Achiral 2-pyridone and 4-aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals.

Enantiomorphous crystals of achiral 2-pyridone and 4-aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5-pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine-5-carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5-pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2-pyridone and 4-aminopyridine.

Asymmetric Autocatalysis as an Efficient Link Between the Origin of Homochirality and Highly Enantioenriched Compounds.

Biological homochirality of essential components such as L-amino acids and D-sugars is prerequisite for the emergence, evolution and the maintenance of life. Implication of biological homochirality is described. Considerable interest has been focused on the origin and the process leading to the homochirality. Asymmetric autocatalysis with amplification of enantiomeric excess (ee), i.e., the Soai reaction, is capable to link the low ee induced by the proposed origins of chirality such as circularly polarized light and high ee of the organic compound. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved in the Soai reaction.

A Synthetic Model for the Possible FeIV2(µ-O)2 Core of Methane Monooxygenase Intermediate Q Derived from a Structurally Characterized FeIIIFeIV(µ-O)2 Complex.

A bis(µ-oxo)diiron(IV,IV) complex as a model for intermediate Q in the methane monooxygenase reaction cycle has been prepared. The precursor complex with a [FeIIIFeIV(µ-O)2] core was fully characterized by X-ray crystallography and other spectroscopic analyses and was converted to the [FeIV2(µ-O)2] complex via electrochemical oxidation at 1000 mV (vs Ag/Ag+) in acetone at 193 K. The UV-vis spectral features, Mössbauer parameters (ΔEQ = 2.079 mm/s and δ = -0.027 mm/s), and EXAFS analysis (Fe-O/N = 1.73/1.96 Å and Fe···Fe = 2.76 Å) support the structure of the low-spin (S = 1, for each Fe) [FeIV2(µ-O)2] core. The rate constants of the hydrogen abstraction reaction from 9,10-dihydroanthracene at 243 K suggest the high reactivity of these synthetic bis(µ-oxo)diiron complexes supported by simple N4 tripodal ligand.

Chiral Dinuclear EuIII , TbIII , and YIII Complexes Supported by P-Stereogenic Linear Tetraphosphine Tetraoxide.

A P-stereogenic linear tetraphosphine tetraoxide, (R,R)- or (S,S)-dpmppm(=O)4 , was synthesized to prepare C2 dinuclear M(hfa)3 complexes (M=Eu, Tb, Y) as the first example of lanthanide(III) complexes with P-chiral multidentate phosphine oxides. The mononuclear M(hfa)3 complexes (M=Eu, Y) with a P-chiral diphosphine dioxide, tpdpb(=O)2 , were also prepared, and comparison of their photophysical properties for the EuIII complexes revealed that significant chiral induction from the P-chiral centers arises on the achiral M(hfa)3 units through intramolecular π-π stacking constraint in the dinuclear system.

Circular dichroism spectroscopy of catalyst preequilibrium in asymmetric autocatalysis of pyrimidyl alkanol.

Mechanistic understanding of the asymmetric autocatalysis of pyrimidyl alkanol is a highly attractive and challenging topic due to its unique feature of amplification of enantiomeric excess. Circular dichroism spectroscopic analysis of this reaction allows monitoring of the structual changes of possible catalyst precursors in the solution state and shows characteristic temperature and solvent dependence. TD-DFT calculations suggest that these spectral changes are induced by a dimer-tetramer equilibrium of zinc alkoxides.

Asymmetric autocatalysis triggered by triglycine sulfate with switchable chirality by altering the direction of the applied electric field.

Triglycine sulfate (TGS) acts as a chiral trigger for asymmetric autocatalysis with amplification of enantiomeric excess, i.e., the Soai reaction. Therefore, molecular chirality of highly enantioenriched organic compounds is controlled by a ferroelectric crystal TGS, whose polarization is altered by an electric field.

Structure and electrochemical properties of (µ-O)2Mn2(iii,iii) and (µ-O)2Mn2(iii,iv) complexes supported by pyridine-, quinoline-, isoquinoline- and quinoxaline-based tetranitrogen ligands.

Seven new bis(µ-oxo)dimanganese complexes with Mn2(iii,iii) or Mn2(iii,iv) oxidation states were prepared using quinoline- and isoquinoline-based tetraamine ligands. The structures of the ligands include ethylenediamine, trans-1,2-cyclohexanediamine and tripodal amine, bearing two or three nitrogen-containing heteroaromatics. Regardless of the skeleton and number of aliphatic nitrogen atoms in the ligands, quinoline complexes stabilize the Mn2(iii,iii) oxidation state, whereas, isoquinoline ligands afford Mn2(iii,iv) complexes. A systematic comparison of the differences in structural parameters and redox potentials of a total of 14 complexes with a (µ-O)2Mn2 diamond core, which includes corresponding pyridine and quinoxaline derivatives as supporting ligands, highlights the distinct deviation of quinoline and tripodal amine motifs in this ligand series.

Chiral approach to investigate mechanism of highly efficient thermally activated delayed fluorescence.

A chiral chromophore with thermally activated delayed fluorescence characteristics is designed. A model describing vibrations of the dihedral angle between donor and acceptor units allowed at room temperature explains the enhanced fluorescence rate of the molecule, including a nearly 100% photoluminescence quantum yield and the absence of circularly polarized emission characteristics from enantiomers of the chromophore.

Switching of Fluorescent Zn/Cd Selectivity in N,N,N',N'-Tetrakis(6-methoxy-2-quinolylmethyl)-1,2-diphenylethylenediamine by One Asymmetric Carbon Atom Inversion.

A quinoline-based hexadentate ligand, (S,S)-N,N,N',N'-tetrakis(6-methoxy-2-quinolylmethyl)-1,2-diphenylethylenediamine ((S,S)-6-MeOTQPh2EN), exhibits fluorescence enhancement at 498 nm upon addition of 1 equiv of Zn2+ (IZn/I0 = 12, φZn = 0.047) in aqueous DMF solution (DMF/H2O = 2:1). Addition of 1 equiv of Cd2+ affords a much smaller fluorescence increase at the same wavelength (ICd/I0 = 2.5, ICd/IZn = 21%). The trivalent metal ions such as Al3+, Cr3+, and Fe3+ also exhibit fluorescence enhancement at 395 nm (IAl/I0 = 22, ICr/I0 = 6 and IFe3+/I0 = 13). In contrast, meso-6-MeOTQPh2EN exhibits a Cd2+-selective fluorescence increase at 405 nm in the presence of 1 equiv of metal ion (ICd/I0 = 11.5, φCd = 0.022), while Zn2+ induces a smaller fluorescent response under the same experimental conditions (IZn/I0 = 3.3, IZn/ICd = 29%). In this case, the fluorescence intensities of meso-6-MeOTQPh2EN in the presence of a large amount of Zn2+ and Cd2+ become similar. This diastereomer-dependent, fluorescent metal ion specificity is derived from the Zn2+-specific intramolecular excimer formation in (S,S)-6-MeOTQPh2EN-Zn2+ complex and higher binding affinity of meso-6-MeOTQPh2EN with Cd2+ in comparison to Zn2+. The more conformationally restricted diastereomeric pair, namely, cis- and trans-TQDACHs (cis- and trans-N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-diaminocyclohexanes), both exhibit Zn2+-specific fluorescence enhancement because of the high metal binding affinity and intramolecular excimer forming property derived from the rigid DACH backbone.

Formation of enantioenriched alkanol with stochastic distribution of enantiomers in the absolute asymmetric synthesis under heterogeneous solid-vapor phase conditions.

Among several theories proposed for the origin of homochirality, absolute asymmetric synthesis is unique because it produces chiral compounds without the intervention of any chiral factor. Here we report on the kinetically controlled heterogeneous solid-vapor phase absolute asymmetric synthesis in conjunction with asymmetric autocatalysis with amplification of chirality. Each reaction, carried out in a test tube, between achiral powder crystals of pyrimidine-5-carbaldehyde and the vapor of diisopropylzinc, is controlled kinetically to afford either (S)- or (R)-pyrimidyl alkanol.

Achiral amino acid glycine acts as an origin of homochirality in asymmetric autocatalysis.

Chiral crystals of the only achiral proteinogenic α-amino acid, glycine induced the asymmetric autocatalysis with amplification of enantiomeric excess (ee). The P31 crystals of γ-glycine, which display positive Cotton effect (CD) at around 215 nm, mediate the asymmetric autocatalysis to yield (R)-pyrimidyl alkanol with high ee. In contrast, the enantiomorphic P32 crystals, which display negative Cotton effect, afford (S)-alkanol after the significant amplification of ee by asymmetric autocatalysis.

Methoxy-substituted tetrakisquinoline analogs of EGTA and BAPTA for fluorescence detection of Cd2+ .

EGTA (ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid) and BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) are well-known Ca2+ chelators that have four carboxylates, two nitrogen atoms and two ether oxygen atoms. In the present study, we prepared EGTQ (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-bis(2-aminoethoxy)ethane) and BAPTQ (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-bis(2-aminophenoxy)ethane) as quinoline alternatives of EGTA and BAPTA, respectively. In methanol-HEPES buffer solution (9 : 1, 50 mM HEPES, 0.1 M KCl, pH = 7.5), EGTQ exhibits fluorescence enhancement induced by Zn2+ and Cd2+ with poor selectivity, but BAPTQ did not exhibit a fluorescence response to either metal ion. Introduction of three methoxy substituents at the 5,6,7-positions of each quinoline moiety in BAPTQ specifically enhanced the fluorescence intensity of the Cd2+ complex, establishing the Cd2+-specific probe TriMeOBAPTQ (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-bis(2-aminophenoxy)ethane). In contrast, TriMeOEGTQ (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-bis(2-aminoethoxy)ethane) maintains a poor Cd2+/Zn2+ selectivity in its fluorescence response. Although the crystal structures of Cd2+/Zn2+ complexes with EGTQ and BAPTQ derivatives reveal the formation of multiple components including mononuclear and dinuclear complexes, the dinuclear Cd2+ and Zn2+ complexes with a linearly extended structure are regarded as possible fluorescent species in the solution. The conformational restriction of BAPTQ due to the orthophenylene moieties in the molecular skeleton is responsible for the formation of the weakly fluorescent, OH-bridged dizinc complex, which is critical to the strict Cd2+-specificity in the fluorescence response of TriMeOBAPTQ.

Pyrophosphate-Induced Intramolecular Excimer Formation in Dinuclear Zinc(II) Complexes with Tetrakisquinoline Ligands.

Dinuclear Zn2+ complexes with HTQHPN ( N,N,N' ,N'-tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine) derivatives have been prepared, and their pyrophosphate (PPi, P2O74-) sensing properties were examined. The ligand library includes six HTQHPN derivatives with electron-donating/withdrawing substituents, an extended aromatic ring, and six-membered chelates upon zinc binding. Complexation of ligand with 2 equiv of Zn2+ promotes small to moderate fluorescence enhancement around 380 nm, but in the cases of HTQHPN, HT(6-FQ)HPN ( N,N,N' ,N'-tetrakis(6-fluoro-2-quinolylmethyl)-2-hydroxy-1,3-propanediamine), and HT(8Q)HPN ( N,N,N' ,N'-tetrakis(8-quinolylmethyl)-2-hydroxy-1,3-propanediamine), subsequent addition of PPi induced a significant fluorescence increase around 450 nm. This fluorescence enhancement in the long-wavelength region is attributed to the conformational change of the bis-(quinolylmethyl)amine moiety which promotes intramolecular excimer formation between adjacent quinolines upon binding with PPi. The structures of PPi- and phosphate-bound dizinc complexes were revealed by X-ray crystallography utilizing phenyl-substituted analogues. The zinc complex with HT(8Q)HPN exhibits the highest signal enhancement ( IPPi/ I0 = 12.5) and selectivity toward PPi sensing ( IATP/ IPPi = 20% and IADP/ IPPi = 25%). The fluorescence enhancement turned to decrease gradually after the addition of more than 1 equiv of PPi due to the removal of zinc ion from the ligand-zinc-PPi ternary complex, allowing the accurate determination of PPi concentrations at the fluorescence maximum composition. The practical application of the present method was demonstrated monitoring the enzymatic activity of pyrophosphatase.

Reversal of the sense of enantioselectivity between 1- and 2-aza[6]helicenes used as chiral inducers of asymmetric autocatalysis.

Reversal of the sense of enantioselectivity was observed between 1-aza[6]helicene 2 and 2-aza[6]helicene 3 employed as chiral inducers of asymmetric autocatalysis of pyrimidyl alkanol. In the presence of (P)-(+)-1-aza[6]helicene 2, the reaction of pyrimidine-5-carbaldehyde 1 with diisopropylzinc afforded, in conjunction with asymmetric autocatalysis, (S)-pyrimidyl alkanol 4 with high ee. Surprisingly, the reaction in the presence of (P)-(+)-2-aza[6]helicene 3 gave the opposite enantiomer of (R)-alkanol 4 with high ee. In the same manner, (M)-(-)-2 and (M)-(-)-3 afforded (R)- and (S)-alkanol 4, respectively. The sense of enantioselectivity is controlled not only by the helicity of the azahelicene derivatives but also by the position of the nitrogen atom.

Achiral Inorganic Gypsum Acts as an Origin of Chirality through Its Enantiotopic Surface in Conjunction with Asymmetric Autocatalysis.

Achiral inorganic gypsum (CaSO4 ⋅2 H2 O) triggers the asymmetric autocatalysis of pyrimidyl alkanol on its two-dimensional enantiotopic faces to give highly enantioenriched alkanol products with absolute configurations corresponding to the respective enantiotopic surfaces. This is the first example of highly enantioselective synthesis on the enantiotopic surface of an achiral mineral.

Point-to-Point Ultra-Remote Asymmetric Control with Flexible Linker.

An ultra-remote intramolecular (point-to-point) asymmetric control through 38 bonds (1,39-asymmetric induction) has been achieved by using the principle of direct supramolecular orientation of catalytic and reactive moieties in asymmetric autocatalysis. We found the highly stereoselective diisopropylzinc addition reaction using designed molecules possessing pyrimidine sites at each terminal of a conformationally flexible simple methylene chain.

Asymmetric Induction by a Nitrogen 14 N/15 N Isotopomer in Conjunction with Asymmetric Autocatalysis.

Chirality arising from isotope substitution, especially with atoms heavier than the hydrogen isotopes, is usually not considered a source of chirality in a chemical reaction. An N2 ,N2 ,N3 ,N3 -tetramethyl-2,3-butanediamine containing nitrogen (14 N/15 N) isotope chirality was synthesized and it was revealed that this isotopically chiral diamine compound acts as a chiral initiator for asymmetric autocatalysis.

Can the analyte-triggered asymmetric autocatalytic Soai reaction serve as a universal analytical tool for measuring enantiopurity and assigning absolute configuration?

An investigation is reported on the use of the autocatalytic enantioselective Soai reaction, known to be influenced by the presence of a wide variety of chiral materials, as a generic tool for measuring the enantiopurity and absolute configuration of any substance. Good generality for the reaction across a small group of test analytes was observed, consistent with literature reports suggesting a diversity of compound types that can influence the stereochemical outcome of this reaction. Some trends in the absolute sense of stereochemical enrichment were noted, suggesting the possible utility of the approach for assigning absolute configuration to unknown compounds, by analogy to closely related species with known outcomes. Considerable variation was observed in the triggering strength of different enantiopure materials, an undesirable characteristic when dealing with mixtures containing minor impurities with strong triggering strength in the presence of major components with weak triggering strength. A strong tendency of the reaction toward an 'all or none' type of behavior makes the reaction most sensitive for detecting enantioenrichment close to zero. Consequently, the ability to discern modest from excellent enantioselectivity was relatively poor. While these properties limit the ability to obtain precise enantiopurity measurements in a simple single addition experiment, prospects may exist for more complex experimental setups that may potentially offer improved performance.

Crystal Structure of the Isopropylzinc Alkoxide of Pyrimidyl Alkanol: Mechanistic Insights for Asymmetric Autocatalysis with Amplification of Enantiomeric Excess.

Asymmetric amplification during self-replication is a key feature that is used to explain the origin of homochirality. Asymmetric autocatalysis of pyrimidyl alkanol in the asymmetric addition of diisopropylzinc to pyrimidine-5-carbaldehyde is a unique example of this phenomenon. Crystallization of zinc alkoxides of this 5-pyrimidyl alkanol and single-crystal X-ray diffraction analysis of the alkoxide crystals reveal the existence of tetramer or higher oligomer structures in this asymmetric autocatalytic system.

Helical mesoporous silica as an inorganic heterogeneous chiral trigger for asymmetric autocatalysis with amplification of enantiomeric excess.

Mesoporous silica has been used as a heterogeneous support for catalysts; however, asymmetric induction by the helicity of inorganic mesoporous silica itself has not yet been achieved. P- and M-helical mesoporous silica was found to act as a chiral inorganic trigger for asymmetric autocatalysis to afford (S) and (R)-pyrimidyl alkanol with >99.5% ee, respectively.