A Modular Strategy for Expanding Electron-Sink Capacity in Noncanonical Cluster Assemblies.

A modular synthetic strategy is described whereby organometallic complexes exhibiting considerable electron-sink capacity may be assembled by using only a few simple molecular components. The Fe2(PPh2)2(CO)5 fragment was selected as a common electroactive component and was assembled around aromatic cores bearing one, two, or three isocyanide functional groups, with the resultant complexes possessing electron-sink capacities of two, four, and six electrons, respectively. The latter complex is noteworthy in that its electron-sink capacity was found to rival that of large multinuclear clusters (e.g., [Ni32C6(CO)36]6- and [Ni38Pt6(CO)48]6-), which are often considered as benchmarks of electron-sink behavior. Moreover, the modular assembly bearing three Fe2(PPh2)2(CO)5 fragments was observed to undergo reduction to a hexaanionic state over a potential window of about -1.4 to -2.1 V (vs Fc/Fc+), the relatively compressed range being attributed to potential inversions operative during the addition of the second, fourth, and sixth electrons. Such complexes may be designated noncanonical clusters because they exhibit redox properties similar to those of large multinuclear clusters yet lack the extensive network of metal-metal bonds and the condensed metallic cores that typify the latter.

Early Neolithic wine of Georgia in the South Caucasus.

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics from sites in Georgia in the South Caucasus region, dating to the early Neolithic period (ca. 6,000-5,000 BC), provide the earliest biomolecular archaeological evidence for grape wine and viniculture from the Near East, at ca. 6,000-5,800 BC. The chemical findings are corroborated by climatic and environmental reconstruction, together with archaeobotanical evidence, including grape pollen, starch, and epidermal remains associated with a jar of similar type and date. The very large-capacity jars, some of the earliest pottery made in the Near East, probably served as combination fermentation, aging, and serving vessels. They are the most numerous pottery type at many sites comprising the so-called "Shulaveri-Shomutepe Culture" of the Neolithic period, which extends into western Azerbaijan and northern Armenia. The discovery of early sixth millennium BC grape wine in this region is crucial to the later history of wine in Europe and the rest of the world.

Spontaneous Oligomerization of Nucleotide Alternatives in Aqueous Solutions.

On early Earth, a primitive polymer that could spontaneously form from likely available precursors may have preceded both RNA and DNA as the first genetic material. Here, we report that heated aqueous solutions containing 5-hydroxymethyluracil (HMU) result in oligomers of uracil, heated solutions containing 5-hydroxymethylcytosine (HMC) result in oligomers of cytosine, and heated solutions containing both HMU and HMC result in mixed oligomers of uracil and cytosine. Oligomerization of hydroxymethylated pyrimidines, which may have been abundant on the primitive Earth, might have been important in the development of simple informational polymers.

Beginning of viniculture in France.

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics of imported Etruscan amphoras (ca. 500-475 B.C.) and into a limestone pressing platform (ca. 425-400 B.C.) at the ancient coastal port site of Lattara in southern France provide the earliest biomolecular archaeological evidence for grape wine and viniculture from this country, which is crucial to the later history of wine in Europe and the rest of the world. The data support the hypothesis that export of wine by ship from Etruria in central Italy to southern Mediterranean France fueled an ever-growing market and interest in wine there, which, in turn, as evidenced by the winepress, led to transplantation of the Eurasian grapevine and the beginning of a Celtic industry in France. Herbal and pine resin additives to the Etruscan wine point to the medicinal role of wine in antiquity, as well as a means of preserving it during marine transport.

Prebiotic alternatives to proteins: structure and function of hyperbranched polyesters.

Proteins are responsible multiple biological functions, such as ligand binding, catalysis, and ion channeling. This functionality is enabled by proteins' three-dimensional structures that require long polypeptides. Since plausibly prebiotic synthesis of functional polypeptides has proven challenging in the laboratory, we propose that these functions may have been initially performed by alternative macromolecular constructs, namely hyperbranched polymers (HBPs), during early stages of chemical evolution. HBPs can be straightforwardly synthesized in one-pot processes, possess globular structures determined by their architecture as opposed to folding in proteins, and have documented ligand binding and catalytic properties. Our initial study focuses on glycerol-citric acid HBPs synthesized via moderate heating in the dry state. The polymerization products consisted of a mixture of isomeric structures of varying molar mass as evidenced by NMR, mass spectrometry and size-exclusion chromatography. Addition of divalent cations during polymerization resulted in increased incorporation of citric acid into the HBPs and the possible formation of cation-oligomer complexes. The chelating properties of citric acid govern the makeup of the resulting polymer, turning the polymerization system into a rudimentary smart material.

Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases.

All terrestrial organisms depend on nucleic acids (RNA and DNA), which use pyrimidine and purine nucleobases to encode genetic information. Carbon-rich meteorites may have been important sources of organic compounds required for the emergence of life on the early Earth; however, the origin and formation of nucleobases in meteorites has been debated for over 50 y. So far, the few nucleobases reported in meteorites are biologically common and lacked the structural diversity typical of other indigenous meteoritic organics. Here, we investigated the abundance and distribution of nucleobases and nucleobase analogs in formic acid extracts of 12 different meteorites by liquid chromatography-mass spectrometry. The Murchison and Lonewolf Nunataks 94102 meteorites contained a diverse suite of nucleobases, which included three unusual and terrestrially rare nucleobase analogs: purine, 2,6-diaminopurine, and 6,8-diaminopurine. In a parallel experiment, we found an identical suite of nucleobases and nucleobase analogs generated in reactions of ammonium cyanide. Additionally, these nucleobase analogs were not detected above our parts-per-billion detection limits in any of the procedural blanks, control samples, a terrestrial soil sample, and an Antarctic ice sample. Our results demonstrate that the purines detected in meteorites are consistent with products of ammonium cyanide chemistry, which provides a plausible mechanism for their synthesis in the asteroid parent bodies, and strongly supports an extraterrestrial origin. The discovery of new nucleobase analogs in meteorites also expands the prebiotic molecular inventory available for constructing the first genetic molecules.

Relevance of the C-5 position to schweinfurthin induced cytotoxicity.

The schweinfurthins are an intriguing group of anti-proliferative agents that display low nanomolar activities against several cell types, including the human-derived glioblastoma cell line SF-295, but have little impact on other cell lines even at micromolar concentrations. This activity has inspired the synthesis of seven of the natural schweinfurthins, all with the correct absolute stereochemistry, and a variety of analogues designed to probe different facets of the pharmacophore. Reported herein is the synthesis of several new schweinfurthin analogues varied at the C-5 position along with data on their biological activity in the NCI 60 cell-line assay.

Structure of 2,4-diaminopyrimidine-theobromine alternate base pairs.

We report the structure of clusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine-cytosine. We have found the four lowest energy structures, which include the Watson-Crick base pairing motif. This Watson-Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs.

Conformational structure of tyrosine, tyrosyl-glycine, and tyrosyl-glycyl-glycine by double resonance spectroscopy.

We investigated the variation in conformation for the amino acid tyrosine (Y), alone and in the small peptides tyrosine-glycine (YG) and tyrosine-glycine-glycine (YGG), in the gas phase by using UV-UV and IR-UV double resonance spectroscopy and density functional theory calculations. For tyrosine we found seven different conformations, for YG we found four different conformations, and for YGG we found three different conformations. As the peptides get larger, we observe fewer stable conformers, despite the increasing complexity and number of degrees of freedom. We find structural trends similar to those in phenylalanine-glycine-glycine (FGG) and tryptophan-glycine-glycine (WGG); however, the effect of dispersive forces in FGG for stabilizing a folded structure is replaced by that of hydrogen bonding in YGG.

Enhanced synthesis of alkyl amino acids in Miller's 1958 H2S experiment.

Stanley Miller's 1958 H(2)S-containing experiment, which included a simulated prebiotic atmosphere of methane (CH(4)), ammonia (NH(3)), carbon dioxide (CO(2)), and hydrogen sulfide (H(2)S) produced several alkyl amino acids, including the α-, ß-, and γ-isomers of aminobutyric acid (ABA) in greater relative yields than had previously been reported from his spark discharge experiments. In the presence of H(2)S, aspartic and glutamic acids could yield alkyl amino acids via the formation of thioimide intermediates. Radical chemistry initiated by passing H(2)S through a spark discharge could have also enhanced alkyl amino acid synthesis by generating alkyl radicals that can help form the aldehyde and ketone precursors to these amino acids. We propose mechanisms that may have influenced the synthesis of certain amino acids in localized environments rich in H(2)S and lightning discharges, similar to conditions near volcanic systems on the early Earth, thus contributing to the prebiotic chemical inventory of the primordial Earth.

Prebiotic synthesis of methionine and other sulfur-containing organic compounds on the primitive Earth: a contemporary reassessment based on an unpublished 1958 Stanley Miller experiment.

Original extracts from an unpublished 1958 experiment conducted by the late Stanley L. Miller were recently found and analyzed using modern state-of-the-art analytical methods. The extracts were produced by the action of an electric discharge on a mixture of methane (CH(4)), hydrogen sulfide (H(2)S), ammonia (NH(3)), and carbon dioxide (CO(2)). Racemic methionine was formed in significant yields, together with other sulfur-bearing organic compounds. The formation of methionine and other compounds from a model prebiotic atmosphere that contained H(2)S suggests that this type of synthesis is robust under reducing conditions, which may have existed either in the global primitive atmosphere or in localized volcanic environments on the early Earth. The presence of a wide array of sulfur-containing organic compounds produced by the decomposition of methionine and cysteine indicates that in addition to abiotic synthetic processes, degradation of organic compounds on the primordial Earth could have been important in diversifying the inventory of molecules of biochemical significance not readily formed from other abiotic reactions, or derived from extraterrestrial delivery.

Effect of substituents on the excited-state dynamics of the modified DNA bases 2,4-diaminopyrimidine and 2,6-diaminopurine.

To explore the excited state dynamics of pyrimidine derivatives, we performed a combined experimental and theoretical study. We present resonant two-photon ionization (R2PI) and IR-UV double resonance spectra of 2,4-diaminopyrimidine and 2,6-diaminopurine seeded in a supersonic jet by laser desorption. For 2,4-diaminopyrimidine (S(0)-->S(1) 34,459 cm(-1)), we observed only the diamino tautomer with an excited state lifetime bracketed between experimental limits of 10 ps and 1 ns. For 2,6-diaminopurine, we observed two tautomers, the 9H- (S(0)-->S(1) 34,881 cm(-1)) and 7H- (S(0)-->S(1) 32,215 cm(-1)) diamino forms, with excited state lifetimes of 6.3±0.4 ns and 8.7±0.8 ns, respectively. We investigated the nature of the excited state of 2,4-diaminopyrimidine by means of multi-reference ab initio methods. The calculations of stationary points in the ground and excited states, minima on the S(0)/S(1) crossing seam and connecting reaction paths show that several paths with negligible barriers exist, allowing ultrafast radiationless deactivation if excited at energies slightly higher than the band origin. The sub-nanosecond lifetime found experimentally is in good agreement with this finding.

The effect of C5 substitution on the photochemistry of uracil.

A combined experimental and theoretical study on the excited-state behavior of the uracil analogues, 5-OH-Ura and 5-NH(2)-Ura is reported. Two-photon ionization and IR/UV double-resonant spectra show that there is only one tautomer present for each with an excited state lifetime of 1.8 ns for 5-OH-Ura and 12.0 ns for 5-NH(2)-Ura as determined from pump-probe experiments. The nature of the excited states of both species is investigated by means of multi-reference ab initio methods. Vertical excitation energies, excited state minima, minima on the crossing seam and reaction paths towards them are determined. Sizeable barriers on these paths are found that provide an explanation for the lifetimes of several nanoseconds observed in the experiment.

A tandem cascade cyclization-electrophilic aromatic substitution: application in the total synthesis of (+)-angelichalcone.

When cascade cyclizations initiated by Lewis acid-mediated opening of an epoxide are terminated through reaction with a MOM-protected phenol, a tandem electrophilic aromatic substitution can be obtained. This highly regioselective tandem process has been employed in the first synthesis of (+)-angelichalcone.

Organometallic compounds as carriers of extraterrestrial cyanide in primitive meteorites.

Extraterrestrial delivery of cyanide may have been crucial for the origin of life on Earth since cyanide is involved in the abiotic synthesis of numerous organic compounds found in extant life; however, little is known about the abundance and species of cyanide present in meteorites. Here, we report cyanide abundance in a set of CM chondrites ranging from 50 ± 1 to 2472 ± 38 nmol·g-1, which relates to the degree of aqueous alteration of the meteorite and indicates that parent body processing influenced cyanide abundance. Analysis of the Lewis Cliff 85311 meteorite shows that its releasable cyanide is primarily in the form of [FeII(CN)5(CO)]3- and [FeII(CN)4(CO)2]2-. Meteoritic delivery of iron cyanocarbonyl complexes to early Earth likely provided an important point source of free cyanide. Iron cyanocarbonyl complexes may have served as precursors to the unusual FeII(CN)(CO) moieties that form the catalytic centers of hydrogenases, which are thought to be among the earliest enzymes.

Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures.

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth.

Isomer discrimination of polycyclic aromatic hydrocarbons in the Murchison meteorite by resonant ionization.

We have used two-color resonant two-photon ionization (2C-R2PI) mass spectrometry to discriminate between isomers of polycyclic aromatic hydrocarbons in the Murchison meteorite. We measured the 2C-R2PI spectra of chrysene and triphenylene seeded in a supersonic jet by laser desorption. Since each isomer differs in its R2PI spectrum, we can distinguish between isomers using wavelength dependent ionization and mass spectrometry. We found both chrysene and triphenylene in sublimates from carbonaceous residue obtained by acid demineralization of the Murchison meteorite. Their R2PI mass spectra show only the molecular ion, even though these samples contain a complex inventory of organic molecules.

Metabolic precursors in astrophysical ice analogs: implications for meteorites and comets.

We report the synthesis of complex organic compounds including nicotinic and quinolinic acid, two members involved in the nicotinamide adenine dinucleotide (NAD) biosynthetic pathway, in irradiated astrophysical ice analogs. If delivered to Earth by meteorites and comets, these compounds may have contributed to the origin and early evolution of life.

Amino acid analysis in micrograms of meteorite sample by nanoliquid chromatography-high-resolution mass spectrometry.

Amino acids and their enantiomers in a 360 microgram sample of Murchison meteorite were unambiguously identified and quantified using chemical derivatization and nanoliquid chromatography coupled to nanoelectrospray ionization high resolution orbitrap mass spectrometry techniques. The distribution and abundance of amino acids were similar to past studies of Murchison meteorite but the samples used here were three orders of magnitude lower. The analytical method was also highly sensitive, and some amino acid reference standards were successfully detected at a level of ∼200 attomoles (on column). These results may open up the possibility for investigating other less studied, sample-limited extraterrestrial samples (e.g., micrometeorites, interplanetary dust particles, and cometary particles) for biologically-relevant organic molecules.