Transfer Of Chiral Information Research Articles

Prebiotic chiral transfer from self-aminoacylating ribozymes may favor either handedness

Modern life is essentially homochiral, containing D-sugars in nucleic acid backbones and L-amino acids in proteins. Since coded proteins are theorized to have developed from a prebiotic RNA World, the homochirality of L-amino acids observed in all known life presumably resulted from chiral transfer from a homochiral D-RNA World. This transfer would have been mediated by aminoacyl-RNAs defining the genetic code. Previous work on aminoacyl transfer using tRNA mimics has suggested that aminoacylation using D-RNA may be inherently biased toward reactivity with L-amino acids, implying a deterministic path from a D-RNA World to L-proteins. Using a model system of self-aminoacylating D-ribozymes and epimerizable activated amino acid analogs, we test the chiral selectivity of 15 ribozymes derived from an exhaustive search of sequence space. All of the ribozymes exhibit detectable selectivity, and a substantial fraction react preferentially to produce the D-enantiomer of the product. Furthermore, chiral preference is conserved within sequence families. These results are consistent with the transfer of chiral information from RNA to proteins but do not support an intrinsic bias of D-RNA for L-amino acids. Different aminoacylation structures result in different directions of chiral selectivity, such that L-proteins need not emerge from a D-RNA World.

Enantioselective synthesis of a two-fold inherently chiral molecular nanographene

AbstractThe introduction and precise control of stereogenic elements in chemical structures is typically a challenging task. Most asymmetric methods require the presence of a heteroatom in the starting substrates acting as an anchor point for the successful transfer of chiral information. For this reason, compounds comprising only carbon atoms, such as optically active molecular nanographenes, are usually obtained as racemates, and isolated by chiral chromatographic separation. Here, we report an enantioselective strategy that uses three stereocontrolled synthetic steps to introduce and extend three different types of stereogenic elements, namely central, axial and helicoidal chirality, into a polycyclic aromatic structure. Thus, two chiral nanographene layers are covalently connected through a chiral triindane core. The final stereocontrolled graphitization Scholl reaction affords the formation of chiral nanographene units with remarkable enantiomeric excesses, high stereochemical stability and good chiroptical properties.

(Invited) Stereoselective Synthesis of Molecular Nanographenes

The precise control of stereogenic elements in chemical structures has always been a higly demanding synthetic task.1 In this regard, most of the currently available asymmetric methods require the presence of a heteroatom in the starting substrates that serves as an anchoring point for the successful transfer of chiral information. This eventually emerges, typically, in the form of a new stereogenic centre while the heteroatom remains in the product. This general procedure could account for the lack of stereoselective protocols in all-carbon atom compounds.2,3 Actually, optically active nanographenes have so far been obtained only by either top-down or bottom-up racemic syntheses, followed by time consuming chiral chromatographic separations.4-6 In this presentation, we will introduce a general overview on the efforts carried out in our group in the search for stereoselectivity to introduce and extend stereogenic elements into polyaromatic sp2 carbon-based molecular nanographenes. Acknowledgements The author acknowledge support from the MICIN of Spain (project: PID2020-114653RB-I00) and the European Research Council (ERC) Synergy Grant “TOMATTO” (Project 951224). References H. Kuang, C. Xu, Z. Tang, “Emerging Chiral Materials”, Adv. Mater. 2020, 32, e2005110.M. Rickhaus, M. Mayor, M. Juricek, “Strain-induced helical chirality in polyaromatic systems”, Chem. Soc. Rev. 2016, 45, 1542-1556.J. M. Fernández-García, P. Izquierdo-Garcia, M. Buendia, S. Filippone, N. Martín, “Synthetic chiral molecular nanographenes: the key figure of the racemization barrier”, Chem. Commun. 2022, 58, 2634-2645.P. J. Evans, J. Ouyang, L. Favereau, J. Crassous, I. Fernández, J. Perles-Hernáez, N. Martín "Synthesis of a Helical Bilayer Nanographene" Angew. Chem. Int. Ed. 2018, 57, 6774 –6779.P. Izquierdo-García, J. M. Fernández-García, I. Fernández, J. Perles, N. Martín, “Helically Arranged Chiral Molecular Nanographenes", J. Am. Chem. Soc., 2021, 143, 11864−11870.M. Vázquez-Nakagawa, L. Rodríguez-Pérez, N. Martín, M. A. Herránz, “Supramolecular Assembly of Edge Functionalized Top-Down Chiral Graphene Quantum Dots”, Angew. Chem. Int. Ed. 2022, 61, e202211365.

Structurally Induced Chirality of an Achiral Chromophore on Self-Assembled Nanofibers: A Twist Makes It Chiral.

The surface domains of self-assembled amphiphiles are well-organized and can perform many physical, chemical, and biological functions. Here, we present the significance of chiral surface domains of these self-assemblies in transferring chirality to achiral chromophores. These aspects are probed using l- and d-isomers of alkyl alanine amphiphiles which self-assemble in water as nanofibers, possessing a negative surface charge. When bound on these nanofibers, positively charged cyanine dyes (CY524 and CY600), each having two quinoline rings bridged by conjugated double bonds, show contrasting chiroptical features. Interestingly, CY600 displays a bisignated circular dichroic (CD) signal with mirror-image symmetry, while CY524 is CD silent. Molecular dynamics simulations reveal that the model cylindrical micelles (CM) derived from the two isomers exhibit surface chirality and the chromophores are buried as monomers in mirror-imaged pockets on their surfaces. The monomeric nature of template-bound chromophores and their binding reversibility are established by concentration- and temperature-dependent spectroscopies and calorimetry. On the CM, CY524 displays two equally populated conformers with opposite sense, whereas CY600 is present as two pairs of twisted conformers in each of which one is in excess, due to differences in weak dye-amphiphile hydrogen bonding interactions. Infrared and NMR spectroscopies support these findings. Reduction of electronic conjugation caused by the twist establishes the two quinoline rings as independent entities. On-resonance coupling between the transition dipoles of these units generates bisignated CD signals with mirror-image symmetry. The results presented herein provide insight on the little-known structurally induced chirality of achiral chromophores through transfer of chiral surface information.

Fascinating chiral information transfer to titania/silica from near to racemic compound self-organized from polyethyleneimine and tartaric acid.

In this work, chiroptical crystalline complexes of PEI/Tart (P/T) consisting of linear poly(ethylemeimine) (PEI) and an enantiomeric excess (ee) of tartaric acid (Tart) were used as chiral catalytic templates in the hydrolytic condensation of titanium bislactates and co-condensation of titanium bislactates and tetramethoxysilane for the preparation of chiral titania (TiO2) and chiral titania/silica (TiO2/SiO2) hybrid. Different from the general case of enantiopure templates excelling in chiral transformation when compared to enantiomeric excess ones, P/T systems with different enantiomer ratios exhibited each activity in the transformation of their chiral information to the resulting minerals titania and titania/silica. Especially, the P/T complexes with ee only by ±4% (D/L = 52/48 or 48/52), which is near the racemic state (D/L = 50/50), served as excellent chiral catalytic templates to generate chiroptical titania and titania/silica with mirror relation of the CD signals. By means of DSC, XRD, SEM and DRCD techniques, the crystalline complexes of PEI/Tart (P/T), the as-prepared TiO2@P/T and TiO2/SiO2@P/T, and the calcined TiO2 and TiO2/SiO2 were thoroughly investigated and the mechanism of the chiral transformation from the enantiomeric excess of P/T to minerals was proposed.

Turning Enantiomeric Relationships into Diastereomeric Ones: Self-Resolving α-Ureidophosphonates and Their Organocatalytic Enantioselective Synthesis

Controlling chiral recognition and chiral information transfer has major implications in areas ranging from drug design and asymmetric catalysis to supra- and macromolecular chemistry. Especially intriguing are phenomena associated with chiral self-recognition. The design of systems that show self-induced recognition of enantiomers, i.e., involving homochiral versus heterochiral dimers, is particularly challenging. Here, we report the chiral self-recognition of α-ureidophosphonates and its application as both a powerful analytical tool for enantiomeric ratio determination by NMR and as a convenient way to increase their enantiomeric purity by simple achiral column chromatography or fractional precipitation. A combination of NMR, X-ray, and DFT studies indicates that the formation of homo- and heterochiral dimers involving self-complementary intermolecular hydrogen bonds is responsible for their self-resolving properties. It is also shown that these often unnoticed chiral recognition phenomena can facilitate the stereochemical analysis during the development of new asymmetric transformations. As a proof of concept, the enantioselective organocatalytic hydrophosphonylation of alkylidene ureas toward self-resolving α-ureidophosphonates is presented, which also led us to the discovery of the largest family of self-resolving compounds reported to date.

A Star of David [2]catenane of single handedness

<h2>Summary</h2> Prime links with multiple interlocked components feature unconditional topological chirality. Although several prime links have been constructed to date, the control of their chirality with high stereoinduction is rare. Here, we report the stereoselective synthesis of an iconic molecular <mml:math><mml:mrow><mml:mn>6</mml:mn><mml:mn>1</mml:mn><mml:mn>2</mml:mn></mml:mrow></mml:math> link (Star of David [2]catenane) comprising two triply entwined 84-membered rings. The single-handed Star of David catenane is generated from the closure of a hexameric copper(I) circular helicate by ring-closing olefin metathesis, and the topological writhe (<i>w</i> = −6) was predetermined by the configuration of the chiral ligand. Conformation of the topology was proven through NMR spectroscopy and mass spectrometry, whereas the handedness of the link was further investigated through circular dichroism. Stereoselective synthesis of molecular nanotopologies with certain topological writhe by chiral information transfer opens the way to probe the consequences and potential of topological stereochemistry in chemistry, materials, and biology.

Single-Handed Helicene Nanoribbons via Transfer of Chiral Information.

Here we show the access to single-handed helicene nanoribbons by utilizing a [6]helicene building block to induce diastereoselective, photochemical formation of [5]helicene units. Specifically, we have synthesized nanoribbons P1 and P2 with different ratios of [6]helicene "sergeants" to [5]helicene "soldiers", which on average consist of between ∼50 and 60 ortho-annulated benzene rings. These are the longest, optically active helicene backbones that have been prepared to date. The chiroptic properties of P1 and P2 reveal the transfer of stereochemical information from "sergeants" to "soldiers". To gain further insight into the stereo-information relay, we apply the same molecular design to discrete, model oligomers 1-5 and confirm that they also preferentially adopt homochiral geometries.

Homologous and Heterologous Chiral Supramolecular Polymerization from Exclusively Achiral Building Blocks

AbstractAmong the enticing issues of chiral origins are: how chirality is born from the initial achiral units and the mechanisms for the transfer of chiral information. In this work, by combining a physical vortex and chiral seeds, a general process is revealed to generate chiral supramolecular polymers from achiral C3‐symmetric molecules. The symmetry‐broken assemblies from the achiral molecules could work as chiral seeds to initiate the polymerization of either homologous or heterologous achiral monomers. Concomitantly, the fragmentation of the polymer caused by the vortex during the nucleation‐elongation stages is shown to enlarge the domains of the chiral nuclei and then guide the polymer to grow into the predominant helicity with a high reactivity ratio. Moreover, the chiral structural information can be stored in different forms of assemblies. These new polymerization modes will provide guidance for the preparation of chiral materials.

Homologous and Heterologous Chiral Supramolecular Polymerization from Exclusively Achiral Building Blocks.

Among the enticing issues of chiral origins are: how chirality is born from the initial achiral units and the mechanisms for the transfer of chiral information. In this work, by combining a physical vortex and chiral seeds, a general process is revealed to generate chiral supramolecular polymers from achiral C3 -symmetric molecules. The symmetry-broken assemblies from the achiral molecules could work as chiral seeds to initiate the polymerization of either homologous or heterologous achiral monomers. Concomitantly, the fragmentation of the polymer caused by the vortex during the nucleation-elongation stages is shown to enlarge the domains of the chiral nuclei and then guide the polymer to grow into the predominant helicity with a high reactivity ratio. Moreover, the chiral structural information can be stored in different forms of assemblies. These new polymerization modes will provide guidance for the preparation of chiral materials.

Supramolecular Nanohelix Fabricated by Pillararene-Based Host–Guest System for Chirality Amplification, Transfer, and Circularly Polarized Luminescence in Water

Supramolecular Nanohelix Fabricated by Pillararene-Based Host–Guest System for Chirality Amplification, Transfer, and Circularly Polarized Luminescence in Water

Adaptive helicity and chiral recognition in bright europium quadruple-stranded helicates induced by host-guest interaction

Chiral information transfer is crucial to design new functions like, for instance, sensing through chiroptical probes in which the input is readout as a consequence of a chiral recognition event. Herein, we report lanthanide quadruple-stranded helicates [Ln 2 L 4 ] 2− that show a guest-to-host chirality transfer. As confirmed by X-ray diffraction (XRD) and density functional theory (DFT) calculations, these cages are present in solution as an equilibrating racemic mixture of left- and right-handed helicates. The helicates adapt their helical conformation by encapsulation of a chiral guest enabling also straightforward enantiomeric excess determination. Asymmetric induction is demonstrated by circular dichroism (CD) and circularly polarized luminescence (CPL), and a helicity inversion mechanism based on a Bailar twist is proposed and studied by DFT calculations. The presented research contributes to the design of helicates with a unique combination of confined cavities, adaptive chirality, and peculiar luminescent properties, finding applications toward the development of optical probes for selective chiral sensing via molecular recognition. • Helicates adapt in response to a recognition process in a confined space • Chiral recognition through host-guest events detected by CD and CPL • Very bright europium helicates with luminescence visible to naked eye • Helicity inversion mechanism, i.e., Bailar twist, is revealed by DFT calculations Rancan et al. report chirality transfer for chiroptical molecular recognition. Very bright europium helicates enable a chiroptical readout toward chiral guests. Helicates adapt their conformation with a guest-to-host hierarchical chirality transfer. The molecular recognition process is detected by induced circular dichroism (CD) and circularly polarized luminescence (CPL).

New-Generation Ligand Design for the Gold-Catalyzed Asymmetric Activation of Alkynes.

Gold(I) catalysts are ideal for the activation of alkynes under very mild conditions. However, unlike allenes or alkenes, the triple bond of alkynes cannot be prochiral. In addition, the linear coordination displayed by gold(I) complexes places the chiral ligand far away from the substrate resulting in an inefficient transfer of chiral information. This poses a significant challenge for the achievement of high enantiocontrol in gold(I)‐catalyzed reactions of alkynes. Although considerable progress on enantioselective gold(I)‐catalyzed transformations has recently been achieved, the asymmetric activation of non‐prochiral alkyne‐containing small molecules still represents a great challenge. Herein we summarize recent advances in intra‐ and intermolecular enantioselective gold(I)‐catalyzed reactions involving alkynes, discussing new chiral ligand designs that lie at the basis of these developments. We also focus on the mode of action of these catalysts, their possible limitations towards a next‐generation of more efficient ligand designs. Finally, square planar chiral gold(III) complexes, which offer an alternative to chiral gold(I) complexes, are also discussed.

Nonlinear Amplification of Chirality in Self-Assembled Plasmonic Nanostructures.

Molecular chirality transfer and amplification is at the heart of the fundamental understanding of chiral origin and fabrication of artificial chiral materials. We investigate here the nonlinear amplification effect in the chiral transfer from small molecules to assembled plasmonic nanoparticles. Our results show clearly a recognizable nonlinear behavior of the electronic and plasmonic circular dichroism activities, demonstrating the validity of the "majority-rules" principle operating in both the three-dimensional interface-confined molecularly chiral environment and the assembled plasmonic nanoparticles. Such twin "majority-rules" effects from the self-assembled organic-inorganic nanocomposite system have not been reported previously. By establishing a direct correlation between the dynamic template of the molecularly chiral environment and the nonlinear chiral amplification in the nanoparticle assemblies, this study may provide an insightful understanding of the hierarchical and cooperative chiral information transfer from molecular levels to nanoscales.

Helical Nanofibers Formed by Palladium-Mediated Assembly of Organic Homochiral Macrocycles Containing Binaphthyl and Pyridyl Units.

Herein, we report the synthesis and characterization of homochiral macrocycles, in which molecular rigidity, combined with the presence of multiple functional groups, allow for the assembly of helical nanostructures. 1,1'-bi-2-naphthol (Binol) units are used as robust chirality inducers, and pyridyl units embedded within the molecular frameworks allow the assembly, upon coordination with Pd(II) metal ions, of the macrocyclic building blocks. CD and NMR spectroscopies show the formation of ordered 1D assembly in solution. AFM studies indicate that the molecular systems are capable of forming nanoscale structures. The effective transfer of chiral information results in helical nanofibers, with lengths ranging from a few hundreds of nanometers to some micrometers. AFM line profiles reveal a helical longitudinal period of about 50 nm and a transverse width of 25 to 45 nm after deconvolution.

Catalytic one-handed helix-induction and memory of amphiphilic poly(biphenylylacetylene)s in water

A series of amphiphilic biphenylylacetylene-based homo- and copolymers (PBPAs) carrying chiral and/or achiral oligo(ethylene glycol) pendants at the 4′-position of the biphenyl units were synthesized and the amplification of the macromolecular helicity through noncovalent and/or covalent chiral interactions followed by the memory of the helicity were investigated in both water and organic solvents. The macromolecular helicity was efficiently induced in the homopolymers of achiral monomers through specific encapsulation of a catalytic amount of hydrophobic chiral guests in water and their induced helicities were stably memorized in water after complete removal of the optically-active guests, while an excess helical sense was not biased at all in the homopolymers in toluene. One-handed macromolecular helicities were also efficiently induced in the chiral homopolymers through chiral information transfer from covalently linked optically-active pendants with a point chirality to biphenyl units with a dynamic axial chirality, whose helical senses were almost perfectly inverted in water and organic solvents. The achiral/chiral copolymers displayed a unique bidirectional (P and M) strong chiral amplification of the macromolecular helicity in water and toluene assisted by the solvent-induced helix-inversion, and their macromolecular helicities were further enhanced or inverted through encapsulation of a catalytic amount of enantiomeric alcohols in water, which could be further memorized in water after removing the encapsulated guests. We also demonstrated that the left- and right-handed circularly polarized lights could be generated through chirality transfer from the one-handed helical polymers with a macromolecular helicity memory, consisting entirely of achiral monomer units, to an achiral fluorescent dye in the blended films. Importantly, the resulting luminescence dissymmetry factors (ca. 2 × 10–3) were virtually the same as those of chiral homopolymers composed of the optically-pure repeating units.

Cover Feature: Transfer of Chiral Information from Silica Hosts to Achiral Luminescent Guests: a Simple Approach to Accessing Circularly Polarized Luminescent Systems (ChemPlusChem 4/2020)

Cover Feature: Transfer of Chiral Information from Silica Hosts to Achiral Luminescent Guests: a Simple Approach to Accessing Circularly Polarized Luminescent Systems (ChemPlusChem 4/2020)

From Pd(OAc)2 to Chiral Catalysts: The Discovery and Development of Bifunctional Mono-N-Protected Amino Acid Ligands for Diverse C-H Functionalization Reactions.

The functionalization of unactivated carbon-hydrogen bonds is a transformative strategy for the rapid construction of molecular complexity given the ubiquitous presence of C-H bonds in organic molecules. It represents a powerful tool for accelerating the synthesis of natural products and bioactive compounds while reducing the environmental and economic costs of synthesis. At the same time, the ubiquity and strength of C-H bonds also present major challenges toward the realization of transformations that are both highly selective and efficient. The development of practical C-H functionalization reactions has thus remained a compelling yet elusive goal in organic chemistry for over a century.Specifically, the capability to form useful new C-C, C-N, C-O, and C-X bonds via direct C-H functionalization would have wide-ranging impacts in organic synthesis. Palladium is especially attractive as a catalyst for such C-H functionalizations because of the diverse reactivity of intermediate palladium-carbon bonds. Early efforts using cyclopalladation with Pd(OAc)2 and related salts led to the development of many Pd-catalyzed C-H functionalization reactions. However, Pd(OAc)2 and other simple Pd salts perform only racemic transformations, which prompted a long search for effective chiral catalysts dating back to the 1970s. Pd salts also have low reactivity with synthetically useful substrates. To address these issues, effective and reliable ligands capable of accelerating and improving the selectivity of Pd-catalyzed C-H functionalizations are needed.In this Account, we highlight the discovery and development of bifunctional mono-N-protected amino acid (MPAA) ligands, which make great strides toward addressing these two challenges. MPAAs enable numerous Pd(II)-catalyzed C(sp2)-H and C(sp3)-H functionalization reactions of synthetically relevant substrates under operationally practical conditions with excellent stereoselectivity when applicable. Mechanistic studies indicate that MPAAs operate as unique bifunctional ligands for C-H activation in which both the carboxylate and amide are coordinated to Pd. The N-acyl group plays an active role in the C-H cleavage step, greatly accelerating C-H activation. The rigid MPAA chelation also results in a predictable transfer of chiral information from a single chiral center on the ligand to the substrate and permits the development of a rational stereomodel to predict the stereochemical outcome of enantioselective reactions.We also describe the application of MPAA-enabled C-H functionalization in total synthesis and provide an outlook for future development in this area. We anticipate that MPAAs and related next-generation ligands will continue to stimulate development in the field of Pd-catalyzed C-H functionalization.

Transfer of Chiral Information from Silica Hosts to Achiral Luminescent Guests: a Simple Approach to Accessing Circularly Polarized Luminescent Systems

Systems that show circularly polarized luminescence (CPL) are usually constructed in one of two possible ways: either covalently binding the chiral moieties (usually organic compounds) to luminophores (inorganic or organic compounds) or associating the luminophores as guests with chiral hosts (usually organic compounds). Herein, we propose inorganic-based CPL-active systems constructed by the "chiral host-luminescent guest" strategy, in which silica acts as a chiral host to endow various luminescent guests with CPL. The chiral silica was modified by silane coupling with amino or phenyl groups to allow interaction with luminescent guests, and then used in combination with acidic achiral dyes, lead-halide type perovskites, and aggregation-induced emission luminogens (AIEgens). Interestingly, when these achiral guests were noncovalently confined in surface-modified chiral silica, the guests showed chiroptical behavior in the circular dichroism (CD) spectra, and thus became CPL active, even though they are not inherently chiral. The surface functional groups on the silica play very important roles in transferring the chiral information from the silica to the guests. This work provides a new concept for constructing CPL-active systems using inorganic materials as a chiral source.

A [2]Rotaxane-Based Circularly Polarized Luminescence Switch.

A rotaxane-based molecular shuttle has been synthesized in which the switching of the position of a fluorescent macrocycle on the thread turns “on” or “off” the circularly polarized luminescence (CPL) of the system while maintaining similar fluorescence profiles and quantum yields in both states. The chiroptical activity relies on the chiral information transfer from an ammonium salt incorporating d- or l-phenylalanine residues as chiral stereogenic covalent units to an otherwise achiral crown ether macrocycle bearing a luminescent 2,2′-bipyrene unit when they interact through hydrogen bonding. Each enantiomeric thread induces CPL responses of opposite signs on the macrocycle. Upon addition of base, the switching of the position of the macrocycle to a triazolium group disables the chiral information transfer to the macrocycle, switching “off” the CPL response. The in situ switching upon several acid/base cycles is also demonstrated.