Evaluating impacts of bambusuril pocket size and sterics on anion binding trends using ChemFET sensors.

Chemically-sensitive Field Effect Transistors (ChemFETs) are a useful tool to evaluate aqueous anion affinity of hydrophobic supramolecular scaffolds. More specifically, ChemFETs can be used to probe impacts of receptor modification to aqueous anion affinity. In this study, ChemFETs are used to evaluate the anion affinity of both dodeca-n-butyl bambus[6]uril and dodecabenzyl bambus[6]uril to assess steric effects in the chemical selectivity of the sensor membrane. The ChemFETs were evaluated through a series of common anions in the Hofmeister series in order to ascertain the difference in detection limit imparted by the specific functionalization of the bambus[6]uril macrocycles, which are quite sensitive to modest steric effects. Significant improvements to perchlorate and nitrate detection limits were observed via n-butyl bambusuril-containing sensor membranes over detection limits recorded with benzyl bambusuril sensors.

Azaphosphinines and their derivatives.

Six-membered heterocycles containing one phosphorus and one nitrogen atom, known as azaphosphinines, have existed in the shadows of their single heteroatom-containing analogues for almost 150 years. Despite this, recent chemistry has seen a rapid increase in publications concerning this uncommon scaffold. Azaphosphinines exist in one of six isomers-there are three possible orientations of the pnictogen atoms and in each of these, the phosphorus is in one of two valences (PIIIvs. PV). This review aims to outline and inform on the synthesis and applications of all six isomers. PV-oxo azaphosphinines are of particular interest to this review as many of the discussed heterocycles either form as the pentavalent species directly or oxidize to this over time. In very recent years the published applications of azaphosphinines have blossomed into subjects spanning several fields of chemistry such as asymmetric catalysis, supramolecular association, cellular imaging, and medicinal chemistry.

Impact of Internal Charge Transfer on the Photophysical Properties of Pyridine-Fused Phosphorus-Nitrogen Heterocycles.

The phosphaquinolinone scaffold has been previously studied as a modular core for a variety of fluorescent species where use of substituent effects has focused on increasing or decreasing electron density in the core rings. We now report the synthesis and analysis of several pyridine-containing phosphaquinolinone species exhibiting notable linear conjugation from the aryl-substituent to electron-withdrawing pyridyl nitrogen. Varying the nature of the aryl substituent from electron-withdrawing to electron-donating leads to the generation of an internal charge-transfer (ICT) band in the absorbance spectrum, which becomes the dominant absorbance in terms of intensity in the most electron-rich -NMe2 example. This heterocycle exhibits improved photophysical properties compared to others in the set including high quantum yield and considerably red-shifted emission. The enhanced ICT can be observed in the X-ray data where a rare example of molecule co-planarity is observed. Computational data show increased localization of negative charge on the pyridyl nitrogen as the electron-donating character of the aryl-substituent increases.

2-λ5-Phosphaquinolin-2-ones as Non-cytotoxic, Targetable, and pH-Stable Fluorophores.

Several phosphaquinolinone derivatives have been synthesized and characterized to explore their usefulness in the realm of cell imaging. Solution-state photophysical properties in both aqueous and organic solutions were collected for these derivatives. Additionally, CCK-8 cell viability assays and fluorescent imaging in HeLa cells incubated with the new heterocyclic derivatives show evidence of favorable cell permeability, cell viability, and moderate intracellular localization when appended with the well-known morpholine targeting motif.

C-H⋯S hydrogen bonding interactions.

The short C-H⋯S contacts found in available structural data for both small molecules and larger biomolecular systems suggest that such contacts are an often overlooked yet important stabilizing interaction. Moreover, many of these short C-H⋯S contacts meet the definition of a hydrogen bonding interaction. Using available structural data from the Cambridge Structural Database (CSD), as well as selected examples from the literature in which important C-H⋯S contacts may have been overlooked, we highlight the generality of C-H⋯S hydrogen bonding as an important stabilizing interaction. To uncover and establish the generality of these interactions, we compare C-H⋯S contacts with other traditional hydrogen bond donors and acceptors as well as investigate how coordination number and metal bonding affect the preferred geometry of interactions in the solid state. This work establishes that the C-H⋯S bond meets the definition of a hydrogen bond and serves as a guide to identify C-H⋯S hydrogen bonds in diverse systems.

Controlling Tautomerization in Pyridine-Fused Phosphorus-Nitrogen Heterocycles.

Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This tautomerization, initially observed in the solid state through X-ray crystallography, is also explained by computational analysis. We prepared an electron deficient analogue (2 e) with a fluorine on the pyridine ring and showed that the weakly basic pyridine resisted tautomerization, providing key insights to why the transformation occurs. To study the difference in solution vs. solid-state heterocycles, alkylated analogues that lock in the quinoidal tautomer were synthesized and their different 1 H NMR and UV/Vis spectra studied. Ultimately, we determined that all heterocycles are the aromatic tautomer in solution and all but 2 e switch to the quinoidal tautomer in the solid state. Better understanding of this transformation and under what circumstances it occurs suggest future use in a switchable on/off hydrogen-bond-directed receptor that can be tuned for complementary hydrogen bonding.

Multilevel Selection on Offspring Size and the Maintenance of Variation.

AbstractMultilevel selection on offspring size occurs when offspring fitness depends on both absolute size (hard selection) and size relative to neighbors (soft selection). We examined multilevel selection on egg size at two biological scales-within clutches and among clutches from different females-using an external fertilizing tube worm. We exposed clutches of eggs to two sperm environments (limiting and saturating) and measured their fertilization success. We then modeled environmental (sperm-dependent) differences in hard and soft selection on individual eggs as well as selection on clutch-level traits (means and variances). Hard and soft selection differed in strength and form depending on sperm availability-hard selection was consistently stabilizing; soft selection was directional and favored eggs relatively larger (sperm limitation) or smaller (sperm saturation) than the clutch mean. At the clutch level, selection on mean egg size was largely concave, while selection on within-clutch variance was weak but generally negative-although some correlational selection occurred between these two traits. Importantly, we found that the optimal clutch mean egg size differed for mothers and offspring, suggesting some antagonism between the levels of selection. We thus identify several pathways that may maintain offspring size variation: environmentally (sperm-) dependent soft selection, antagonistic multilevel selection, and correlational selection on clutch means and variances. Multilevel approaches are powerful but seldom-used tools for studies of offspring size, and we encourage their future use.

Tuning Supramolecular Selectivity for Hydrosulfide: Linear Free Energy Relationships Reveal Preferential C-H Hydrogen Bond Interactions.

Supramolecular anion receptors can be used to study the molecular recognition properties of the reactive yet biologically critical hydrochalcogenide anions (HCh-). Achieving selectivity for HCh- over the halides is challenging but necessary for not only developing future supramolecular probes for HCh- binding and detection, but also for understanding the fundamental properties that govern these binding and recognition events. Here we demonstrate that linear free energy relationships (LFERs)-including Hammett and Swain-Lupton plots-reveal a clear difference in sensitivity to the polarity of an aryl C-H hydrogen bond (HB) donor for HS- over other HCh- and halides. Analysis using electrostatic potential maps highlights that this difference in sensitivity results from a preference of the aryl C-H HB donor for HS- in this host scaffold. From this study, we demonstrate that LFERs are a powerful tool to gain interpretative insight into motif design for future anion-selective supramolecular receptors and highlight the importance of C-H HB donors for HS- recognition. From our results, we suggest that aryl C-H HB donors should be investigated in the next generation of HS- selective receptors based on the enhanced HS- selectivity over other competing anions in this system.

Solvent-Dependent Linear Free-Energy Relationship in a Flexible Host-Guest System.

Supramolecular chemistry provides an effective strategy for the molecular recognition of diverse molecules. Significant efforts to design synthetic hosts have enabled the successful binding of many types of guests; however, less is known about how host-guest environments influence binding. Herein, we present a comprehensive study in which we measure the host-guest binding of a bis(arylethynyl phenylurea) host with a chloride guest in eight solvents spanning ET(30) values ranging from nonpolar (40.7 kcal mol-1) to polar (47.4 kcal mol-1). Polar solvents show significantly weaker binding in comparison to nonpolar solvents, and the bulk solvent polarity parameter, ET(30), shows a linear free-energy relationship with respect to the free energy of binding in the host-guest complex. These studies provide a better understanding of how host-guest binding in flexible receptors is governed by their environments and highlight the importance of host reorganization contributions in the free energy of binding. In addition, these studies highlight that preorganization may not be as important as previously thought for weak binding in which enthalpic contributions are smaller versus in polar solvents where solvent effects are magnified.

Amplification of the Quantum Yields of 2-λ5-Phosphaquinolin-2-ones through Phosphorus Center Modification.

We report the synthesis and characterization of P-phenyl modified phosphorus- and nitrogen-containing phosphaquinolinone heterocycles. The change from -OPh to -Ph results in a marked increase in the quantum yield of the scaffold as well as a moderate red-shifting of the emission. While calculations suggest that π to π* transitions are dominant, intramolecular charge transfer (ICT) also contributes in the excited state. Solution- and solid-state studies of the dimerization of this new congener to the P-phenoxy variant are also reported, showing retention of the dimerization behavior in this scaffold.

Hydrosulfide Oxidation at a Molybdenum Tetrasulfido Complex.

Hydrogen sulfide (H2S) is an important biological signaling molecule and one of three established gasotransmitters. Upon oxidation, H2S can form reactive sulfur species (RSS) that play a central role in protein persulfidation. Here we report that a molybdenum tetrasulfide can react directly with hydrosulfide to form polysulfides and oxidize the Mo center. Specifically, [NBu4][TpMoS(S4)] reacts with 2 equiv of [NBu4][SH] to form [NBu4][TpMoS3]. Trapping experiments with BnBr confirm the formation of polysulfides, as evidenced by the direct trapping of Bn2S2. This work demonstrates new reaction pathways for H2S oxidation and RSS generation from metal-bound polysulfides that will increase our understanding of the potential roles that metals play in signaling processes.

Local adaptation of antipredator behaviors in populations of a temperate reef fish.

The temperament of animals can vary among individuals and among populations, but it is often unclear whether spatial variation in temperament is the result of acclimation to local environmental conditions or genetic adaptation to spatial differences in natural selection. This study tested whether populations of a marine fish that experience different levels of mortality and fishing exhibited local adaptation in behaviors related to predator avoidance and evasion. First, we measured variation in reactivity to perceived risk in wild populations of black surfperch (Embiotoca jacksoni). We compared flight initiation distances (FID) between populations with significantly different mortality rates. After finding that FID values were substantially lower in the low-risk locations, we tested for local adaptation by rearing lab-born offspring from both high- and low-risk populations in a common environment before measuring their behavior. Lab-reared offspring from high- and low-risk populations exhibited significant differences in several behaviors related to reactivity. Between 23 and 43% of the total variation in behaviors we measured could be attributed to source population. These results thus suggest that a substantial amount of spatial variation in behaviors related to predator evasion may represent local adaptation. In addition, behaviors we measured had an average, broad-sense heritability of 0.24, suggesting that the behavioral tendencies of these populations have some capacity to evolve further in response to any changes in selection.

"Design of Experiments" as a Method to Optimize Dynamic Disulfide Assemblies: Cages and Functionalizable Macrocycles.

Cyclophanes are a venerable class of macrocyclic and cage compounds that often contain unusual conformations, high strain, and unusual properties. However, synthesis of complex, functional derivatives remains difficult due to low functional group tolerance, high dilution, extreme reaction conditions, and sometimes low yields using traditional stepwise synthetic methods. "Design of experiments" (DOE) is a method employed for the optimization of reaction conditions, and we showcase this approach to generate a dramatic increase in the yield of specific targets from two different self-assembling systems. These examples demonstrate that DOE provides an additional tool in tuning self-assembling, dynamic covalent systems.

Self-Assembly of a Trithioorthoformate-Capped Cyclophane and Its Endohedral Inclusion of a Methine Group.

An unusual trithioorthoformate-capped cyclophane cage was assembled via antimony-activated iodine oxidation of thiols as confirmed by 1 H-NMR spectroscopy and X-ray crystallography. The disulfide bridges can undergo desulfurization with hexamethylphosphorous triamide (HMPT) at ambient temperature to capture a trithioether cyclophane cage capped by the trithioorthoformate. In both cages a methine proton points directly into the small cavity. This unexpected structure is hypothesized to have formed as a result of haloform insertion during oxidation.

Naphtho[2,1- e]-1,2-azaphosphorine 2-Oxide Derivatives: Synthesis, Optoelectronic Properties, and Self-Dimerization Phenomena.

A family of naphtho[2,1- e]-fused 1,2-azaphosphorine 2-oxides that contain electron-withdrawing and -donating substituents on the 3-phenyl groups has been prepared and characterized. This new series of phosphorus- and nitrogen-containing heterocycles is brightly fluorescent with tunable emission wavelengths (λem = 441-493 nm, ΦF = 0.19-0.93). Their strong self-dimerization behavior through N-H and P═O hydrogen bond donors/acceptors was investigated experimentally and theoretically. The pendant phenyl group can be used to modify the intrinsic optoelectronic properties as well as the self-association of the PN-heterocycles. The results presented herein are expected to enable the development of new photofunctional materials and provide important insights in diverse areas of supramolecular chemistry.

Exploiting the Hydrogen Bond Donor/Acceptor Properties of PN-Heterocycles: Selective Anion Receptors for Hydrogen Sulfate.

We describe two novel hybrid receptors combining a phosphorus-/nitrogen-containing (PN) phosphonamidate heterocycle with urea recognition units in an arylethynyl backbone. Structural, spectroscopic and computational studies reveal that the origin of superior binding for hydrogen sulfate (HSO4- ) anion is correlated with the formation of strong hetero-complementary hydrogen bonds with the phosphonamidate motif. We further demonstrate that the hybrid host system is capable of capturing/transporting the HSO4- anion from an aqueous, biphasic system.

Integrating larval connectivity with local demography reveals regional dynamics of a marine metapopulation.

Many ocean species exist within what are called marine metapopulations: networks of otherwise isolated local populations connected by the exchange of larval offspring. In order to manage these species as effectively as possible (e.g., by designing and implementing effective networks of marine protected areas), we must know how many offspring are produced within each local population (i.e., local demography), and where those offspring disperse (i.e., larval connectivity). Although there is much interest in estimating connectivity in the relatively simple sense of identifying the locations of spawning parents and their settling offspring, true measures of demographic connectivity that account for among-site variation in offspring production have been lacking. We combined detailed studies of local reproductive output and larval dispersal of a coral reef fish to quantify demographic connectivity within a regional metapopulation that included four widely spaced islands in the Bahamas. We present a new method for estimating demographic connectivity when the levels of dispersal among populations are inferred by the collection of genetically "tagged" offspring. We estimated that 13.3% of recruits returned to natal islands, on average (95% CI = 1.1-50.3%), that local retention was high on one of the islands (41%, 95% CI = 6.0-97.0%), and that larval connectivity was appreciable, even between islands 129 km apart (mean = 1.6%, 95% CI = 0.20-8.8%). Our results emphasize the importance of properly integrating measurements of production with measurements of connectivity. Had we not accounted for among-site variation in offspring production, our estimates of connectivity would have been inaccurate by a factor as much as 6.5. At a generational timescale, lifetime offspring production varied substantially (a fivefold difference among islands) and the importance of each island to long-term metapopulation growth was dictated by both larval production and connectivity. At the scale of our study (local populations inhabiting 5-ha reefs), the regional metapopulation could not grow without external input. However, an exploratory analysis simulating a network of four marine protected areas suggested that reserves of >65 ha each would ensure persistence of this network. Thus, integrating studies of larval connectivity and local demography hold promise for both managing and conserving marine metapopulations effectively.

Coupling Metaloid-Directed Self-Assembly and Dynamic Covalent Systems as a Route to Large Organic Cages and Cyclophanes.

The synthesis of large cyclic and caged disulfide structures was achieved by pnictogen-assisted iodine oxidation starting from self-assembled pnictogen thiolate complexes. The directing behavior of pnictogen enables rapid and selective syntheses of many discrete disulfide assemblies over competing oligomers/polymers, ranging from structures that are small and strained to those that are large and multifaceted, including 3D cages. Traditional cyclization reactions carried out under kinetic control are generally low-yielding, which often results in the formation of insoluble oligomers and polymers as unwanted side products. The prospect of self-assembling organic structures efficiently under thermodynamic control adds an attractive tool for the synthesis of cyclophanes and other large cage compounds. This method of metaloid-directed self-assembly within a dynamic covalent system allows for the rapid and discriminant self-assembly of disulfide cyclophanes without the consequences sometimes seen in traditional cyclophane syntheses such as poor yields, long reaction times, low ring-closing selectivity, and extensive purifications. The present paper provides an overview of this approach, explores the role of the pnictogen additive and solvent in this reaction, begins to test the limits of this strategy in complex 3D molecule formation, and extends our strategy to include one-pot syntheses that do not require the use of a pnictogen additive. This Viewpoint also includes an extended introduction to serve as a minireview highlighting the utility of a self-assembly approach to create organic cage structures. From a practical standpoint, the cyclophanes isolated from this method can serve as precursors in the production of insulating plastics (e.g., through the widely used parylene polymerization process, which uses derivatives of paracyclophane as monomers) or as potential hosts for molecular separations or capture.

Computational and Experimental Evidence of Emergent Equilibrium Isotope Effects in Anion Receptor Complexes.

The measurement of a deuterium equilibrium isotope effect (EIE) for the aryl CH···Cl- interaction of anion receptor 1H/1D is reported. Computations corroborate the results of solution measurements for a small, normal EIE in the full complex (KaH/KaD = 1.019 ± 0.010). Interestingly, isotope effects involving fragments of the anion receptor (urea, aryl ring, etc.) are predicted to produce an inverse effect. This points to an unusual and subtle structural organization effect of the anion receptor complex that changes the nature of the combined interactions to a normal isotope effect. The reversal of EIE values suggests that overall architecture of the anion receptor can dramatically impact the nature of bonding in these complexes.

Same Precursor, Two Different Products: Comparing the Structural Evolution of In-Ga-O "Gel-Derived" Powders and Solution-Cast Films Using Pair Distribution Function Analysis.

Amorphous metal oxides are central to a variety of technological applications. In particular, indium gallium oxide has garnered attention as a thin-film transistor channel layer material. In this work we examine the structural evolution of indium gallium oxide gel-derived powders and thin films using infrared vibrational spectroscopy, X-ray diffraction, and pair distribution function (PDF) analysis of X-ray total scattering from standard and normal incidence thin-film geometries (tfPDF). We find that the gel-derived powders and films from the same aqueous precursor evolve differently with temperature, forming mixtures of Ga-substituted In2O3 and In-substituted ß-Ga2O3 with different degrees of substitution. X-ray total scattering and PDF analysis indicate that the majority phase for both the powders and films is an amorphous/nanocrystalline ß-Ga2O3 phase, with a minor constituent of In2O3 with significantly larger coherence lengths. This amorphous ß-Ga2O3 phase could not be identified using the conventional Bragg diffraction techniques traditionally used to study crystalline metal oxide thin films. The combination of Bragg diffraction and tfPDF provides a much more complete description of film composition and structure, which can be used to detail the effect of processing conditions and structure-property relationships. This study also demonstrates how structural features of amorphous materials, traditionally difficult to characterize by standard diffraction, can be elucidated using tfPDF.