振动圆二色谱: 一种确定手性分子绝对构型的新方法

手性分子绝对构型的确定是一个极其重要且长期存在的问题. 振动圆二色谱是在红外波长区域测定分子圆二色性的一种新方法, 极大地扩展了圆二色谱的应用范围. 振动圆二色谱法通过构象搜索、量子化学计算等手段准确预测手性分子的振动圆二色谱图, 进而与实测谱图进行比较确定其绝对构型. 该方法已经得到了越来越广泛的应用, 必将成为一种有效测定手性分子绝对构型的常规方法.     

分子旋光度的密度泛函计算及Soman绝对构型确定

手性化合物绝对构型的确定一直是有机化学特别是手性药物合成研究过程中经常遇到的问题之一. 利用密度泛函DFT/B3LYP量子化学计算方法, 通过计算两种已知旋光度分子的旋光度, 确认计算条件和验证计算结果的可靠性, 并将此方法应用于Soman旋光度的计算. 结合文献报道的Soman分子实验旋光度测定结果, 首次采用理论计算方法确定了梭曼(Soman)分子四个异构体的绝对构型, 分别为P(R),C(S)-Soman→P(＋)C(＋), P(R),C(R)-Soman→P(＋)C(－), P(S),C(S)-Soman→P(－)C(＋), P(S),C(R)-Soman→P(－)C(－).     

Conformations of Serine in Aqueous Solutions as Revealed by Vibrational Circular Dichroism

Vibrational circular dichroism (VCD) spectroscopy is utilized to reveal the detailed conformational distributions of the dominant serine species in aqueous solutions under three representative pH conditions of 1.0, 5.7, and 13.0, together with vibrational absorption (VA) spectroscopy, density functional theory (DFT), and molecular dynamics simulation. The experimental VA and VCD spectra of serine in H₂O and D₂O in the fingerprint region under three pH values are obtained. DFT calculations at the B3LYP/6‐311++G(d,p) level are carried out for the protonated, zwitterionic, and deprotonated serine species. The lowest‐energy conformers of all three species are identified and their corresponding VA and VCD spectra simulated. A comparison between the gas‐phase simulations and the experimental VA and VCD spectra suggests that one or two of the most stable conformers of each species contribute predominantly to the observed data, although some discrepancies are noted. To account for the solvent effects, both the polarizable continuum model and the explicit solvation model are considered. Hydrogen‐bonded protonated, zwitterionic, and deprotonated serine–(water)₆ clusters are constructed based on radial distribution function analyses and molecular dynamics snapshots. Geometry optimization and VA and VCD simulations are performed for these clusters at the B3LYP/6‐311++G(d,p) level. Inclusion of the explicit water molecules is found to improve the agreement between theory and experiment noticeably in all three cases, thus enabling conclusive conformational distribution analyses of serine in aqueous solutions directly.     

Determination of the Absolute Configuration of Perylene Quinone‐Derived Mycotoxins by Measurement and Calculation of Electronic Circular Dichroism Spectra and Specific Rotations

Altertoxins I–III, alterlosins I and II, alteichin (alterperylenol), stemphyltoxins I–IV, stemphyperylenol, stemphytriol, 7‐epi‐8‐hydroxyaltertoxin I, and 6‐epi‐stemphytriol are mycotoxins derived from perylene quinone, for which the absolute configuration was not known. Electronic circular dichroism (ECD) spectra were calculated for these compounds and compared with measured spectra of altertoxins I–III, alteichin, and stemphyltoxin III and with reported Cotton effects. Specific rotations were calculated and compared with reported specific rotations. The absolute configuration of all the toxins, except for stemphyltoxin IV, could thus be determined. The validity of the assignment was high whenever reported ECD data were available for comparison, and the validity was lower when the assignment was based only on the comparison of calculated and reported specific rotations. ECD spectra are intrinsically different for toxins with a biphenyl substructure and for toxins derived from dihydroanthracene.     

Beta Sheets with a Twist: The Conformation of Helical Polyisocyanopeptides Determined by Using Vibrational Circular Dichroism

Detailed information on the architecture of polyisocyanopeptides based on vibrational circular dichroism (VCD) spectroscopy in combination with DFT calculations is presented. It is demonstrated that the screw sense of the helical polyisocyanides can be determined directly from the C?N‐stretch vibrational region of the VCD spectrum. Analysis of the VCD signals associated with the amide I and amide II modes provides detailed information on the peptide side‐chain arrangement in the polymer and indicates the presence of a helical β‐sheet architecture, in which the dihedral angles are slightly different to those of natural β‐sheet helices.     

应用电子圆二色光谱方法确定手性金属配合物的绝对构型

与电子能级跃迁相关的电子圆二色(ECD)光谱因其研究对象宽泛,与涉及振动能级的振动圆二色(VCD)光谱互补,已成为应用于手性立体化学研究的集成手性光谱的主流表征手段。本文概述了确定手性金属配合物绝对构型的三种主要方法,详细介绍了ECD光谱法在确定手性金属配合物绝对构型中的应用,其中着重强调了激子手性方法,并对集成手性光谱学未来的发展趋势做出了展望。     

An Investigation of Lanthanum Coordination Compounds by Using Solid‐State 139La NMR Spectroscopy and Relativistic Density Functional Theory

Lanthanum‐139 NMR spectra of stationary samples of several solid La^III coordination compounds have been obtained at applied magnetic fields of 11.75 and 17.60 T. The breadth and shape of the ¹³⁹La NMR spectra of the central transition are dominated by the interaction between the ¹³⁹La nuclear quadrupole moment and the electric field gradient (EFG) at that nucleus; however, the influence of chemical‐shift anisotropy on the NMR spectra is non‐negligible for the majority of the compounds investigated. Analysis of the experimental NMR spectra reveals that the ¹³⁹La quadrupolar coupling constants (C_Q) range from 10.0 to 35.6 MHz, the spans of the chemical‐shift tensor (Ω) range from 50 to 260 ppm, and the isotropic chemical shifts (δ_iso) range from ?80 to 178 ppm. In general, there is a correlation between the magnitudes of C_Q and Ω, and δ_iso is shown to depend on the La coordination number. Magnetic‐shielding tensors, calculated by using relativistic zeroth‐order regular approximation density functional theory (ZORA‐DFT) and incorporating scalar only or scalar plus spin–orbit relativistic effects, qualitatively reproduce the experimental chemical‐shift tensors. In general, the inclusion of spin–orbit coupling yields results that are in better agreement with those from the experiment. The magnetic‐shielding calculations and experimentally determined Euler angles can be used to predict the orientation of the chemical‐shift and EFG tensors in the molecular frame. This study demonstrates that solid‐state ¹³⁹La NMR spectroscopy is a useful characterization method and can provide insight into the molecular structure of lanthanum coordination compounds.     

Vibrational Circular Dichroism Spectroscopy of Three Multidentate Nitrogen Donor Ligands: Conformational Flexibility and Solvent Effects

A series of multidentate nitrogen donor ligands have been synthesized and characterized and their conformational distributions in solution have been investigated. Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy, complemented with DFT calculations, have been used to probe the conformations of these important ligands in solution directly. These three ligands demonstrate very different conformational flexibility; the pyridine subunits and amine groups may adopt a number of different conformations. Experimental VA and VCD data measured in CDCl₃ have been compared to the theoretical spectra of all possible most stable conformers. Solvent effects have been taken into account by using the implicit polarizable continuum model and explicit solvation model. The explicit hydrogen‐bonding solvation model is important for explaining the VCD sign‐reverse phenomenon in the amide I region. Good agreement has been achieved between experimental and predicted spectra for all three ligands; thus allowing detailed examination of the related conformational structures and distributions in solution.     

Investigation of (1R,2S)‐(−)‐Ephedrine by Cryogenic Terahertz Spectroscopy and Solid‐State Density Functional Theory

The terahertz (THz) spectrum of the pharmaceutical (1R,2S)‐(?)‐ephedrine from 8.0 to 100.0 cm^?1 is investigated at liquid‐nitrogen (78.4 K) temperature. The spectrum exhibits several distinct features in this range that are characteristic of the crystal form of the compound. A complete structural analysis and vibrational assignment of the experimental spectrum is performed using solid‐state density functional theory (DFT) and cryogenic single‐crystal X‐ray diffraction. Theoretical modeling of the compound includes an array of density functionals and basis sets with the final assignment of the THz spectrum performed at a PW91/6‐311G(d,p) level of theory, which provides excellent solid‐state simulation agreement with experiment. The solid‐state analysis indicates that the seven experimental spectral features observed at low temperature consist of 13 IR‐active vibrational modes. Of these modes, nine are external crystal vibrations and provide approximately 57 % of the predicted spectral intensity. This study demonstrates that the THz spectra of complex pharmaceuticals may be well reproduced by solid‐state DFT calculations and that inclusion of the crystalline environment is necessary for realistic and accurate simulations.     

Strength by Joining Methods: Combining Synthesis with NMR,IR, and Vibrational Circular Dichroism Spectroscopy for the Determination of the Relative Configuration in Hemicalide

The relative configuration of a key subunit of hemicalide, a recently isolated, highly bioactive marine natural product having potent antiproliferative activity against a panel of human cancer cell lines, was assigned by combining stereocontrolled synthesis of model substrates with NMR, IR, and vibrational circular dichroism (VCD) spectroscopy. The assignment of the absolute configuration of asymmetric carbon center C42 in two structurally complex epimeric substructures containing six stereocenters by VCD analysis illustrates the power and reliability of combining methods.     

Stereochemistry of the Reaction Intermediates of Prolinol Ether Catalyzed Reactions Characterized by Vibrational Circular Dichroism Spectroscopy

Spectroscopic characterizations of key reaction intermediates are often considered the final confirmation of a reaction mechanism. This proof-of-principle study showcases the application of vibrational circular dichroism (VCD) spectroscopy for the characterization of in situ generated reaction intermediates using the key intermediates of enamine catalysis of Jørgensen–Hayashi-type prolinol ether catalysts as model system. By comparison of experimental and computed spectra, the enamines are shown to preferentially adopt an anti-conformation with E-configured C=C bond. For the parent prolinol catalyst, the structure and stereochemistry of the oxazolidine side product is determined as well. This study thus demonstrates that VCD spectra can provide insights into structural preferences of organocatalysts that utilize a covalent activation mechanism. Thereby it outlines new fields of applications for VCD spectroscopy and finally adds the technique to the toolbox of physical organic chemistry for in-depth mechanistic studies.     

Theoretical Simulation of Vibrational Sum‐Frequency Generation Spectra from Density Functional Theory: Application to p‐Nitrothiophenol and 2,4‐Dinitroaniline

The molecular orientation of adsorbed molecules forming self‐assembled monolayers can be determined by combining vibrational sum‐frequency generation (SFG) measurements with quantum chemical calculations. Herein, we present a theoretical methodology used to simulate the SFG spectra for different combinations of polarizations. These simulations are based on calculations of the IR vectors and Raman tensors, which are obtained from density functional theory computations. The dependency of the SFG vibrational signature with respect to the molecular orientation is presented for the molecules p‐nitrothiophenol and 2,4‐dinitroaniline. It is found that a suitable choice of basis set as well as of exchange‐correlation (XC) functional is mandatory to correctly simulate the SFG intensities and consequently provide an accurate estimation of the adsorbed molecule orientation. Comparison with experimental data shows that calculations performed at the B3LYP/6‐311++G(d,p) level of approximation provide good agreement with experimental frequencies, and with IR and Raman intensities. In particular, it is demonstrated that polarization and diffuse functions are compulsory for reproducing the IR and Raman spectra, and consequently vibrational SFG spectra, of systems such as p‐nitrothiophenol. Moreover, the investigated XC functionals reveal their influence on the relative intensities, which show rather systematic variations with the amount of Hartree–Fock exchange. Finally, further aspects of the modeling are revealed by considering the frequency dependence of the Raman tensors.     

DFT‐Aided Vibrational Circular Dichroism Spectroscopy Study of (−)‐S‐cotinine

The implementation of a strategy comprising the use of vibrational circular dichroism spectroscopy and DFT calculations allows determination of the solution‐state conformational distribution in (?)‐S‐cotinine, giving further proof of the extra conformer‐discriminating potential of this experimental technique, which may offer unique molecular fingerprints of subtly dissimilar molecular conformers of chiral samples. Natural bond orbital electronic structure calculations of the rotational barrier height between the two main conformers of the species indicate that hyperconjugative effects are the key force governing the conformational equilibrium. The negligible effect of the solvent’s polarity over both structure and conformational energy profile supports this result.     

Self‐Assembly Structures of 1H‐Indazoles in the Solution and Solid Phases: A Vibrational (IR,FIR, Raman,and VCD) Spectroscopy and Computational Study

1H‐indazoles are good candidates for studying the phenomena of molecular association and spontaneous resolution of chiral compounds. Thus, because the 1H‐indazoles can crystallize as dimers, trimers, or catemers, depending on their structure and the phase that they are in, the difficulty in the experimental analysis of the structure of the family of 1H‐indazoles becomes clear. This difficulty leads us to contemplate several questions: How can we determine the presence of different structures of a given molecular species if they change according to the phase? Could these different structures be present in the same phase simultaneously? How can they be determined? To shed light on these questions, we outline a very complete strategy by using various vibrational spectroscopic techniques that are sensitive (VCD) and insensitive (IR, FIR, and Raman) towards the chirality, together with quantum chemical calculations.     

Vibrational Property of α-Borophene Determined by Tip-Enhanced Raman Spectroscopy

We report a Raman characterization of the α borophene polymorph by scanning tunneling microscopy combined with tip-enhanced Raman spectroscopy. A series of Raman peaks were discovered, which can be well related with the phonon modes calculated based on an asymmetric buckled α structure. The unusual enhancement of high-frequency Raman peaks in TERS spectra of α borophene is found and associated with its unique buckling when landed on the Ag(111) surface. Our paper demonstrates the advantages of TERS, namely high spatial resolution and selective enhancement rule, in studying the local vibrational properties of materials in nanoscale.     

Analyzing the Vibrational Signatures of Thiophenol Adsorbed on Small Gold Clusters by DFT Calculations

Using density functional theory, we calculate the IR and Raman signatures of the thiophenol (TP) molecule adsorbed on gold clusters by mimicking the different types of adsorption sites, and we analyze these signatures by using advanced tools implemented into the pyvib2 program. First, we follow the evolution of the vibrational normal modes from the isolated TP molecule to those of TP adsorbed on different clusters to highlight the influence of the site of adsorption on the vibrational motions. The use of the overlap matrix between the modes enables mode permutations, mode mixings, and mode splittings to be highlighted, all of which depend not only on the adsorption but also on the type of cluster and its symmetry. Second, the IR and Raman signatures were analyzed by using group coupling matrices and atomic contribution patterns based on the Hug decomposition scheme. Key results include 1) the fact that Raman spectroscopy is more sensitive than IR spectroscopy with respect to the nature of the coordination site, 2) an IR criterion that distinguishes between on‐top coordination (onefold coordinated) with respect to the bridge (twofold coordinated) and hexagonal close‐packed hollow site coordination (threefold coordinated), and 3) the best agreement to the experimental Raman spectrum with regard to signatures in the 500 to 1200 cm^?1 region is obtained for bridged, twofold coordination.     

The Pentabromine(1+) Cation,Br5+. Local Density Functional Calculations and Vibrational Spectra

The geometry, vibrational spectra and charge distribution of Br₅⁺ were calculated by the use of the local density functional (LDF) method. The results show that for free Br₅⁺ the lowest energy configuration is a skew structure with the three central Br atoms forming an angle of 168.6° und the two terminal Br atoms exhibiting a dihedral angle of 82°. This skew configuration is in contrast to the planar trans configuration of C_2h symmetry found for Br₅⁺ in solid Br₅⁺MF₆^? (M = As, Sb). The small energy difference of 1.2 kcal mol^?1 between the skew and the trans configurations, combined with crystal packing effects, can account for the planar trans configuration of Br₅⁺ in solid Br₅⁺MF₆^?. The computed vibrational spectra were used to select the most likely set from three sets of previously published and widely diverging spectra. Contrary to previous STO-3G calculations for Cl₅⁺, the present LDF calculations for Br₅⁺ and Cl₅⁺ result in charge distributions which agree with a previously proposed simple valence bond model for pentahalogen(1+) cations.