Chimeric XNA: An Unconventional Design for Orthogonal Informational Systems.

The paradigm of homogenous-sugar-backbone of RNA and DNA has reliably guided the construction of many functional and useful xeno nucleic acid (XNA) systems to date. Deviations from this monotonous and canonical design, in many cases, results in oligonucleotide systems that lack base pairing with themselves, or with RNA or DNA. Here we show that nucleotides of two such compromised XNA systems can be combined with RNA and DNA in specific patterns to produce chimeric-backbone oligonucleotides, which in certain cases demonstrate base pairing properties comparable to-or stronger than-canonical systems, while also altering the conventional Watson-Crick pairing behavior.

Nucleobase modification by an RNA enzyme.

Ribozymes can catalyze phosphoryl or nucleotidyl transfer onto ribose hydroxyls of RNA chains. We report a single ribozyme that performs both reactions, with a nucleobase serving as initial acceptor moiety. This unprecedented combined reaction was revealed while investigating potential contributions of ribose hydroxyls to catalysis by kinase ribozyme K28.

RNA-DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World.

The RNA world hypothesis posits that DNA and proteins were later inventions of early life, or the chemistry that gave rise to life. Most scenarios put forth for the emergence of DNA assume a clean separation of RNA and DNA polymer, and a smooth transition between RNA and DNA. However, based on the reality of "clutter" and lack of sophisticated separation/discrimination mechanisms in a protobiological (and/or prebiological) world, heterogeneous RNA-DNA backbone containing chimeric sequences could have been common-and have not been fully considered in models transitioning from an RNA world to an RNA-DNA world.

A Deep Cavitand Templates Lactam Formation in Water.

Cyclization reactions are common processes in organic chemistry and show familiar patterns of reaction rates vs ring size. While the details vary with the nature of bond being made and the number of unsaturated atoms, small rings typically form quickly despite angle strain, medium size rings form very slowly due to internal strains, and large rings form slowly (when they form at all) because fewer and less probable conformations bring the ends of the substrate together. High dilution is commonly used to slow the competing bi- and higher molecular processes.

The effects of hexafluoroisopropanol on guest binding by water-soluble capsule and cavitand hosts.

Encapsulation of amphiphilic guests in a water-soluble cavitand is enhanced by the addition of hexafluoroisopropanol (HFIP). While binding of n-alkanes in cavitands in HFIP/D2O mixtures was similar to that observed in 100% D2O, the binding of guests with terminal polar groups was quite different. Several α,ω-bolaamphiphiles: alkyldiols (C10-C12), a dinitrile (C14) and a diacid (C16) became encapsulated in HFIP/D2O solutions.

Folded alkyl chains in water-soluble capsules and cavitands.

A deep cavitand with ionic "feet" dimerizes around hydrophobic compounds in D2O. Longer n-alkane guests, C14-C18, are encapsulated in contorted conformations and NMR is used to deduce their shapes. Competition experiments establish the driving forces involved and how they compensate for the steric clashes in the folded structures of the encapsulated alkanes.

Exploring Anion-Induced Conformational Flexibility and Molecular Switching in a Series of Heteroaryl-Urea Receptors.

Anion binding studies of 1,10-phenanthroline- and 2-pyridyl-substituted urea-based receptors reveal that guest-dependent conformations exist in structural variants related to a previously investigated bipyridyl-based receptor. Dynamic conformational switching persists in a monofunctional pyridyl-urea receptor, and the preorganization provided by a phenanthroline-based analogue promotes convergence of anion coordinating groups to a single guest. Despite this predisposition for anion coordination, the conformational flexibility of the bipyridyl-based receptor provides the most selective motif for HPO coordination.

Intramolecular N-H···Cl hydrogen bonds in the outer coordination sphere of a bipyridyl bisurea-based ligand stabilize a tetrahedral FeLCl2 complex.

A bipyridyl-based anion receptor is utilized as a ligand in a tetrahedral FeCl2 complex and demonstrates secondary coordination sphere influence through intramolecular hydrogen bonding to the chloride ligands as evidenced by X-ray crystallography.

Complexation of alkyl groups and ghrelin in a deep, water-soluble cavitand.

A cavitand with ionic, but nonionizable "feet" folds around hydrophobic guests in D2O. Short alkanes and ibuprofen are included and exchange rates are slow on the NMR timescale. Normal octanoyl groups show good affinity for the cavitand and the gastric peptide ghrelin is bound at low pH and physiological temperature.

Alkyl groups fold to fit within a water-soluble cavitand.

We report here a widened, deep cavitand host that binds hydrophobic and amphiphilic guests in D2O. Small alkanes (C6 to C11) are bound in compressed conformations and tumble rapidly within the space. Longer n-alkanes (C13 to C14), n-alcohols, and α,ω-diols are taken up in folded conformations.

An anion-modulated three-way supramolecular switch that selectively binds dihydrogen phosphate, H2PO4-.

Unlabelled:

An Anionic Three-way Switch: A bipyridyl bisurea-based anion receptor that is highly selective for dihydrogen phosphate demonstrates spectroscopically distinct anion bound conformations toward halides and select oxoanions. H NMR studies show the differing anion induced conformations are reversible allowing this system to function as a three-way molecular switch.

Lithium-selective phosphine oxide-based ditopic receptors show enhanced halide binding upon alkali metal ion coordination.

Previous work on a ditopic receptor based on a tripodal phosphine oxide core demonstrated preferential enhancement of bromide binding over chloride or iodide in the presence of lithium cation. Current studies on an elongated receptor provide evidence that preferential bromide binding enhancement in the presence of lithium cation is common to this receptor class in general, and that lengthening of the receptor results in an overall increase in halide association. Furthermore, the extended receptor shows a strong preference for Li binding in solution.

Lithium cation enhances anion binding in a tripodal phosphine oxide-based ditopic receptor.

A tripodal ditopic receptor presents H-bond donors and a phosphine oxide to potential guests. In the idealized binding conformation, an endohedral P=O functionality provides enhanced halide binding in the presence of lithium with the greatest ΔΔG° observed for bromide, while minimal changes in K(a) are observed in the presence of sodium.

Fluorous effects in amide-based receptors for anions.

Hybrid receptors designed to recognize both the sulfonate headgroup and the fluorous tail of perfluorooctanesulfonate (CF(3)(CF(2))(7)SO(3)(-), "PFOS") were prepared by coupling fluorinated carboxylic acids onto poly(aminomethyl)benzene scaffolds. Binding to PFOS, CF(3)SO(3)(-), p-TsO(-), and Cl(-) was monitored by (1)H NMR and isothermal titration calorimetry (ITC). In chloroform solvent, hydrogen-bonding to anions is accompanied by downfield shifts in the amide NH protons of the fluorinated receptors and by evolution of heat.

Hydrogen bonding vs steric gearing in a hexasubstituted benzene.

Treatment of hexakis(bromomethyl)benzene with excess NaN 3, followed by hydrogenation of the resultant polyazide, affords hexamine 3 in high yield. Coupling to six equivalents of nonanoic acid provides hexamide 5 without chromatographic purification. The NH resonance of 5 appears far downfield (approximately 9.