Chiral Macromolecules Research Articles

Angle-Resolved Linear Dichroism to Probe the Organization of Highly Ordered Collagen Biomaterials.

Controlling the assembly of high-order structures is central to soft-matter and biomaterial engineering. Angle-resolved linear dichroism can probe the ordering of chiral collagen molecules in the dense state. Collagen triple helices were aligned by solvent evaporation. Their ordering gives a strong linear dichroism (LD) that changes sign and intensity with varying sample orientations with respect to the beam linear polarization. Being complementary to circular dichroism, which probes the structure of chiral (bio)molecules, LD can shift from the molecular to the supramolecular scale and from the investigation of the conformation to interactions. Supported by multiphoton microscopy and X-ray scattering, we show that LD provides a straightforward route to probe collagen alignment, determine the packing density, and monitor denaturation. This approach could be adapted to any assembly of chiral (bio)macromolecules, with key advantages in detecting large-scale assemblies with high specificity to aligned and chiral molecules and improved sensitivity compared to conventional techniques.

Coordination recognition of differential template units of lanthanide chiral chain.

Coordination-driven self-assembly processes often produce remarkable structures. In particular, self-assembly processes mediated by chiral template units have provided research ideas for analyzing the formation of chiral macromolecules in living organisms. In this study, by regulating the proportion of reaction raw materials in the "one-pot" synthesis of lanthanide complexes, we constructed chiral template units with different coordination orientations. As a result, lanthanide chiral chains connected to different structures were obtained through the self-assembly process of coordination recognition. In particular, driven by coordination, chiral template units with codirectional coordination points (called cis configuration) coordinate solely with cis template units during the self-assembly process to obtain a one-dimensional (1D) chain R-1/S-1 with an "S"-shaped distribution. Moreover, chiral template units with reversed coordination sites (called trans configuration) and twisted chiral template units are connected solely to templates with the same configuration to form a 1D chain R-2/S-2 with an axial helix. A circular dichroism spectrum shows that R-1/S-1 and R-2/S-2 are two pairs of enantiomers. The controllable construction of these two differential 1D chains is of great significance for studying coordination recognition at the molecular level. To the best of our knowledge, this is the first study to construct a 1D lanthanide chain through the self-assembly process of coordination recognition. The assembly process of nucleotides to form a hierarchical structure is simulated. This work provides a vivid example of the controllable synthesis of lanthanide complexes with precise structures and offers a new perspective on the formation process of chiral macromolecules that simulates natural processes.

Cellulose assembles into helical bundles of uniform handedness in cell walls with abnormal pectin composition.

Plant cells and organs grow into a remarkable diversity of shapes, as directed by cell walls composed primarily of polysaccharides such as cellulose and multiple structurally distinct pectins. The properties of the cell wall that allow for precise control of morphogenesis are distinct from those of the individual polysaccharide components. For example, cellulose, the primary determinant of cell morphology, is a chiral macromolecule that can self-assemble in vitro into larger-scale structures of consistent chirality, and yet most plant cells do not display consistent chirality in their growth. One interesting exception is the Arabidopsis thaliana rhm1 mutant, which has decreased levels of the pectin rhamnogalacturonan-I and causes conical petal epidermal cells to grow with a left-handed helical twist. Here, we show that in rhm1 the cellulose is bundled into large macrofibrils, unlike the evenly distributed microfibrils of the wild type. This cellulose bundling becomes increasingly severe over time, consistent with cellulose being synthesized normally and then self-associating into macrofibrils. We also show that in the wild type, cellulose is oriented transversely, whereas in rhm1 mutants, the cellulose forms right-handed helices that can account for the helical morphology of the petal cells. Our results indicate that when the composition of pectin is altered, cellulose can form cellular-scale chiral structures in vivo, analogous to the helicoids formed in vitro by cellulose nano-crystals. We propose that an important emergent property of the interplay between rhamnogalacturonan-I and cellulose is to permit the assembly of nonbundled cellulose structures, providing plants flexibility to orient cellulose and direct morphogenesis.

Chiral metallic anticancer drugs: A brief-review

Chiral metallic drugs are becoming the hottest point of discussion in the field of medicinal chemistry. As we know that more than 80% drugs are chiral in nature, and prescribed in the racemic form. The main problem with chiral drugs is the different biological activities of different enantiomers. This is because the human body has a chiral environment, as there is the presence of protein, carbohydrates, enzymes, and other chiral macromolecules. Hence, if a chiral anticancer drug is being prescribed to the patient in the racemic form, it means two or more drugs are being prescribed. Therefore, the chiral separation and analysis of chiral anticancer drugs are important for improving the quality of chiral drug medication. Many metal complexes are used as anticancer drugs, but the conditions become more critical if they have chirality or a chiral moiety, because of which they exist in two or more forms. Because of the presence of chirality or chiral moiety, the complex of metals is termed a chiral metallic complex. Of course, the enantioseparation of the chiral metallic complexes must be done before their prescription. Enantioseparation of the chiral metallic complex will not only provide a pharmaceutically active form to the patient but also reduce the side effects caused by the racemic mixture. Hence, the accessible article reviews the chiral metallic complexes having ruthenium, osmium, palladium, gold, silver, and platinum, etc. as central metal atoms. Besides, the future perspectives regarding the chiral metallic anticancer drugs and the role of their enantioseparation are also discussed.

Chirality Transfer from Polylactide to Achiral Fluorophore in Hierarchical Crystallization for Realizing Handedness-Tunable and Nonreciprocal Circularly Polarized Luminescence

Realizing chiral crystals from achiral compounds is an important but challenging issue. Here, a kebab-structured chiral supra-crystallization complex is constructed in accomplishing hierarchical chiral crystallization of achiral fluorescent compound (1,8-naphthalic anhydride, NA) employing synthetic chiral macromolecules (polylactide, PLA) as a template. Chirality transfer efficiently takes place from PLA to NA crystal during the co-crystallization process, endowing the initial achiral NA crystal with intense optical activity. More importantly, the obtained chiral supra-crystals show remarkable circularly polarized luminescence (CPL) properties, with the highest luminescence dissymmetric factor up to 5 × 10–2. Moreover, handedness-tunable and nonreciprocal CPL emissions are further realized in one single sample by simply flipping and rotating the supra-crystallization composite film, following a polarization mechanism. The work presents the first polymer-based hierarchical chiral supra-crystal with switchable CPL emissions and provides a simple and universal strategy for constructing nonreciprocal CPL materials.

Simulation of the Chiral Sum Frequency Generation Response of Supramolecular Structures Requires Vibrational Couplings.

Chiral vibrational sum frequency generation (SFG) spectroscopy probes the structure of the solvation shell around chiral macromolecules. The dominant theoretical framework for understanding the origin of chiral SFG signals is based on the analysis of molecular symmetry, which assumes no interaction between molecules. However, water contains strong intermolecular interactions that significantly affect its properties. Here, the role of intermolecular vibrational coupling in the chiral SFG response of the O-H stretch of water surrounding an antiparallel β-sheet at the vacuum-water interface is investigated. Both intramolecular and intermolecular couplings between O-H groups are required to simulate the full lineshape of the chiral SFG signal. This dependence is also observed for a chiral water dimer, illustrating that this phenomenon is not specific to larger systems. We also find that a dimer of C3v molecules predicted to be chirally SFG-inactive by the symmetry-based theory can generate a chiral SFG signal when intermolecular couplings are considered, suggesting that even highly symmetric solvent molecules may produce chiral SFG signals when interacting with a chiral solute. The consideration of intermolecular couplings extends the prevailing theory of the chiral SFG response to structures larger than individual molecules and provides guidelines for future modeling.

Adaptive Chirality of an Achiral Cucurbit[8]uril‐Based Supramolecular Organic Framework for Chirality Induction in Water

AbstractChiral framework materials have been developed for many applications including chiral recognition, chiral separation, asymmetric catalysis, and chiroptical materials. Herein, we report that an achiral cucurbit[8]uril‐based supramolecular organic framework (SOF‐1) with the dynamic rotational conformation of tetraphenylethene units can exhibit adaptive chirality to produce M‐SOF‐1 or P‐SOF‐1 with mirror‐image circular dichroism (CD) with gabs≈±10−4 and circularly polarized luminescence (CPL) with glum≈±10−4 induced by L‐/D‐phenylalanine in water, respectively. The chirality induction in CD (gabs≈−10−4) and CPL (glum≈−10−4) of P‐SOF‐1 from achiral SOF‐1 can be presented by using a small amount of adenosine‐5′‐triphosphate disodium (ATP) or adenosine‐5′‐diphosphate disodium (ADP) (only 0.4 equiv) in water. Furthermore, the adaptive chirality of SOF‐1 can be used to determine dipeptide sequences (e.g., Phe‐Ala and Ala‐Phe) and distinguish polypeptides/proteins (e.g., somatostatin and human insulin) with characteristic CD spectra. Therefore, achiral SOF‐1 as an ideal chiroptical platform with adaptive chirality may be applied to determine the enantiopurity of amino acids (e.g., L‐/D‐phenylalanine), develop aqueous CPL materials, and distinguish biological chiral macromolecules (e.g., peptides/proteins) via chirality induction in water.

Adaptive Chirality of an Achiral Cucurbit[8]uril-Based Supramolecular Organic Framework for Chirality Induction in Water.

Chiral framework materials have been developed for many applications including chiral recognition, chiral separation, asymmetric catalysis, and chiroptical materials. Herein, we report that an achiral cucurbit[8]uril-based supramolecular organic framework (SOF-1) with the dynamic rotational conformation of tetraphenylethene units can exhibit adaptive chirality to produce M-SOF-1 or P-SOF-1 with mirror-image circular dichroism (CD) with gabs ≈±10-4 and circularly polarized luminescence (CPL) with glum ≈±10-4 induced by L-/D-phenylalanine in water, respectively. The chirality induction in CD (gabs ≈-10-4 ) and CPL (glum ≈-10-4 ) of P-SOF-1 from achiral SOF-1 can be presented by using a small amount of adenosine-5'-triphosphate disodium (ATP) or adenosine-5'-diphosphate disodium (ADP) (only 0.4 equiv) in water. Furthermore, the adaptive chirality of SOF-1 can be used to determine dipeptide sequences (e.g., Phe-Ala and Ala-Phe) and distinguish polypeptides/proteins (e.g., somatostatin and human insulin) with characteristic CD spectra. Therefore, achiral SOF-1 as an ideal chiroptical platform with adaptive chirality may be applied to determine the enantiopurity of amino acids (e.g., L-/D-phenylalanine), develop aqueous CPL materials, and distinguish biological chiral macromolecules (e.g., peptides/proteins) via chirality induction in water.

Optically Active Polymers with Cationic Units Connected through Neutral Spacers: Helical Conformation and Chirality Transfer to External Molecules

Cationic chiral polymers consisting of a chiral “Arg monomeric unit” consisting of two l-arginine moieties joined together through an oxyhexane-1,6-diyloxy spacer unit and achiral “Sp monomeric unit” based on the spermine moiety where the two units are connected through a 1,4-dioxobutane-1,4-diyl spacer unit (“C2 monomeric unit”) were prepared in the cationic form as a salt of p-toluenesulfonic acid. Polymer conformation could not be directly deduced from circular dichroism (CD) spectra based on the amide group bands (200–240 nm), which are generally used to quantify α-helical, β-sheet, and random coil residues because of spectral overlapping with the p-toluenesulfonate bands. On the other hand, a helical conformation was proposed on the basis of the relation between CD intensity and Arg monomeric unit ratio of polymers, while the proposed conformation may not be highly ordered but rather fragmented and partial. The helix-forming propensity of a polymer consisting of a higher Arg monomeric unit ratio was supported by MD simulations in water and in vacuum. The copolymer consisting of 100% Arg monomeric units [poly(Arg100-C2)], the one consisting of 42% Arg monomeric units and 58% Sp monomeric units [poly(Arg50-C2–Sp50-C2)], and the one consisting of 20% Arg monomeric units and 80% Sp monomeric units [poly(Arg25-C2–Sp75-C2)] exhibited chirality transfer to methyl orange (MO), where transfer was most efficient with poly(Arg50-C2–Sp50-C2). Chirality transfer efficiency also remarkably varied depending on the standing time of polymer solution in H2O before it is mixed with MO, the time after mixing, and the concentration of the polymer. Theoretical calculations of absorbance and CD spectra of polymer–MO complexes suggested that the induced CD spectra mostly having bisignet spectral patterns are not based on exciton coupling between two MO molecules bound to the polymer chain but are composed of independent excitation bands. The design of chiral macromolecules introduced in this work based on a chain composed of charged chiral and achiral units separated by neutral achiral linker (spacer) units has not been studied from a view of chiral polymeric materials. Such a design of polymer chain may be applicable to a wider variety of chemical structures and will largely widen the scope of optically active polymers with helical conformation.

Use of a Stereochemical Strategy To Probe the Mechanism of Phenol-Soluble Modulin α3 Toxicity.

Phenol-soluble modulin α3 (PSMα3) is a cytotoxic peptide secreted by virulent strains of Staphylococcus aureus. We used a stereochemical strategy to examine the mechanism of PSMα3-mediated toxicity. One hypothesis is that PSMα3 toxicity requires fibril formation; an alternative is that toxicity is caused by soluble forms of PSMα3, possibly oligomeric. We find that the unnatural enantiomer (D residues) displays cytotoxicity comparable to that of L-PSMα3. Racemic PSMα3 is similarly toxic to enantiopure PSMα3 (L or D) under some conditions, but the toxicity is lost under conditions that cause racemic PSMα3 to aggregate. A crystal structure of racemic PSMα3-NH2 displays an α-helical secondary structure and a packing pattern that is reminiscent of the cross-α arrangement recently discovered in crystals of L-PSMα3. Our data suggest that the cytotoxicity of PSMα3 does not depend on stereospecific engagement of a target protein or other chiral macromolecule, an observation that supports a mechanism based on membrane disruption. In addition, our data support the hypothesis that toxicity is exerted by a soluble form rather than an insoluble fibrillar form.

Chiral analysis of macromolecules

Around us, we have many chiral macromolecules such as protein, carbohydrate, nucleic acid, steroids, peptides and phospholipids. Hence, these compounds exist in enantiomeric forms and we know that only one of the enantiomeric forms is important to us and another may or may not be useful. Therefore, chiral analysis of macromolecules has taken a unique place in analytical chemistry. The chiral separation of such macromolecules by analytical techniques is very difficult so only few papers were found in the literature, which has been discussed in this chapter. The presented chapter describes chiral analysis of macromolecule only by two analytical techniques i.e. high performance liquid chromatography and capillary electrophoresis. Besides, the efforts were made to discuss the future perspective regarding enantio-separation of such chiral macromolecules.

Structure elucidation of the Pribnow box consensus promoter sequence by racemic DNA crystallography.

It has previously been shown that the use of racemic mixtures of naturally chiral macromolecules such as protein and DNA can significantly aid the crystallogenesis process, thereby addressing one of the major bottlenecks to structure determination by X-ray crystallographic methods—that of crystal growth. Although previous studies have provided convincing evidence of the applicability of the racemic crystallization technique to DNA through the study of well-characterized DNA structures, we sought to apply this method to a historically challenging DNA sequence. For this purpose we chose a non-self-complementary DNA duplex containing the biologically-relevant Pribnow box consensus sequence ‘TATAAT’. Four racemic crystal structures of this previously un-crystallizable DNA target are reported (with resolutions in the range of 1.65–2.3 Å), with further crystallographic studies and structural analysis providing insight into the racemic crystallization process as well as structural details of this highly pertinent DNA sequence.

Communication: Probing the absolute configuration of chiral molecules at aqueous interfaces.

We demonstrate that the enantiomers of chiral macromolecules at an aqueous interface can be distinguished with monolayer sensitivity using heterodyne-detected vibrational sum-frequency generation (VSFG). We perform VSFG spectroscopy with a polarization combination that selectively probes chiral molecular structures. By using frequencies far detuned from electronic resonances, we probe the chiral macromolecular structures with high surface specificity. The phase of the sum-frequency light generated by the chiral molecules is determined using heterodyne detection. With this approach, we can distinguish right-handed and left-handed helical peptides at a water-air interface. We thus show that heterodyne-detected VSFG is sensitive to the absolute configuration of complex, interfacial macromolecules and has the potential to determine the absolute configuration of enantiomers at interfaces.

Turning Cucurbit[8]uril into a Supramolecular Nanoreactor for Asymmetric Catalysis.

Chiral macromolecules have been widely used as synthetic pockets to mimic natural enzymes and promote asymmetric reactions. An achiral host, cucurbit[8]uril (CB[8]), was used for an asymmetric Lewis acid catalyzed Diels–Alder reaction. We achieved a remarkable increase in enantioselectivity and a large rate acceleration in the presence of the nanoreactor by using an amino acid as the chiral source. Mechanistic and computational studies revealed that both the amino acid–Cu2+ complex and the dienophile substrate are included inside the macrocyclic host cavity, suggesting that contiguity and conformational constraints are fundamental to the catalytic process and rate enhancement. These results pave the way towards new studies on asymmetric reactions catalyzed in confined achiral cavities.

Turning Cucurbit[8]uril into a Supramolecular Nanoreactor for Asymmetric Catalysis.

Chiral macromolecules have been widely used as synthetic pockets to mimic natural enzymes and promote asymmetric reactions. An achiral host, cucurbit[8]uril (CB[8]), was used for an asymmetric Lewis acid catalyzed Diels–Alder reaction. We achieved a remarkable increase in enantioselectivity and a large rate acceleration in the presence of the nanoreactor by using an amino acid as the chiral source. Mechanistic and computational studies revealed that both the amino acid–Cu2+ complex and the dienophile substrate are included inside the macrocyclic host cavity, suggesting that contiguity and conformational constraints are fundamental to the catalytic process and rate enhancement. These results pave the way towards new studies on asymmetric reactions catalyzed in confined achiral cavities.

Silica biomineralization via the self-assembly of helical biomolecules.

The biomimetic synthesis of relevant silica materials using biological macromolecules as templates via silica biomineralization processes attract rapidly rising attention toward natural and artificial materials. Biomimetic synthesis studies are useful for improving the understanding of the formation mechanism of the hierarchical structures found in living organisms (such as diatoms and sponges) and for promoting significant developments in the biotechnology, nanotechnology and materials chemistry fields. Chirality is a ubiquitous phenomenon in nature and is an inherent feature of biomolecular components in organisms. Helical biomolecules, one of the most important types of chiral macromolecules, can self-assemble into multiple liquid-crystal structures and be used as biotemplates for silica biomineralization, which renders them particularly useful for fabricating complex silica materials under ambient conditions. Over the past two decades, many new silica materials with hierarchical structures and complex morphologies have been created using helical biomolecules. In this review, the developments in this field are described and the recent progress in silica biomineralization templating using several classes of helical biomolecules, including DNA, polypeptides, cellulose and rod-like viruses is summarized. Particular focus is placed on the formation mechanism of biomolecule-silica materials (BSMs) with hierarchical structures. Finally, current research challenges and future developments are discussed in the conclusion.

Cooperative self-assembly of peptide gelators and proteins.

Molecular self-assembly provides a versatile route for the production of nanoscale materials for medical and technological applications. Herein, we demonstrate that the cooperative self-assembly of amphiphilic small molecules and proteins can have drastic effects on supramolecular nanostructuring of resulting materials. We report that mesoscale, fractal-like clusters of proteins form at concentrations that are orders of magnitude lower compared to those usually associated with molecular crowding at room temperature. These protein clusters have pronounced effects on the molecular self-assembly of aromatic peptide amphiphiles (fluorenylmethoxycarbonyl- dipeptides), resulting in a reversal of chiral organization and enhanced order through templating and binding. Moreover, the morphological and mechanical properties of the resultant nanostructured gels can be controlled by the cooperative self-assembly of peptides and protein fractal clusters, having implications for biomedical applications where proteins and peptides are both present. In addition, fundamental insights into cooperative interplay of molecular interactions and confinement by clusters of chiral macromolecules is relevant to gaining understanding of the molecular mechanisms of relevance to the origin of life and development of synthetic mimics of living systems.

Novel, thermally stable and chiral poly(amide-imide)s derived from a new diamine containing pyridine ring and various amino acid-based diacids

In this investigation, several novel optically active and potentially biodegradable poly(amide-imide)s were synthesized through direct polycondensation reaction. First, a new aromatic diamine compound including pyridine ring was synthesized, which was reacted with diimide dicarboxylic acids containing different natural amino acids such as l-alanine, l-leucine, l-isoleucine and l-methionine under green condition, using molten tetrabutylammonium bromide. These new chiral macromolecules were characterized using Fourier transform infrared spectroscopy, proton and carbon nuclear magnetic resonance, field emission scanning electron microscopy (FE-SEM), x-ray diffraction (XRD) and elemental and thermogravimetric analysis techniques. They show high solubility in polar organic solvents, such as N, N′-dimethylacetamide, N-methyl-2-pyrrolidone and dimethyl sulfoxide at room temperature. XRD and FE-SEM studies show that all the obtained polymers exhibit noncrystalline and nanostructure morphology. Due to the existence of amino acids in their structures, these polymers can show a potential biodegradability and biocompatibility behavior.

Biomimetic self-templating supramolecular structures

In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.

ChemInform Abstract: Chiral Conducting Polymers

AbstractReview: 153 refs.