Detection and identification of optical activity using polarimetry – applications to biophotonics,biomedicine and biochemistry

Polarized light that is reflected or transmitted through chiral specimens can be used to detect and identify biological and chemical materials including human tissue. The determination of the silent footprints of the chiral properties of the biological materials on scattered polarized light is the basis for these investigations. It is of primary importance to identify which combinations of the elements of the Mueller matrix for reflected or for transmitted light can be used to determine the optical activity of the biochemical materials. The optical activity of chiral materials is characterized by optical rotation and circular dichroism. The explicit analytical dependence of these specific elements of the Mueller matrix, upon the angles of incidence and scatter, upon the wavelength and upon the type of chirality has the potential to provide experimentalists with guidance in determining the optimum use of optical polarimetric scatterometers. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Expressions for the interpretation of circular intensity differential scattering of chiral aggregates

The derivation of compact expressions of the circular intensity differential scattering (CIDS) of chiral molecules is presented in the first Born approximation of the fields. The expressions derived are valid for a suspension of scattering chiral particles free to adopt any orientation in solution. The connection is established between the preferential scattering cross section for right- vs left-circularly polarized light for a given scattering angle and the geometrical parameters of the molecule. As observed experimentally, the equations predict that the circular differential scattering patterns must show as a function of the scattering angle a series of lobes of alternating sign. In between these lobes, zeros in the differential scattering cross section occur. For the case of two dipole moments arranged in chiral fashion, an expression is derived that shows how the relative arrangement of the dipoles and their separation relative to the wavelength of light control the number and the position of the zeros. A compact expression predicting the CIDS of a sample for very small angles of scattering is derived for a system of helices whose dimensions are small compared with the wavelength of light. Finally, the presence of CIDS in a sample is related to the appearance of anomalous signals in the CD spectrum of chiral systems. Expressions and computations of the magnitudes and sign of the anomalies are presented. The expressions obtained confirm the main features of the experimental CIDS patterns of chiral molecules previously published.     

Chirality Switching Via Rotation of Bilayer Fourfold Meta-Structure

Chiral effects have been observed from the interaction of chiral plasmonics nanostructures with light. Such nanostructures enhance the chiral response of molecules and provide an ideal platform for biological and chemical sensing. Here, we investigate the chiral switching effects of an array of subwavelength nanostructures with a unit cell composed of four double-layered nanostrips arranged to be rotationally symmetric. We observe chiral switching leading to a change in circular dichroism (CD) signature when the mutual angle between the first and second layer increases from 0° to 90° with respect to each other. This mutual angle can be manipulated to switch the handedness of the nanostructure and cause a change in the outgoing light. We also investigated the field distribution of each mode when circularly polarized light is normally incident into the structure. These modes can be categorized into longitudinal and transverse modes depending on the orientation of their dipole moments. The mode studies clearly show the nature of each plasmonics mode.     

Thermooptic effect in chloroplast thylakoid membranes. Thermal and light stability of pigment arrays with different levels of structural complexity

In chloroplast thylakoid membranes, chiral macrodomains, i.e., large arrays of pigment molecules with long-range chiral order, have earlier been shown to undergo light-induced reversible and irreversible structural changes; such reorganizations did not affect the short-range, excitonic pigment-pigment interactions. These structural changes and similar changes in lamellar aggregates of the main chlorophyll a/b light-harvesting complexes exhibited a linear dependence on the intensity of light that was not utilized in photosynthesis. It has been hypothesized that the light-induced rearrangements are driven by a thermooptic effect, i.e., thermal fluctuations due to the dissipation of excess excitation energies [Barzda, V., et al. (1996) Biochemistry 35, 8981-8985]. To test this hypothesis, we have utilized circular dichroism (CD) spectroscopy to investigate the structural stability of the chiral macrodomains and the constituent bulk pigment-protein complexes of granal thylakoid membranes against heat and prolonged, intense illumination. (i) In intact thylakoid membranes, the chiral macrodomains displayed high stability below 40 degrees C, but they were gradually disassembled between 50 and 60 degrees C; the thermal stability of the chiral macrodomains could be decreased substantially by suspending the membranes in reaction media that were hypotonic or had low ionic strength. (ii) The chiral macrodomains were also susceptible to high light: prolonged illumination with intense white light (25 min, 2500 microE m(-)(2) s(-)(1), 25 degrees C) induced similar, irreversible disassembly to that observed at high temperatures; in different preparations, lower thermal stability was coupled to lower light stability. (iii) The light stability depended significantly on the temperature: between about 5 and 15 degrees C, the macrodomains in the intact thylakoids were virtually not susceptible to high light; in contrast, the same preillumination at 35-40 degrees C almost completely destroyed the chiral macrodomains. (iv) As testified by the excitonic CD bands, the molecular organization of the pigment-protein complexes in all samples exhibited very high thermal stability between about 15 and 65 degrees C, and virtually total immunity against intense illumination. These data are fully consistent with the hypothesis of a thermooptic effect, and are interpreted within the frame of a simple model.     

Nonlinear optical spectroscopy of chiral molecules

We review nonlinear optical processes that are specific to chiral molecules in solution and on surfaces. In contrast to conventional natural optical activity phenomena, which depend linearly on the electric field strength of the optical field, we discuss how optical processes that are nonlinear (quadratic, cubic, and quartic) functions of the electromagnetic field strength may probe optically active centers and chiral vibrations. We show that nonlinear techniques open entirely new ways of exploring chirality in chemical and biological systems: The cubic processes give rise to nonlinear circular dichroism and nonlinear optical rotation and make it possible to observe dynamic chiral processes at ultrafast time scales. The quadratic second-harmonic and sum-frequency-generation phenomena and the quartic processes may arise entirely in the electric-dipole approximation and do not require the use of circularly polarized light to detect chirality. They provide surface selectivity and their observables can be relatively much larger than in linear optical activity. These processes also give rise to the generation of light at a new color, and in liquids this frequency conversion only occurs if the solution is optically active. We survey recent chiral nonlinear optical experiments and give examples of their application to problems of biophysical interest.     

Asymmetric epoxidation of unfunctionalized alkenes catalyzed by sugar moiety-modified chiral salen-Mn(III) complexes

Several chiral Schiff-base ligands with sugar moieties at C-3 (3′) or C-5 (5′) of salicylaldehyde were synthesized from reaction of salicylaldehyde derivatives with diamine. These ligands coordinated with Mn(III) to afford the corresponding chiral salen-Mn(III) complexes characterized by FT-IR, MS, and elementary analysis. These complexes were used as catalysts for the asymmetric epoxidation of unfunctionalized alkenes. Only weak enantioselectivity is induced by the chiral sugar moieties at C-3 (3′) or C-5 (5′) in the case of absence of chirality in the diimine bridge moiety. It was also shown that the sugars at C-5 (5′) having the same rotation direction of polarized light as the diimine bridge in the catalyst could enhance the chiral induction in the asymmetric epoxidation, but the sugars with the opposite rotation direction would reduce the chiral induction.     

Chiral memory: induction, amplification, and switching in porphyrin assemblies

The interaction between the tetra-anionic porphyrin H2TPPS and its copper derivative, CuTPPS, with the tetra-cationic porphyrin H2T4 and its copper derivative, CuT4, leads, in aqueous solution, to the formation of remarkably stable and kinetically inert heteroaggregates. The aggregation process is under hierarchic control and, in the presence of a suitable chiral mold, leads to the formation of chiral porphyrin heteroassemblies as stable and inert as the achiral ones. Because of these properties, the chirality of the porphyrin "imprinted" heteroaggregates not only survives the disruption of the template, but also to its complete removal from the solution. Notably, the template-free chiral porphyrin system is an excellent mold for its own self-replication. The relevant characteristics of these chiral heteroaggregates together with the knowledge of the forces that guide the aggregation processes permitted us to design a new but similar system. This system not only is able to store chiral information, but also is capable to release and restore it reversibly, in a cyclic manner. This has been achieved by modulating the charges carried by one of the two coupled porphyrins through protonation under various pH conditions. The role of the central metal ion and the template-free chiral structure of the CuT4-H2TPPS heteroaggregate, determined through EDXD analysis, are also presented.     

Raman optical activity of proteins, carbohydrates and glycoproteins

On account of its sensitivity to chirality, Raman optical activity (ROA), which may be measured as a small difference in the intensity of vibrational Raman scattering from chiral molecules in right- and left-circularly polarized incident light, or as the intensity of a small circularly polarized component in the scattered light, is a powerful probe of the structure of biomolecules. Protein ROA spectra provide information on secondary and tertiary structures of polypeptide backbones, backbone hydration and side-chain conformations, and on structural elements present in unfolded states. Carbohydrate ROA spectra provide information on the central features of carbohydrate stereochemistry, especially that of the glycosidic link. Glycoprotein ROA spectra provide information on both the polypeptide and carbohydrate components. This article describes the ROA technique and presents and discusses the ROA spectra of a selection of proteins, carbohydrates, and a glycoprotein. The many structure-sensitive bands in protein ROA spectra are favorable for applying pattern recognition techniques, illustrated here using nonlinear mapping, to determine structural relationships between different proteins.     

Enantiomeric impurities in chiral catalysts,auxiliaries, and synthons used in enantioselective syntheses. Part 5

The enantiomeric excess of chiral starting materials is one of the important factors determining the enantiopurity of products in asymmetric synthesis. Fifty‐one commercially available chiral reagents used as building blocks, catalysts, and auxiliaries in various enantioselective syntheses were assayed for their enantiomeric purity. The test results were classified within five impurities level (ie, <0.01%, 0.01%‐0.1%, 0.1%‐1%, 1%‐10%, >10%). Previously from 1998 to 2013, several reports have been published on the enantiomeric composition of more than 300 chiral reagents. This series of papers is necessitated by the fact that new reagents are forthcoming and that the enantiomeric purity of the same reagent can vary from batch to batch and/or from supplier to supplier. This report presents chiral liquid chromatography (LC) and gas chromatography (GC) methods to separate enantiomers of chiral compounds and evaluate their enantiomeric purities. The accurate and efficient LC analysis was done using newly introduced superficially porous particle (SPP 2.7 μm) based chiral stationary phases (TeicoShell, VancoShell, LarihcShell‐P, and NicoShell).     

A Sequential Scenario for the Origin of Biological Chirality

A sequential model is proposed regarding the origin of biological chirality. Three major stages are presumed: a symmetry breaking (prebiotic chiral disruption in enantiomeric mixtures of monomers), a chiral amplification (prebiotic increase of the chiral character of the monomers affected first by the symmetry breaking), and a chiral expansion (proto biological increase of the chiral character and spread of the chirality to molecules which were less affected by prebiotic chiralizations). As a symmetry-breaking mechanism, the model proposed by Deutsch (1991) is used, which involves a dissymmetric exposure of amino acids (AA) to ultraviolet circularly polarized light (UV-CPL) on evaporative seashores. It is presumed that the chiral amplification, up to a protobiologic significance, was influenced by a periodic overlapping of two abiotic events, a synchronization between tidal-based hydrous–anhydrous cycles, and littoral asymmetric photolysis cycles. This long-term astronomic asymmetry acted around 3.8–4.2 billion years ago and was unique to the Earth in our solar system. It is also presumed that the abiotic symmetry breaking is heterogenous, that only a few l-AAs were used in the beginning, and that the chirality expanded later to all 20 AAs based on a coevolutionary strategy of the genetic code and on a physiological relationship between AAs. In this scenario the d-chirality of pentoses in polynucleotides was attributed to both d-pentose/l-AA relationships and to a structural evolution. Received: 10 May 1996 / Accepted: 13 August 1996     

Copper-catalyzed divergent kinetic resolution of racemic allylic substrates

When a racemic mixture is fully consumed the products may still be enantiomerically enriched. In particular, the regiodivergent kinetic resolution is a process in which a single chiral catalyst or reagent reacts with a racemic substrate to form regioisomers possessing an opposite configuration on the newly-formed stereogenic centers. This review reports the major advances in the field of the copper-catalyzed regiodivergent and stereodivergent kinetic resolution of allylic substrates with organometallic reagents. The chiral recognition matching phenomena found with particular allylic substrates with the absolute configuration of the chiral catalyst allows in some cases an excellent control of the regio- and stereoselectivity, sheding some light on the so-called "black-box" mechanism of a copper-catalyzed asymmetric allylic alkylation.     

Asymmetric Spatiotemporal Evolution of Prebiotic Homochirality

The role of asymmetry on the evolution of prebiotic homochirality is investigated in the context of autocatalytic polymerization reaction networks. A model featuring enantiometric cross-inhibition and chiral bias is used to study the diffusion equations controlling the spatiotemporal development of left and right-handed domains. Bounds on the chiral bias are obtained based on present-day constraints on the emergence of life on early Earth. The viability of biasing mechanisms such as weak neutral currents and circularly polarized UV light is discussed. The results can be applied to any hypothetical planetary platform.     

Chiral dialkyl ditellurides: Conformation of chiral chromophore by circular dichroism and DFT calculation

The twisted structure of ditellurides, in a similar way as in other dichalcogenes, leads to different absorption of circularly polarized light by quasi‐enantiomeric chiral orbitals. Chiral optically active ditellurides are not common compounds and this phenomenon is not widely reported. As chiral ditellurides found an application in asymmetric synthesis, their molecular structure, understood as their conformation, became an important factor for understanding their reactivity. Until now there are few examples of chiral ditellurides known and their structure was not analyzed in details. This article presents the results of our most recent research on the structure of chiral ditellurides investigated by electronic circular spectroscopy (ECD) supported by quantum‐chemical calculation. This enables us to suggest a relationship between chirality of alkyl substituent and chirality (conformation) of ditelluride.     

Absorption Circular Dichroism Induced by Contorted Electrical Oscillations in Rectangular Nanoholes

The chiroptical response of plasmonic chiral nanostructures can be tuned by combining different structures. In this paper, an L-shaped metal strip is introduced into a rectangular metal nanohole to generate absorption circular dichroism (ACD). The results of a finite-element method calculation show that ACD effects result from contorted electrical oscillations in the L-shaped strip. Additional calculations show that the ACD effects of the proposed metasurface depend strongly on the structure parameters. These findings provide not only a mechanism for enhancing chiroptical responses in planar structures but also a general strategy for the chiral manipulation of light and creation of chiroptical devices.

     

Fundamentals of chirality,resolution, and enantiopure molecule synthesis methods

The chirality of molecules is a concept that explains the interactions in nature. We may observe the same formula but different organizations revolving around the chiral center. Since Pasteur's meticulous observation of sodium ammonium tartrate crystals' structure, scientists have discovered many features of chiral molecules. The number of newly approved single enantiomeric drugs increases every year and takes place in the market. Thus, separation or resolution methods of racemic mixtures are of continued importance in the efficacy of drugs, installation of affordable production processes, and convenient synthetic chemistry practice. This article presents the asymmetric synthesis approaches and the classification of direct resolution methods of chiral molecules.     

Parity violation and chiral symmetry breaking of a racemic mixture

The chiral symmetry breaking of a racemic mixture by the parity violating weak interaction is considered. Particular attention is given to a mechanism recently proposed by Mason and Tranter whereby the weak neutral current interaction in chiral molecules leads to the differential absorption of unpolarized light by D vs. L enantiomers. After extending the usual theory of optical activity to include weak neutral currents, it is found that for spin-allowed transitions in typical organic molecules the weak photoabsorption asymmetry is much smaller than the value obtained using the reasoning of Mason and Tranter. Upon making a comparison with other mechanisms, it is concluded that differential radiolysis by beta electrons is likely to produce the largest symmetry breaking effect by the weak interaction.     

Supernovae, neutron stars and biomolecular chirality

Recent theoretical and experimental investigations of the origin of biomolecular chirality are reviewed briefly. Biotic and abiotic theories are evaluated critically with the conclusion that asymmetric photochemical processes with circulary polarized light (CPL), particularly asymmetric photolyses, constitute the most viable mechanisms. Solar CPL sources appear too weak and random to be effective. We suggest an alternative CPL source, namely, the synchrotron radiation from the neutron star remnants of supernova explosions. This could asymmetrically process racemic compounds in the organic mantles of the dust grains in interstellar clouds, and the resulting chiral molecules could be transferred to Earth by cold accretion as the solar system periodically traverses these interstellar clouds.     

Controlling the reflection wavelength of iridescent solid films of nanocrystalline cellulose

Nanocrystalline cellulose (NCC) self-assembles in suspension to form iridescent chiral nematic films upon drying that can reflect circularly polarized light at specific wavelengths. Ultrasound treatment has now been found to increase the chiral nematic pitch in suspension and red-shift the reflection wavelength of NCC films as the applied energy increases. Sonication and electrolyte addition combined allow the reflective properties of the film to be predictably tuned. The effects of sonicating an NCC suspension are cumulative and permanent. Suspensions sonicated with different energy inputs may be mixed to give an NCC film having a reflection band intermediate between those obtained from the individual suspensions. The data suggest that the ultrasound-induced red-shift is electrostatic in nature.