficiencies of ΔL ∗ -Q versus ΛL ∗ -Q quenching processes differ by factors > 3.2, indicating an extraordinary degree of chiral discrimination in the underlying interaction processes.

Influence of chiral carvones on selectivity of pure lipase-B from Candida antarctica

In the esterification reaction in non-aqueous media lipase-B from Candida antarctica is stereoselective towards the R-isomer of ketoprofen in an achiral solvent such as isobutyl methyl ketone and in S(+) carvone. On the contrary, S(+) ketroprofen is esterified quicker in R(−) carvone. In addition, the esterification yield changes depending on the stereochemistry of the carvone used as solvent. The formation of disteromeric complexes (chiral solvent + chiral substrates) may explain this finding.

NMR investigations of the enantiomeric excess effects in solutions with weak intermolecular association

AbstractThe main features of statistically controlled associate diasteromerism (SCAD) in solution as measured by nuclear magnetic resonance (NMR) are discussed. In an achiral solvent, (R)‐ and (S)‐enantiomers can demonstrate distinct NMR signals, with the intensity ratio equal to the concentration ratio. The previous theory of SCADA (anisochronism of nuclear magnetic moments caused by SCAD) is supplemented by treatment of enantiomeric excess phenomena in relation with the hypothesis that a sample consists totally of short‐living diastereomeric dimers which are involved in fast (on the NMR time scale) exchange by enantiomers. Thermodynamic parameters of SCAD as well as limits for enantioselectivity phenomena are estimated. © 1995 Wiley‐Liss, Inc.

An 1H NMR determination of the three‐dimensional structures of mirror‐image forms of a Leu‐5 variant of the trypsin inhibitor from Ecballium elaterium (EETI‐II)

The 3-dimensional structures of mirror-image forms of a Leu-5 variant of the trypsin inhibitor Ecballium elaterium (EETI-II) have been determined by 1H NMR spectroscopy and simulated annealing calculations incorporating NOE-derived distance constraints. Spectra were assigned using 2-dimensional NMR methods at 400 MHz, and internuclear distances were determined from NOESY experiments. Three-bond spin-spin couplings between C alpha H and amide protons, amide exchange rates, and the temperature dependence of amide chemical shifts were also measured. The structure consists largely of loops and turns, with a short region of beta-sheet. The Leu-5 substitution produces a substantial reduction in affinity for trypsin relative to native EETI-II, which contains an Ile at this position. The global structure of the Leu-5 analogue studied here is similar to that reported for native EETI-II (Heitz A, Chiche L, Le-Nguyen D, Castro B, 1989, Biochemistry 28:2392-2398) and to X-ray and NMR structures of the related proteinase inhibitor CMTI-I (Bode W et al., 1989, FEBS Lett 242:285-292; Holak TA et al., 1989a, J Mol Biol 210:649-654; Holak TA, Gondol D, Otlewski J, Wilusz T, 1989b, J Mol Biol 210:635-648; Holak TA, Habazettl J, Oschkinat H, Otlewski J, 1991, J Am Chem Soc 113:3196-3198). The region near the scissile bond is the most disordered part of the structure, based on geometric superimposition of 40 calculated structures. This disorder most likely reflects additional motion being present in this region relative to the rest of the protein. This motional disorder is increased in the Leu-5 analogue relative to the native form and may be responsible for its reduced trypsin binding. A second form of the protein synthesized with all (D) amino acids was also studied by NMR and found to have a spectrum identical with that of the (L) form. This is consistent with the (D) form being a mirror image of the (L) form and not distinguishable by NMR in an achiral solvent (i.e., H2O). The (D) form has no activity against trypsin, as would be expected for a mirror-image form.

Circular dichroism as a probe of chiral solvent structure around chiral molecules

Molecular dynamics simulations have been used to study solvent effects on the circular dichroism (CD) of the n–π* carbonyl transition in camphor and 9, 10-dibromocamphor. It is found that achiral solvents may contribute as much as 10–20% of the CD intensity; this arises because the camphors induce solvation structure that is chiral even when the solvent molecules themselves are achiral. The magnitude of the solvent effect is found to depend strongly upon the nature of both the solute and the solvent. This has implications for enhancing the enantiomeric selectivity of chiral syntheses.

Photochemistry with circularly polarized light: A new method

A new method is presented which uses photoelastically modulated elliptically polarized light in chemical kinetics. The method exploits the fact that in a polarimeter using photoelastic modulation the chirality of the light is fixed and its average polarization state is about 50% circularly polarized. This method makes possible the partial resolution and racemization rate measurement of rapidly inverting molecules dissolved in achiral solvents. The necessary theory is developed, and experimental evidence supporting the theory is given. Results agree with published values for the relatively slow racemization of the cation oxolatobis (1,10-phenanthroline) chromate (III). As an advance in the measurement of faster inversion reactions, combined thermal- and photochemical racemization of rhodamine 6G was measured between 10 and 1000 ms: Preliminary results indicate a thermal relaxation time of about 6 s at 15° for the dye in an ethanol solution.

Asymmetric amplifying phenomena in enantioselective addition of diethylzinc to benzaldehyde

BACKGROUND In 1986, Puchot et al. established rigorously that the earlier proposal of Wynberg and Feringa concerning the effect of enantiomers on one another had general validity. Puchot et al. showed experimentally that the general assumption, namely, that products could never have an e.e. greater than that of the chiral auxiliary (catalyst, modifier, etc), was invalid. The basis for this apparent anomaly, as was discussed theoretically in 1976, is the possible association of enantiomeric catalyst molecules with new (better and worse) catalyst properties. Early proof of association phenomena of chiral molecules to form diastereomers (particularly, chiral hydroxy amines) had been obtained by a classic experiment of Williams et al. The latter showed that in a solution of enantiomerically impure quinine, distinct NMR absorptions could be detected for the ( + ) ( + ), ( – ) ( – ), and ( + ) ( – ) “dimeric complexes” in achiral solvents. It is, of course, not surprising (except in the sense that we did not recognize this much earlier!) that an efficient chiral catalyst, which by its very behavior must complex strongly with the achiral substrates, also complexes with itself. It should also come as no surprise, therefore, that such associative dimers (or trimers, etc.) might show different (better or worse) catalytic properties.