Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations

The RNA‐world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.     

Ordinal algorithms for packing with target center of gravity

The problem of arranging N unit length weights on a line segment of length N, given a target center of gravity on this line segment, is examined under the assumption that the only information we have about the weights is their order, i.e., a ₁ a ₂ ... a _N . Lower bounds on worst case performance of algorithms for this problem are developed, and algorithms (permutations) which come close to achieving these bounds are provided.This work was partially supported under Natural Sciences and Engineering Research Council (NSERC) of Canada research grant number OGP0002507.     

Are All Uniform Algebras Amnm?

A Banach algebra a is AMNM if whenever a linear functional on a and a positive number satisfy |(ab)–(a)(b)|||a||·||b||for all a, b a, there is a multiplicative linear functional on a such that ||–||=o(1) as 0. K. Jarosz [1] asked whetherevery Banach algebra, or every uniform algebra, is AMNM. B.E. Johnson [3] studied the AMNM property and constructed a commutativesemisimple Banach algebra that is not AMNM. In this note weconstruct uniform algebras that are not AMNM. 1991 MathematicsSubject Classification 46J10.     

The amidoalkylation of aromatic hydrocarbons

The Nyberg procedure (the use of trifluoroacetic acid in chloroform) for the efficient amidoalkylation of aromatic hydrocarbons is limited to substrates more nucleophilic than benzene. The reaction involves protonation of the electrophile, cleavage to a carbonium ion and alkylation of the nucleophile by the carbonium ion. Either the cleavage step or the alkylation step may be rate-determining. The present work identifies some cases where a carbonium ion is formed but fails to alkylate the nucleophile (with benzene and nitro-substituted benzenes as nucleophiles) and other cases where the reaction conditions are not sufficient to permit cleavage of the protonated electrophile (the reactions of N-phthalimidomethylamides).     

ULTRAVIOLET ACTION SPECTRUM FOR FLUOROGEN PRODUCTION IN THE OCULAR LENS

Abstract— …Previous work has demonstrated that fluorescent material (360nm excitation, 440nm emission), whose concentration normally increases with age in human lenses, can be generated artificially by exposing cultured human or animal lenses to UV radiation. In the present paper we report measurements of the rate of production of this fluorescent material in rat lenses in vitro as a function of UV irradiation wavelength. A plot of the observed rate of fluorogen production normalized to constant photon flux vs irradiation wavelength shows little action at 360 or 320nm, increases sharply at 300nm, remains relatively constant in the range 300–280nm, and then exhibits a further gradual rise from 270–250nm. The results on rat lenses are compared with results reported elsewhere for tryptophan in aqueous solution. The action spectrum for photochemical destruction of tryptophan in solution closely parallels that for fluorogen production in rat lenses. This result and other evidence suggest that photochemical destruction of tryptophan might be the initial event in UV-induced fluorogen production in the ocular lens.     

A stereocontrolled synthesis of delta-trans-tocotrienoloic acid

[reaction: see text] A concise stereoselective total synthesis of a naturally occurring polymerase beta inhibitor, delta-trans-tocotrienoloic acid (2), is described. The key step in the synthesis is an acid-catalyzed cyclodehydration reaction. Additionally, this report corrects a previously reported structural assignment, defines the absolute stereochemistry of 2, and defines key structural requirements for polymerase beta inhibition.     

Foldamer dynamics expressed via Markov state models. II. State space decomposition

The structural landscape of poly-phenylacetylene (pPA), otherwise known as m-phenylene ethynylene oligomers, has been shown to consist of a very diverse set of conformations, including helices, turns, and knots. Defining a state space decomposition to classify these conformations into easily identifiable states is an important step in understanding the dynamics in relation to Markov state models. We define the state decomposition of pPA oligomers in terms of the sequence of discretized dihedral angles between adjacent phenyl rings along the oligomer backbone. Furthermore, we derive in mathematical detail an approach to further reduce the number of states by grouping symmetrically equivalent states into a single parent state. A more challenging problem requires a formal definition for knotted states in the structural landscape. Assuming that the oligomer chain can only cross the ideal helix path once, we propose a technique to define a knotted state derived from a helical state determined by the position along the helical nucleus where the chain crosses the ideal helix path. Several examples of helical states and knotted states from the pPA 12-mer illustrate the principles outlined in this article.     

First soluble M@C60 derivatives provide enhanced access to metallofullerenes and permit in vivo evaluation of Gd@C60[C(COOH)2]10 as a MRI contrast agent

M@C(60) and related endohedral metallofullerenes comprise a significant portion of the metallofullerene yield in the traditional arc synthesis, but their chemistry and potential applications have been largely overlooked because of their sparse solubility. In this work, procedures are described to solublize Gd@C(60) species for the first time by forming the derivative, Gd@C(60)[C(COOCH(2)CH(3))(2)](10), and its hydrolyzed water-soluble form, Gd@C(60)[C(COOH)(2)](10). Imparting water solubility to Gd@C(60) permits its evaluation as a magnetic resonance imaging (MRI) contrast agent. Relaxometry measurements for Gd@C(60)[C(COOH)(2)](10) reveal it to possess a relaxivity (4.6 mM(-1) s(-1) at 20 MHz and 40 degrees C) comparable to that of commercially available Gd(III) chelate-based MRI agents. An in vivo MRI biodistribution study in a rodent model reveals Gd@C(60)[C(COOH)(2)](10) to possess the first non-reticuloendothelial system (RES) localizing behavior for a water-soluble endohedral metallofullerene species, consistent with its lack of intermolecular aggregation in solution as determined by light-scattering measurements. This first derivatization and use of a M@C(60) species suggests new potential for metallofullerene technologies by reducing reliance on the chromatographic purification procedures normally employed for the far less abundant M@C(82) and related endohedrals. The recognition that water-soluble fullerene derivatives can be designed to avoid high levels of RES uptake is an important step toward fullerene-based pharmaceutical development.