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Reactions of cyanamide–glyoxal mixtures under prebiotic aqueous conditions open the door to new carbonaceous nitride structures.

This work is aimed at providing a systematic and comprehensive analysis of the anomeric effect exerted by the isothiocyanato (NCS) group taking the xylopyranose ring as a scaffold because enhanced effects have been detected in that ring-bearing halogen and pseudohalogen substituents. To this end, both α- and β-anomers of tri-O-acetoxypyranosyl-D-xylose have been prepared and thoroughly characterized. The axial preference of the isothiocyanato group reflects a dominant anomeric effect, whose origin could be determined through DFT calculations with identification of the stereoelectronic interactions as revealed by Natural Bond Orbital (NBO) analysis. In this way, this study expands the repertoire of groups biasing the conformation and reactivity of monosaccharides and related heterocycles.

During translation, nascent polypeptide chains travel from the peptidyl transferase center through the nascent polypeptide exit tunnel (NPET) to emerge from 60S subunits. The NPET includes portions of five of the six 25S/5.8S rRNA domains and ribosomal proteins uL4, uL22, and eL39. Internal loops of uL4 and uL22 form the constriction sites of the NPET and are important for both assembly and function of ribosomes. Here, we investigated the roles of eL39 in tunnel construction, 60S biogenesis, and protein synthesis. We show that eL39 is important for proper protein folding during translation. Consistent with a delay in processing of 27S and 7S pre-rRNAs, eL39 functions in pre-60S assembly during middle nucleolar stages. Our biochemical assays suggest the presence of eL39 in particles at these stages, although it is not visualized in them by cryo-electron microscopy. This indicates that eL39 takes part in assembly even when it is not fully accommodated into the body of pre-60S particles. eL39 is also important for later steps of assembly, rotation of the 5S ribonucleoprotein complex, likely through long range rRNA interactions. Finally, our data strongly suggest the presence of alternative pathways of ribosome assembly, previously observed in the biogenesis of bacterial ribosomal subunits., This publication is part of the project R+D+i PID2019-103850-GB-I00 funded by MCIN/AEI/10.13039/501100011033 to J. de la Cruz. We also acknowledge the Andalusian Regional Government [P20_00581, BIO-271 to J. de la Cruz]; J. Fernández-Fernández acknowledges an FPI fellowship from MCIN [BES-2017-080876]; the research performed in the USA was supported by the National Institutes of Health [R01GM028301 to J.L.W. Jr.]. Funding for open access charge: PID2019-103850-GB-I00 funded by MCIN/AEI/10.13039/501100011033 (to J. de la Cruz).

A multichannel, non-thermolytic and efficient pathway is described toward the formation of functionalized carbon nitride-like oligomers, starting from readily available cyanamide and glyoxal (in ratios2), in aqueous media under mild conditions. Such oligomers can be isolated as stable solids that result from structures involving cyanamide self-additions along with structures formally derived from the condensation of cyanamide, dicyandiamide or melamine with glyoxal, leading occasionally to oxygen-containing units. The oligomeric aggregates have masses up to 500 u, as inferred from mass spectra analyses, and their formation can be rationalized in terms of polyadditions of cyanamide (up to 10-mer) and glyoxal. The latter is not only a willing reaction partner, but also promotes facile condensation by enhancing the reactivity of nitrile fragments and inducing a significant lowering of the energy barriers. This mechanistic surmise is also supported by DFT calculations of the early condensation steps. As a result, melamine/triazine-type structures are obtained in aquatic environments under much milder conditions than those usually required by other synthetic procedures. Moreover, our results also help unveil the abiotic processes affording complex organic matter on celestial bodies and early earth.

In line with the postulated intermediacy of aminoxazoles derived from small sugars toward the direct assembly of nucleoside precursors, we show here a potential prebiotic scenario where aminoxazolines might have also played further roles as complexing and/or sequestering agents of other primeval blocks, namely amino acids. To this end, a bis-aminoxazoline derivative, generated from dihydroxyacetone and cyanamide, gives rise to stable co-crystal forms with dicarboxylic amino acids (Asp and Glu), while ionic interactions owing to proton transfer are inferred from spectroscopic data in aqueous solution. The structure of a 1:2 aminoxazoline: aspartic acid complex, discussed in detail, was elucidated by X-ray diffractometry. Optimized geometries of such ionic structures with bulk aqueous solvation were assessed by DFT calculations, which disclose preferential arrangements that validate the experimental data. Peripherally, we were able to detect in a few cases amino acid dimerization (i.e. dipeptide formation) after prolonged incubation with the bis-aminoxazole derivative. A mechanistic simulation aided by computation provides some predictive conclusions for future explorations and catalytic design.

A fundamental question in origin-of-life studies and astrochemistry concerns the actual processes that initiate the formation of reactive monomers and their oligomerization. Answers lie partly in the accurate description of reaction mechanisms compatible with environments plausible on early Earth as well as cosmological scenarios in planetary factories. Here we show in detail that reactions of urea-as archetypal prebiotic substance-and reactive carbonyls-exemplified by glyoxal-lead to a vast repertoire of oligomers, in which different five- and six-membered non-aromatic heterocycles self-assemble and insert into chains or dendritic-like structures with masses up to 1000 Da. Such regular patterns have been interpreted by experimental and computational methods. A salient conclusion is that such processes most likely occur through SN-type mechanisms on hydrated or protonated species. Remarkably, such supramolecular oligomeric mixtures can be easily isolated from organic solvents, thus opening the door to the generation of novel urea-containing polymers with potential applications in materials chemistry and beyond.

The synthesis of cytoplasmic eukaryotic ribosomes is an extraordinarily energy-demanding cellular activity that occurs progressively from the nucleolus to the cytoplasm. In the nucleolus, precursor rRNAs associate with a myriad of trans-acting factors and some ribosomal proteins to form pre-ribosomal particles. These factors include snoRNPs, nucleases, ATPases, GTPases, RNA helicases, and a vast list of proteins with no predicted enzymatic activity. Their coordinate activity orchestrates in a spatiotemporal manner the modification and processing of precursor rRNAs, the rearrangement reactions required for the formation of productive RNA folding intermediates, the ordered assembly of the ribosomal proteins, and the export of pre-ribosomal particles to the cytoplasm; thus, providing speed, directionality and accuracy to the overall process of formation of translation-competent ribosomes. Here, we review a particular class of trans-acting factors known as "placeholders". Placeholder factors temporarily bind selected ribosomal sites until these have achieved a structural context that is appropriate for exchanging the placeholder with another site-specific binding factor. By this strategy, placeholders sterically prevent premature recruitment of subsequently binding factors, premature formation of structures, avoid possible folding traps, and act as molecular clocks that supervise the correct progression of pre-ribosomal particles into functional ribosomal subunits. We summarize the current understanding of those factors that delay the assembly of distinct ribosomal proteins or subsequently bind key sites in pre-ribosomal particles. We also discuss recurrent examples of RNA-protein and protein-protein mimicry between rRNAs and/or factors, which have clear functional implications for the ribosome biogenesis pathway. España, MINECO BFU2013-42958-P and BFU2016-75352-P

We report a combined experimental and computational study on the cycloadditions of bicyclic 1,3-thiazolium-4-olates, derived from thiazolidin-2-thiones, with asymmetrically-substituted acetylenes. These results provide further mechanistic insights into the above dipolar cycloadditions and enable an unequivocal characterization by NMR spectroscopy of regiochemical patterns as previous derivatives had substituents at both C-2 (in the dipole) and C-6 (in products). Accordingly, new dihydrothiazolopyrid-2-ones have been obtained from a thioisomunchnone lacking substitution at C-2. With the aim of assessing the steric hindrance as well as the facial stereoselection induced by a bulky group on the Si face (relative to C-7a) of the mesoionic heterocycle, a chiral thioisomunchnone has also been obtained along with the resulting optically active thiazolopyridones. A computational study of these particular cycloadditions, largely based on an NBO analysis, allowed us to evaluate the influence of substituents on intermolecular steric repulsions, charge transfers, as well as solvent effects.

We report a detailed investigation into the nature of products that are generated by the reactions of cyanamide and glyoxal, two small molecules of astrochemical and prebiotic significance, under different experimental conditions. The experimental data suggest that the formation of oligomeric structures is related in part to the formation of insoluble tholins in the presence of oxygen-containing molecules. Although oligomerization proceeds well in water, product isolation turned out to be impractical. Instead, solid precipitates were obtained easily in acetone. Crude mixtures have been thoroughly scrutinized by spectroscopic methods, in particular NMR and mass spectroscopy (ESI mode), which are all consistent with the generation of a few functional groups that are embedded into regular chains of five- and six-membered rings, thereby pointing to a supramolecular organization. Three different models of cross-condensation and chain growth are suggested. These synthetic explorations provide further insights into the formation of complex organic matter in interstellar scenarios and extraterrestrial bodies that might have played a pivotal role in chemical evolution.

This paper examines in detail the tautomerism of 2-aryl-substituted malondialdehydes, mainly focused on enolal structures, by means of gas-phase and solvent-based DFT calculations performed at the M06-2X/6-311++G(d,p) level. Open and pseudo-cyclic structures can be envisaged, the latter being decorated by an intramolecular hydrogen bond acting in symbiosis with π-electron delocalization. We have checked the relationship between the computed hydrogen bond energies and a variety of descriptors for electron delocalization. Application of the natural bond orbital (NBO) method to interrogate the nature of donor-acceptor interactions unravels that stabilization energies mainly arise from lone-pair and σ-antibonding interactions. Transition structures involved in proton transfer along the reaction pathway could be identified and TS exhibit a nearly complete electron delocalization characteristic of aromatic systems. All data gathered herein provide a description of quasi-aromaticity more consistent with hydrogen-bonding-assisted resonance (HBAR) than the widely held RAHB (resonance-assisted hydrogen bonding) formalism. Overall, the paper does not invoke a new concept, but rather the fact that the effects of H-bonding on delocalization and the effects of the latter on H-bonding can accurately be captured by computation, yet representing two sides of the same coin.

The mutarotation equilibrium, by which reducing carbohydrates exist in solution as the α and β anomers of cyclic (furanoid and pyranoid) structures, along with open-chain (aldehyde and hydrate) forms, and whose ratios are depending on factors such as temperature, pH and solvent, portraits a phenomenon involved in numerous processes of chemical and biological importance. Herein, we have developed a DFT-based rationale that provides a broader landscape for anomerizations and ring-open chain interconversions, together with the pivotal role exerted not only by the aldehyde intermediate (essentially the only acyclic structure taken into account so far), but also the hydrate form (often more abundant at the equilibrium). These calculations reveal a more complex and richer scenario than was thought, and identify different mutarotation mechanisms that hinge on every monosaccharide. It is noteworthy that pyranose-furanose interconversion may actually occur without the intermediacy of open-chain forms. For the aldoses evaluated, namely d-glucose, d-ribose, and d-xylose, all structures involved in mutarotation undergo interconversion pathways, whose energy barriers calculated at the M06-2X/6-311++G(d,p) level, are in good agreement with previous experimental measurements.

Monoaza- and diaza-derivatives of malondialdehydes, in short aminoacroleins and vinamidines, are prototypical examples of open-chain structures prone to π-electron delocalization, for which intramolecular hydrogen bonding enhances (or diminishes) their pseudoaromaticity depending on the substitution pattern. This interplay is illustrated herein by DFT-based calculations of aromaticity indices in the gas phase and polar solvents. Elucidation of transition structures involved in tautomeric conversions helps to solve how the intramolecular hydrogen transfer occurs. While TSs exhibit a high degree of aromaticity, the dichotomy between forward and backward pathways points to a complex trajectory. Addition of thermal corrections to the electronic energy decreases both the enthalpy and free energy leading to negative ΔH(‡) and ΔG(‡) values. This variational effect accounts for the otherwise elusive distinction between transition structures and saddle points (usually overlooked for high electronic barriers). Also, this rationale fits well within the framework of Marcus' theory.

The condensation of cyanamide and glyoxal, two well-known prebiotic monomers, in an aqueous phase has been investigated in great detail, demonstrating the formation of oligomeric species of varied structure, though consistent with generalizable patterns. This chemistry involving structurally simple substances also illustrates the possibility of building molecular complexity under prebiotically plausible conditions, not only on Earth, but also in extraterrestrial scenarios. We show that cyanamide-glyoxal reactions in water lead to mixtures comprising both acyclic and cyclic fragments, largely based on fused five- and six-membered rings, which can be predicted by computation. Remarkably, such a mixture could be identified using high-resolution electrospray ionization (ESI) mass spectrometry and spectroscopic methods. A few mechanistic pathways can be postulated, most involving the intermediacy of glyoxal cyanoimine and further chain growth, thus increasing the diversity of the observed products. This rationale is supported by theoretical analyses with clear-cut identification of all of the stationary points and transition-state structures. The properties and structural differences of oligomers obtained under thermodynamic conditions in water as opposed to those isolated by precipitation from organic media are also discussed.

Mono- and diaza-derivatives of malondialdehydes, namely 3-alkyl(aryl)amino-2-arylacroleins and 1,5-dialkyl(aryl)-3-arylvinamidines are open-chain systems in which extended electron delocalization and pseudoaromaticity can be envisaged. A set of diversely functionalized compounds has been synthesized and characterized by spectroscopic data and X-ray diffractometry. Quantum-chemical calculations were performed for all possible neutral tautomers and conformers in the gas phase and compared to those in polar solvents (CHCl3, DMSO, and EtOH) at the M06-2X/6-311++G(d,p) level. Tautomeric equilibria and conformational preferences can be rationalized in terms of structural factors, which can be roughly estimated as summation or subtractions of intramolecular interactions. As expected, a key role is played by intramolecular hydrogen bonds whose strength varies from the gas phase to polar ethanol. This issue also delves into the concept of resonance-assisted H-bond, where the donor and acceptor atoms are connected by a π-conjugated system. The most stable conformers (structures a and c) possess a high degree of pseudoaromaticity as inferred from HOMA indexes and other delocalization parameters.

An improved preparation of mesoionic heterocycles 1,3-diazolium-4-thiolates by [3 + 2] cycloadditions of münchnones with aryl isothiocyanates is reported. The process takes place with high or complete regioselectivity, and fast and clean transformations are observed under microwave heating in DMF. DFT calculations support that this cycloaddition proceeds preferably through a stepwise mechanism. Given the pattern substitution around the mesoionic ring resulting in a push-pull system, theoretical estimations predict large hyperpolarizabilities in some cases, which is typical of molecules exhibiting nonlinear optical responses.

The Ti6Al4V surface, commonly employed in biomedical prostheses, has been chemically functionalized by non-covalent binding to obtain improved antibacterial responses. The methodology combines the well-known antibacterial activity of silver(I) ions with those of other common antimicrobials such as carboxylic acids, trans -cinnamaldehyde, farnesol, and the broad-range antibiotic chloramphenicol. To this end, on previously aminosilanizated Ti6Al4V surfaces (Material A) were attached via saline bonds (involving both ionic and dipole interactions) acetic, propanoic, benzoic, and sorbic acids (Material B). Likewise silver(I) acetate undergoes non-covalent cross-linking with the aminosiloxane-coated surface (Material C) after incubation at 60 °C for 48 h, thus resulting in a density of ca. 4.11 × 10 − 8 mol cm − 2 . The coordinating ability of Ag(I) ions enables further attachment of the above-mentioned carboxylic acids onto the surface (Material D) and other neutral antimicrobials (Material E). Surface characterization has been accomplished using infrared spectroscopy and X-ray photoelectron spectroscopy, which support non-covalent binding. In particular, the existence of ammonium and carboxylate groups together with other intact functional groups (carbonyl, hydroxyl and amino) reveals that aminosiloxane-coated surfaces adhere via both ionic and weak interactions. As a proof of concept, adhesion and viability tests of Staphylococcus aureus on the functionalized surfaces show the adequate performance of the coverage at short and medium contact times with the surrounding cells.

From the great variety of BODIPY based-chemosensors able to determine Hg(2+), only a small portion has been applied to its determination in environmental and/or biological samples. The lack of studies on the analytical performance of the latter sensors makes interesting the development of investigations oriented to their possible analytical applications. The synthesis of a BODIPY derivative armed with a tetrapod receptor is described. The procedure is based on a previous publication, and the modifications performed to improve the synthesis include alternative procedures with different objectives, as the consecution of a multigram synthesis, improving the low yields of some of the previously proposed procedure steps, simplifying the experimental steps, achieving the desired purity requirements for use with analytical purposes, and enriching the characterization of the implied structures. The characteristics of its selectivity towards Hg(2+) have been investigated, and the OFF-ON fluorometric response, based on a photo-electron transfer (PET) mechanism, served as the base for the development of a method able to determine Hg(2+) in environmental waters at ng mL(-1) levels. The intrinsic fluorescence of the BODIPY core is inhibited and the probe exhibits a weak fluorescence (i.e. "OFF" state due to the deactivating PET effect). Upon complexation, Hg(2+) interacts with the lone-pair electrons on the nitrogen atoms of the receptor moiety so that the electronic transfer from the receptor to the photo-excited fluorophore is slowed down or switched off (i.e. "ON" state due to the suppression of the deactivating PET effect by coordination of the analyte to the probe). Regarding the complex photostability in aqueous solution, it is mandatory to conduct the experiments at darkness due to its photodegradation. The stoichiometry studies indicated a 1:2 relationship for the BODIPY-Hg(2+) complex. The high selectivity towards mercuric ions is considerably influenced by pH, being necessary to conduct the experiments in a pH value higher than 6. Calibration samples were prepared by adding appropriate amounts of Hg(2+) between 20.0-120.0 ng mL(-1), at a constant BODIPY concentration of 1 µmol L(-1). After agitating for 5 min at darkness, phosphate buffer (pH=7.50) was added, and it was diluted to the mark with water. Fluorescence measurements were carried out at 18 °C, exciting at 515 nm, and obtaining fluorescence emission at 538 nm. The method has been satisfactory applied to Hg(2+) determination in environmental water samples.

Most ribosomal proteins play essential roles in ribosome synthesis and function. In this study, we have analysed the contribution of yeast ribosomal protein L16 to ribosome biogenesis. We show that in vivo depletion of the essential L16 protein results in a deficit in 60S subunits and the appearance of half-mer polysomes. This phenotype is likely due to the instability and rapid turnover of early and intermediate pre-60S particles, as evidenced by the reduced steady-state levels of 27SBS and 7SL /S pre-rRNA, and the low amounts of de novo synthesized 27S pre-rRNA and 25S rRNA. Additionally, depletion of L16 blocks nucleocytoplasmic export of pre-60S particles. Moreover, we show that L16 assembles in the nucleolus and binds to early 90S preribosomal particles. Many evolutionarily conserved ribosomal proteins possess extra eukaryote-specific amino- or carboxy-terminal extensions and/or internal loops. Here, we have also investigated the role of the eukaryote-specific carboxy-terminal extension of L16. Progressive truncation of this extension recapitulates, albeit to a lesser extent, the growth and ribosome biogenesis defects of the L16 depletion. We conclude that L16 assembly is a prerequisite to properly stabilize rRNA structures within early pre-60S particles, thereby favouring efficient 27S pre-rRNA processing within the internal transcribed spacer 1 at sites A3 and B1 . Upon depletion of L16, the lack of this stabilization aborts early pre-60S particle assembly and subjects these intermediates to turnover.

Ribosomal proteins play important roles in ribosome biogenesis and function. Here, we study the evolutionarily conserved L26 in Saccharomyces cerevisiae, which assembles into pre-60S ribosomal particles in the nucle(ol)us. Yeast L26 is one of the many ribosomal proteins encoded by two functional genes. We have disrupted both genes; surprisingly, the growth of the resulting rpl26 null mutant is apparently identical to that of the isogenic wild-type strain. The absence of L26 minimally alters 60S ribosomal subunit biogenesis. Polysome analysis revealed the appearance of half-mers. Analysis of pre-rRNA processing indicated that L26 is mainly required to optimize 27S pre-rRNA maturation, without which the release of pre-60S particles from the nucle(ol)us is partially impaired. Ribosomes lacking L26 exhibit differential reactivity to dimethylsulfate in domain I of 25S/5.8S rRNAs but apparently are able to support translation in vivo with wild-type accuracy. The bacterial homologue of yeast L26, L24, is a primary rRNA binding protein required for 50S ribosomal subunit assembly in vitro and in vivo. Our results underscore potential differences between prokaryotic and eukaryotic ribosome assembly. We discuss the reasons why yeast L26 plays such an apparently nonessential role in the cell.

What accounts for a particular chiral selection in the case of a few sugars of prebiotic relevance, thereby mirroring the asymmetry observed in nature? By using first-principles calculations, the generation of pentoses from glycolaldehyde (the initial product of the autocatalytic formose reaction), which has been detected in outer space), has been modeled by using L-Val-L-Val as a primeval catalyst. Our theoretical study provides insight into the mechanism of this reaction and satisfactorily explains a few key molecular events. Our rationale agrees with the reported experimental data and shows that the D-configuration is only favored for ribose. L-pentoses are usually favored in the presence of L-configured dipeptides, as observed experimentally, although no chiral selection could be observed in the case of xylose. These results confirm that a prebiotic sugar soup could be fine-tuned in the presence of shorter peptides as catalysts and that D-ribose would have also resulted in an advantageous imbalance for further amplification and chemical evolution.

Through a well-established enzymatic transformation glucosinolates release reactive isothiocyanates that can undergo further metabolic pathways affording a plethora of reactive metabolites. This study explores in detail the reaction of benzyl isothiocyanate, which possesses antitumor activity as alkylating agent, with d -glucosamine, commonly employed in oral treatments against osteoarthritis and inflammation. Structures of the resulting products and their evolution have been assessed and compared with those involving d -glucose, reported previously. Chemical results suggest that clinical treatments with d -glucosamine could reduce the beneficial effects associated with diets based on glucosinolate-rich foods.

This manuscript describes an easy, accurate, and expeditious methodology to locate all the stationary points in common organic reactions. The protocol is based on the analysis of potential energy surfaces (PES) by fitting the calculated data to a mathematical function. The method has been tested in several organic reactions, especially cycloadditions. In all cases, we succeeded in locating the bond parameters for the existing saddle points and intermediates, which were further corroborated by conventional geometry optimizations of the corresponding stationary points. Thus, the concerted or stepwise character of a typical cycloaddition can easily be predicted. It should be emphasized that this protocol is not intended to replace the current computational methodology to construct a PES, which is otherwise a long and rather tedious procedure, usually applied to very discrete molecular system. We prove instead that the present surrogate represents a valuable shortcut to identify stationary points at a given level of theory, which is in turn both reproducible and accurate and should be of interest to a large readership of practitioners engaged in mechanistic studies, who often fear quantum computational methods. Copyright © 2011 John Wiley & Sons, Ltd.

Three Schiff bases generated by conventional condensation of a simple aminopolyol (TRIS) and 5-bromo- and 5-iodosalicylaldehyde, and 2-hydroxy-1-naphthaldehyde, have been fully characterized, both in solution and in the solid state. This study provides a complete analysis of imine–enamine equilibria, and sheds light onto the mechanism of hydrogen transfer, which has been controversial in the literature. Low-temperature X-ray diffraction accompanied by electron-density maps have further been complemented by theoretical studies at the B3LYP/6-31G* and M06-2X/6-311++G** levels. To ascertain the influence of crystal packing on tautomeric stability, the lattice has also been simulated by computation. This protocol involves the assessment of a supramolecular cluster around a core tautomer possessing either imine or enamine structures. Such an analysis, in full agreement with solid-state data, reveals the greater stability of zwitterionic structures for the salicyl derivatives. In contrast, these substances show preferential imine forms in solution, whereas the naphthyl-based compound exhibits a prevalent keto-enamine structure in all cases

Schiff bases derived from 2-hydroxy-1-naphthaldehyde, or 1-hydroxy-2-naphthaldehyde, and different saturated N-aminoheterocycles have been prepared. Their structures have been elucidated in both solution and the solid state, including unequivocal X-ray diffraction analyses. Experimental data evidence the presence of imine (or hydrazone) structures as the most stable tautomers, while all attempts to switch to enamine (or enhydrazine) structures based on electronic and steric considerations were unsuccessful. A complete conformational analysis assisted by DFT calculations at B3LYP/6-31G? and M06-2X/6-311++G?? levels has been performed on each series of representative structures.

The fluorescent characteristics of a fluorimetric chemosensor for mercuric ion, Hg2+, employing a synthesized Rhodamine 6G derivative, have been analyzed. For that, a portable spectrofluorimeter composed of a 515 nm LED as excitation source, two fiber-optics and a CCD camera as detector, has been used, intended for “in situ” analysis. A highly selective Rhodamine based probe for Hg2+, that is water soluble and gives a positive response upon analyte binding, is reported. The reagent is bearing a monothiospirolactone group in a Rhodamine 6G architecture and the thiol atom served for the direct attack of thiophilic Hg2+. The fluorescence enhancement is attributed to the spirolactone ring opening and the coordination of two sulphur atoms to Hg2+ giving a 2:1 reagent: Hg2+ stoichiometry complex.

This paper describes the synthesis and structural elucidation of 1,3-oxazolidines derived from tris(hydroxymethyl)aminomethane (TRIS) and pyridine-based aldehydes. Divergent results were obtained with other formylpyridines, such aspyridoxal, in which intramolecular hydrogen-bonding largely stabilizes the iminic structure. The oxazolidines may undergo ring-opening under acetylating conditions to afford imines through different mechanistic pathways, which have also been evaluated by DFT calculations

A series of oxazolidines derived from tris(hydroxymethyl)aminomethane (TRIS; 1), have been prepared efficiently. Geometries optimized at the B3LYP/6-31G* level of theory, along with the crystal data of compounds 9 and 12 and NOESY correlations, point to a strong endo anomeric effect that anchors a preferential conformation and subsequently dictates the completely regioselective ring-opening of the oxazolidine moiety under acetylating conditions to afford imines instead of N-acetyloxazolidines. This process was monitored by 1H NMR spectroscopy, corroborated by synthesis, and rationalized by the intermediacy of an iminium ion. Oxazolidine–imine equilibria are also described for TRIS and other aminopolyols. The equilibria are shifted to the heterocyclic partner as the number of reactive hydroxy groups increases. The structures of an unprotected imine (31) and a per-O-acetylated derivative (43) have also been established by crystallographic analyses.

This report revises and scrutinizes recent arguments, theories, and hypotheses related to the emergence of homochirality. Since the whole treatment would involve multiple and varied scenarios, emphasis is put only on some processes, believed (or claimed) to be prebiotically credible. A particular purpose is to introduce less-travelled paths in which enantioenrichment does not emerge from amplification mechanisms. Some food for thought is provided in an attempt to reduce the gap between existing abiotic hypotheses and the more elusive and conjecturable biotic proposals. A series of novel models have been suggested to reconcile and incorporate chirogenesis into chemical evolution fueled by prebiotic building blocks. All in all, we want to offer new vistas into a never-ending pursuit in the hope that the present considerations will elicit further stimulus, analysis, and experiments in various domains.

Despite the comprehensive literature and enormous versatility of chiral imines derived from aminosugars and aldehydes, the corresponding counterparts generated from ketones remain an underestimated research subject. Filling in the gap, this manuscript sheds light on the synthetic and structural aspects of such substances and updates the few antecedents reported so far.

This paper describes a methodology that correlates experimental chemical shifts (at the alpha proton) of proteins with their geometrical data (both dihedral angles and distances) obtained from 13 representative proteins, which are taken from the Protein Data Bank (PDB) and the BioMagRes Data Bank (BMRB). To this end, the experimentally measured proton chemical shifts of simple amides have been correlated with DFT-based calculated structures, at the B3PW91/6-31G* level. This results in a series of mathematical relationships, which are extrapolated to the above-mentioned proteins giving rise to a modified equation for such skeleta. It is relevant to note that the equation is also supported by a clear comparison with NMR data of a protein beyond the chosen set, such as insulin, even with lower errors. The model also relates the dependence of chemical shifts on hydrophobic and anisotropic effects at the amino acid residues.

Mesoionic heterocycles derived from 1,3-thiazolium-4-olates (thioisomunchnones) undergo thionation with aryl isothiocyanates to afford the corresponding 4-thiolate derivatives. Here, we document this transformation in detail, giving a crystallographic characterization of the solid-state structures. From the mechanistic viewpoint, the formal thionation process could be consistent with a [2 + 2] reaction of the exocyclic C-O bond of the thioisomunchnone with the C=S double bond of the isothiocyanate moiety, which would be competing with a (3 + 2) process as usual in mesoionic rings. Theoretical computations at the [B3LYP/6-31G(d):PM3] level, in which only bond-forming and bond-breaking reactions and neighboring atoms are treated at the DFT level, do reproduce the experimental results and rule out the expected pathway. Calculations instead suggest the existence of a four-step domino pathway through several polar intermediates that agrees with the electronic nature of the substituents involved. The mechanistic hypothesis has further been corroborated by an experiment with isotopically (13)C-labeled PhNCS that unambiguously shows the way in which the exchange reaction occurs.

This article describes the sys- tematic preparation of a novel family of carbohydrate amphiphiles and bo- laamphiphiles in which hydrophilic and hydrophobic units are connected via a ureido or bisA moiety. The sugar core is derived from aminopolyols such as D-glucamine (1), N-methyl-d-gluca- mine (2), or the sugar-like species tris(hydroxymethyl)aminomethane (3). The O-unprotected derivatives behave as self-organizing nonionic surfactants with good water gelation ability, which can be induced under thermal or ultra- sound-driven stimuli. In addition, some derivatives of 1 and 2, and rarely 3 also formed lyotropic liquid crystals with la- mellar or hexagonal structures that ex- hibit low-temperature transitions.

A one-pot procedure for preparing chiral 1,3-oxazolidines derived from N-methyl-d-glucamine and aryl aldehydes is described. It has been carried out by using readily available reagents and operationally simple conditions allowing the preparation of the acyclic C-nucleoside analogs in high yields. The structure of these derivatives has been fully characterized by NMR correlations and single-crystal X-ray diffraction. Some reactions also provide access to the corresponding tetrahydro-1,3-oxazines by an alternative ring closure. Mechanistic considerations account for the observed steric course.

A series of chiral imines derived from 1-amino-1-deoxyalditols such as d-glucamine, a rather unexplored raw material from the chiral pool, have been serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by means of an unexpected acetylation. The structure of these substances is supported by spectroscopic and crystallographic data. The acetylates also trigger a complex dynamic transformation, in which an initially configured trans oxazolidine converts into a more stable cis-configured derivative. Both isomers can also exist as rotational conformers (E,Z) as a consequence of the restricted rotation around the N-acetyl bond. The barriers to rotation have been determined by variable-temperature experiments. Overall, this transformation most likely involves the intermediacy of a chiral iminium ion, which has been documented in the synthesis of nitrogen heterocycles, thus explaining the experimental facts.

This manuscript explores in detail the combined effect of solid supports or microwave irradiation in ionic liquids on a series of Diels–Alder reactions involving 1,3-cyclopentadiene and numerous dienophiles.

On the basis of our synthetic methodologies employing mesoionic synthons, the nucleophilic character of 2-alkyl-1,3-thiazolium-4-olates (2-alkylthioisomunchnones) has been envisaged and developed, at the expenses of their common role as masked 1,3-dipoles. Reactions with aliphatic acid chlorides lead to monoketones derived from thiazolidin-4-ones, whose structure can be rationalized in terms of orbital interactions by computational studies. Aromatic acid chlorides invariably produce 1,3-dicarbonyl compounds, yet maintaining the mesoionic core. Unlike [3+2]-cycloadditions reported previously for thioisomunchnones with isocyanates and isothiocyanates, these heterocumulenes react with 2-alkylthioisomunchnones affording conjugated amides or thioamides.

A mesoionic acyclic C-nucleoside (4), serves as the starting chiron to construct highly functionalized 2-aza-7-thiabicyclo[2.2.1]heptanes and heptenes by means of a [3+2] cycloaddition with acetylenic and olefinic dipolarophiles. Further elimination of either sulfur or hydrogen sulfide leads to acyclic C-nucleosides bearing a heterocyclic moiety of 2-pyridone.

The present work describes a facile and practical route to carbohydrate-based isocyanates, a reactive and appealing family of chiral heterocumulenes, wich can be easily converted into disaccharides and pseudodisaccharides interconnected by urea moieties. A full characterization of these substances by X-ray diffraction analysis and spectroscopic methods reveals further insights into their structures and preferred conformation.

The present work describes in detail the preparation and structural characterization of a series of heteroaryls in which an o,o?-disubstituted phenyl ring is connected through a single C–N bond to a heterocyclic fragment of a chiral imidazolidine-2-one or 2-thione. As a consequence of hindered rotation, some of these substances exist as stable rotamers at room temperature and can easily be separated and characterized. Molecular mechanic calculations have also been carried out to evaluate the barriers to rotation.

NMR spectroscopy has proven to be an enabling methodology in elucidating the axial chirality of a series of non-biaryl atropisomers attached to a carbohydrate moiety, based on deshielding effects caused by the aromatic ring.

This paper describes a general preparation of a series of 1,3-thiazolium-4-olates, each bearing an alkyl group at C-2, through reactions between N-arylthiocarboxamides and α-haloacyl halides. Unlike the 2-aryl-substituted derivatives, such alkylated mesoionic compounds exist in equilibria with their non-dipolar tautomers, the corresponding 2-alkylidene-1,3-thiazolidin-4-ones. The unambiguous characterization of such tautomers and their relative stabilities have now been assessed by spectroscopic and computational studies. The presence of o,o′-disubstituted aryl groups at N-3 of the heterocyclic ring slows down free rotation around the N−Ar bond, thus opening access to a promising class of non-biaryl atropisomers. Finally, treatment of N-arylthioformamides with α-haloacyl halides gives rise to N-acylthioformamides instead of the corresponding mesoionic species. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A series of highly funtionalized beta-lactams and thiiranes can be generated on treatment of 1,3-thiazolium-4-olates (thioisomünchnones) with aliphatic aldehydes. Although in some cases a variety of products have been obtained, the present paper now provides a mechanistic rationale to explain the product distribution based on stereoelectronic effects. Thus, ring fragmentation of the initial [3+2] cycloadduct is essentially dictated by the electronic character of the aryl substituent on the nitrogen atom of the parent thioisomünchnone. However, further evolution of such cycloadducts into beta-lactams or thiiranes is governed by steric effects to a large extent. Evidence for such interactions has been obtained by computing PM3-optimized diastereomeric transition structures in the reaction of a thioisomünchnone with a chiral aliphatic aldehyde.

This work describes the reactivity of 2-alkyl thioisomunchnones, exemplified here by the 2-methyl derivative, which behaves as nucleophile in the presence of both aliphatic and aromatic acid chlorides to give 2-heteroaryl ketones or 2-heteroaryl-1,3-diketones, respectively. However, 2-alkyl thioisomunchnones exhibit its characteristic 1,3-dipole behavior toward unsaturated systems.

The present contribution discloses a simple and unexpected acid-catalyzed cleavage of tetrahydrotetrazines leading to 1,2-bis(hydrazones). Incorporation of a chiral fragment derived from carbohydrates enables the rapid preparation of glycosazones, a family of compounds employed by Emil Fischer to elucidate the configuration of sugars. In addition, a mechanistic proposal accounts for experimental observations.

A mesoionic acyclic C-nucleoside 4, generated readily from δ-gluconolactone in a few synthetic steps, serves as the chiral core to construct a series of functionalized nucleosides bearing 2-aza-7-thiabicycle[2.2.1]heptane or 2-(1H)-pyridone moieties as the aglycon. The key step involves a [3+2] cycloaddition of 4 with several olefinic dipolarophiles followed by hydrogen sulfide elimination with mercury(II) acetate.

DFT calculations support a predominant stepwise mechanism competing with a concerted process leading to isomeric products (III) and (IV) for instance.

This paper extends previous studies on hydrazones derived from hydroxyl naphthaldehydes to aromatic N-aminoheterocycles (exemplified herein by triazole derivatives), in an attempt to freeze enamine structures either by altering the electronic properties of the non-iminic nitrogen or through steric hindrance leading to coplanar dispositions between the lone pairs. By comparing experimentally obtained results (NMR in solution and crystal data) to computationally simulated ones (via DFT calculations in the gas phase and CHCl3), the structures of the preferential conformers and tautomers can be confidently assigned. All data are consistent with enhanced stability of imine forms with respect to their enamine counterparts. DFT calculations have the ability to identify the orbital interactions responsible for electron delocalization and the energy of intramolecular hydrogen bonding. In addition, all transition structures for conformational and tautomeric equilibria are located and characterized.