Kinetic model for the chiral symmetry breaking transition in the growth front of a conglomerate crystal phase

In its molten phase, 1,1'-binaphthyl is racemic due to its high racemization rate, but it can crystallize as a conglomerate of R and S crystals. Our experiments have indicated that, under some conditions, the crystal growth front of 1,1'-binaphthyl shows many of the characteristics of an open system in which chiral symmetry is broken; i.e., the growing solid phase becomes predominantly R or S. Here we present a kinetic model to explain the observed chiral symmetry breaking. The model is based on growth due to attachment of R or S growth units to a crystal surface in a supercooled melt. Chiral symmetry breaking occurs due to chirally autocatalytic formation of R or S growth units on the growth surface. Unlike the many models suggested and studied in the 1980s, there is no cross-inhibition between R- and S-enantiomer in the model presented here. In our model, asymmetric and symmetric steady-state solutions that do not intersect were found. Through linear stability analysis, the critical point, at which a symmetric solution becomes unstable and makes a transition to an asymmetric solution, is determined.     

Mechanism-based chemical understanding of chiral symmetry breaking in the Soai reaction. A combined probabilistic and deterministic description of chemical reactions

The experimentally observed distribution of enantiomers in the Soai reaction is interpreted in this Article on the basis of a chemical mechanism using a newly developed stochastic kinetic method, accelerated Monte Carlo simulation combined with deterministic continuation and symmetrization. The method is in principle suitable for handling large mechanisms with realistic particle numbers and could be useful for any case where the kinetics of a process shows inherent random fluctuations. The mechanism shows how a slow initial reaction combined with efficient and highly enantioselective autocatalysis can give rise to chiral symmetry breaking under completely nonchiral external conditions.     

Spoilt for choice: assessing phase behavior models for the evolution of homochirality

The observation of single chirality in biological systems has intrigued scientists for more than one hundred years. Here we discuss several recent experimental studies showing amplification of enantiomeric excess based on amino acid phase behavior. Comparing observations of solution-solid and gas-solid phase transitions highlights the underlying fundamental physical chemistry principles that rationalize the observed enantioenrichment in both cases.     

Spontaneous resolution of a novel chiral coordination polymer through supramolecular interactions and solvent symmetry breaking

The spontaneous resolution reaction of racemic trans-2,3-dihydro-2,3-dipyridyl-benzo[e]indole 1 with Cd(ClO₄)₂·6H₂O in the presence of 2-butanol under solvothermal reaction conditions favors the formation of crystal 2 [P-Cd(R,R,-1)₂(ClO₄)₂], while a similar reaction in the presence of ethanol only favors the formation of crystal 3 [M-Cd(S,S,-1)₂(ClO₄)₂]. The crystal structural determination shows that both 2 and 3 crystallize in chiral enantiomorphous space groups (P6₁22 and P6₅22) and their structures are 1D infinite chain, and are just enantiomorphous pairs most like. The spontaneous resolution process displays estimated ee values of ca. +0.6 for 2-butanol and ca. −0.4 for ethanol. Enantiomerically pure (S,S)-trans-2,3-dihydro-2,3-dipyridyl-benzo[e]indole (S,S,-1) can be obtained through the decomposition of mechanically separated 3. Additionally (S,S,-1) also crystallizes in a chiral space group (P2₁). The CD (circular dichroism) spectra of both 2 and 3 in the solid state are also approximately enantiomorphous pairs. However, their fluorescent spectra in the solid state display a moderate difference in maximum emission peaks (Δλ = 19 nm). Crystal data for 2: C₄₄H₃₄Cl₂N₆O₈Cd, M = 958.07, hexagonal, P6₁22, a = 10.5488(5), c = 68.256(4) Å, α = γ = 90°, β = 120°, V = 6577.8(6) Å³, Z = 6, D_c = 1.451 mg m⁻³, R₁ = 0.0498, wR₂ = 0.1124, μ = 0.679 mm⁻¹, S = 0.623, Flack χ = −0.02(6). For space group P6₅22, R₁ = 0.0670, wR₂ = 0.1602, S = 0.725 with a Flack value of 1.03(7); Crystal data for 3, C₄₄H₃₄Cl₂N₆O₈Cd, M = 958.07, hexagonal, P6₅22, a = 10.5446(3), c = 68.265(3) Å, V = 6573.3(4) Å³, Z = 6, D_c = 1.452 mg m⁻³, R₁ = 0.0444,wR₂ = 0.1002, μ = 0.679 mm⁻¹, S = 0.558, Flack χ = 0.01(5). For space group P6₁22, R₁ = 0.0501, wR₂ = 0.1178, S = 0.599 with a Flack value of 1.00(5). The low Flack parameter indicates that the absolute configurations of 2 and 3 are stated; Crystal data for (S,S)-1, C₂₂H₁₇N₂, M = 323.39, orthorhombic, P2₁2₁2₁, a = 9.2598(7), b = 9.4617(8), c = 19.1452(16) Å, V = 1677.4(2) Å³, Z = 4, D_c = 1.281 mg m⁻³, R₁ = 0.0417, wR₂ = 0.1191, T = 293 K, μ = 0.077 mm⁻¹, S = 0.862.     

Excited-state symmetry breaking in cofacial and linear dimers of a green perylenediimide chlorophyll analogue leading to ultrafast charge separation

Photoexcitation of chromophoric dimers constrained to a symmetric pi-stacked geometry by their molecular structure usually produces excimers independent of solvent polarity, while dimers with edge-to-edge perpendicular pi systems undergo excited-state symmetry breaking in highly polar solvents leading to intradimer charge separation. We present direct evidence for symmetry breaking in the lowest excited singlet state of a symmetric cofacial dimer of 1,7-bis(pyrrolidin-1'-yl)-perylene-3,4:9,10-bis(dicarboximide) (5PDI) in the low polarity solvent toluene to produce a radical ion pair quantitatively. This dimer, cof-5PDI2, was synthesized by attaching two 5PDI chromophores via imide groups to a xanthene spacer. For comparison, a linear symmetric dimer, lin-5PDI2, was prepared in which the 5PDI chromophores are linked end-to-end via a N-N single bond between their imides. The edge-to-edge pi systems of the 5PDI chromophores within lin-5PDI2 are perpendicular to one another. Ground-state absorption spectra of both 5PDI dimers show exciton coupling, which is consistent with the orientation of the 5PDI chromophores relative to one another. Ultrafast transient absorption spectroscopy following excitation of the dimers with 700 nm, 100 fs laser pulses shows that quantitative intradimer electron transfer occurs in cof-5PDI2 in toluene with tau = 0.17 ps followed by charge recombination to the ground state with tau = 222 ps. Similar measurements on lin-5PDI2 reveal that photoinduced electron transfer does not occur in toluene, but occurs in more polar solvents such as 2-methyltetrahydrofuran, wherein tau = 55 ps for charge separation and tau = 99 ps for charge recombination. Excited-state symmetry breaking in 5PDI dimers provides new routes to biomimetic charge separation and storage assemblies that can be more easily prepared and modified than those based on multiple tetrapyrrole macrocycles.     

Hydrogen bond induced chiral symmetry breaking in the crystallization of nickel(II) complexes

A pair of enantiomers formulated as {Δ-cis-[Ni(en)₂OAc][ClO₄]} _n (Δ-1) and {Λ-cis-[Ni(en)₂OAc][ClO₄]} _n (Λ-1) (en = diaminoethane, OAc^? = acetate anion) were obtained when nickel acetate was reacted with diaminoethane and sodium perchlorate in the absence of any chiral source, whereas the reactions of nickel acetate with 1,3-propanediamine and sodium perchlorate only gave a centrosymmetric complex [Ni(1,3-pn)₂OAc][ClO₄] (2) (1,3-pn = 1,3-propanediamine). Single-crystal X-ray diffraction analyses of all three complexes indicated that the central Ni(II) atoms all have a distorted octahedral coordination geometry, being coordinated by four nitrogen atoms of the diamine ligands, plus two oxygen atoms of OAc^?. In complexes Δ-1 and Λ-1, the monomers of {Δ-cis-[Ni(en)₂OAc]}⁺ and {Λ-cis-[Ni(en)₂OAc]}⁺ are connected through intermolecular hydrogen bonds to generate one-dimensional right- and left-handed homochiral helical chains, respectively, while the monomers of [Ni(1,3-pn)₂OAc]⁺ are linked by similar intermolecular hydrogen bonds to form one-dimensional zigzag chains instead of helical chains. The chiral natures of complexes Δ-1 and Λ-1 have been confirmed by circular dichroism spectroscopy.     

Compression induced chiral symmetry breaking of monolayers comprised of banana-shaped achiral molecules at an air-water interface: Williams-Bragg approach

Chirality of monolayers comprised of banana-shaped achiral molecules at an air-water interface was investigated theoretically, and a forming mechanism of chiral structure as an assembly of achiral molecules was argued. A model of such monolayers was constructed taking into account the short-range repulsive interaction between constituent banana-shaped achiral molecules, and the free energy density functional of the model was derived as a generalization of Williams-Bragg approach. It was predicted that chiral symmetry breaking occurs by monolayer compression, where two-dimensional characteristics of monolayers at an interface plays an important role in the formation of chiral structure by banana-shaped achiral molecules.     

Group of symmetry of the periodic system of chemical elements

The concurrence of the group of symmetry of the periodic system of elements with the group of dynamical symmetry of a hydrogenlike atom is employed in the theoretical investigation of atoms. The character of the degeneracy of the eigenvalues of a hydrogenlike atom Hamiltonian, without changing its eigenfunctions, was changed by introducing into this Hamiltonian a term which violates the symmetry in relation to transformations from the subgroup O(4) of the group SO(4, 2). In consequence, it was realized that such “reorganization” of the states of a hydrogenlike atom, which form a representation of the group SO(4, 2), effects the splitting of this representation into finite‐dimensional multiplets, first of which are in full agreement with the experimentally observable composition of electron shells of atoms, and retains the physical meaning of quantum numbers that define electron states. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 72: 499–508, 1999     

Strategies for protein-based nanofabrication: Ni-NTA as a chemical mask to control biologically imposed symmetry

Background: Technologies that improve control of protein orientation on surfaces or in solution, through designed molecular recognition, will expand the range of proteins that are useful for biosensors, molecular devices and biomaterials. A limitation of some proteins is their biologically imposed symmetry, which results in indistinguishable recognition surfaces. Here, we have explored methods for modifying the symmetry of an oligomeric protein that exhibits useful self-assembly properties.Results:Escherichia coli glutamine synthetase (GS) contains 24 solvent-exposed histidines on two symmetry-related surfaces. These histidines drive a metal-dependent self-assembly of GS tubes. Immobilization of GS on the affinity resin Ni²⁺-NTA followed by on-column modification with diethyl pyrocarbonate affords asymmetrically modified GS that self-assembles only to the extent of ‘short’ dimeric GS tubes, as demonstrated by electron microscopy, dynamic light scattering and atomic force microscopy. The utility of Ni²⁺-NTA as a chemical mask was also demonstrated for asymmetric modification of engineered cysteines adjacent to the natural histidines.Conclusions: Current genetic methods do not provide distinguishable recognition elements on symmetry-related surfaces of biologically assembled proteins. Ni²⁺-NTA serves as a mask to control chemical modification in vitro of residues within symmetry-related pairs, on proteins containing functional Histags. This strategy may be extended to modification of a wide range of amino acids with a myriad of reagents.     

Dynamic processes in the copper-catalyzed substitution of chiral allylic acetates leading to loss of chiral information

Copper-catalyzed alpha-substitution of enantiomerically pure secondary allylic esters with Grignard reagents was studied with the aim to find conditions that give racemic products. It was observed that the degree of chiral transfer is strongly dependent on the temperature. The loss of chiral information is consistent with an equilibration of the Cu(III)(allyl) intermediates prior to product formation. Equilibration of the reaction intermediates is of importance for a possible development of a dynamic kinetic asymmetric transformation (DYKAT) process, in which a chiral catalyst is used to produce an optically active product from a racemic substrate, by means of a dynamic equilibrium of the diastereomeric reaction intermediates.     

Real or artifactual symmetry breaking in the BNB radical: a multireference coupled cluster viewpoint

The ground state of the linear BNB radical has been examined via the recently developed reduced multireference coupled cluster method with singles and doubles that is perturbatively corrected for triples [RMR CCSD(T)] using the correlation consistent basis sets (cc-pVXZ, X=D, T, and Q). Similar to earlier results that were based on the single reference CCSD(T) and BD(T) approaches, the RMR CCSD(T) method also predicts an asymmetric structure with two BN bonds of unequal length, even though the MR effects significantly reduce the barrier height. The computed frequencies for the symmetric and antisymmetric stretching modes agree reasonably well with the experimental data.     

Phase separation of polymer mixtures induced by polarization‐selective chemical reactions: spatial symmetry breaking and mode selection

Phase separation of polystyrene/poly (vinyl methyl ether) (PS/PVME) blends was induced and controlled by irradiation with linearly polarized light. The PS component was made photosensitive by chemically labeled with either anthracene or trans‐stilbene. The former was used to crosslink the PS component whereas the latter induces phase separation by changing polymer segmental volumes. The phase separation and reaction kinetics were observed and discussed in terms of mode‐selection process.     

Determining symmetry changes during a chemical reaction: the case of diazene isomerization

Analysis of reaction paths in terms of the Continuous Symmetry Measure (CSM) provides an alternative way to analyze the geometrical changes that take place during a reaction. Unique symmetry-profiles, describing the symmetry changes along the internal reaction coordinate were calculated for the cis-trans isomerization reaction of N₂H₂ and for its halogeno derivatives. A “symmetry transition point” is identified at the extremum point along the symmetry-profiles. At this point, the deviation of the molecule from the rotational symmetry of the reactant is the same as its deviation from the rotational symmetry of the product. In a second application we show that the CSM can be used as an alternative reaction coordinate. Calculations at the MP2 and DFT levels result in similar symmetry profiles.     

Historical incidents leading to the evolution of good manufacturing practice

The concept of good manufacturing practice (GMP) is not new; its roots are very old. The incidents that gave birth to the concept of GMP are summarized in this article. The journey from the FDA toward GMP is highlighted in chronological order. These regulations are mandatory for pharmaceutical industries in order to manufacture quality products.     

From the double-stranded helix to the chiral nematic phase of B-DNA: a molecular model

B-DNA solutions of suitable concentration form left-handed chiral nematic phases (cholesterics). Such phases have also been observed in solutions of other stiff or semiflexible chiral polymers; magnitude and handedness of the cholesteric pitch are uniquely related to the molecular features. In this work we present a theoretical method and a numerical procedure which, starting from the structure of polyelectrolytes, lead to the prediction of the cholesteric pitch. Molecular expressions for the free energy of the system are obtained on the basis of steric and electrostatic interactions between polymers; the former are described in terms of excluded volume, while a mean field approximation is used for the latter. Calculations have been performed for 130 base pair fragments of B-DNA. The theoretical predictions provide an explanation for the experimental behavior, by showing the counteracting role played by shape and charge chirality of the molecule.     

Nucleophilic addition of methanol and methanethiol to acetylene in the superbasic system KOH-DMSO: a quantum chemical model

Cluster-continuum models (KOH·nDMSO, n = 1, 5) were used to model the superbasic system “alkali metal hydroxide-dimethyl sulfoxide” within the framework of MP2/6-311++G**/ and B3LYP/6-31G* methods. The KOH molecule surrounded by five DMSO molecules exists as “solvate-loosened” ion pair with elongated K-O distance. It is proposed to consider the “solvate-loosened” ion pair of potassium cation with hydroxide anion in the surroundings of five solvent molecules as the catalytic coordination sphere of the superbasic system KOH-DMSO. Methanol and methanethiol molecules can be incorporated with ease into the first coordination sphere of potassium cation to form methoxide and methanethiolate ions. The possibility of nucleophilic attack of methoxide and methanethiolate ions on acetylene molecule in the first coordination sphere of potassium cation was studied. The model reaction system C₂H₂-CH₃OK-H₂O with one DMSO molecule included explicitly to maintain the “solvate-loosened” [CH₃O]^?...K⁺ ion pair and additional inclusion of solvent effects within the framework of the IEFPCM continuum model is the most preferable for serial calculations.     

Solid-to-solid formation at the solid-liquid interface leading to a chiral coordination polymer from an achiral monomer

An achiral crystal of a simple mononuclear copper complex [Cu(II)(C(6)H(8)N(2))(2)SO(4)]·H(2)O (1), on dipping into an aqueous azide solution, transforms into a chiral crystal of a coordination polymer [Cu(II)(C(6)H(8)N(2))(N(3))(2)](n) (2) in a solid-liquid interface reaction demonstrating replacement of a sulfate anion by an azide anion from an aqueous solution.