Prochiral Molecules Research Articles

Chirally-modified metal surfaces: energetics of interaction with chiral molecules.

Imparting chirality to non-chiral metal surfaces by adsorption of chiral modifiers is a highly promising route to create effective heterogeneously catalyzed processes for the production of enantiopure pharmaceuticals. One of the major current challenges in heterogeneous chiral catalysis is the fundamental-level understanding of how such chirally-modified surfaces interact with chiral and prochiral molecules to induce their enantioselective transformations. Herein we report the first direct calorimetric measurement of the adsorption energy of chiral molecules onto well-defined chirally-modified surfaces. Two model modifiers 1-(1-naphthyl)ethylamine and 2-methylbutanoic acid were used to impart chirality to Pt(111) and their interaction with propylene oxide was investigated by means of single-crystal adsorption calorimetry. Differential adsorption energies and absolute surface uptakes were obtained for the R- and S-enantiomers of propylene oxide under clean ultrahigh vacuum conditions. Two types of adsorption behavior were observed for different chiral modifiers, pointing to different mechanisms of imparting chirality to metal surfaces. The results are analyzed and discussed in view of previously reported stereoselectivity of adsorption processes.

Chiral surface networks of 3-HPLN — A molecular analog of rounded triangle assembly

The self-assembly of 3-hydroxyphenalenone (3-HPLN) on the Ag(111) surface has been studied with scanning tunneling microscopy and first-principles computations. The prochiral 3-HPLN molecule forms zipper-like chains when deposited on the Ag(111) surface, representing a 2D analog of their arrangement in bulk crystals. Upon annealing, local chiral trimer motifs form and serve as building blocks in extended 2D supramolecular networks not observed in 3D crystals. The extended network is porous and is held together via weak van der Waals interactions. The dispersion forces between trimers suggest that their handedness is overall racemic, but the asymmetric packing of 3-HPLN trimers around the pores leads to a chiral network. The offset alignment of neighboring 3-HPLN molecules in the unit cell resembles the offset between neighboring particles that are seen in the most efficient packings of rounded triangles. Computations illustrate that charge is transferred from the Ag(111) surface to the lowest unoccupied orbital of 3-HPLN, and a number of networks (including a honeycomb, as well as an alternative close-packed arrangement) are investigated.

A metal surface with chiral memory

Adsorption of maleic acid onto the copper(110) surface in ultrahigh vacuum induces restructuring of the surface such that its original mirror symmetry is locally broken. Scanning tunnelling microscopy performed on areas, which contain no molecules after annealing, reveals that Cu adatoms are still lined up on the surface in a chiral fashion.

Analysis of a chemical model system leading to chiral symmetry breaking: Implications for the evolution of homochirality

Explaining the evolution of a predominantly homochiral environment on the early Earth remains an outstanding challenge in chemistry. We explore here the mathematical features of a simple chemical model system that simulates chiral symmetry breaking and amplification towards homochirality. The model simulates the reaction of a prochiral molecule to yield enantiomers via interaction with an achiral surface. Kinetically, the reactions and rate constants are chosen so as to treat the two enantiomeric forms symmetrically. The system, however, incorporates a mechanism whereby a random event might trigger chiral symmetry breaking and the formation of a dominant enantiomer; the non-linear dynamics of the chemical system are such that small perturbations may be amplified to near homochirality. Mathematical analysis of the behavior of the chemical system is verified by both deterministic and stochastic numerical simulations. Kinetic description of the model system will facilitate exploration of experimental validation. Our model system also supports the notion that one dominant enantiomeric structure might be a template for other critical molecules.

Chirality induction by E–Z photoisomerization in [2,2]paracyclophane-bridged azobenzene dimer

We designed and synthesized a new prochiral molecule in which two azobenzene moieties were embedded in [2,2]paracyclophane and showed the chirality induction by E–Z photoisomerization. We also demonstrated the on/off switching of asymmetry by irradiation and reflux respectively.

Front Cover: Molecular chirality at surfaces (Phys. Status Solidi B 11/2012)

Chirality is ubiquitous in our world, but only during the last two decades the role it plays in two-dimensional systems has attracted the interest of surface scientists. The cover image - an adaptation from a scanning tunneling micrograph - shows a handed pinwheel pattern of six helical (M)-heptahelicene molecules on a copper(111) surface. Each “mountain” represents a single left-handed molecule. The right-handed (P)-enantiomer forms the corresponding mirror-image motif. Such transfer of handedness from single molecules into self-assembled supramolecular structures is one example of how molecular structure affects the shape of assemblies, not only on surfaces, but even up to crystal morphology. The Review Article by Karl-Heinz Ernst on pp. 2057–2088 gives a topical overview of different aspects of molecular chirality at surfaces and introduces principles of mirror symmetry breaking upon adsorption and two-dimensional self-assembly. The article gives also a historical view on chirality and different definitions available. Main topics are chiral and prochiral molecules at surfaces, amplification due to small chiral bias, chiral restructuring due to adsorption, intrinsically chiral surfaces and chiral switching.

Molecular chirality at surfaces

AbstractWith the adsorption of larger molecules being increasingly tackled by surface scientists, the aspect of chirality often plays a role. This paper gives a topical review of molecular chirality at surfaces and gives a phenomenological overview of different aspects of adsorption and self‐assembly of chiral and prochiral molecules and the principles of mirror‐symmetry breaking at a surface. After a brief introduction into the history of molecular chirality and the important role it played for understanding the spatial structure of molecules, definitions of chirality are presented. Topics treated here are principle ways to create single chiral adsorbates, chiral ensembles, and monolayers by achiral molecules, adsorption of intrinsically chiral molecules at achiral and chiral surfaces, long‐range symmetry breaking in two‐dimensional (2D) crystals due to additional chiral bias, chiral restructuring of solid surfaces under the influence of chiral molecules, switching the handedness of adsorbates, and chirality at the liquid/air interface. An outlook onto further potential research directions and recommendations for further reading, including nonsurface‐related sources of chiral topics completes this paper.

Isocyanurates with Planar Chirality: Design, Optical Resolution, and Isomerization

Designs and syntheses of isocyanurates (1-3) are described on the basis of a novel concept that two enantiotopic faces of C(s) -symmetric, prochiral planar molecules are differentiated with a location of groups at the top or bottom of the planar skeleton using a rigid linker. Such isocyanurates are atropisomeric. The planar-chiral structures of 1 and 2(anti) (anti-conformer of 2) were confirmed by single-crystal X-ray analyses, and the space groups were P1 (for 1) and P2(1)/c (for 2(anti)), resulting that the crystals were racemates. Optical resolutions of 1-3 were successfully accomplished by using chiral high-performance liquid chromatography technique in combination with circular dichroism, absorption, and nuclear magnetic resonance spectroscopies and mass spectrometry. Furthermore, the rotational barriers (ΔG(‡)s) related to isomerizations of 1-3 were estimated to be 27.2 (for 1 at 50 °C), 27.6 (for 2(anti) at 50 °C), and 40.6 (for 3(syn) at 150 °C) kcal/mol. The ΔG(‡)s of 2 and 3 were higher than that of 1 and, in particular, that of 3 was highest among them. This result indicates that an introduction of bulky substituents and an intramolecular bridging are effective for inhibitions of the isomerizations.

Viewing and Inducing Symmetry Breaking at the Single-Molecule Limit

Symmetry breaking by photons, electrons, and molecular interactions lies at the heart of many important problems as varied as the origin of homochiral life to enantioselective drug production. Herein we report a system in which symmetry breaking can be induced and measured in situ at the single-molecule level using scanning tunneling microscopy. We demonstrate that electrical excitation of a prochiral molecule on an achiral surface produces large enantiomeric excesses in the chiral adsorbed state of up to 39%. The degree of symmetry breaking was monitored as a function of scanning probe tip state, and the results revealed that enantiomeric excesses are correlated with the intrinsic chirality in scanning probe tips themselves, as evidenced by height differences between single molecule enantiomers. While this work has consequences for the study of two-dimensional chirality, more importantly, it offers a new method for interrogating the coupling of photons, electrons, and combinations of physical fields to achiral starting systems in a reproducible manner. This will allow the mechanism of chirality transfer to be studied in a system in which enantiomeric excesses are quantified accurately by counting individual molecules.

Induction of Point Chirality by E/Z Photoisomerization

Shining a light on it: E/Z photoisomerization generates an asymmetric center and the corresponding separable enantiomers in an azobenzene-based prochiral molecule. This asymmetric center is formed by light-induced changes to the substituents on the central atom, and Z/E thermal isomerization regenerates the initial symmetry in the molecule. This switching of the asymmetry can be performed repeatedly.

Conformation and Dynamics of 18-Membered Hexathiametacyclophanes: A Two Step Racemization as Studied by Deuterium NMR in Chiral Lyotropic Liquid Crystals

The conformation and interconversion dynamics of two derivatives of the 18-membered hexathia metacyclophane 1 and 2 were studied by (1)H NMR spectroscopy in isotropic solvents and by (2)H NMR in chiral liquid crystalline (CLC) solutions, as well as by molecular structure computations. For the analysis of the dynamic effects, we made use of the concepts of "average symmetry" and "isodynamic groups", introduced by Altmann (Altmann, Proc. R. Soc.1967, 184, A298). Compound 1, which is unsubstituted in the inner aromatic site, has, according to the NMR and molecular force field calculations, a boat shaped ground conformation with C(2) symmetry. It is highly flexible and in the NMR spectrum exhibits two successive dynamic processes. There is a low temperature (170-210 K, E(a) = 10.5 kcal/mol) alternate "wing flipping", which corresponds to interchange between pairs of enantiomers and results, in the fast exchange limit, in an average prochiral molecule with C(2v) symmetry. This process is followed, at higher temperatures (290-320 K, E(a) = 28.5 kcal/mol), by an umbrella flipping type inversion with an average structure of D(2h) symmetry. This second process involves averaging of effective enantiotopic into homotopic sites and can only be studied in chiral solvents. The origin of the chiral discrimination and of their stepwise averaging is discussed. Compound 2, which is substituted with methoxy groups at the inner sites of the benzene rings, is much less flexible and exhibits dynamic effects in the NMR spectrum only at temperatures above 370 K. We were able to study the kinetic parameters of this process in isotropic solvents (E(a) = 21.4 kcal/mol). As for 1, the detailed mechanism of this process can in principle be established using dynamic NMR in CLC; however, experimental limitation precluded us from doing so. Possible alternatives and their effect on the 1D and 2D exchange spectra in CLC are discussed in a concluding section.

Growth of Textured Adenine Thin Films to Exhibit only Chiral Faces

The growth of adenine on Au(111) from the submonolayer up to several microns film thickness is studied by combining STM and surface X-ray diffraction techniques. The study shows that adenine thin films are composed of highly textured crystallites with the reported α-adenine crystal structure in such a way that they only exhibit (001)-faces. Such faces, with chiral p2 symmetry planes, have an average size of 15 nm. Thus, the formed adenine films reported herein, which expose only chiral and biocompatible faces, might find applications such as enantioselective heterogeneous catalysts for the chemical and pharmaceutical industries.

Locking the free-rotation of a prochiral star-shaped guest molecule inside a two-dimensional nanoporous network by introduction of chlorine atoms

Two star-shaped triazatrinaphthylene (TrisK) derivatives form highly-organized nanoporous honeycomb networks when adsorbed at the n-tetradecane/HOPG interface. STM reveals that replacing three H-atoms by three Cl-atoms in the chemical structure of the TrisK skeleton results in locking the free-rotation of the guest molecules inside the pore of the host network as a result of symmetry breaking.

ChemInform Abstract: Amplification of Chirality at Solid Surfaces

AbstractReview: 45 refs.

Monolayer Structure of Arachidic Acid on Graphite

The self-assembly of arachidic acid (C19H39COOH) at the liquid−solid interface between 1-phenyloctane (C6H5(CH2)7CH3) and highly oriented pyrolytic graphite (HOPG) is studied by scanning tunneling microscopy (STM) to identify the structure of the monomolecular film. We observe the formation of highly ordered domains with molecules oriented in three different orientations compatible with the symmetry of the HOPG substrate, a spontaneous enantiomeric separation of the pro-chiral molecules, and reveal structural details with submolecular resolution. To determine the surface unit cell with an intrinsic calibration to the substrate atomic structure, the intermolecular distance is precisely determined from the analysis of a STM image exhibiting a moire pattern created by the superposition of current contributions from the molecular structure with contributions from the graphite atomic lattice. The dimensions of the unit cell accommodating two molecules are |a| = 0.94 nm and |b| = 2.83 nm with an angle of 85° be...

ChemInform Abstract: The Concept of Prochirality Applied to Coordination Compounds

Abstract The concept of prochirality, widely used for organic molecules, is extended here to mononuclear octahedral (OC-6), square pyramidal (SP-5), square planar (SP-4) and trigonal bipyramidal (TB-5) coordination compounds. A prochiral coordination compound (Cs symmetry) is characterized by a prochiral center, namely the metal atom, and by the existence of two heterotopic elements. The elements can be ligands, faces or planes, depending on the geometry of the complex. The most common reactions that can transform the prochiral metal center into a chiral one are treated in detail. Interactions of prochiral complexes with prochiral organic molecules are also treated. Applications of particular interest for prochiral coordination compounds can be envisaged in the fields of asymmetric synthesis and bioinorganic chemistry.

Direct Observation of Enantiospecific Substitution in a Two-Dimensional Chiral Phase Transition

Initial stages of a chiral phase transition in the monolayer of a quinacridone derivative on the Au(111) surface were investigated by scanning tunneling microscopy at submolecular resolution. The prochiral molecules form a homochiral lamella phase at low coverages upon adsorption. A transition to a racemate lattice is observed with increasing coverage. Enantiomers of a homochiral lamella line become specifically substituted by opposite enantiomers such that a heterochiral structure evolves. Due to the higher density, lateral alkyl chains are bent away from the surface. Our findings are significant for the understanding and control of chiral phase transitions in related molecular systems like liquid crystals.

Chirality and Rotation of Asymmetric Surface-Bound Thioethers

A combination of theory and experiment is used to interrogate the surface bonding geometry and rotational dynamics of a simple asymmetric thioether, butyl methyl sulfide. Calculations predict that binding occurs to a Au surface through one of the lone pairs on the sulfur atom and that the alkyl tails lie almost parallel to the surface. The unbonded lone pair remains unperturbed, and the geometry around the S atom is essentially tetrahedral, and hence two surface-bound enantiomers of the prochiral molecule are formed with an R−S inversion barrier that is predicted to be large. The rapidly rotating molecules can be clearly distinguished upon atomic-scale imaging by their mirror image pinwheel appearance. The binding of asymmetric dialkyl sulfides leads to the formation of surface-bound enantiomers, which has important consequences for studies in which thioether linkers are used in conjunction with chiral moieties and indicates that diastereomeric effects may be at play in these systems.

Supramolecular Organization and Chiral Resolution of p‐Terphenyl‐m‐Dicarbonitrile on the Ag(111) Surface

The supramolecular organization and layer formation of the non-linear, prochiral molecule [1, 1';4',1'']-terphenyl-3,3"-dicarbonitrile adsorbed on the Ag(111) surface is investigated by scanning tunneling microscopy (STM) and near-edge X-ray absorption fine-structure spectroscopy (NEXAFS). Upon two-dimensional confinement the molecules are deconvoluted in three stereoisomers, that is, two mirror-symmetric trans- and one cis-species. STM measurements reveal large and regular islands following room temperature deposition, whereby NEXAFS confirms a flat adsorption geometry with the electronic pi-system parallel to the surface plane. The ordering within the expressed supramolecular arrays reflects a substrate templating effect, steric constraints and the operation of weak lateral interactions mainly originating from the carbonitrile endgroups. High-resolution data at room temperature reveal enantiormorphic characteristics of the molecular packing schemes in different domains of the arrays, indicative of chiral resolution during the 2D molecular self-assembly process. At submonolayer coverage supramolecular islands coexist with a disordered fluid phase of highly mobile molecules. Following thermal quenching (down to 6 K) we find extended supramolecular ribbons stabilised again by attractive and directional noncovalent interactions, the formation of which reflects a chiral resolution of trans-species.

Steering Organizational and Conformational Surface Chirality by Controlling Molecular Chemical Functionality

Molecular chirality on surfaces has been widely explored, both for intrinsically chiral molecules and for prochiral molecules that become chiral upon adsorption due to the reduced symmetry which follows from surface confinement. However, little attention has been devoted to chiral effects that originate from conformational degrees of freedom for adsorbed molecules. Here we have used scanning tunneling microscopy to investigate the self-assembled structures formed when a class of six linear, organic molecules (oligo-phenylene-ethynylenes) are adsorbed on a Au(111) surface under ultrahigh vacuum conditions. All of the investigated compounds are intrinsically achiral, but most display conformational chirality in the sense that the molecules can adsorb on the surface in different conformations giving rise to either one of two chiral surface enantiomers or a mirror-symmetric achiral meso form. A total of eleven observed adsorption structures are systematically investigated with respect to conformational chirality as well as point chirality (arising where molecular adsorption locally breaks the substrate symmetry) and organizational chirality (arising from the tiling pattern of the molecular backbones). A number of interesting correlations are identified between these different levels of chirality. Most importantly, we demonstrate that it is possible through control of the terminal group functionalization to steer the oligo(phenylene-ethynylene) molecular backbones into surface assemblies that either display pronounced organizational chirality or have mirror symmetric tiling patterns, and that it is furthermore possible to control the conformational surface chirality so the compounds preferentially assume either chiral or achiral surface conformers.