Application of (S)‐TBMB carboxylic acid‐based on‐line HPLC‐exciton CD analysis to acyclic vicinal alcohols and amino alcohols

Applications of the on‐line HPLC‐exciton CD analysis using (S)‐2‐tert‐butyl‐2‐methyl‐1,3‐benzodioxole‐4‐carboxylic acid [(S)‐TBMBC‐OH] that can simultaneously determine the enantiomeric compositions and the absolute configuration of cyclohexane‐1,2‐diols and diamines as well as acyclic vicinal diols and amino alcohols were studied. Di‐O‐ or di‐N,O‐(S)‐TBMBC derivatives of acyclic terminal vicinal diols, 2‐hydroxy‐1‐amines, and nonterminal vicinal diols gave symmetrical exciton CD spectra between enantiomers, indicating their absolute configurations. However, Di‐N,O‐(S)‐TBMBC derivatives of 2‐amino‐1‐ols did not always give symmetrical exciton CD spectra between enantiomers, but their 2‐phthalimido‐1‐O‐(S)‐TBMBC derivatives gave symmetrical exciton CD spectra, indicating their absolute configurations. All these (S)‐TBMBC derivatives were separated by normal‐phase HPLC and unequivocally determined by the on‐line HPLC‐exciton CD analysis without recourse to reference samples. Chirality 11:149–159, 1999. © 1999 Wiley‐Liss, Inc.     

Extending substrate sensing capabilities of zinc tris(2‐pyridylmethyl)amine‐based stereodynamic probe

Tripodal metal complexes have been widely used for catalysis and more recently also for molecular recognition applications. Their ability in recognition and signal amplification of chiral substrates is because of the setup of the ligand around the metal in a propeller shape. Within this subject, we have recently reported tris(2‐pyridylmethyl)amine‐ and triphenolamine‐based complexes for the determination of the enantiomeric excess of various substrates. Herein, we show the versatility of the zinc tris(2‐pyridylmethyl)amine‐based stereodynamic probe by performing a detailed study of the imine formation process, by the extension of the sensing capabilities to other chiral compounds. A principal component analysis study of the system together with TD‐DFT studies highlights the molecular origin of the observed chiroptical properties.     

Theoretical and Molecular Docking Study of Ketoconazole on Heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin as Chiral Selector

A molecular docking study, using molecular mechanics calculations with AutoDock and semi‐empirical PM3 calculations, was used to predict the enantiodiscrimination of heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TMβCD) and ketoconazole (KTZ) enantiomers. A Density Functional Theory (DFT) single‐point calculation at the level of B3LYP/6‐311G (d,p) was performed for the PM3‐optimized complexes to obtain more accurate binding energy and the electronic structures of the complexes. The difference in energies of the inclusion complexes between the KTZ enantiomers and TMβCD is probably a measure of chiral discrimination, which results in the separation of the enantiomers as observed in the experimental studies. Chirality 28:209–214, 2016. © 2015 Wiley Periodicals, Inc.     

Vibrational and electronic circular dichroism monitoring of copper(II) coordination with a chiral ligand

Novel copper(II) coordination compounds with chiral macrocyclic imine ligands derived from R-/S-camphor were asymmetrically synthesized and characterized with the aid of chiroptical spectroscopies. Crystal structures of both enantiomers were determined by single crystal X-ray diffraction analysis. Circular dichroism (CD) spectra were analyzed using a simplified exciton model as well as quantum chemical computations. The absolute configuration of the copper(II) coordination compounds determined from CD was found consistent with the crystal data. The copper(II) complexes were further investigated by vibrational CD (VCD) measurement combined with density functional theory calculation. The complex formation was evidenced by spectral shifts of the characteristic bands in the CD and VCD spectra.     

Chiroptical Spectra of Tetrakis (+)‐3‐Heptafluorobutylrylcamphorate Ln(III) Complexes with an Encapsulated Alkali Metal Ion: Solution Structures as Revealed by Chiroptical Spectra

The preparation of tetrakis((+)‐hfbc) lanthanide(III) complexes with an encapsulated alkali metal and ammonium ions M[Ln((+)‐hfbc)₄] (hereafter abbreviated as M‐Ln : (+)‐hfbc, (+)‐heptafluorobutyrylcamphorate; M, ammonium or benzyl ammonium ions as well as alkali metal ions) was reported and discussed. The electronic circular dichroism (CD) spectra in the intraligand π?π* transition of M–Ln were examined in view of the solvent effect. Here, the concentration, alkali metal, and ammonium ion dependences are compared with the solid CD, ⁵D₀ ← ⁷F₀(Eu(III)) excitation spectra, circularly polarized luminescence, and vibrational circular dichroism. It has been revealed that the dodecahedral eight coordinate DD‐8‐M‐Ln complexes in crystals are equilibrated between the diastereoselectively formed square antiprism eight coordinate SAPR‐8‐M‐Ln and [Ln((+)‐hfbc)₃] in EtOH and CH₃CN solutions or between the SAPR‐8‐M‐Ln and DD‐D_2d(mmmm)‐8‐M‐Ln complexes in CHCl₃ solution. The observed CD couplets are found to reflect the exciton CD couplets which are useful to determine the four‐bladed SAPR‐(llll) absolute configuration around the lanthanide(III) ion. Chirality 24:1055–1062, 2012. © 2012 Wiley Periodicals, Inc.     

Theoretical optical properties of poly-L-proline

A non-perturbational technique is used to calculate the circular dichroism and absorption spectra of polypeptide chains having conformations similar to that of poly-L -proline II. The method employs a Bogoliubov exciton formalism, from which the various optical terms associated with parallel and perpendicular components of the exciton band are obtained. A simple model for the peptide unit, consisting of three Gaussian absorption bands, leads to reasonable results for the polymer spectra, provided the lowest energy peptide π → π* transition is taken at 207 mμ and the value of the Ramachandran angle Ψ is taken to be 390°. The calculations suggest that the polymer circular dichroism spectrum is the resultant of strong interference among the two Gaussian exciton terms and the non-Gaussian helix term. Consequently, the CD spectrum is very sensitive to the value of Ψ. It is found that the small positive CD band in the vicinity of 230 mμ arises partly from the effect of the static (crystal) field interactions on the n → π* CD band.     

Luminescent studies of binuclear ternary europium(III) pyridineoxide tetrazolate complexes containing bis‐phosphine oxide as auxiliary co‐ligands

A new class of antenna chromophores so called ‘tetrazolates’ have not been explored much for lanthanide luminescencent complexes. However, we have already published several articles considering pyridineoxide tetrazolates as sensitizer with lanthanide ions. Although this class of antenna attracted much less attention because of its poor photoluminescence quantum yields (tris‐pyridineoxide tetrazolate europium complex = 13% in solution) we tried and successfully achieved to improve the photoluminescence quantum yields for this particular antenna molecule by replacing coordinated water from the inner coordination sphere of europium ion by introducing phosphine oxides as additional chromophore. In the present article the two bis‐phosphine oxides attach two molecules of tris‐pyridineoxide tetrazolate europium(III) complex which leads to the improvement of the overall molar absorption coefficients as well as photo‐physical properties of the complexes. We found more than two‐fold increase (31% in solution) in photoluminescence quantum yield with one of the coordinated phosphine oxides comparing with that of tris‐pyridineoxide tetrazolate europium(III) complex.     

Circular Dichroism Spectroscopy Study of Crystalline‐to‐Amorphous Transformation in Chiral Platinum(II) Complexes

Two couples of enantiomeric platinum(II) complexes: Pt(L_1a)Cl ( 1a ), Pt(L_1b)Cl ( 1b ) and Pt(L_1a)(C ≡ C ? Ph) ( 2a ), Pt(L_1b)(C ≡ C ? Ph) ( 2b ) (L_1a = (+)‐1,3‐di‐(2‐(4,5‐pinene)pyridyl)benzene, L_1b = (?)‐1,3‐di‐(2‐(4,5‐pinene)pyridyl)benzene) were synthesized and characterized. Their absolute configurations were determined by single crystal X‐ray diffraction and further verified by circular dichroism (CD) spectra (including electronic circular dichroism [ECD] and vibrational circular dichroism [VCD]). These complexes show interesting mechanoluminescence and/or vapoluminescence due to crystalline‐to‐amorphous transformation. The crystalline solids, grinding‐induced amorphous powders, and vapor‐induced amorphous powders of complexes 2a and 2b were comparatively investigated by solid‐state ECD and VCD spectra. The transformation from crystalline solids to amorphous powders was accompanied by significant variances of the spectral feature in both ECD and VCD spectra. Chirality 25:384–392, 2013. © 2013 Wiley Periodicals, Inc.     

Theoretical simulation of the electronic circular dichroism spectrum of calicheamicin

The aglycon, or so-called 'warhead' portion, of several potent 10-membered ring enediyne antitumor antibiotics contain dienonecarbamate and enediyne chromophores in an unusual bicyclic ring structure in which these two subunits are essentially orthogonal to each other. The circular dichroism (CD) spectra of the calicheamicin, esperamicin, and shisijimicin A families, all of which contain this bicyclic ring system, exhibit a characteristic negative exciton coupled CD at about 310 and 270 nm. This signature CD feature suggested the absolute stereochemical relationship between these chromophores as originally assigned and which was later confirmed by stereospecific total synthesis. Because of the unique nature of this chromophoric interaction and the importance of using this CD spectral feature in the assignment of the absolute stereochemistry of other related enediynes, we report here simulations of the CD spectra of the calicheamicin aglycon A, and of two other truncated models, B and C, by using density functional theory (DFT) and the DeVoe coupled oscillator approach. The DFT calculations provide a strong theoretical basis that the planar enediyne chromophore alone gives a negligible CD contribution, while that coming from the twisted dienonecarbamate is much more substantial. However, the shape and the largest part of the intensity of experimental CD spectrum can only be reproduced when the two unsaturated moieties are simultaneously present. Thus, the exciton coupling between the two chromophores provides the most important contribution to the experimental CD spectrum of calicheamicin. This conclusion is in full agreement with the results from the DeVoe calculation.     

Synthesis,Chiroptical Properties and Density Functional Theory Calculations of 3,3’‐Biphenyl‐2,2’‐BiTropone

The synthesis of new bitropone derivatives, namely, 3,3'‐biphenyl‐2,2'‐bitropone and 7,7’‐biphenyl‐2,2'‐bitropone, are reported. Isolation of enantiomers arising from restricted rotation around the C‐C bond connecting the tropone moieties was attempted by means of chiral high performance liquid chromatography (HPLC). No separation was obtained for 7,7’‐biphenyl‐2,2'‐bitropone. For 3,3'‐biphenyl‐2,2'‐bitropone, difficulties were encountered because of the low separation factor of the peaks and the presence of a rapid racemization process. However, quantitative chiroptical data on the antipodes were obtained by linking a circular dichroism (CD) spectrometer and a UV–vis spectrophotometric detector in series to the HPLC instrument. The analysis of the CD and UV–vis spectra in terms of absolute conformations was done with the help of theoretical calculations performed at the Density Functional Theory (DFT) level. The most stable conformations of the 3,3'‐biphenyl‐2,2'‐bitropone in its ground state were obtained. Starting from these minimum energy conformations, it was possible to compute theoretical CD and UV absorption spectra that fit well with the experimental ones. From this comparison the absolute configuration to the antipodes was assigned. Finally, the effect of the presence of the two lateral phenyl substituents on the structure of the bitropone and hence on the CD spectrum is discussed. Chirality 25:648–655, 2013. © 2013 Wiley Periodicals, Inc.     

CD‐sensitive Zn‐porphyrin tweezer host‐guest complexes,part 1: MC/OPLS‐2005 computational approach for predicting preferred interporphyrin helicity

This article describes a computational study on dimeric zinc porphyrin tweezer complexes with primary/secondary amines and secondary alcohols that validates the use of Optimized Potential for Liquid Simulations (OPLS‐2005) as the lead computational choice for assisting the tweezer methodology in the absolute configurational assignment of organic compounds. A supramolecular, microscale approach known as the tweezer method has been widely applied in the past decade for determining the absolute configuration of chiral substrates that are difficult to study by other readily available methods. The method relies on a host/guest complexation mechanism between a porphyrin tweezer moiety and a substrate, after its conversion into a bidentate conjugate. The formation of 1:1 complexes is a stereodifferentiating process: upon complexation, the originally achiral tweezer adopts a preferential interporphyrin helicity, dictated by the absolute configuration of the chiral substrate. By correctly predicting the sign of the interporphyrin helicity in the complex, OPLS‐2005 provides a correlation between the observed circular dichroism (CD) signal and the absolute configuration of the substrate. It also offers a great degree of insight into the structural factors responsible for chiral recognition and the amplitude of exciton couplets. Moreover, the preferential binding sites between the Zn‐tweezer and secondary amine conjugates were revealed by using the new computational approach. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Stopped‐Flow Enantioselective HPLC‐CD Analysis and TD‐DFT Stereochemical Characterization of Methyl Trans‐3‐(3,4‐Dimethoxyphenyl)Glycidate

Caffeic acid‐derived polyethers are a class of natural products isolated from the root extracts of comfrey and bugloss, which are endowed with intriguing pharmacological properties as anticancer agents. The synthesis of new polyether derivatives is achieved through ring‐opening polymerization of chiral 2,3‐disubstituted oxiranes, whose absolute configurations define the overall stereochemistry of the produced polymer. The absolute stereochemistry of one of these building blocks, methyl trans‐3‐(3,4‐dimethoxy‐phenyl)glycidate ( 3 ), was therefore characterized by the combination of enantioselective high‐performance liquid chromatography (HPLC), electronic circular dichroism (ECD) spectroscopy, and time‐dependent density functional theory (TD‐DFT) calculations. Initial efforts aiming at the isolation of enantiomers by means of a standard preparative HPLC protocol followed by offline ECD analysis failed due to unexpected degradation of the samples after collection. The stopped‐flow HPLC‐CD approach, by which the ECD spectra of enantiomers are measured online with the HPLC system, was applied to overcome this issue and allowed a fast, reliable, and chemical‐saving analysis, while avoiding the risks of sample degradation during the collection and processing of enantiomeric fractions. Subsequent TD‐DFT calculations identified ( (2S,3R)-3 as the first eluted enantiomeric fraction on the Lux Cellulose‐2 column, therefore achieving a full stereochemical characterization of the chiral oxirane under investigation. Chirality 27:914–918, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis,characterization and luminescent properties of europium complexes with 2,4,6‐tris‐(2‐pyridyl)‐s‐triazine as highly efficient sensitizers

Using 2,4,6‐tris‐(2‐pyridyl)‐s‐triazine (TPTZ) as a neutral ligand, and p‐hydroxybenzoic acid, terephthalic acid and nitrate as anion ligands, five novel europium complexes have been synthesized. These complexes were characterized using elemental analysis, rare earth coordination titrations, UV/vis absorption spectroscopy and infrared spectroscopy. Luminescence spectra, luminescence lifetime and quantum efficiency were investigated and the mechanism discussed in depth. The results show that the complexes have excellent emission intensities, long emission lifetimes and high quantum efficiencies. The superior luminescent properties of the complexes may be because the triplet energy level of the ligands matches well with the lowest excitation state energy level of Eu³⁺. Moreover, changing the ratio of the ligands and metal ions leads to different luminescent properties. Among the complexes, Eu₂(TPTZ)₂(C₈H₄O₄)(NO₃)₄(C₂H₅OH)·H₂O shows the strongest luminescence intensity, longest emission lifetime and highest quantum efficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

Enantiomeric separation of chiral ruthenium(II) complexes using capillary electrophoresis

Capillary zone electrophoresis (CZE) and micellar capillary electrophoresis (MCE) were applied for the enantiomeric separation of nine mononuclear tris(diimine)ruthenium(II) complexes as well as the separation of all stereoisomers of a dinuclear tris(diimine)ruthenium(II) complex. Nine cyclodextrin (CD) based chiral selectors were examined as run buffer additives to evaluate their effectiveness in the enantiomeric separation of tris(diimine)ruthenium(II) complexes. Seven showed enantioselectivity. Sulfated gamma-cyclodextrin (SGC), with four baseline and three partial separations, was found to be the most useful chiral selector. In CZE mode, the derivatized gamma-CDs were more effective than beta-CDs while sulfated CDs work better than carboxymethyl CDs. In MCE mode, hydroxypropyl beta-CD separated the greatest number of tris(diimine) ruthenium(II) complexes. The effects of chiral selector concentration, run buffer pH and concentration, the concentration ratio between chiral selector and other factors were investigated.     

Polymer‐Supported Optically Active fac(S)‐Tris(thiotato)rhodium(III) Complex for Sulfur‐Bridging Reaction With Precious Metal Ions

The optically active mixed‐ligand fac(S)‐tris(thiolato)rhodium(III) complexes, Δ_L‐fac(S)‐[Rh(aet)₂(L‐cys‐N,S)]^? (aet = 2‐aminoethanethiolate, L‐cys = L‐cysteinate) ( 1 ) and Δ_LL‐fac(S)‐[Rh(aet)(L‐cys‐N,S)₂]^2? were newly prepared by the equatorial preference of the carboxyl group in the coordinated L‐cys ligand. The amide formation reaction of 1 with 1,10‐diaminodecane and polyallylamine gave the diamine‐bridged dinuclear Rh(III) complex and the single‐chain polymer‐supported Rh(III) complex with retention of the Δ_L configuration of 1 , respectively. These Rh(III) complexes reacted with Co(III) or Co(II) to give the linear‐type trinuclear structure with the S‐bridged Co(III) center and the two Δ‐Rh(III) terminal moieties. The polymer‐supported Rh(III) complex was applied not only to the CD spectropolarimetric detection and determination of a trace of precious metal ions such as Au(III), Pt(II), and Pd(II) but also to concentration and extraction of these metal ions into the solid polymer phase. Chirality 28:85–91, 2016. © 2015 Wiley Periodicals, Inc.     

Synthesis of Diastereomeric Bicyclo[3.3.1]nonane Dibenzoyl Esters and Study of Their Chiroptical Properties

A synthesis of diastereomeric bicyclic dibenzoyl esters derived from enantiomerically pure (1S,5S)‐bicyclo[3.3.1]nonane‐2,6‐dione was accomplished. Molecules containing two benzoyl chromophores with different configuration in the bicyclic framework were obtained. Chiroptical properties of the synthesized enantiomerically pure molecules were studied. Diastereomeric esters exhibited exciton couplets in the circular dichroism (CD) spectra because of transannular interaction between non‐conjugated benzoate chromophores. The conformational effects and solvent impact on the exciton coupling were examined by CD spectroscopy. Theoretical computation of the CD spectra of diastereomers correctly reproduced the sign of the exciton couplets in the studied molecules, however, no major solvent dielectric constant influence and conformational effects per se on the exciton coupling was observed. Chirality 24:810–816, 2012. © 2012 Wiley Periodicals, Inc.     

Synthesis and conformational analysis of salivary proline‐rich peptide P‐B

The 57‐amino acid human salivary polypeptide P‐B has been synthesized by the solid‐phase method using 9‐fluorenylmethoxycarbonyl (Fmoc) strategy. The circular dichroism (CD) spectroscopy, Fourier‐transform infrared spectroscopy (FTIR) and molecular modeling methods have been used for conformational studies of P‐B. Examination of the CD spectra of P‐B showed the content of the secondary structure to be independent of temperature over the range 0–60 °C at pH = 7 as well as over the pH range of 2–12 at 37 °C. P‐B adopts predominantly unordered structure with locally appearing β‐turns. The cumulative results obtained using the CD and FTIR spectroscopic techniques indicate the percentage of the polyproline type‐II (PPII) helix being as low as about 10%. Similarly, the molecular dynamics (MD) simulations reveal only a short PPII helix in the C‐terminal fragment of the peptide (Pro⁵¹–Pro⁵⁴), which constitutes 7%. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Absorption flattening as one cause of distortion of circular dichroism spectra of Delta-RuPhen3 . H2TPPS complex

To extend the model that explains why and how much absorption flattening (AF) influences circular dichroism (CD) signals, we have investigated the interesting case of exciton CD in the Soret region of a noncovalent complex formed by (Delta-RuPhen(3))(2+) and the tetraanionic porphyrin H(2)TPPS. Different concentrations have been studied by using an AF emulator and spectra simulation. The CD spectra of this compound occasionally show distortions in the solution sampling mode with the increase of concentration; the inhomogeneous distribution in the cell volume is due to aggregation and is the source of the AF effect. On the basis of these results, we conclude that AF is an important cause of distortions in CD spectra for Delta-RuPhen(3) . H(2)TPPS complexes and might affect the CD bands of other aggregated systems as well.     

Unusual CD couplet pattern observed for the pi*<--n transition of enantiopure (Z)-8-methoxy-4-cyclooctenone: an experimental and theoretical study by electronic and vibrational circular dichroism spectroscopy and density functional theory calculation

Ultraviolet absorption (UV) and electronic circular dichroism (ECD) spectra of enantiopure (Z)-8-methoxy-4-cyclooctenone (MCO) were measured in hexane to give a normal single UV absorption band at 298 nm, which is assigned to the carbonyl's pi*<--n transition. Unexpectedly, the ECD spectrum exhibited an apparent couplet pattern with vibrational fine structures. Obviously, the conventional CD exciton coupling mechanism cannot be applied to this bisignate CD signal observed for single-chromophoric MCO. Variable temperature-ECD and vibrational circular dichroism (VCD) spectral measurements, simultaneous UV and ECD spectral band resolution, and density functional theory (DFT) calculations of energy and structure revealed that this apparent CD couplet originates from a rather complicated spectral overlap of more than three conformers of MCO, two of which exhibit mirror-imaged ECD spectra at appreciably deviated wavelengths. In the simultaneous band-resolution analysis, the observed UV and ECD spectra were best fitted to four overlapping bands. Two major conformers were identified by comparing the experimental IR and VCD spectra with the simulated ones, and the other two by comparing the observed UV and ECD spectra with the theoretical ones obtained by time-dependent DFT calculations. It was shown that the combined use of experimental ECD and VCD spectra and theoretical DFT calculations can give a reasonable interpretation for the Cotton effects of the conformationally flexible molecule MCO.