2-Acyl-dimedones as UV-active protective agents for chiral amino acids: enantiomer separations of the derivatives on chiral anion exchangers

2-Acetyldimedone and 12 related compounds were employed as UV-active pre-column derivatizing agents for amino acids. Direct enantioseparation of the products was achieved using chiral anion exchanger stationary phases in polar-organic mobile phase mode. Under basic conditions, the reagents´ cyclic β-tricarbonyl motifs can give rise to exo- and endocyclic enols through tautomerization. However, with primary amines (proteinogenic and unusual amino acids, aminosulfonic and aminophosphonic acids), we exclusively observed the formation of exocyclic enamine-type products. Reaction yields depended strongly on the 2-acyl modification of the reagent; in particular, we observed a significant decrease when electronegative or sterically demanding substituents were present in α-position to the exocyclic carbonyl group. In addition to improving UV detectability of the products, the introduction of this protective group facilitated successful enantiomer separations of the amino acid derivatives on Cinchona-based chiral anion exchangers. Particularly high enantiomer selectivity was observed in combination with stationary phases bearing a new variation of selectors with π-acidic (electron-poor) bis(trifluoromethyl)phenyl groups. No racemization of the analytes occurred at any stage of the analytical method including the deprotection, which was achieved with hydrazine.

Interstellar problems and matrix solutions.

The application of the matrix isolation technique, which is but one of the experimental techniques pioneered in George Pimentel's laboratories, to interstellar problems is described. Following a brief discussion of the interstellar medium (ISM) three areas are reviewed in which matrix experiments are particularly well-suited to contribute the information which is sorely needed to further our understanding of the ISM. The first involves the measurement of the spectroscopic properties of reactive species. The second is the determination of reaction rates and the elucidation of reaction pathways involving atoms, radicals and ions which are likely to interact on grain surfaces and in grain mantles. The third entails the determination of the spectroscopic, photochemical and photophysical properties of interstellar and cometary ice analogs. Significant, but limited, progress has been made in these three areas and a tremendous amount of work is required to fully address the variety of unique chemical and spectroscopic questions posed by the astronomical observations.     

星际媒介H2NCH2CN与H2O反应中的H2O分子偶合质子转移机理和氢隧道效应

H2NCH2CN+H2O→H2NCH2C(OH)NH是一个重要的反应, 涉及到星际媒介中甘氨酸的形成, 与早期地球上的氨基酸起源有关. 如果没有考虑氢隧道效应, 在MP2/6-311+G(d,p)级别上计算反应能垒是254.7 kJ·mol-1, 在星际媒介中该气相反应很难进行. 在星际媒介冰颗粒表面上, 水分子催化反应增强了该化学反应的活性. H2NCH2CN与(H2O)3反应中的两个水分子作为催化剂降低活化能77.5 kJ·mol-1和活化自由能70.9 kJ·mol-1, 并且通过氢键桥协同传递质子. 量子氢隧道对于该反应进行至关紧要,采用小弯曲隧道(SCT)近似和正则变分过渡态理论(CVT)方法研究. 温度50 K时, 速率常数kSCT/CVT为1.86×10-23 cm3·molecule-1·s-1, 表明在星际媒介中通过质子隧道机理该反应容易进行. 研究结果与地球上的氨基酸起源于地球本身物质的观点相一致.     

The mechanism of hexamethylenetetramine (HMT) formation in the solid state at low temperature

There is convincing evidence that the formation of complex organic molecules occurred in a variety of environments. One possible scenario highlights the universe as a giant reactor for the synthesis of organic complex molecules, which is confirmed by numerous identifications of interstellar molecules. Among them, precursors of biomolecules are of particular significance due to their exobiological implications, and some current targets concern their search in the interstellar medium as well as understanding the mechanisms of their formation. Hexamethylenetetramine (HMT, C(6)H(12)N(4)) is one of these complex organic molecules and is of prime interest since its acid hydrolysis seems to form amino acids. In the present work, the mechanism for HMT formation at low temperature and pressure (i.e. resembling interstellar conditions) has been determined by combining experimental techniques and DFT calculations. Fourier transform infra-red spectroscopy and mass spectrometry techniques have been used to follow experimentally the formation of HMT as well as its precursors from thermal reaction of NH(3):H(2)CO:HCOOH and CH(2)NH:HCOOH ice mixtures, from 20 K to 330 K. DFT calculations have been used to compute the mechanistic steps through which HMT can be formed starting from the experimental reactants observed in solid phase. The fruitful interplay between theory and experiment has allowed establishing that the mechanism in the solid state at low temperature is different from the one proposed in liquid phase, in which a new intermediate (1,3,5-triazinane, C(3)H(9)N(3)) has been identified. In the meantime, aminomethanol has been unambiguously confirmed as the first intermediate whereas the hypothesis of methylenimine as the second is further strengthened.     

在星际媒介中合成H2NCH2CN分子的理论研究

在早期地球原始化学生命起源过程中, 氨基酸是重要的必需的生物化合物, 生成肽和蛋白. 为了探究一个可能的新的氨基酸起源, 采用密度泛函理论(B3LYP)在6-311++G(d, p) 基组水平上研究了在星际媒介条件下在气相中和在模拟的冰颗粒表面上的化学反应: CH2NH分子和两个异构体分子HNC/HCN通过Strecker合成生成H2NCH2CN(氨基乙氰, 一个重要的苷氨基酸前置分子). 在研究体系中, CH2NH、HCN、HNC 和H2O分子存在于星际密集分子云中, 且早于地球广泛存在. 研究证明, 这些分子之间在星际媒介条件下和在冰颗粒表面上通过Strecker合成路线很容易生成H2NCH2CN. 所以, H2NCH2CN分子在宇宙的星际密集分子云中是广泛存在的. 还讨论了H2NCH2CN分子在新的氨基酸起源中所起的作用, 以及在通过“原始汤”生命起源理论解析早期地球生命起源中可能所起的作用.     

UV photodesorption of interstellar CO ice analogues: from subsurface excitation to surface desorption

Carbon monoxide is after H(2) the most abundant molecule identified in the interstellar medium (ISM), and is used as a major tracer for the gas phase physical conditions. Accreted at the surface of water-rich icy grains, CO is considered to be the starting point of a complex organic--presumably prebiotic--chemistry. Non-thermal desorption processes, and especially photodesorption by UV photons, are seen as the main cause that drives the gas-to-ice CO balance in the colder parts of the ISM. The process is known to be efficient and wavelength-dependent, but, the underlying mechanism and the physical-chemical parameters governing the photodesorption are still largely unknown. Using monochromatized photons from a synchrotron beamline, we reveal that the molecular mechanism responsible for CO photoejection is an indirect, (sub)surface-located process. The local environment of the molecules plays a key role in the photodesorption efficiency, and is quenched by at least an order of magnitude for CO interacting with a water ice surface.     

Simultaneous analysis of underivatized chiral amino acids by liquid chromatography-ionspray tandem mass spectrometry using a teicoplanin chiral stationary phase

Simultaneous chiral separations of underivatized amino acids have been performed using a teicoplanin-based chiral stationary phase and ionspray tandem mass spectrometry for their ionisation and detection. Different amino acid enantiomer pairs were separated simultaneously, including those of positional isomeric amino acids (e.g., L,D-Leu/Ile, or L,D-Val/Iva). Due to the specificity of tandem mass spectrometry, co-eluting enantiomers of different amino acids could also be determined. Fifteen chiral underivatized proteinogenic and non-proteinogenic amino acids were analysed simultaneously under isocratic conditions (acetonitrile-water, 75:25) in less than 25 min. For maximum sensitivity, post-column addition of 500 mM aqueous HCOOH was necessary. Detection limits varied from 2.5 to 50 microg l(-1) depending on the amino acid. The signal vs. concentration relationship was linear for all D- and L-amino acids (0.9995 < or = r2 < or = 1) for three orders of magnitude.     

A Synthetic Adenylation‐Domain‐Based tRNA‐Aminoacylation Catalyst

The incorporation of non‐proteinogenic amino acids represents a major challenge for the creation of functionalized proteins. The ribosomal pathway is limited to the 20–22 proteinogenic amino acids while nonribosomal peptide synthetases (NRPSs) are able to select from hundreds of different monomers. Introduced herein is a fusion‐protein‐based design for synthetic tRNA‐aminoacylation catalysts based on combining NRPS adenylation domains and a small eukaryotic tRNA‐binding domain (Arc1p‐C). Using rational design, guided by structural insights and molecular modeling, the adenylation domain PheA was fused with Arc1p‐C using flexible linkers and achieved tRNA‐aminoacylation with both proteinogenic and non‐proteinogenic amino acids. The resulting aminoacyl‐tRNAs were functionally validated and the catalysts showed broad substrate specificity towards the acceptor tRNA. Our strategy shows how functional tRNA‐aminoacylation catalysts can be created for bridging the ribosomal and nonribosomal worlds. This opens up new avenues for the aminoacylation of tRNAs with functional non‐proteinogenic amino acids.     

The role of phosphorus in chemical evolution

In this tutorial review we consider the role of phosphorus and its compounds within the context of chemical evolution in galaxies. Following an interdisciplinary approach we first discuss the position of P among the main biogenic elements by considering its relevance in most essential biochemical functions as well as its peculiar chemistry under different physicochemical conditions. Then we review the phosphorus distribution in different cosmic sites, such as terrestrial planets, interplanetary dust particles, cometary dust, planetary atmospheres and the interstellar medium (ISM). In this way we realize that this element is both scarce and ubiquitous in the universe. These features can be related to the complex nucleosynthesis of P nuclide in the cores of massive stars under explosive conditions favouring a wide distribution of this element through the ISM, where it would be ready to react with other available atoms. A general tendency towards more oxidized phosphorus compounds is clearly appreciated as chemical evolution proceeds from circumstellar and ISM materials to protoplanetary and planetary condensed matter phases. To conclude we discuss some possible routes allowing for the incorporation of phosphorus compounds of prebiotic interest during the earlier stages of solar system formation.     

In Situ Cyclization of Native Proteins: Structure‐Based Design of a Bicyclic Enzyme

Increased tolerance of enzymes towards thermal and chemical stress is required for many applications and can be achieved by macrocyclization of the enzyme resulting in the stabilizing of its tertiary structure. Thus far, macrocyclization approaches utilize a very limited structural diversity, which complicates the design process. Herein, we report an approach that enables cyclization through the installation of modular crosslinks into native proteins composed entirely of proteinogenic amino acids. Our stabilization procedure involves the introduction of three surface‐exposed cysteine residues, which are reacted with a triselectrophile, resulting in the in situ cyclization of the protein (INCYPRO). A bicyclic version of sortase A was designed that exhibits increased tolerance towards thermal as well as chemical denaturation, and proved to be efficient in protein labeling under denaturing conditions. In addition, we applied INCYPRO to the KIX domain, resulting in up to 24 °C increased thermal stability.     

Singlet excited states of silicon-containing anions relevant to interstellar chemistry

As the number of anions detected in the interstellar medium (ISM) increases, knowledge of their chemical properties is crucial in expanding our understanding of the chemistry of space. In this work we build on a previous study done in our group to examine the excited-state properties of five anions likely to exist in the ISM: SiCCN(-), CSiCN(-), CCSiN(-), SiCN(-), and SiNC(-). Our coupled cluster results indicate that SiCCN(-) and SiNC(-) possess dipole-bound singlet excited states while SiCCN(-) also has one valence state and CCSiN(-) potentially has two. Nearly all of the associated transition energies fall within the visible to near-IR region of the electromagnetic spectrum, making them applicable to the study of phenomena such as the diffuse interstellar bands.     

Arrangement of Proteinogenic α‐Amino Acids on a Cyclic Peptide Comprising Alternate Biphenyl‐Cored ζ‐Amino Acids

Aiming at precisely arranging several proteinogenic α‐amino acids on a folded scaffold, we have developed a cyclic hexapeptide comprising an alternate sequence of biphenyl‐cored ζ‐amino acids and proteinogenic α‐amino acids such as l ‐leucine. The amino acids were connected by typical peptide synthesis, and the resultant linear hexapeptide was intramolecularly cyclized to form a target cyclic peptide. Theoretical analyses and NMR spectroscopy suggested that the cyclic peptide was folded into an unsymmetrical conformation, and the structure was likely to be flexible in CHCl₃. The optical properties including UV/Vis absorption, fluorescence, and circular dichroism (CD) were also evaluated. Furthermore, the cyclic peptide became soluble in water by introducing three carboxylate groups at the periphery of the cyclic skeleton. This α/ζ‐alternating cyclic peptide is therefore expected to serve as a unique scaffold for arranging several functionalities.     

Multiply-charged ions and interstellar chemistry

Gaseous molecules and ions, and even dust grains, can accumulate charge in the interstellar medium (ISM) by harvesting the energy of UV photons, cosmic rays, helium ions and metastable atoms. This Perspective views the various modes of gas-phase formation of multiply-charged cations and the possible impact of their reactions on the chemical and ionization structure of the ISM, in the light of what is still very limited knowledge. Emphasis is given to gas-phase reactions of multiply-charged cations with atoms, molecules and electrons that lead to charge reduction, charge separation and chemical bond formation and these are examined for multiply-charged atoms, small molecules, hydrocarbons, polycyclic aromatic hydrocarbons and fullerenes, primarily as dications but also as a function of charge state. The increased electrostatic interaction due to multiple charge is seen to promote bonding to individual charge sites on large molecules (e.g. fullerenes) and allow ensuing "surface" chemistry under the influence of Coulomb repulsion. The unique ability of multiply charged cations to undergo charge separation reactions, either unimolecular or bimolecular, can feature in the production in the ISM of internally cold, but translationally hot, cations of lower charge state or hot atoms that may provide the driving force for subsequent chemical reactions in what is otherwise an ultracold environment. Available chemical kinetic models that account for the role of multiply-charged ions in the ISM are few and of limited scope and the observation of these ions in the ISM has remained elusive.     

Intermolecular acetaldehyde and dimethoxymethane formation mechanisms via ethenol and methoxymethylene precursors in reactions of atomic carbon with methanol: a computational study

Atomic carbon, a reactive intermediate abundant in the interstellar medium (ISM) can participate in various energetically demanding reactions in its extremely long living (69 min) first excited singlet state ((1)D). Several studies on reactions of oxygen containing species with carbon atoms have been reported, however mechanistic details of the title reaction remain obscure. We report here quantum chemical studies on reactions of methanol with (3)P and (1)D carbon atoms at the CCSD(T)/cc-pVTZ level of theory, with which experimentally well known facile CO production, intermolecular acetaldehyde formation, and intermolecular dimethoxymethane production mechanisms are explained. Energetics of the fragmentation, O-H insertion, C-H insertion, and O-C insertion channels on the triplet and singlet surfaces are studied. The CO production mechanism by C ((1)D) is identified as an oxygen abstraction and a triplet PES seems non-operative. Presenting novel features for the intermolecular reaction channels, current findings may be applicable to C + ROR reactions.     

β-Homoamino acids as catalysts in enantioselective intra- and intermolecular aldol reactions

β³-Homoamino acids catalyze the intra- (cf. the Hajos-Parrish-Eder-Sauer-Wiechert reaction) as well as the intermolecular aldol reaction. The stereochemical outcome with selectivities of up to 83% ee is reversed in the intramolecular reaction, when we go from the proteinogenic amino acids to the homologues, and reaction time increases dramatically for both reactions. In contrast, in the intermolecular reaction Me-β³hPhe-OH gives the same enantiomer as (S)-proline does, but with lower enantiomeric excess (54% vs 48% ee).     

Chiral ligand exchange countercurrent chromatography: Enantioseparation of amino acids

This work deals with the enantioseparation of α‐amino acids by chiral ligand exchange high‐speed countercurrent chromatography using N‐n‐dodecyl‐l ‐hydroxyproline as a chiral ligand and copper(II) as a transition metal ion. A biphasic solvent system composed of n‐hexane/n‐butanol/aqueous phase with different volume ratios was selected for each α‐amino acid. The enantioseparation conditions were optimized by enantioselective liquid–liquid extractions, in which the main influence factors, including type of chiral ligand, concentration of chiral ligand and transition metal ion, separation temperature, and pH of the aqueous phase, were investigated for racemic phenylalanine. Altogether, we tried to enantioseparate 15 racemic α‐amino acids by the analytical countercurrent chromatography, of which only five of them could be successfully enantioseparated. Different elution sequence for phenylalanine enantiomer was observed compared with traditional liquid chromatography and the proposed interactions between chiral ligand, transition metal ion (Cu²⁺), and enantiomer are discussed.     

Thin-layer chromatographic enantiomeric resolution via ligand exchange

A thin-layer chromatographic technique for the separation of proteinogenic and non-proteinogenic amino acids, dipeptides and alpha-hydroxy acids is described. Other examples are given from the field of alpha-methyl, N-alkyl and halogenated amino acids. The separation of the enantiomers is achieved, without derivatization, by means of ligand exchange on a reversed-phase silica gel as stationary phase, which is covered with a chiral selector (proline derivative). The resolution is so good that the respective enantiomers can be determined at trace levels (greater than or equal to 0.25%). The proposed method is simple, inexpensive and needs no sophisticated instruments.     

Volatility Study of Amino Acids by Knudsen Effusion with QCM Mass Loss Detection

This work presents a new Knudsen effusion apparatus employing continuous monitoring of sample deposition using a quartz-crystal microbalance sensor with internal calibration by gravimetric determination of the sample mass loss. The apparatus was tested with anthracene and 1,3,5-triphenylbenzene and subsequently used for the study of sublimation behavior of several proteinogenic amino acids. Their low volatility and thermal instability strongly limit possibilities of studying their sublimation behavior and available literature data. The results presented in this work are unique in their temperature range and low uncertainty required for benchmarking theoretical studies of sublimation behavior of molecular crystals. The possibility of dimerization in the gas phase that would invalidate the effusion experiments is addressed and disproved by theoretical calculations. The enthalpy of sublimation of each amino acid is analyzed based on the contributions in two hypothetical sublimation paths involving the proton transfer in the solid and in the gas phase.     

Preferred conformers of proteinogenic glutamic acid

The molecular shape of proteinogenic glutamic acid has been determined for the first time. Vaporization of the solid amino acid by laser ablation in combination with Fourier transform microwave spectroscopy made possible the detection of five different structures in a supersonic jet. These structures have been identified through their rotational and (14)N quadrupole coupling constants. All conformers show hydrogen bonds linking the amino and alpha carboxylic group through N-H···O═C (type I) or N···H-O (type II) interactions. In three of them there are additional hydrogen bonds established between the amino group and the carboxylic group in the gamma position. Entropic effects related to the side chain have been found to be significant in determining the most populated conformations.