Negatively-charged halide adducts of homochiral serine octamers

Negatively charged halide adducts of serine octamers, (Ser(8)+2Cl)(2-) and (Ser(8)+2Br)(2-), appear as magic number clusters in the negative ion electrospray mass spectra of solutions containing serine and the halide. Like the well-known protonated serine octamer, these negatively charged adducts are formed with homochiral preference and also undergo chiroselective substitution reactions with other amino acids. Tandem mass spectra of negatively charged halide adducts of serine octamers show that these ions also have a characteristic fragmentation signature. The fact that octamers of both polarities display analogous chemical properties suggests that these may be characteristics of the so-far-unknown neutral octamer. If serine played a key role in the origin of homochirality on the primitive earth, it was likely through both the neutral octamer and the ionic adducts. Unlike the octamers, the formation of halide-containing serine cluster ions of particular sizes is unfavorable under the conditions of the experiment. Signals corresponding to the ions (Ser(9)+2Br)(2-) and (Ser(15)+2Br)(2-) are particularly low in intensity, giving rise to gaps in the distribution of serine/bromide clusters in the negative ion electrospray mass spectra. These cluster sizes are likely to correspond to unstable "anti-magic number" clusters recently reported by Clemmer.     

Serine octamers: cluster formation, reactions, and implications for biomolecule homochirality

The emergence of homochirality continues to be one of the most challenging topics associated with the origin of life. One possible scenario is that aggregates of amino acids might have been involved in a sequence of chemical events that led to chiral biomolecules in self-replicating systems, that is, to homochirogenesis. Serine is the amino acid of principal interest, since it forms "magic-number" ionic clusters composed of eight amino acid units, and the clusters have a remarkable preference for homochirality. These serine octamer clusters (Ser8) can be generated under simulated prebiotic conditions and react selectively with other biomolecules. These observations led to the hypothesis that serine reactions were responsible for the first chiral selection in nature which was then passed through chemical reactions to other amino acids, saccharides, and peptides. This Review evaluates the chemistry of Ser8 clusters and the experimental evidence that supports their possible role in homochirogenesis.     

Amino acid cluster formation studied by electrospray ionization mass spectrometry

The association properties of natural and non-natural amino acids were studied in detail using electrospray ionization mass spectrometry. The results show a highly diverse cluster formation behavior of amino acids. There are differences regarding the degree of clustering (average cluster size), the presence or absence of one or several 'magic' clusters of special stability and the influence of chirality on cluster stability. Cluster formation does not show a good correlation with simple physico-chemical properties (such as solubility), indicating that it is a specific process and not only a simple aggregation during evaporation/ionization. A systematic study of cluster formation of serine derivatives reveals that all functional groups play a prominent role in the binding of the magic octamer. The results support the idea of the zwitterionic character of the octamer. Electrospray ionization of the side-chain acetylated serine shows the formation of a very stable tetramer with a strong preference for homochirality. The results suggest that Ser8 is made up of two tetramer subunits, held together by hydrogen bonds of the side-chain.     

Alkali metal-cationized serine clusters studied by sonic spray ionization tandem mass spectrometry

Serine solutions containing salts of alkali metals yield magic number clusters of the type (Ser(4)+C)(+), (Ser(8)+C)(+), (Ser(12)+C)(+), and (Ser(17)+2C)(+2) (where C = Li(+), Na(+), K(+), Rb(+), or Cs(+)), in relative abundances which are strongly dependent on the cation size. Strong selectivity for homochirality is involved in the formation of serine tetramers cationized by K(+), Rb(+), and Cs(+). This is also the case for the octamers cationized by the smaller alkalis but there is a strong preference for heterochirality in the octamers cationized by the larger alkali cations. Tandem mass spectrometry shows that the octamers and dodecamers cationized by K(+), Rb(+), and Cs(+) dissociate mainly by the loss of Ser(4) units, suggesting that the neutral tetramers are the stable building blocks of the observed larger aggregates, (Ser(8)+C)(+) and (Ser(12)+C)(+). Remarkably, although the Ser(4) units are formed with a strong preference for homochirality, they aggregate further regardless of their handedness and, therefore, with a preference for the nominally racemic 4D:4L structure and an overall strong heterochiral preference. The octamers cationized by K(+), Rb(+), or Cs(+) therefore represent a new type of cluster ion that is homochiral in its internal subunits, which then assemble in a random fashion to form octamers. We tentatively interpret the homochirality of these tetramers as a consequence of assembly of the serine molecules around a central metal ion. The data provide additional evidence that the neutral serine octamer is homochiral and is readily cationized by smaller ions.     

Inelastic neutron scattering studies of the interaction between water and some amino acids

The interaction between water and some of amino acids (glycine, L-glutamine, L-threonine, L-cysteine and L-serine) was studied by inelastic incoherent neutron scattering (IINS). The vibrational spectra of dry amino acids and amino acids with a water content (e.g., 1 mol water/1 mol amino acid) were recorded. Comparing the difference spectra obtained by subtracting the spectrum of dry sample from those of wet sample with the spectra of ice Ih, we obtained that the difference spectrum for serine changed greatly from normal ice spectrum; but on the other hand, the difference spectra for the other amino acids such as glycine, glutamine, threonine, and cysteine changed slightly. The results demonstrate that serine has stronger hydrophilic character than glycine, glutamine, threonine, and cysteine. This is the first time the hydrophilic or hydrophobic character of amino acids was studied by using inelastic neutron scattering techniques, which provides important information for theoretical modeling and force field refinement for the interaction between water and the amino acids studied here.     

Letter: some more aspects of formation and stability of the protonated serine octamer cluster

The formation of protonated serine octamer clusters from homochiral and heterochiral monomer solutions was investigated. The well-established preference for homochiral cluster formation was found to originate from collision-induced dissociation of the less stable ion population B prior to reaching the mass spectrometer's analyzer cell. In addition, collision-induced dissociation experiments were undertaken to investigate the relative stabilities of populations A and B and infrared multi-photon dissociation experiments addressed the relative stabilities of the protonated serine octamer cluster and its metaclusters. Isotopically-labeled serine was used throughout the experiments.     

Formation of the serine octamer: Ion evaporation or charge residue

The mechanism of formation for clusters of serine generated by electrospray ionization is hypothesized to play a critical role in determining their ultimate properties. Under carefully manipulated electrospray source conditions, two distinct and well-separated distributions of clusters can be observed. The characteristics of the two cluster populations are consistent with different formation mechanisms, namely ion evaporation and charge residue. Upon further inspection, it is proposed that the magic number intensity, homochiral selectivity, and unique formation of the serine octamer are best explained within the context of the ion evaporation mechanism. As a consequence, solution phase properties of the octamer become important, particularly in relation to interface effects present on the surface of the charged droplet. In contrast, other clusters of serine, including the B form of the octamer, are probably generated by the charge residue mechanism and may have no connection to condensed phase phenomena.     

Spontaneous anti-resolution in heterochiral clusters of serine

Chirality plays an important role in the formation and stability of noncovalent clusters which are made of chiral molecules. It is shown that clusters can exhibit a preference for both homochirality and heterochirality. Serine cluster formation is dominated by the formation of heterochiral aggregates, with the exception of the previously observed homochiral serine octamer. Thus, the majority of serine clusters lead to chiral anti-resolution, or the racemic mixing of enantiomers.     

Benzophenone Schiff bases of glycine derivatives: Versatile starting materials for the synthesis of amino acids and their derivatives

This review focuses on the introduction and early development, in solution, of phase-transfer catalyzed (PTC) reactions to afford racemic or enantioenriched natural and unnatural amino acids. To form monosubstituted amino acids alkylation reactions are performed on the benzophenone Schiff base of glycine. For α,α-disubstituted amino acids the activated intermediate is an aldimine derivative of the monosubstituted amino acid. Enantioenriched products are produced by organocatalysis using derivatives of Cinchona alkaloids as the phase-transfer catalyst. Selectivity for monoalkylatation and lack of product racemization depend on the acidities of the glycine imines, and dialkylated products are formed from aldimine esters of monoalkyl amino acids. The racemic and catalytic enantioselective reactions of a cationic glycine equivalent with organoboranes, organometallics and malonate anion are discussed as are other reactions of these versatile Schiff bases derivatives.     

Chiral enrichment of serine via formation,dissociation, and soft-landing of octameric cluster ions

Chiral enrichment of serine is achieved in experiments that involve formation of serine octamers starting from non-racemic serine solutions. Serine octamers were generated by means of electrospray and sonic spray ionization of aqueous solutions of d(3)-L-serine (108 Da) and D-serine (105 Da) having different molar ratios of enantiomers. A cyclic process involving the formation of chirally-enriched octameric cluster ions and their dissociation, viz. Ser(1) --> Ser(8) --> Ser(1), allows serine monomers to be regenerated with increased enantiomeric excess as shown in two types of experiments: (1) Chiral enrichment in serine was observed in MS/MS/MS experiments in a quadrupole ion trap in which the entire distribution of serine octamers formed from non-racemic solutions was isolated, collisionally activated, and fragmented. Monomeric serine was regenerated with increased enantiomeric excess upon dissociation of octamers when compared with the enantiomeric composition of the original solution. (2) Chiral enrichment was observed in the products of soft-landing of mass-selected protonated serine octamers. These ions were generated by means of electrospray or sonic spray ionization, mass selected, and collected on a gold surface using ion soft-landing. Chiral enrichment of the soft-landed serine was established by redissolving the recovered material and comparing the intensities of protonated molecular ions of d(3)-L-serine and D-serine after APCI-MS analysis. Both of these experiments showed comparable results, suggesting that formation of serine octamers depends only on the enantiomeric composition of the serine solution and that the magnitude of the chiral preference is intrinsic to octamers formed from solutions of given chiral composition.     

Detection of Serine Octamer by Desorption Electrospray Ionization Mass Spectrometry in Resultant Mixture of Aspartic Acid Exposed to Sunshine Under Natural Conditions

Serine,one of the nonessential amino acids,is of principal interest because of its capability to form magic-number ionic clusters,which provide a remarkable preference for homochirality.With L-aspartic acid as the precursor,this study provides experimental evidence for serine formation in weak acidified aqueous solutions in the presence of iron,with exposure to sunlight,which simulates the natural conditions of the prebiotic aqueous environment.The resultant mixture is directly analyzed via desorption electrospray ionization mass spectrometry(DESI-MS),without any sample preseparation.The serine monomer is successfully detected as protonated molecules,giving a peak at m/z 106,which is confirmed by the MS/MS fragments.Protonated serine octamer(m/z 841)is also observed with significant abundance in the MS spectra and is confirmed by the MS/MS data,which shows the formation of the serine octamer by a synthesized serine in the resultant mixture.It is also found that the serine octamer yielded equivalent abundance in the DESI mass spectra in a wide pH range(pH=1-5),and that existence of ferrous salt and sunshine are essential for the conversion of aspartic acid to serine in the acidic water solution.     

A peptide containing aspartic acid, glutamic acid and serine in calf brain synaptic vesicles

Free amino acids and other amino compounds in calf brain synaptic vesicles were identified and determined by thin-layer chromatography and ion-exchange chromatography. The vesicles contained ten identified amino acids with glutamic acid, aspartic acid, taurine and gamma-aminobutyric acid in the highest concentrations, and also cysteic acid (or cysteinesulfinic acid), glutamine, alanine, serine, glycine and lysine. The vesicles also contained certain unknown acid-labile, ninhydrin-positive compounds, one of which was a peptide yielding, after acid hydrolysis, about 40% aspartic acid, 30% serine, 15% glutamic acid, 10% glycine and possibly some alanine and lysine. The concentration of the peptide in the vesicles was as high as that of all the other amino compounds together.     

Origin of chiral selectivity in gas-phase serine tetramers

Serine "magic-number" clusters have attracted substantial experimental and theoretical interest since their discovery. Serine undergoes marked chiral enrichment upon sublimation, which has been associated with the homochiral selectivity of the octamer. This process has been implicated in one possible mechanism leading to the origin of biological homochirality. While the octamer is the best known of the serine clusters, here we focus on the tetramer, the smallest serine cluster known to exhibit homochiral preference. This choice is based on its greater simplicity and tractability with accessible computational resources. Basin-hopping molecular dynamics simulations coupled to density functional theory calculations yield a "structural landscape" for low-lying configurations on the potential energy surface. The full range of enantiomeric compositions and charge states is investigated. Global energy minimum serine tetramers consist of a cage structure bonded by zwitterionic terminal groups. The participation of the serine hydroxyl side chains in hydrogen bonds with adjacent monomers drives the homochiral selectivity of serine tetramers. The configuration of the hydrogen bonding network is strongly dependent on enantiomeric composition and charge state. Smaller cations are incorporated into the center of the tetramer cage and effectively disable all side chain hydrogen bonding, while larger cations appear not to incorporate into the tetramer cage and are stabilized outside only in the homochiral case. The current theoretical data requires the introduction of a kinetic barrier to complete the model, limiting rearrangement from the basic cage configuration in some cases, which is discussed and probed directly by doubly-nudged elastic band transition state searches. These calculations elucidate a large barrier for reorganization of the cage, completing the theoretical understanding of the tetramers.     

Synthetic studies on stevastelins. 2. Synthesis of lipidic- and peptidic-modified analogues

[Chemical reaction: See text] The synthesis of a series of stevastelin analogues with modification of the susbstituent at the C-2 position of the stearic acid chain (compounds 28 and 31), variation of the amino acids (compounds 41, 42, 73, and 78), or lacking the lipidic chain (compound 91) is described. The replacement of L-valine and L-threonine with other amino acids proceeded without difficulties for the synthesis of analogues 41 and 42; however, the substitution of L-serine with simple amino acids, such as glycine or L-alanine, proved to be elusive, which was adscribed to factors of conformational flexibility. Finally, the substitution with L-valine or L-threonine proceeded without difficulties to provide the analogues 73 and 78 respectively.     

A general,highly enantioselective method for the synthesis of D and L alpha-amino acids and allylic amines

Catalytic and enantioselective synthesis of amino acids is a subject of intense interest in the field of asymmetric catalysis. Traditionally, researchers have concentrated their efforts largely on the design and discovery of enantiopure catalysts for the Strecker reaction, alkylation of tert-butyl gylcinate-benzophenone, electrophilic amination of carbonyl compounds, and hydrogenation of N-acyl-aminoacrylic acid; however, the scope of these reactions is limited. In this paper, we report on a different approach to amino acids based on an expeditious route to enantiopure allylic amines. A highly enantioselective and catalytic vinylation of aldehydes leads to allylic alcohols that are then transformed to the allylic amines via Overman's [3,3]-sigmatropic rearrangement of imidates. Oxidative cleavage of the allylic amines furnishes the amino acids in good yields and excellent ee's. The scope and utility of this method are demonstrated by the synthesis of challenging allylic amines and their subsequent transformation to valuable nonproteinogenic amino acids, including both D and L configured (1-adamantyl)glycine.     

Determination of primary amino acids in wines by high performance liquid magneto-chromatography

Eight amino acids (ethanolamine, glycine, alanine, β-aminobutyric acid, leucine, methionine, histidine and asparagine) were identified and quantified in Spanish wines by high performance liquid magneto-chromatography (HPLMC) with UV-V spectrophotometry. For this method, the amino acids are first complexed with mono(1,10-phenanthroline)-Cu(II) to confer them paramagnetic properties, and then separated by application of a low magnetic field intensity (5.5 mT) to the stationary phase contained in the chromatographic column. Principal components analysis of the results obtained grouped together the wine samples according to their denomination of origin: “Ribera del Duero”, “Rueda” or “Rioja” (Spain). Through cluster analysis, a series of correlations was also observed among certain amino acids, and between these groupings and the type of wine. These clusters were found to reflect the role played by the amino acids as primary or secondary nutrients for the bacteria involved in alcoholic and malolactic fermentation.     

Chiral symmetry breaking via crystallization of the glycine and α-amino acid system: a mathematical model

We introduce and numerically solve a mathematical model of the experimentally established mechanisms responsible for the symmetry breaking transition observed in the chiral crystallization experiments reported by I. Weissbuch, L. Addadi, L. Leiserowitz and M. Lahav, J. Am. Chem. Soc., 1988, 110, 561-567. The mathematical model is based on five basic processes: (1) the formation of achiral glycine clusters in solution, (2) the nucleation of oriented glycine crystals at the air/water interface in the presence of hydrophobic amino acids, (3) a kinetic orienting effect which inhibits crystal growth, (4) the enantioselective occlusion of the amino acids from solution, and (5) the growth of oriented host glycine crystals at the interface. We translate these processes into differential rate equations. We first study the model with the orienting process (2) without (3) and then combine both allowing us to make detailed comparisons of both orienting effects which actually act in unison in the experiment. Numerical results indicate that the model can yield a high percentage orientation of the mixed crystals at the interface and the consequent resolution of the initially racemic mixture of amino acids in solution. The model thus leads to separation of enantiomeric territories, the generation and amplification of optical activity by enantioselective occlusion of chiral additives through chiral surfaces of glycine crystals.     

Analysis of amino acids in latent fingerprint residue by capillary electrophoresis‐mass spectrometry

The analysis of the chemical composition of fingerprints is important for the development and improvement of existing fingerprint enhancement techniques. This study demonstrates the first analysis of a latent fingerprint sample, using an optimized CE‐MS method. In total 12 amino acids were detected in the fingerprint sample. MS/MS fragmentation was used to provide additional identity confirmation, for which eight of the twelve detected amino acids generated confirmatory product ions. Nine amino acids were quantified and their relative abundances were consistent with previous studies with serine and glycine being the most abundant. The successful detection of amino acids from latent fingerprints demonstrates that CE‐MS is a potential future technique for further study of such compounds in fingerprint samples.     

α-氨基酸在水-乙醇中羟基质子化热力学

α 氨基酸为重要的两性物质 ,其酸碱性质对于维持生物体内的酸碱平衡和蛋白质的生物活性起着十分重要的作用．α 氨基酸在纯水溶剂中的质子化反应热力学性质已进行了广泛的研究［１ -６］,但对球形蛋白来说 ,蛋白亚基间的作用是处在一个大量但不完全由水组成的非水环境中 ,因此 ,研究氨基酸在水 有机物混合溶剂中的质子化热力学性质具有重要意义．但这方面的工作 ,特别是用量热法直接研究溶剂对质子化焓变的影响开展得不多．本文选择乙醇和水组成的混合溶剂模拟蛋白质亚基所处的介质环境 ,利用精密微量流动热量计测定２９８．１５Ｋ时甘氨…     

α-氨基酸在水-乙醇中羧基质子化热力学

Enthalpy changes for the protonation of carboxyl group of four α-amino acids(glycine,L-α-alanine,L-valine and L-serine) were measured in water-ethanol mixtures (10－ 70wt％) at 298.15K using LKB-2277 Bioactivity Monitor.The corresponding entropy and Gibbs energy changes were also calculated.The results show that both enthalpy changes and entropy changes are favorable to the protonation of carboxyl groups of the investigated amino acids in water-ethanol mixtures.However,the influence of the composition of ethanol in the mixed solvents on the enthalpy change and entropy changes is complicated.Both sδ and sδ ,the differences of enthalpy changes and entropy changes in mixed solvents and in pure water respectively,show a minimum approximately at xEtOH=0.1.The effects of side chains on the enthalpy change and entropy changes were also investigated using the proton transfer process between glycine and the other three amino acids.The results demonstrate that the proton transfer processes for alanine and valine are spontaneous but not for serine,which could be interpreted in terms of the electrostatic interaction between amino group and carboxyl group within the molecule and the interaction between carboxyl group and the solvent.