Enantioselective Autocatalysis. V. The Spontaneous Resolution of Tri-o-Thymotide

We have attempted to appraise experimentally the allegation that minute chemical and physical differences due to the parity violating energy difference (PVED) between enantiomers are, after suitable autocatalytic amplification, ultimately responsible for the homochirality of contemporary biomolecules. The autocatalytic amplification technique employed involved the spontaneous resolution under racemizing conditions (SRURC) of a conglomerate during crystallization, and the system studied was the known crystallization of P(+)- or M(–)-tri-o-thymotide (TOT) as its optically active inclusion compound (clathrate) with benzene. Our premise was that if a PVED effect were operative, there should be a strong and consistent bias favoring the crystallization of one enantiomer of the TOT-benzene clathrate. Repetitive preparations of the clathrate, however, yielded crystalline products showing random optical activity. These results thus afford no evidence whatsoever for stereoselective bias due to a PVED, and are in accord with earlier statistical studies demonstrating random SRURC in other conglomerate crystallizations, again indicating the inefficacy of PVEDs to promote a preferred chirality in such systems.     

Chiroptical signatures of life and fundamental physics

This paper aims to inspire experimentalists to carry out proposed new chiroptical experiments springing from the theoretical study of the role of parity violation in the origin of biomolecular homochirality and to provide a brief update on the current status of calculations of the electroweak parity-violating energy difference (PVED) between enantiomers. If the PVED did select life's handedness, we would expect to find life on other planets consistently using the same hand as terrestrial biochemistry. Much more importantly, even finding the "wrong" hand (rather than a racemic mixture) on another planet could be the homochiral signature of life, and we discuss our proposal for chiroptical detection of life on extra-solar planets. The PVED may also have an exciting future as a "molecular footprint" of fundamental physics: comparison of calculated PVEDs with measured values could one day allow chemists to do "table-top particle physics" more cheaply with improved chiroptical techniques instead of ever larger particle accelerators. We discuss our proposed chiroptical method to measure the PVED by using molecular beams. To our knowledge, optical rotation has not yet been measured in molecular beams, but the rewards of doing so include a host of other "first ever" results in addition to measurement of the PVED. Chirality 24:764-769, 2012. ? 2012 Wiley Periodicals, Inc.     

Enantioselective autocatalysis. Spontaneous resolution and the prebiotic generation of chirality

Theoretical and experimental models for autocatalytic systems leading to the prebiotic origin of chiralityvia the spontaneous symmetry breaking (resolution) of racemic substrates are reviewed. Of the experimental models so far studied, only 2nd order assymetric transformations during crystallization of optically labile enantiometers, leading to their spontaneous resolution under racemizing conditions (SRURC) have been successful. Our objective was to investigate in further detail the most promising of these systems from the point of view of its overall efficiency and its potential viability as a mechanism for the spontaneous generation of molecular chirality on the prebiotic Earth. To this end the 1,4-benzo-diazepinooxazole derivative XI, having a single asymmetric carbon atom, has been synthesized. We here confirm a report in the literature that (±)-XI undergoes SRURC in methanol, both on crystallization and as a slurry. The total spontaneous resolution of (±)-XI has been achieved in a yield of 99%, of which 80% had an optical purity ofca. 93%. Arguments are presented that SRURC of racemic substrates, while thus demonstrably effective in laboratory experiments, was probably not of major importance for the origin or amplification of molecular chirality on the primitive earth.     

Cosmic Chirality both True and False

The discrete symmetries of parity P, time reversal T, and charge conjugation C may be used to characterize the properties of chiral systems. It is well known that parity violation infiltrates into ordinary matter via an interaction between the nucleons and electrons, mediated by the Z⁰ particle, that lifts the degeneracy of the mirror‐image enantiomers of a chiral molecule. Being odd under P but even under T, this P‐violating interaction exhibits true chirality and so may induce absolute enantioselection under all circumstances. It has been suggested that CP violation may also infiltrate into ordinary matter via a P‐odd, T‐odd interaction mediated by the (as yet undetected) axion. This CP‐violating interaction exhibits false chirality and so may induce absolute enantioselection in processes far from equilibrium. Both true and false cosmic chirality should be considered together as possible sources of homochirality in the molecules of life. Chirality 24:957‐958, 2012.© 2012 Wiley Periodicals, Inc.     

Synthesis and Antiaggregative Activity of a New RGDF Mimetic

m-[4-Oxo-4-(piperazin-1-yl)butyrylamino)benzoyl-D,L--(3,4-methylenedioxyphenyl)--alanine, a new mimetic of the peptide RGDF, was synthesized. This compound inhibited ADP-induced platelet aggregation in human blood plasma enriched with platelets with IC₅₀ = 3.5 × 10^–8 M.     

Evaluation of Coupled Perturbed and Density Functional Methods of Computing the Parity-Violating Energy Difference between Enantiomers

We present new coupled-perturbed Hartree-Fock (CPHF) and density functional theory (DFT) computations of the parity-violating energy difference (PVED) between enantiomers for H₂O₂ and H₂S₂. Our DFT PVED computations are the first for H₂S₂ and the first with the new HCTH and OLYP functionals. Like other “second generation” PVED computations, our results are an order of magnitude larger than the original “first generation” uncoupled-perturbed Hartree-Fock computations of Mason and Tranter. We offer an explanation for the dramatically larger size in terms of cancellation of contributions of opposing signs, which also explains the basis set sensitivity of the PVED, and its conformational hypersensitivity (addressed in the following paper). This paper also serves as a review of the different types of “second generation” PVED computations: we set our work in context, comparing our results with those of four other groups, and noting the good agreement between results obtained by very different methods. DFT PVEDs tend to be somewhat inflated compared to the CPHF values, but this is not a problem when only sign and order of magnitude are required. Our results with the new OLYP functional are less inflated than those with other functionals, and OLYP is also more efficient computationally. We therefore conclude that DFT computation offers a promising approach for low-cost extension to larger biosystems, especially polymers. The following two papers extend to terrestrial and extra-terrestrial amino acids respectively, and later work will extend to polymers.     

Molecular dynamics and free energy studies of chirality specificity effects on aminobenzo[a]quinolizine inhibitors binding to DPP-IV

The aminobenzo[a]quinolizines were investigated as a novel class of DPP-IV inhibitors. The stereochemistry of this class plays an important role in the bioactivity. In this study, the mechanisms of how different configuration of three chiral centers of this class influences the binding affinity were investigated by molecular dynamics simulations, free energy decomposition analysis. The S configuration for chiral center 3* is decisive for isomers to maintain high bioactivity; the chirality effect of chiral center 2* on the binding affinity is largely dependent, while the S configuration for chiral center 2* is preferable to R configuration for the bioactivity gain; the effect of chiral center 11b* on the binding affinity is insignificant. The chirality specificity for three chiral centers is responsible for distinction of two van der Waals contacts with Tyr547 and Phe357, and of H-bonding interactions with Arg125 and Glu206. Particularly, the Arg125 to act as a bridge in the H-bonding network contributes to stable H-bonding interactions of isomer in DPP-IV active site.

Quantum mechanical considerations on the algebraic structure of central molecular chirality

The chiral algebra of tetrahedral molecules, derived from Fischer's projections, is discussed in the framework of quantum mechanics. A "quantum chiral algebra" is obtained whose operators, acting as rotations or inversions, commute with the Hamiltonian of the system. It is shown that energy and chirality eigenstates are strictly related through the Heisenberg relations, while chirality operators "conserve" parity eigenstates.     

Metabolism of non-phenolic β-O-4 lignin model compounds by the white-rot fungus Phlebia radiata

Summary The degradation of three non-phenolic -O-4 diarylpropane lignin model compounds was studied in cultures of the white-rot fungus Phlebia radiata. The degradation pattern of the model compound 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol (I) was also compared with that of Phanerochaete chrysosporium under conditions where both fungi were cultivated without agitation in an oxygen atmosphere. Compound I was readily degraded by both fungi, and qualitatively the degradation patterns were quite similar. The product, after C-C bond cleavage, was veratraldehyde (IV) which was almost stoichiometrically reduced to veratryl alcohol (V). However, large amounts of V were detected only in P. chrysosporium cultures. Experiments with the model compound 1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol (II) showed that in the presence of II, the total amount of veratryl compounds accounted for 15–33 m in standing cultures of Phlebia radiata. The model compound 1-(3,4-dimethoxyphenyl)-2-(4-methoxyphenoxy) propane-1,3-diol (III) was more readily degraded than I and II. The results indicated that, in P. radiata cultures, the acting enzymes were lignin peroxidases and IV reducing enzyme, while laccase was less important. Offprint requests to: A. Hatakka     

Chirality and Gravitational Parity Violation

In this review, parity‐violating gravitational potentials are presented as possible sources of both true and false chirality. In particular, whereas phenomenological long‐range spin‐dependent gravitational potentials contain both truly and falsely chiral terms, it is shown that there are models that extend general relativity including also coupling of fermionic degrees of freedom to gravity in the presence of torsion, which give place to short‐range truly chiral interactions similar to that usually considered in molecular physics. Physical mechanisms which give place to gravitational parity violation together with the expected size of the effects and their experimental constraints are discussed. Finally, the possible role of parity‐violating gravity in the origin of homochirality and a road map for future research works in quantum chemistry is presented. Chirality 27:375–381, 2015.© 2015 Wiley Periodicals, Inc.     

Shell chirality in Cambrian gastropods and sinistral members of the genus <Emphasis Type="Italic">Aldanella</Emphasis> Vostokova, 1962

Shell chirality among Cambrian gastropods is discussed. It is demonstrated that the earliest members of the class include chiral aberrations with abnormal opposite coiling of the shell. It is assumed that, in Cambrian gastropods, speciation could have occurred by mutation in the locus determining the chirality, as is proposed for extant gastropods. In contrast to modern gastropods, the existence of chiral morphs within single species has not been recorded in Cambrian mollusks, whereas the presence of chiral twin species is possible. The systematic position of sinistral representatives of the genus Aldanella Vostokova, 1962 is considered. Aldanella golubevi sp. nov. with sinistral shell is described from the base of the Tommotian Stage of the Anabar Region. Aberrant sinistral specimens of the normally dextral species Aldanella utchurica Missarzhevsky in Rozanov et al., 1969 and Pelagiella adunca Missarzhevsky in Rozanov et al., 1969 are figured.     

Synthesis and enantiomeric analysis of cyclotriphosphazene derivatives with one centre of chirality

A series of chiral cyclotriphosphazene compounds 2-9 in which the spiro 3-amino-1-propanoxy moiety provides the one centre of chirality have been synthesised and characterised by elemental analysis, MS, ¹H and ³¹P NMR spectroscopies. The enantiomers of newly synthesised compounds have been analysed by the changes in the ³¹P NMR spectra on addition of a Chiral Solvating Agent (CSA), (S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol. HPLC methods have been developed for the enantiomeric separations of chiral cyclotriphosphazenes containing one centre of chirality. It is found that chiral HPLC gave a good resolution of enantiomers of the racemic compounds 2-9 with resolution factors between 2.49 and 7.50 making them good candidates for enantiomeric separations and determination of absolute configuration.     

Asymmetric Autocatalysis Induced by Chiral Crystals of Achiral Tetraphenylethylenes

The achiral hydrocarbon tetraphenylethylene crystallizes in enantiomorphous forms (chiral space group: P2₁) to afford right- and left-handed hemihedral crystals, which can be recognized by solid-state circular dichroism spectroscopic analysis. Chiral organic crystals of tetraphenylethylene mediated enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to give, in conjunction with asymmetric autocatalysis with amplification of chirality, almost enantiomerically pure (S)- and (R)-5-pyrimidyl alkanols whose absolute configurations were controlled efficiently by the crystalline chirality of the tetraphenylethylene substrate. Tetrakis(p-chlorophenyl)ethylene and tetrakis(p-bromophenyl)ethylene also show chirality in the crystalline state, which can also act as a chiral substrate and induce enantioselectivity of diisopropylzinc addition to pyrimidine-5-carbaldehyde in asymmetric autocatalysis to give enantiomerically enriched 5-pyrimidyl alkanols with the absolute configuration correlated with that of the chiral crystals. Highly enantioselective synthesis has been achieved using chiral crystals composed of achiral hydrocarbons, tetraphenylethylenes, as chiral inducers. This chemical system enables significant amplification of the amount of chirality using spontaneously formed chiral crystals of achiral organic compounds as the seed for the chirality of asymmetric autocatalysis.     

The apocytochrome b gene of Chlamydomonas smithii contains a mobile intron related to both Saccharomyces and Neurospora introns.

Summary The mitochondrial DNA of the two interfertile algal species Chlamydomonas smithii and Chlamydomonas reinhardtii are co-linear with the exception of ca. 1 kb insertion (the a insert) present in C. smithii DNA only. In vegetative diploids resulting from interspecific crosses, mitochondrial genomes are transmitted biparentally except for the a insert which is transmitted to all C. reinhardtii molecules in a manner reminiscent of the intron-mediated conversion event that occurs at the omega locus in yeast mitochondria, under the action of the I-SceI endonuclease. Here we report that the insert corresponds to a typical group I intron of 1075 bp, inserted within the gene for apocytochrome b and containing a 237 codon open reading frame (ORF). We also report the complete sequence of the apocytochrome b gene of C. smithii. Comparison with the sequence of the same gene in C. reinhardtii reveals the precise intron insertion site. These data, together with the previous genetic data provide the first example of intron mobility in mitochondria of the plant kingdom. The product of the intronic ORF shows 36% amino acid identity with the I-SceI endonuclease whereas the intron ribozyme shows a 60% identity at the nucleotide level with the Neurospora crassa cob · 1 intron. The possibility of a recent horizontal transfer of introns between fungi and algae is discussed.     

Transformation of dehydroepiandrosterone and pregnenolone by Mucor piriformis

The mode of transformation of dehydroepiandrosterone (I, 3-hydroxyandrost-5-en-17-one) and pregnenolone (II, 3-hydroxypregn-5-en-20-one) was studied using Mucor piriformis. Biotransformation products formed from I were 3,17-dihydroxyandrost-5-ene (Ia), 3-hydroxyandrost-5-ene-7,17-dione (Ib), 3,17-dihydroxyandrost-5-en-7-one (Ic), 3,7-dihydroxyandrost-5-en-17-one (Ie). Biotransformation products formed from compound II were 3,7-dihydroxypregn-5-en-20-one (IIa) and 3,7,11-trihydroxypregn-5-en-20-one (IIb). The organism did not carry out isomerization of the 5-en-3-ol to a 4-en-3-one system in the steroid molecules tested. In addition, it failed to carry out 14-hydroxylation possibly because of the lack of a 4-en-3-one system in I and II, and stereospecific hydroxylation at the C-7 position in I and II.     

Identification of wheat-Agropyron cristatum monosomic addition lines by RFLP analysis using a set of assigned wheat DNA probes

A non-radioactive digoxigenin-labelled DNA method was used successfully to identify RFLP markers in 54 Triticum aestivum cv Chinese Spring — Agropyron cristatum (2n=28, genome PPPP) P-genome monosomic addition lines. Southern analysis using a set of 14 DNA probes identifying each homoeologous chromosome arm, combined with two restriction enzymes HindIII and EcoRI, indicated that six A. cristatum chromosomes (1P, 2P, 3P, 4P, 5P and 6P) and five A. cristatum chromosome arms (2PS, 2PL, 5PL, 6PS and 6PL) have been individually added to the wheat genome. The added chromosomes of three lines were Agropyron translocated chromosomes. It was also found that two addition plants possessed an Agropyron-wheat translocation. These results showed that RFLP analysis using the set of assigned wheat probes was a powerful tool in detecting and establishing homoeology of alien A. cristatum chromosomes, or arms, added to wheat, as well as in screening the alien addition material. The creation of the monosomic addition lines should be useful for the transfer of disease-resistance genes from A. cristatum to wheat.     

Heterometallic coordination polymers constructed by linear ligands

Eight lanthanide–copper coordination polymers of linear rigid 4-(4-pyridyl)benzoate(L¹) and isonicotinate(L²), [LnCuI(L¹)₂(OAc) (H₂O)]_n (Ln = Pr, 1; Nd, 2; Sm, 3; Eu, 4; Gd, 5), [Ln₂Cu₄I₃(L²)₇ (H₂O)]_n (Ln = La, 6; Pr, 7), and [Nd₂Cu₇I₆(L²)₇ (H₂O)₆]_n·2.5nH₂O (8), were hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. The three-dimensional frameworks of 1–5 can be described as wave-like layer modules of [Ln(L¹)₂(OAc)(H₂O)]_n linking with each other through dimeric units of Cu₂I₂, whereas that of compounds 6 and 7 are constructed by layer modules of and Cu₄I₃ clusters. As for 8, dimeric units of Nd₂(L²)₇(H₂O)₆ connect layered polymeric forming a 3D framework.     

Radiolysis,racemization and the origin of molecular asymmetry in the biosphere

Summary An investigation has been undertaken to determine whether ionizing radiation might engender racemization of optically active amino acids, along with their usual radiolysis. As prototypes, crystalline D- and L-leucine, as well as aqueous solutions of their sodium salts were exposed to the radiation from a 3000 Ci⁶⁰Co-ray source.-ray doses which caused about 68% radiolysis of solid leucine left a residue which was about 5% racemized, while racemization proved even greater at lower doses for the dissolved sodium salts. In aqueous solution both percent degradation and percent racemization of the sodium salts were proportional to-ray dosage within the range employed (1–27 · 10⁶ rads). Implications of these observations for the origin of molecular asymmetry by the-decay parity violation mechanism are discussed.     

Chiral recognition of aromatic compounds by β-cyclodextrin based on bimodal complexation

The chiral recognition of the selected aromatic chiral compounds by native -cyclodextrin (-CD) based on bimodal complexation was studied using a flexible docking algorithm FDOCK. A quantitative empirical free energy relationship model was employed to predict the complex stability constants and the preferred binding modes. The results showed that the calculated complex stability constants are in good agreement with the experimental data. Furthermore, the main force responsible for host-guest complexation is the van der Waals force and the chiral molecules are completely included into the -CD cavity. The chiral recognition for the selected aromatic chiral compounds is the result of the van der Waals force counterbalancing with the other effects, such as the electrostatic interaction and the hydrophobic effect.Figure The favorable structures for the inclusion complexes of (S)_phenylbutyric with -CD. View in the plane normal to the Z-axis. -CD is shown in surface and (S)_phenylbutyric in CPK representation.