New Insights on Solvent-Induced Changes in Refractivity and Specific Rotation of Poly(propylene oxide) Systems Extracted from Channeled Spectra.

Investigation of chiroptical polymers in the solution phase is paramount for designing supramolecular architectures for photonic or biomedical devices. This work is devoted to the case study of poly(propylene oxide) (PPO) optical activity in several solvents: benzonitrile, carbon disulfide, chloroform, ethyl acetate, and p-dioxane. To attain information on the interactions in these systems, rheological testing was undertaken, showing distinct variations of the rheological parameters as a function of the solvent type. These aspects are also reflected in the refractive index dispersive behavior, from which linear and non-linear optical properties are extracted. To determine the circular birefringence and specific rotation of the PPO solutions, the alternative method of the channeled spectra was employed. The spectral data were correlated with the molecular modeling of the PPO structural unit in the selected solvents. Density functional theory (DFT) computational data indicated that the torsional potential energy-related to the O1-C2-C3-O4 dihedral angle from the polymer repeating unit-was hindered in solvation environments characterized by high polarity and the ability to interact via hydrogen bonding. This was in agreement with the optical characterization of the samples, which indicated a lower circular birefringence and specific rotation for the solutions of PPO in ethyl acetate and p-dioxane. Also, the shape of optical rotatory dispersion curves was slightly modified for PPO in these solvents compared with the other ones.

Synthesis, characterization and absolute configurations of methyl ladderanoates.

Methyl esters of [5]-ladderanoic acid and [3]-ladderanoic acid were prepared by esterification of the acids isolated from biomass at a wastewater treatment plant. Optical rotations at six different wavelengths (633, 589, 546, 436, 405 and 365 nm) and vibrational circular dichroism (VCD) spectra in the 1800-900 cm-1 region were measured in CDCl3 solvent and compared with quantum chemical (QC) predictions using B3LYP functional and 6-311++G(2d,2p) basis set with polarizing continuum model representing the solvent. QC predictions gave negative optical rotations at all six wavelengths for (R)-methyl [5]-ladderanoate and positive optical rotations for (R)-methyl [3]-ladderanoate, the same signs as previously reported for the corresponding acids. The crystal structure of (-)-methyl [5]-ladderanoate independently confirmed (R) configuration. The QC-predicted VCD spectra using Boltzmann population weighted spectra of individual conformers did not provide satisfactory quantitative agreement with the experimental VCD spectra. An improved quantitative agreement for VCD spectra could be obtained when conformer populations were optimized to maximize the similarity between experimental and predicted VCD spectra, but more improvements in VCD predictions are needed.

Chiroptical spectroscopic studies for the absolute configuration determination of hexahydrocurcumin and octahydrocurcumin.

Hexahydrocurcumin (HHC) and octahydrocurcumin (OHC) were synthesized, and their enantiomers were separated using supercritical fluid chromatography. The absolute configurations (ACs) of HHC and OHC were independently determined using experimental measurements and quantum theoretical predictions of vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion. These studies lead to AC assignments of (-)-(R)-HHC and (+)-(R,R)-OHC. The AC of OHC is further confirmed by its structure determined from single crystal x-ray diffraction.

Absolute configuration of seco-eudesmanolide inuloxin D from experimental and predicted chiroptical studies of its 4-O-acetyl derivative.

Sesquitepenoids inuloxins A-D, belonging to different subgroups, were isolated from Dittrichia viscosa and showed potential biocontrol of some parasitic plants as Pelipanche, Orobanche, and Cuscuta species. The absolute configurations of the first three inuloxins A-C were previously determined by using experimental and computational chiroptical spectroscopic methods. The absolute configuration of inuloxin D remains to be established. The bioactive inuloxin E, closely related to inuloxin D, was recently isolated from the same plant organic extract. The same relative configuration of inuloxin D was assigned to inuloxin E by comparison of their NMR spectroscopic data. The absolute configurations of inuloxin D and inuloxin E are suggested in this work by analysis of the experimental and predicted chiroptical properties of the 4-O-acetyl derivative of inuloxin D.

Electronic Currents Induced by Optical Fields and Rotatory Power Density in Chiral Molecules.

The electric dipole-magnetic dipole polarizability tensor κ', introduced to interpret the optical activity of chiral molecules, has been expressed in terms of a series of density functions kαß', which can be integrated all over the three-dimensional space to evaluate components καß' and trace καα'. A computational approach to kαß', based on frequency-dependent electronic current densities induced by monochromatic light shining on a probe molecule, has been developed. The dependence of kαß' on the origin of the coordinate system has been investigated in connection with the corresponding change of καß'. It is shown that only the trace kαα' of the density function defined via dynamic current density evaluated using the continuous translation of the origin of the coordinate system is invariant of the origin. Accordingly, this function is recommended as a tool that is quite useful for determining the molecular domains that determine optical activity to a major extent. A series of computations on the hydrogen peroxide molecule, for a number of different HO-OH dihedral angles, is shown to provide a pictorial documentation of the proposed method.

A molecular orbital selection approach for fast calculations of specific rotation with density functional theory.

In this work, we describe a simple approach to select the most important molecular orbitals (MOs) to compute the optical rotation tensor through linear response (LR) Kohn-Sham density functional theory (KS-DFT). Taking advantage of the iterative nature of the algorithms commonly used to solve the LR equations, we select the MOs with contributions to the guess perturbed density that are larger than a certain threshold and solve the LR equations with the selected MOs only. We propose two criteria for the selection, and two definitions of the selection threshold. We then test the approach with two functionals (B3LYP and CAM-B3LYP) and two basis sets (aug-cc-pVDZ and aug-cc-pVTZ) on a set of 51 organic molecules with specific rotation spanning five orders of magnitude, 100 -104 deg (dm-1 (g/mL)-1 ). We show that this approach indeed can provide very accurate values of specific rotation with estimated speedup that ranges from 2 to 8× with the most conservative selection criterion, and up to 20 to 30× with the intermediate criterion.

Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity.

A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high-pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO-A selectively and competitively. In particular, the R enantiomer was detected as an exceptionally potent and a selective MAO-A inhibitor (Ki  = 0.85 × 10-3  ± 0.05 × 10-3  µM and SI: 2.35 × 10-5 ), whereas S was determined as poorer compound than R in terms of Ki and SI (0.184 ± 0.007 and 0.001). The selectivity of the enantiomers was explained by molecular modeling docking studies based on the PDB enzymatic models of MAO isoforms.

Comparison of measured and predicted specific optical rotation in gas and solution phases: A test for the polarizable continuum model of solvation.

A comparative theoretical and experimental study of dispersive optical activity is presented for a set of small, rigid organic molecules in gas and solution phases. Target species were chosen to facilitate wavelength-resolved measurements of specific rotation in rarefied vapors and in organic solvents having different polarities, while avoiding complications due to conformational flexibility. Calculations were performed with two density functionals (B3LYP and CAM-B3LYP) and with the coupled-cluster singles and doubles (CCSD) ansatz, and solvent effects were included through use of the polarizable continuum model (PCM). Across the various theoretical methods surveyed, CCSD with the modified velocity gauge provided the best overall performance for both isolated and solvated conditions. Zero-point vibrational corrections to equilibrium calculations of chiroptical response tended to improve agreement with gas-phase experiments, but the quality of performance realized for solutions varied markedly. Direct comparison of measured and predicted specific-rotation suggests that PCM, in general, is not able to reproduce attendant solvent shifts (neither between gas and solution phases nor among solvents) and fares better in estimating actual medium-dependent values of this property (although the error is rather system dependent). Thus, more elaborate solvation models seem necessary for a proper theoretical description of solvation in dispersive optical activity.

The determination of enantiomer composition of 1-((3-chlorophenyl)-(phenyl)methyl) amine and 1-((3-chlorophenyl)(phenyl)-methyl) urea (Galodif) by NMR spectroscopy, chiral HPLC, and polarimetry.

For the first time, a method for enantiomer resolution of the anticonvulsant Galodif (1-((3-chlorophenyl)(phenyl)methyl) urea) by chiral HPLC was developed, whereas the enantiomeric composition of 1-((3-chlorophenyl)(phenyl)methyl) amine-precursor in Galodif synthesis-cannot be resolved by this method. However, starting 1-((3-chlorophenyl)(phenyl)methyl) amine quantitatively forms diastereomeric N-((3-chlorophenyl)(phenyl)methyl)-1-camphorsulfonamides in reaction with chiral (1R)-(+)- or (1S)-(-)-camphor-10-sulfonyl chlorides. The diastereomeric ratio of obtained camphorsulfonamides can be easily determined by NMR 1 H and 13 C spectroscopy. The DFT calculations of specific rotation of Galodif enantiomers showed good agreement with experimental data. The absolute configuration of enantiomers was proposed for the first time.

A Wavefront Division Polarimeter for the Measurements of Solute Concentrations in Solutions.

Polarimeters are useful instruments that measure concentrations of optically active substances in a given solution. The conventional polarimetric principle consists of measuring the rotation angle of linearly polarized light. Here, we present a novel polarimeter based on the study of interference patterns. A Mach-Zehnder interferometer with linearly polarized light at the input is used. One beam passes through the liquid sample and the other is a reference beam. As the linearly polarized sample beam propagates through the optically active solution the vibration plane of the electric field will rotate. As a result, the visibility of the interference pattern at the interferometer output will decrease. Fringe contrast will be maximum when both beams present a polarization perpendicular to the plane of incidence. However, minimum visibility is obtained when, after propagation through the sample the polarization of the sample beam is oriented parallel to the plane of incidence. By using different solute concentrations, a calibration plot is obtained showing the behavior of visibility.

Structural Analysis Using Chiroptical Spectroscopy: Insights and Cautions.

Chiroptical spectroscopy has evolved into a promising tool for chiral molecular structural determination in the last four decades. Determination of the absolute configurations (ACs) of bromochlorofluoromethane and [(2) H1 ,(2) H2 ,(2) H3 ]-neopentane demonstrated the enviable advantages of chiroptical spectroscopy. Furthermore, uncovering the errors in the ACs reported in the literature established a glimpse of what can be accomplished with the modern chiroptical spectroscopic methods. Despite these triumphs, it is important to exercise caution in the practice of chiroptical spectroscopic methods, because certain widely practiced approaches can lead to erroneous conclusions. Selected major accomplishments and special precautions needed for future applications are emphasized. Chirality 28:445-452, 2016. © 2016 Wiley Periodicals, Inc.

Specific Optical Rotations and the Horeau Effect.

The observation of nonequivalence of optical and enantiomeric purities, referred to as the Horeau effect, is thought to arise from molecular aggregation in liquid solutions. Although this effect was first observed in 1969, the conditions under which this effect may, or may not, be observable are not established. Considering the formation of dimers as the simplest form of aggregation, the expressions for specific optical rotations in the presence of homochiral and heterochiral monomer-dimer equilibria are presented. Analysis of these equations indicates that the Horeau effect will not be observable even in the presence of aggregation under either of the following two situations: 1) The specific optical rotation of the monomeric species is equal to that of the dimeric species; 2) The heterochiral equilibrium constant is twice that of the homochiral equilibrium constant.

A combined experimental and computational chiroptical approach to establish the biosynthesis and absolute configuration of licochalcone L.

Often, chiral natural products exist as single stereoisomers; however, simultaneous occurrences of both enantiomers can exist in nature, resulting in scalemic or racemic mixtures. Ascertaining theabsolute configuration (AC) of natural products is pivotal for attributing their specific biological signature. Specific rotation data commonly characterize chiral non-racemic natural products; however, measurement conditions, viz., solvent and concentration, can influence the sign of specific rotation values, especially when characterizing natural products possessing small values. For example, licochalcone L, a minor constituent of Glycyrrhiza inflata, was reported with a specific rotation of [α]D22= +13 (c 0.1, CHCl3); however, not establishing the AC and the reported zero specific rotation for an identical compound, licochalcone AF1, resulted in debatable chirality and its biogenesis. In this study, a combined experimental and computational chiroptical approach involving specific rotation and electronic circular dichroism (ECD) data, supported by time-dependent density functional theory (TDDFT), were effectively utilized to establish the AC of licochalcone L as the (E, 2″S)-isomer. Establishing the 2″S absolute configuration permitted the conception of a reasonable biosynthetic pathway involving intramolecular '5-exo-tet' ring opening of a chiral oxirane to form chiral licochalcone L in G. inflata.

Endo-fenchyl acetate rich essential oil of Strobilanthes sessilis Nees inflorescence and its characterisation using GC, GC-MS, and NMR techniques.

Strobilanthes Blume is a genus in the family Acanthaceae, with many species endemic to the Indian subcontinent. Strobilanthes sessilis Nees is endemic to the southern Western Ghats of India. The essential oil of dried inflorescence of S. sessilis was extracted using hydrodistillation method and the chemical composition was determined using GC and GC-MS techniques, which revealed the major compound to be endo-fenchyl acetate (89.33%). Other minor compounds like endo-fenchol (3.74%), (E)-caryophyllene (1.07%), and limonene and ß-phellandrene (0.55%) were also observed. The major diastereomer of fenchyl acetate was determined using 2D-NMR techniques like HSQC, HMBC, and ROESY to confirm the endo configuration. The optical rotation of the oil in different solvents deduced that the laevorotatory enantiomer of endo-fenchyl acetate as the major or single compound. S. sessilis could be further explored as a major source of endo-fenchyl acetate, which has high importance in flavouring and other biological applications.

Antifungal Diterpene Alkaloids from the Caribbean Sponge Agelas citrina: Unified Configurational Assignments of Agelasidines and Agelasines.

Three new diterpene alkaloids - the hypotaurocyamines, (-)-agelasidines E and F (5-6), and the adeninium salt, agelasine N (9) - were isolated from the Caribbean sponge Agelas citrina along with six known natural products agelasines B-E (7, 10-12), 2-oxo-agelasine B (8), and (-)-agelasidine C (3). The chemical structures of 5, 6 and 9 were elucidated by analysis of NMR spectra and mass spectrometry. This represents the first report of natural products from the sponge A. citrina. Unified assignment of absolute configurations of the new compounds and known compounds were achieved by chemical correlation, quantitative measurements of molar rotations, and comparative analysis by van't Hoff's principle of optical superposition. (-)-Agelasidine C (3) exhibited potent antifungal and modest cytotoxic activity against human chronic lymphocytic leukemia (CLL) cells.

Structural analysis of unusual alkaloids isolated from Narcissus pseudonarcissus cv. Carlton.

Narciindole A, the first representative of Amaryllidaceae alkaloids with an indol-3-ylmethanone framework, was isolated from bulbs of Narcissus pseudonarcissus (L.) cv. Carlton, together with carltonine D and carltonine E, which share the same unusual structural motif as dimeric carltonine C (reported in 2020), exhibiting atropisomerism. Unambiguous structure elucidations have been achieved by NMR spectroscopy, HRMS, and comparison with literature data of related alkaloids. Furthermore, the chirality of known alkaloids with a galanthindole biaryl core was revised using optical rotation. Last, but not least, a biosynthetic pathway for dimeric carltonine-type alkaloids was proposed. Unfortunately, in terms of biological activity, the isolated alkaloids showed only moderate inhibition of human acetylcholinesterase and/or butyrylcholinesterase.

HPLC profiling of antimicrobial and antioxidant phyco sugars isolated from the South West coast of India.

Phyco sugars isolated from the South West coast of India are commercially and therapeutically interesting due to their various biological activities. These sugars were isolated from six (three red and three green) seaweed species using water at 100°C followed by precipitation using ethanol. The physical, chemical and biological characteristics were explored with specific highlights onto the specific rotation, HPLC-RI sugar speciation, antioxidant and antimicrobial activities. The biological properties were evaluated based on multiple methods and standards, such that the actual nature of the sugar is understood. G. corticata var. cylindrica (31.66%) had the highest sugar content. All the sugars had levo rotatory specific rotation and interesting chemical characteristics. Sugars isolated had competitive biological activities and had the presence of seven monosaccharides and one disaccharide. The results highlighted the socio-economic importance of seaweeds which could be developed as a potential source of bioactive compounds in the upcoming future.

Theoretical searches and spectral computations of preferred conformations of various absolute configurations for a cyclodipeptide, cordycedipeptide A from the culture liquid of Cordyceps sinensis.

A cyclic dipeptide often has the multiple configurations and the abundant conformations. The density functional theory (DFT) method is used to search the preferred conformation of the most probable configuration for cordycedipeptide A isolated from the culture liquid of Cordyceps sinensis. The time-dependent DFT approach is exploited to describe the profile of electronic circular dichroism (CD). The calculated results show that the most probable configuration is 3S6R7S, whose preferred conformation has a negative optical rotation and a positive lowest energy electronic CD band.

New method to determine the optical rotatory dispersion of inorganic crystals applied to some samples of Carpathian Quartz.

A new method to determine the optical rotatory dispersion (ORD) in the visible range, based on a channeled spectrum obtained with a uniax inorganic crystal introduced between two crossed polarizers with its optical axis parallel to the light propagation direction is detailed in this paper. When the studied inorganic crystals are transparent, this method permits the estimation of the optical rotatory dispersion in the visible range, for which the cheap polarizers are available. The speed of the measurements is very high, because the estimations are made from the channeled spectrum obtained for a single arrangement of the optical components. By using a computer, ORD is quickly determined for the visible range. The results obtained by this method for some Carpathian Quartz samples are consistent with those from literature. The proposed method can be also applied in UV and IR spectral ranges, when the anisotropic layers are transparent and the linearly polarized radiations can be obtained.