Molecular Asymmetry Research Articles

Amplification of Molecular Asymmetry during the Hierarchical Self-Assembly of Foldable Azobenzene Dyads into Nanotoroids and Nanotubes.

The amplification of molecular asymmetry through self-assembly is a phenomenon that not only comprehends the origin of homochirality in nature but also produces chiroptically active functional materials from molecules with minimal enantiomeric purity. Understanding how molecular asymmetry can be transferred and amplified into higher-order structures in a hierarchical self-assembly system is important but still unexplored. Herein, we present an intriguing example of the amplification of molecular asymmetry in hierarchically self-assembled nanotubes that feature discrete and isolatable toroidal intermediates. The hierarchical self-assembly is initiated via asymmetric intramolecular folding of scissor-shaped azobenzene dyads furnished with chiral side chains. When scalemic mixtures of the enantiomers are dissolved in a non-polar solvent and cooled to 20 °C, single-handed nanotoroids are formed, as confirmed using atomic force microscopy and circular dichroism analyses. A strong majority-rules effect at the nanotoroid level is observed and can be explained by a low mismatch penalty and a high helix-reversal penalty. The single-handed nanotoroids stack upon cooling to 0 °C to exclusively afford their respective single-handed nanotubes. Thus, the same degree of amplification of molecular asymmetry is realized at the nanotube level. The internal packing efficiency of molecules within nanotubes prepared from the pure enantiomers or their scalemic mixtures is likely different, as suggested by the absence of higher-order structure (supercoil) formation in the latter. X-ray diffraction analysis of the anisotropically oriented nanotube films revealed looser molecular packing within the scalemic nanotubes, which clearly reflects the lower enantiomeric purity of their internal chiral side chains.

Parameter-free retrieval of subcycle asymmetry of polar molecules by high-order harmonic spectroscopy

Retrieving atomic and molecular properties from entangling macroscopic measurements is an ambitious task. In particular, the phase difference between the adjacent attosecond bursts emitted from polar molecules is of interest and has been reconstructed from measured high-order harmonic generation (HHG) when molecules are exposed to an intense laser pulse. However, besides the ratio of intensities between the even and odd harmonic orders which can be measured directly, the suggested construction method requires nonmeasured parameters that can be supplied through theoretical calculations. The complexity or comprehensiveness of this theory clearly affects the accuracy of the retrieval procedure. In this study we propose a robust parameter-free method to retrieve the subtle molecular asymmetry, i.e., both the spectral phase difference and intensity ratio of two adjacent attosecond bursts, from purely experimental measurements of HHG. For this purpose, we first figure out that the phase difference is an intrinsic feature of polar molecules, almost independent of the external laser's parameters. After that, we design a detailed procedure to quantitatively extract these features via the time-frequency profile from the intensity and phase measurements of HHG emitted from partially oriented molecular samples. In this step, we develop the analytical formula to convert the phase difference and intensity ratio of a partially oriented sample to those of a single molecule. The accuracy and robustness of the methods are validated by numerical data.

Molecular asymmetry of a photosynthetic supercomplex from green sulfur bacteria

The photochemical reaction center (RC) features a dimeric architecture for charge separation across the membrane. In green sulfur bacteria (GSB), the trimeric Fenna-Matthews-Olson (FMO) complex mediates the transfer of light energy from the chlorosome antenna complex to the RC. Here we determine the structure of the photosynthetic supercomplex from the GSB Chlorobaculum tepidum using single-particle cryogenic electron microscopy (cryo-EM) and identify the cytochrome c subunit (PscC), two accessory protein subunits (PscE and PscF), a second FMO trimeric complex, and a linker pigment between FMO and the RC core. The protein subunits that are assembled with the symmetric RC core generate an asymmetric photosynthetic supercomplex. One linker bacteriochlorophyll (BChl) is located in one of the two FMO-PscA interfaces, leading to differential efficiencies of the two energy transfer branches. The two FMO trimeric complexes establish two different binding interfaces with the RC cytoplasmic surface, driven by the associated accessory subunits. This structure of the GSB photosynthetic supercomplex provides mechanistic insight into the light excitation energy transfer routes and a possible evolutionary transition intermediate of the bacterial photosynthetic supercomplex from the primitive homodimeric RC.

Achieving 19% Power Conversion Efficiency in Planar-Mixed Heterojunction Organic Solar Cells Using a Pseudosymmetric Electron Acceptor.

A record power conversion efficiency (PCE) of over 19% is realized in planar-mixed heterojunction (PMHJ) organic solar cells (OSCs) by adopting the asymmetric selenium substitution strategy in making a pseudosymmetric electron acceptor, BS3TSe-4F. The combined molecular asymmetry with more polarizable selenium substitution increases the dielectric constant of the D18/BS3TSe-4F blend, helping lower the exciton binding energy. On the other hand, dimer packing in BS3TSe-4F is facilitated to enable free charge generation, helping more efficient exciton dissociation and lowering the radiative recombination loss (ΔE2 ) of OSCs. As a result, PMHJ OSCs based on D18/BS3TSe-4F achieve a PCE of 18.48%. By incorporating another mid-bandgap acceptor Y6-O into D18/BS3TSe-4F to form a ternary PMHJ, a higher open-circuit voltage (VOC ) can be achieved to realize an impressive PCE of 19.03%. The findings of using pseudosymmetric electron acceptors in enhancing device efficiency provides an effective way to develop highly efficient acceptor materials for OSCs.

Луи Пастьор (1822 – 1895) – химикът. По повод 200 години от рождението му

The article is dedicated to the 200-year anniversary of the great Louis Pasteur and aims to represent his work focusing on his less famous contributions as a chemist. By examining his accomplishments in the historical context of chemistry’s development – isomerism (between Berzelius and Van’t Hoff) and theory of fermentation (between Liebig and Berthelot). Based on his research on optically active substances (mainly tartaric acid and its salts) he distinguishes optical activity caused by crystal structure and molecular asymmetry, hypothesizes that the way atoms are positioned in a molecule is the cause for optical activity, defining a new form of isomerism thus paving the way for stereochemistry. The later scientific achievements of Pasteur are related to him entering the world of microorganisms – fermentation, disproving the theory of spontaneous generation, clarifying the origin and prevention of infectious diseases. It is emphasized that he is a scientist who takes his work out of the laboratory and ‘into the world’: examining the diseases of the silk worm, difficulties in brewing, wine and vinegar production. He communicates with people affected by the problem, exchanges knowledge and experience with them, offers advice, includes them in his search for solutions. Generally describing his work as a physicochemist, biochemist, microbiologist, immunologist and his personality with emphasis on his morality as a scientist. He is a patriot, citizen, humanist and a true benefactor of humanity.

Impact of Molecular Symmetry/Asymmetry on Insulin-Sensitizing Treatments for Type 2 Diabetes

Although the advantages and disadvantages of asymmetrical thiazolidinediones as insulin-sensitizers have been well-studied, the relevance of symmetry and asymmetry for thiazolidinediones and biguanides has scarcely been explored. Regarding symmetrical molecules, only one thiazolidinedione and no biguanides have been evaluated and proposed as an antihyperglycemic agent for treating type 2 diabetes. Since molecular structure defines physicochemical, pharmacological, and toxicological properties, it is important to gain greater insights into poorly investigated patterns. For example, compounds with intrinsic antioxidant properties commonly have low toxicity. Additionally, the molecular symmetry and asymmetry of ligands are each associated with affinity for certain types of receptors. An advantageous response obtained in one therapeutic application may imply a poor or even adverse effect in another. Within the context of general patterns, each compound must be assessed individually. The current review aimed to summarize the available evidence for the advantages and disadvantages of utilizing symmetrical and asymmetrical thiazolidinediones and biguanides as insulin sensitizers in patients with type 2 diabetes. Other applications of these same compounds are also examined as well as the various uses of additional symmetrical molecules. More research is needed to exploit the potential of symmetrical molecules as insulin sensitizers.

Liquid chromatographic enantioseparation, determination, bioassay and isolation of enantiomers of Ketorolac: A review

Abstract Ketorolac (Ket) is a potent non-narcotic analgesic drug (among the nonsteroidal anti-inflammatory drugs). The physiological activity of Ket resides with (S)-(−)-Ket while the drug is marketed and administered as a racemic mixture. Therefore, it is desirable that the pharmacokinetics is measured and quantified for enantiomers individually and not as a total drug. The present paper is focused on relevant literature on LC enantioseparation of (RS)-Ket along with bioassay, pharmacokinetic and clinical studies within the discipline of analytical chemistry. HPLC and Thin layer chromatography (TLC) methods using both direct and indirect approaches are discussed. The methods provide chirality recognition even in the absence of pure enantiomers. Besides, a brief discussion on resolution by crystallization and enzymatic methods is included. The most interesting aspects include establishment of structure and molecular asymmetry of diastereomeric derivatives using LC-MS, proton nuclear magnetic resonance spectrometry, and by drawing conformations in three dimensional views by using certain software. A brief discussion has also been provided on the recovery of native enantiomers by TLC.

Quantum phonon transport through channels and molecules—A Perspective

Phonon transport is a dominant mechanism of thermal conduction in solids that has been studied for decades. A good understanding of many transport regimes in micro- and nanostructures has been established, including ballistic and diffusive transport, mode softening, or band structure engineering in phononic crystals. However, the limit of quantized transport and the engineering of single transport channels is much less explored. In this Perspective, we discuss concepts and theoretical and experimental progress in the field of quantized phonon transport in channels, such as molecular systems. We particularly highlight open questions and research opportunities that should be within experimental reach. Challenges in experimental sensitivity and control hinder fast experimental progress. Recently, however, heat transport measurements through quantum channels and single molecules have become available at room temperature using break junction techniques. These techniques are well established in the molecular electronics community and have recently been expanded to the measurement of heat transport on the single-molecule level. Given the new experimental capabilities, it is now inviting to address the rather unexplored area of molecular phonon-engineering. Several interesting theoretical predictions concern the realization of the phonon quantum interference effect, suppression of phonon current via the introduction of side groups to molecules, and the construction of a phonon diode device based on molecular anharmonicity and asymmetry. This Perspective should serve the experimental and theory community by listing key challenges, thus a roadmap for making progress in the field of quantized phonon transport.

Effect of Molecular Architecture and Symmetry on Self-Assembly: A Quantitative Revisit Using Discrete ABA Triblock Copolymers.

The inherent statistical heterogeneities associated with chain length, composition, and architecture of synthetic block copolymers compromise the quantitative interpretation of their self-assembly process. This study scrutinizes the contribution of molecular architecture on phase behaviors using discrete ABA triblock copolymers with precise chemical structure and uniform chain length. A group of discrete triblock copolymers with varying composition and symmetry were modularly synthesized through a combination of iterative growth methods and efficient coupling reactions. The symmetric ABA triblock copolymers self-assemble into long-range ordered structures with expanded domain spacings and enhanced phase stability, compared with the diblock counterparts snipped at the middle point. By tuning the relative chain length of two end blocks, the molecular asymmetry reduces the packing frustration, and thus increases the order-to-disorder transition temperature and enlarges the domain sizes. This study would serve as a quantitative model system to correlate the experimental observations with the theoretical assessments and to provide quantitative understandings for the relationship between molecular architecture and self-assembly.

Gradients of PI(4,5)P2 and PI(3,5)P2 Jointly Participate in Shaping the Back State of Dictyostelium Cells.

Polarity, which refers to the molecular or structural asymmetry in cells, is essential for diverse cellular functions. Dictyostelium has proven to be a valuable system for dissecting the molecular mechanisms of cell polarity. Previous studies in Dictyostelium have revealed a range of signaling and cytoskeletal proteins that function at the leading edge to promote pseudopod extension and migration. In contrast, how proteins are localized to the trailing edge is not well understood. By screening for asymmetrically localized proteins, we identified a novel trailing-edge protein we named Teep1. We show that a charged surface formed by two pleckstrin homology (PH) domains in Teep1 is necessary and sufficient for targeting it to the rear of cells. Combining biochemical and imaging analyses, we demonstrate that Teep1 interacts preferentially with PI(4,5)P2 and PI(3,5)P2 in vitro and simultaneous elimination of these lipid species in cells blocks the membrane association of Teep1. Furthermore, a leading-edge localized myotubularin phosphatase likely mediates the removal of PI(3,5)P2 from the front, as well as the formation of a back-to-front gradient of PI(3,5)P2. Together our data indicate that PI(4,5)P2 and PI(3,5)P2 on the plasma membrane jointly participate in shaping the back state of Dictyostelium cells.

Surfaces Decorated with Enantiomorphically Pure Polymer Nanohelices via Hierarchical Chirality Transfer across Multiple Length Scales.

Mesoscale chiral materials are prepared by lithographic methods, assembly of chiral building blocks, and through syntheses in the presence of polarized light. Typically, these processes result in micrometer-sized structures, require complex top-down manipulation, or rely on tedious asymmetric separation. Chemical vapor deposition (CVD) polymerization of chiral precursors into supported films of liquid crystals (LCs) are discovered to result in superhierarchical arrangements of enantiomorphically pure nanofibers. Depending on the molecular chirality of the 1-hydroxyethyl [2.2]paracyclophane precursor, extended arrays of enantiomorphic nanohelices are formed from achiral nematic templates. Arrays of chiral nanohelices extend over hundreds of micrometers and consistently display enantiomorphic micropatterns. The pitch of individual nanohelices depends on the enantiomeric excess and the purity of the chiral precursor, consistent with the theoretical model of a doubly twisted LC director configuration. During CVD of chiral precursors into cholesteric LC films, aspects of molecular and mesoscale asymmetry combine constructively to form regularly twisted nanohelices. Enantiomorphic surfaces permit the tailoring of a wide range of functional properties, such as the asymmetric induction of weak chiral systems.

Swelling of asymmetric pom-pom polymers in dilute solutions

In this paper we continue our recent analysis [K. Haydukivska et al., J. Mol. Liq., 2021, 328, 115456] of complex molecules with two branching points at both ends of the linear backbone with f1 and f2 side arms starting from them, known as the pom-pom polymers. Here, we analyze the asymmetric case, f1 ≠ f2, by applying both the analytical approach, based on the direct polymer renormalization, and computer simulations using both dissipative particle dynamics and Monte Carlo methods. We study the role played by the molecular asymmetry of average polymer conformations, considering the infinite dilution regime and good solvent conditions.The quantitative estimates are reported for the set of universal size and shape characteristics of such molecules and for their individual branches, all the functions of f1 and f2. In particular, we evaluate the size ratio of the gyration radii of symmetric and asymmetric pom-pom topologies with the same molecular weight and quantitatively reveal an increase of the effective size of a molecule caused by its asymmetry. We also introduce and analyse the asymmetry factor and estimate the shift of the center of mass caused by the presence of side stars, which can serve as another characteristic of the asymmetry of pom-pom structure.

Engineering of inorganic nanostructures with hierarchy of chiral geometries at multiple scales

Engineering of inorganic nanostructures with hierarchy of chiral geometries at multiple scales

Impact of Molecular Asymmetry of Block Copolymers on the Stability of Defects in Aligned Lamellae

The stability of prototypical dislocation defects occurring in the ordered lamellar morphologies of block copolymers is of particular interest for both practical applications and fundamental research. Here, we study the impact of the segregation strength, compositional asymmetry, and architectural asymmetry on the evolution kinetics of single dislocation as well as the stability of its derivative disconnection defect occurring in the lamellar morphologies formed by AB diblock and AB2 miktoarm star copolymers using self-consistent field theory coupled with the string method and single-chain-in-mean-field simulations. Our results indicate that the segregation strength generally increases the stability of the two defects, whereas the two other factors of asymmetry lower the stability of the single dislocation and significantly enhance the stability of the single disconnection due to the effect of spontaneous curvature. In particular, the single disconnection becomes metastable and can survive for a long period at intermediate segregation and thus may be promisingly applicable for the fabrication of regularly broken lines.

Temporal Control over Two‐ and Three‐State Living Coordinative Chain Transfer Polymerization for Modulating the Molecular Weight Distribution Profile of Polyolefins

AbstractA highly versatile new strategy for manipulating the molecular weight profiles, including breadth, asymmetry (skewness) and modal nature (mono‐, bi‐, and multimodal), of a variety of different polyolefins is reported. It involves temporal control over two‐ and three‐state living coordinative chain transfer polymerization (LCCTP) of olefins in a programmable way. By changing the identity of the R′ groups of the chain transfer agent, ER′n, with time, different populations of chains within a bi‐ or multimodal polyolefin product can be selectively tagged with different end‐groups. By changing the nature of the main‐group metal of the CTA, programmed manipulation of the relative magnitudes of the dispersities of the different maxima that make up the final MWD profile can be achieved. This strategy can be implemented with existing LCCTP materials and conventional reactor methods to provide access to scalable and practical quantities of an unlimited array of new polyolefin materials.

Synthesis and Racemization Studies of Winding Vine‐Shaped Biphenyl Derivatives

AbstractWinding vine‐shaped biphenyl derivatives were synthesized through the annulation reaction of nosylated (2‐nitrobenzenesulfonyl) ethylenediamine and the E‐selective ring‐closing metathesis reaction. The structures of the cyclized products were confirmed by measurements of 1H and 13C NMR spectra and single crystal X‐ray analyses. The obtained cyclic product was revealed to exhibit molecular asymmetry, which was confirmed by HPLC analyses on chiral stationary phase. Compared with our previous results on the related bithiophene derivatives, the obtained vine‐shaped biphenyls were shown to hardly racemize under ambient conditions and experimental studies on racemization behaviors suggested energy barriers of 134 kJmol−1 to 211 kJmol−1. These results reasonably agreed with those of the calculated values based on DFT.

Recent Advances in Catalytic Asymmetric Construction of Atropisomers.

Atropisomerism is a stereochemical behavior portrayed by three-dimensional molecules that bear rotationally restricted σ bond. Akin to the well-represented point-chiral molecules, atropisomerically chiral compounds are finding increasing utilities in many disciplines where molecular asymmetry is influential. This provides steady demand on atroposelective synthesis, where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods while expanding the structural diversity of atropisomers. This review summarizes key achievements in stereoselective preparation of biaryl, heterobiaryl, and nonbiaryl atropisomers documented between 2015 and 2020. Emphasis is placed on the synthetic strategies for each structural class, while examples are cited to illustrate the potential applications of the accessed atropochiral targets.

Photodynamics of Asymmetric Di-Iron-Cyano Hydrogenases Examined by Time-Resolved Mid-Infrared Spectroscopy.

Two anionic asymmetric Fe-Fe hydrogenase model compounds containing a single cyano (CN) and five carboxyl (CO) ligands, [Et4N][Fe2(μ-S2C3H6)(CO)5(CN)1] and [Et4N][Fe2(μ-S2C2H4)(CO)5(CN)1], dissolved in room-temperature acetonitrile, are examined. The molecular asymmetry affects the redox potentials of the central iron atoms, thus changing the photophysics and possible catalytic properties of the compounds. Femtosecond ultraviolet excitation with mid-infrared probe spectroscopy of the model compounds was employed to better understand the ultrafast dynamics of the enzyme-active site. Continuous ultraviolet lamp excitation with Fourier transform infrared (FTIR) spectroscopy was also used to explore stable product formation on the second timescale. For both model compounds, two timescales are observed; a 20-30 ps decay and the formation of a long-lived photoproduct. The picosecond decay is assigned to vibrational cooling and rotational dynamics, while the residual spectra remain for up to 300 ps, suggesting the formation of new photoproducts. Static FTIR spectroscopy yielded a different stable photoproduct than that observed on the ultrafast timescale. Density functional theory calculations simulated photoproducts for CO-loss and CN-loss isomers, and the resulting photoproduct spectra suggest that the picosecond transients arise from a complex mixture of isomerization after CO-loss, while dimerization and formation of a CN-containing Fe-CO-Fe bridged species are also considered.

Absolute Stereochemical Determination of Organic Molecules through Induction of Helicity in Host-Guest Complexes.

Stereochemistry is a fundamental molecular property with important ramifications for structure, function, and activity of organic molecules. The basic building blocks of living organisms (amino acids and sugars) exhibit a precisely selected set of molecular handedness that has evolved over millions of years. The absolute stereochemistry of these building blocks is manifested in the structure and function of the cell machinery (e.g., enzymes, proteins, etc.), which are essential components of life. In the many chemical subdisciplines, molecular stereochemistry is exceedingly important and is often a strong determinant of structure and function. Besides its biological implications, the centrally important role of stereochemistry in many disciplines of chemistry and related fields has led to tremendous effort and activity, highlighted by the success in stereoselective syntheses of a host of functionalities. In the present climate, it is often the difficulty of assigning absolute stereochemistry as opposed to synthesis, which has become a nontrivial challenge, requiring the attention of the community. There will not be a general solution to this problem, as each system will have its own unique requirements and challenges; however, the need for rapid, routine, and microscale analysis is apparent. This is especially true with parallel and high-throughput arrays for screening conditions and catalysts, generating a large number of samples that require analysis.In this Account, we summarize our contribution to this field through the development of molecular receptors for sensing molecular asymmetry. These methodologies strive to unambiguously assign the absolute configuration of asymmetric center(s). To accomplish this task, our laboratory has designed a variety of host molecules, bearing various binding elements, to form stable complexes with chiral molecules (guests). During this complexation event, the stereochemistry of a target molecule induces a supramolecular chirality (i.e., helicity) within the host system. The design of the host system is such that the helicity of the host/guest complex can be observed and assigned via Exciton Coupled Circular Dichroism (ECCD), a nonempirical technique for identifying handedness, which is correlated back to the absolute stereochemistry of the bound chiral molecule. Taking advantage of the high sensitivity of chiroptical techniques (in terms of the required amount of sample for analysis) and fast response time, these methodologies offer a microscale, rapid, and nonempirical solution for assignment of absolute stereochemistry.The first part of this Account describes application of porphyrin tweezers as reporters of chirality for the absolute stereochemical determination of various classes of organic molecules. This methodology is suitable to report the absolute configuration of organic molecules that contain two binding elements (nitrogen or oxygen based functionalities). In the second part, host systems that do not require two sites of attachment to form ECCD active complexes will be described. This enables the absolute stereochemical assignment of challenging chiral molecules with functional groups lacking routine techniques for analysis.

Simplicity in mean-field phase behavior of two-component miktoarm star copolymers.

Using self-consistent field theory, we systematically explore the microphase separation in the class of two-component miktoarm star copolymers containing a single conjunction point between different blocks by considering an extended list of candidate microphases. We plot mean-field phase diagrams in the plane of segregation strength and composition for an array of representative star copolymers. Three principal phase diagram topologies, dictated by different phase stabilities, are exposed, displaying a hierarchy in complexity by increasing the molecular asymmetry. Our investigation indicates that the phase diagram topology depends on the ratios of arm numbers and Kuhn segment lengths, which highlights the role of the coordination number ratio between different polymers at the domain interface. These findings reveal the simplicity of the general phase behavior and suggest a complete list of stable microphases for the entire class, which provide useful insight into studying copolymers with more complicated architectures and conformational properties.